A Dose-escalating Clinical Trial With KH176

Mitochondrial Disease Clinical Trial

Official title:

A Phase I, Randomized, Double Blind, Placebo-controlled, Dose-escalating Clinical Trial With KH176

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02544217
• Other study ID #: KH176-101
• Status: Completed
• Phase: Phase 1
• Start date: May 2015
• Est. completion date: October 2015

Study information

• Verified date: February 2016
• Source: Khondrion BV
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Mitochondrial Diseases are rare progressive, multi-system, often early fatal disorders affecting both children and adults. KH176 is a novel chemical entity currently under development for the treatment of inherited mitochondrial diseases, including MELAS (Mitochondrial Encephalomyopathy, Lactic acidosis, and Stroke-like episodes), Leigh's Disease and Leber's Hereditary Optic Neuropathy (LHON). KH176 is a potent intracellular redox modulating agent targeting the reactive oxygen species which are important in the pathogenesis of disorders of mitochondrial oxidative phosphorylation. After demonstrating a favourable safety profile in the pre-clinical testing, the safety, tolerability and pharmacokinetic and pharmacodynamic characteristics of the compound will now be evaluated in healthy male subjects in this trial

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: October 2015
• Est. primary completion date: September 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Healthy as assessed by medical history, physical examination, Vital Signs, Clinical Laboratory, ECG

Exclusion Criteria:

• Allergies,

• Concomitant medication,

• concomitant disease,

• relevant surgery,

• recent blood donation

Related Conditions & MeSH terms

• Leigh Disease
• Leigh Syndrome
• LHON
• MELAS
• Mitochondrial Disease
• Mitochondrial Diseases
• Mitochondrial DNA tRNALeu(UUR) m.3243A<G Mutation

Intervention

Drug:
• KH176

• placebo

Locations

Country	Name	City	State
Belgium	Drug Research Unit Ghent	Ghent

Sponsors (2)

Lead Sponsor	Collaborator
Khondrion BV	Drug Research Unit Ghent, Belgium

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	SAD: Change From Baseline in ECG Results by Timepoint: Corrected QT Interval According to Fridericia's Formula (QTcF)	The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation of the corrected QT intervals the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing. QTcF is calculated as the quotient between the QT interval in milliseconds and the cube root of the RR interval in seconds, according to Fridericia's formula.	Baseline, 1, 2, 4, 6, 8, 12, 24 hours, 7 day follow up
Primary	Pharmacodynamics of KH176	Change from baseline in biochemistry related to Oxidative Phosphorylation (OXPHOS) (glutathione, lactate); MAD group	Day 1, day 7
Primary	Relationship to Study Drug and Severity of Treatment-emergent Adverse Events		4 months
Primary	Change From Baseline in Hematology Laboratory Test Results by Timepoint: Red Blood Cell Count. SAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), 24h post dose, FU (7 days after last dosing)
Primary	Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Sedimentation Rate (SAD Group)		Baseline (pre-dose Day1), 24h post dose, FU (7 days after last dosing)
Primary	Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Sedimentation Rate MAD Group		Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days after last dosing)
Primary	Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hematocrit SAD Group	Hematocrit is a measure of the ratio of red blood cells (RBCs) in the blood by volume. Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), 24 h postdose, FU (7 days after last dosing)
Primary	Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Haemoglobin. SAD	Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), 24 h post dose, FU (7 days after last dosing)
Primary	Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Hemoglobin Concentration - SAD	Erythrocyte mean corpuscular hemoglobin concentration (MCHC) is a measure of the average concentration of hemoglobin per red blood cell. Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), 24 h post dose, FU (7 days after last dosing)
Primary	Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Volume - SAD	Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), 24 h post dose, FU (7 days after last dosing)
Primary	MAD: Change From Baseline in ECG Results by Time Point: QTcF	The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation of the corrected QT intervals the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing, or around the expected Cmax on Day 1 or 7 for the multiple-dose part.; QTcF is calculated as the quotient between the QT interval in milliseconds and the cube root of the RR interval in seconds, according to Fridericia's formula.	Baseline, Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7
Primary	Change From Baseline in Hematology Laboratory Test Results by Timepoint: White Blood Cell Count. SAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), 24h post dose, FU (7 days after last dosing)
Primary	Change From Baseline in Hematology Laboratory Test Results by Timepoint: Lymphocytes. SAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Primary	Change From Baseline in Hematology Laboratory Test Results by Timepoint: Neutrophils. SAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), 24h post dose, FU (7 days after last dosing)
Primary	Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hematocrit MAD Group	Hematocrit is a measure of the ratio of red blood cells (RBCs) in the blood by volume. Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value	Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
Primary	Change From Baseline in Hematology Laboratory Test Results by Timepoint: Eosinophils. SAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), 24h post dose, FU (7 days after last dosing)
Primary	Change From Baseline in Hematology Laboratory Test Results by Timepoint: Thrombocytes. SAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), 24h, FU (7 days post-dose)
Primary	Change From Baseline in Hematology Laboratory Test Results by Timepoint: Basophils. SAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value ateach timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), 24h post dose, FU (7 days post-dose)
Primary	Change From Baseline in Hematology Laboratory Test Results by Timepoint: Monocytes. SAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), 24h post dose, FU (7 days post-dose)
Primary	Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Volume. MAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
Primary	Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hemoglobin. MAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
Primary	Change From Baseline in Hematology Laboratory Test Results by Timepoint: White Blood Cell Count. MAD	Blood samples were collected from participants at the indicated time points for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each time point are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
Primary	Change From Baseline in Hematology Laboratory Test Results by Timepoint: Neutrophils. MAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
Primary	Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Haemoglobin Concentration. MAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
Primary	Change From Baseline in Hematology Laboratory Test Results by Timepoint: Lymphocytes. MAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
Primary	Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Hemoglobin. MAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
Primary	Change From Baseline in Hematology Laboratory Test Results by Timepoint: Red Blood Cell Count. MAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
Primary	Change From Baseline in Hematology Laboratory Test Results by Timepoint: Eosinophils. MAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
Primary	Change From Baseline in Hematology Laboratory Test Results by Timepoint: Monocytes. MAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
Primary	Change From Baseline in Hematology Laboratory Test Results by Timepoint: Thrombocytes. MAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
Primary	Change From Baseline in Hematology Laboratory Test Results by Timepoint: Basophils. MAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Aspartate Aminotransferase. SAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Total Protein. SAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Gamma-GT. SAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value	Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Alkaline Phosphatase. SAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Creatinine. SAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Chloride. SAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Total Bilirubin. SAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Alanine Aminotransferase. SAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Creatinine Kinase. SAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Urea. SAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Sodium. SAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Potassium. SAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Phosphate. SAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Calcium (Corrected for Albumin). SAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Uric Acid. SAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Triiodothyronine (T3). SAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Lipase. SAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Timepoint: (Fasting) Glucose. SAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Human Serum Albumin. SAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Cholesterol. SAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Timepoint: High Density Lipoproteins. SAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Triglycerides. SAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Low Density Lipoproteins. SAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Bicarbonate. SAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Thyroid-stimulating Hormone. SAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Thyroxine (T4). SAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Lactate. SAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Time Point: Total Protein. MAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline (pre-dose Day1), Day 3, Day 8, FU (one week after last dosing)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Time Point: Alkaline Phosphatase. MAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline, Day 3, Day 8, FU (one week after last dosing)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Time Point: Aspartate Aminotransferase. MAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline, Day 3, Day 8, FU (one week after last dosing)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Time Point: Creatine Kinase. MAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline, Day 3, Day 8, FU (one week after last dosing)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Time Point: Gamma GT. MAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline, Day 3, Day 8, FU (one week after last dosing)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Time Point: Total Bilirubin. MAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline, Day 3, Day 8, FU (one week after last dosing)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Time Point: Urea. MAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline, Day 3, Day 8, FU (one week after last dosing)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Time Point: Creatinine. MAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline, Day 3, Day 8, FU (one week after last dosing)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Time Point: Sodium. MAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline, Day 3, Day 8, FU (one week after last dosing)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Time Point: Potassium. MAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline, Day 3, Day 8, FU (one week after last dosing)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Time Point: Chloride. MAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline, Day 3, Day 8, FU (one week after last dosing)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Time Point: Calcium (Corrected for Albumin). MAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline, Day 3, Day 8, FU (one week after last dosing)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Time Point: Uric Acid. MAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline, Day 3, Day 8, FU (one week after last dosing)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Time Point: Lipase. MAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline, Day 3, Day 8, FU (one week after last dosing)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Time Point: Alanine Aminotransferase. MAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline, Day 3, Day 8, FU (one week after last dosing)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Time Point: Phosphate. MAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline, Day 3, Day 8, FU (one week after last dosing)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Time Point: Human Serum Albumin. MAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline, Day 3, Day 8, FU (one week after last dosing)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Time Point: Fasting Glucose. MAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline, Day 3, Day 8, FU (one week after last dosing)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Time Point: Cholesterol. MAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline, Day 3, Day 8, FU (one week after last dosing)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Time Point: Triglycerides. MAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline, Day 3, Day 8, FU (one week after last dosing)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Time Point: Low Density Lipoproteins. MAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline, Day 3, Day 8, FU (one week after last dosing)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Time Point: High Density Lipoproteins. MAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline, Day 3, Day 8, FU (one week after last dosing)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Time Point: Thyroid-stimulating Hormone. MAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline, Day 3, Day 8, FU (one week after last dosing)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Time Point: Trilodothyronine (T3). MAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline, Day 3, Day 8, FU (one week after last dosing)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Time Point: Thyroxine (T4). MAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline, Day 3, Day 8, FU (one week after last dosing)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Time Point: Bicarbonate. MAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline, Day 3, Day 8, FU (one week after last dosing)
Primary	Change From Baseline in Chemistry Laboratory Test Results by Time Point: Lactate. MAD Group	Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.	Baseline, Day 3, Day 8, FU (one week after last dosing)
Primary	Phospholipidosis	Change from Day 1 to Day 7 in di-docosahexaenoyl (22:6)-bis(monoacylglycerol) phosphate (di-22:6-BMP) and normalized di-22:6-BMP (urine) - MAD	Day 1, Day 7
Primary	MAD: Change From Baseline in ECG Results by Time Point: Corrected QT Interval According to Barret's Formaula (QTcB)	The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing, or around the expected Cmax on Day 1 or 7 for the multiple- dose part.	Baseline (pre-dose Day 1), Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Follow-up
Primary	MAD: Change From Baseline in ECG Results by Time Point: P Wave-Q Wave Interval (PQ Interval)	The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation of the PQ interval the average of the 3 recordings will be taken as baseline.	Baseline (pre-dose Day 1), Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Follow-up
Primary	MAD: Change From Baseline in ECG Results by Time Point: the Interval That Denotes Depolarization of the Ventricles, Between the Beginning of the Q Wave and the End of the S Wave (QRS Interval)	The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing, or around the expected Cmax on Day 1 or 7 for the multiple- dose part.	Baseline (pre-dose Day 1), Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Follow-up
Primary	MAD: Change From Baseline in ECG Results by Time Point: QT Interval	The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing, or around the expected Cmax on Day 1 or 7 for the multiple- dose part.	Baseline (pre-dose Day 1), Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Follow-up
Primary	SAD: Change From Baseline in ECG Results by Time Point: PQ Interval	The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline.	Pre-dose, Day 1, Day 7
Primary	SAD: Change From Baseline in ECG Results by Time Point: QRS Interval	The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline.	Pre-dose, Day 1, Day 7
Primary	SAD: Change From Baseline in ECG Results by Time Point: QT Interval	The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline.	Pre-dose, Day 1, Day 7
Primary	SAD: Change From Baseline in ECG Results by Time Point: QTcB Interval	The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline.	Pre-dose, Day1, Day 7
Primary	Terminal Elimination Half-life (T1/2) of KH176 Over 24 Hours: SAD	Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.	Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose
Primary	Terminal Elimination Half-life (T1/2) of KH183: SAD	Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d.	Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose
Primary	Maximum Concentration (Cmax) of KH176: SAD Group	Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.	Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose
Primary	Maximum Concentration (Cmax) of KH183 Over 24 Hours: SAD	Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d.	Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose
Primary	Maximum Concentration (Cmax) of KH183 (Active Metabolite of KH176): MAD Group	Plasma concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.: Cmax was obtained directly from the concentration-time data.	Predose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours
Primary	Maximum Concentration (Cmax) of KH176: MAD	Plasma concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.	pre-dose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours
Primary	Time to Maximum Concentration (Tmax) of KH176 Over 24 Hours: SAD	Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.	Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose
Primary	Time to Reach Peak Plasma Concentration (Tmax) of KH183: SAD	Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.	Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose
Primary	Time to Maximum Concentration (Tmax) of KH176 at Day 1, Day 7: MAD Group	Plasma concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.	pre-dose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours
Primary	Time to Maximum Concentration (Tmax) of KH183 (Active Metabolite of KH176): MAD Group	Plasma concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.. tmax was obtained directly from the concentration-time data.	Predose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours
Primary	Accumulation Factor (Racc) of KH176 Over 7 Days: MAD Group	Plasma concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.. Racc was calculated as follows: AUCtau day 7/ AUCtau day 1.	Pre-dose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours
Primary	Accumulation Factor (Racc) of KH183 (Active Metabolite of KH176): MAD Group	Plasma concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.: Accumulation factor was calculated as follows: AUCtau day 7/ AUCtau day 1.	Predose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours
Primary	Area Under the Plasma Concentration Versus Time Curve (AUClast) of KH183: SAD Group	Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d.	Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose
Primary	Area Under the Plasma Concentration Versus Time Curve (AUClast) of KH176: SAD Group	Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.	pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose
Primary	Area Under the Plasma Concentration-time Curve (AUCtau) of KH176: MAD Group:	Plasma concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.	Pre-dose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours
Primary	Area Under the Plasma Concentration-time Curve During a Dose Interval (AUCtau) of KH183 (Active Metabolite of KH176): MAD Group	Plasma concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.	Predose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours
Primary	Area Under the Plasma Concentration-time Curve From Time Zero Until Infinity (AUCl0-inf) of KH183: SAD	Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d.	Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose
Primary	Area Under the Plasma Concentration-time Curve From Time Zero Until Infinity (AUCl0-inf) of KH176: SAD	Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d.	Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose
Primary	KH176: Percentage of Administered Dose Excreted in Urine: SAD	Urine concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.	24 hours post-dose
Primary	KH183: Percentage of Administered Dose Excreted in Urine: SAD	Urine concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.	24 hours post-dose
Primary	KH176 + KH183: Percentage of Administered Dose Excreted in Urine: SAD	Urine concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.	24 hours post-dose
Primary	KH176: Percentage of Administered Dose Excreted in Urine: MAD	Urine concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.	Day 7 post dose
Primary	KH183: Percentage of Administered Dose Excreted in Urine: MAD	Urine concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.	Post dose Day 7
Primary	KH173 + KH183: Percentage of Administered Dose Excreted in Urine: MAD	Urine concentrations of KH176 and KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.	Day 7 Post dose