Study of the Product QGC001 as a Single Dose and Multiple Doses Administered Orally to Healthy Adult Subjects

Essential Hypertension Clinical Trial

Official title:

Part 1: Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Ascending Single Dose and Food Influence Study of QGC001 Administered Orally To Healthy Adult Subjects, Part 2: Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Ascending Multiple Dose Study of QGC001 Administered Orally To Healthy Adult Subjects.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01900184
• Other study ID #: QGC001/1QG2
• Status: Completed
• Phase: Phase 1
• First received: June 27, 2013
• Last updated: July 11, 2013
• Start date: December 2012
• Est. completion date: March 2013

Study information

• Verified date: July 2013
• Source: Quantum Genomics SA
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé (ANSM, Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

1QG2 is a Phase 1 study aiming to assess the safety and tolerability of ascending single/multiple oral doses (SAD & MAD) in healthy young subjects, the preliminary food interaction and the effect of QGC001 on blood pressure and heart rate, but also to determine pharmacokinetic preliminary profiles of QGC001 and its metabolite EC33 and pharmacodynamic preliminary profiles of QGC001 and its metabolite EC33 especially effects on the renin-angiotensin-aldosterone and copeptin systems.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 69
• Est. completion date: March 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• Caucasian, male healthy subjects of 18 to 45 years of age (inclusive).

• Body weight =50 kg, with a body mass index calculated as weight in kg/(height in m2) from 18 to 27 kg/m2 at screening.

• Subjects will sign and date an informed consent form before any study-specific screening procedure is performed.

• Healthy, as determined by the investigator on the basis of medical history, physical examination findings, clinical laboratory test results, vital sign measurements, and digital 12 lead ECG readings.

• Non-smoker or smoker of fewer than 5 cigarettes per day as determined by history. Must be able to abstain from smoking during the inpatient stay.

• Have a high probability for compliance with and completion of the study.

Exclusion Criteria:

• Any significant cardiovascular, hepatic, renal, respiratory, gastrointestinal, endocrine, immunologic, dermatological, haematological, neurologic, psychiatric disease or history of any clinically important drug allergy.

• Acute disease state within 7 days before study day 1.

• History of drug abuse within 1 year before study day 1.

• History of alcoholism within 1 year before day 1. Consumption of more than 50 g of ethanol per day.

• Positive serologic findings for human immunodeficiency virus antibodies, hepatitis B surface antigen, and/or hepatitis C virus antibodies.

• Positive findings of urine drug screen (e.g., amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, opiates, MDMA)

• History of any clinically important drug allergy.

• Prohibited Treatments: use of any investigational drug within 90 days or prescription drug within 30 days before investigational medical product administration.

• Consumption of any caffeine-containing products in excess of 6 cups per day (or equivalent), of grapefruit, grapefruit-containing products, or alcoholic beverages within 24 hours before study day 1.

• Use of any over-the-counter drugs including herbal supplements (except for the occasional use of acetaminophen [paracetamol], aspirin and vitamins =100% recommended daily allowance) within 7 days before investigational medicinal product administration.

• Donation of blood (i.e. 450 ml) within 90 days before study day 1.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor)

Related Conditions & MeSH terms

• Essential Hypertension
• Hypertension

Intervention

Drug:
• QGC001 [(3S,3'S)-4,4'-dithiobis (3-aminobutane-1-sulfonic acid)]

• Placebo
Contains magnesium stearate, silica dental type, anhydrous lactose

Locations

Country	Name	City	State
France	Biotrial PARIS	Rueil-Malmaison

Sponsors (1)

Lead Sponsor	Collaborator
Quantum Genomics SA

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events		up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD	Yes
Primary	Red blood cell count		up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD	Yes
Primary	Haemoglobin		up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD	Yes
Primary	Haematocrit		up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD	Yes
Primary	White blood cell count with differential		up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD	Yes
Primary	Platelet count		up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD	Yes
Primary	Plasma sodium		up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD	Yes
Primary	Plasma potassium		up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD	Yes
Primary	Plasma calcium		up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD	Yes
Primary	Plasma total bilirubin		up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD	Yes
Primary	Plasma conjugated bilirubin		up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD	Yes
Primary	Plasma Aspartate Amino Transferase (ASAT)		up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD	Yes
Primary	Plasma Alanine Amino Transferase (ALAT)		up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD	Yes
Primary	Plasma Gamma Glutamyl Transferase (GGT)		up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD	Yes
Primary	Plasma alkaline phosphatases		up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD	Yes
Primary	Plasma total protein		up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD	Yes
Primary	Plasma Creatine PhosphoKinase (CPK)		up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD	Yes
Primary	Plasma creatinine		up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD	Yes
Primary	Plasma glucose		up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD	Yes
Primary	Plasma cholesterol		up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD	Yes
Primary	Plasma triglycerides		up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD	Yes
Primary	Urinary pH		up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD	Yes
Primary	Urinary protein		up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD	Yes
Primary	Urinary glucose		up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD	Yes
Primary	Urinary leukocytes		up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD	Yes
Primary	Urinary nitrites		up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD	Yes
Primary	Urinary ketones		up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD	Yes
Primary	Urinary blood		up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD	Yes
Primary	Weight assessment (kg)		up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD	Yes
Primary	Body temperature (°C)		up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD	Yes
Primary	Supine and orthostatic (systolic and diastolic) blood pressure		up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD	Yes
Primary	Heart rate		up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD	Yes
Primary	12-lead ECG		up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD	Yes
Secondary	Maximum observed plasma concentration (Cmax) of QGC001	Cohorts SAD 1 to 4 and MAD 1 to 3.	up to 3 days for SAD and FI, up to 9 days for MAD	No
Secondary	Time at which Cmax is observed (tmax) of QGC001	Cohorts SAD 1 to 4 and MAD 1 to 3.	up to 3 days for SAD and FI, up to 9 days for MAD	No
Secondary	Elimination rate constant (?z) of QGC001	Cohorts SAD 1 to 4 and MAD 1 to 3.	up to 3 days for SAD and FI, up to 9 days for MAD	No
Secondary	Terminal half-life (t1/2,z) of QGC001	Cohorts SAD 1 to 4 and MAD 1 to 3.	up to 3 days for SAD and FI, up to 9 days for MAD	No
Secondary	Area Under the Concentration-time curve (AUClast and AUC0-8) of QGC001	Cohorts SAD 1 to 4 and MAD 1 to 3.	up to 3 days for SAD and FI, up to 9 days for MAD	No
Secondary	Maximum observed plasma concentration (MRCmax) of metabolic ratios	Cohorts SAD 1 to 4 and MAD 1 to 3.	up to 3 days for SAD and FI, up to 9 days for MAD	No
Secondary	Area Under the Concentration-time curve (MRAUC) of metabolic ratios	Cohorts SAD 1 to 4 and MAD 1 to 3.	up to 3 days for SAD and FI, up to 9 days for MAD	No
Secondary	Cumulative amount eliminated (Ae)	Cohorts SAD 1 to 4 and MAD 1 to 3.	up to 2 days for SAD and FI, up to 8 days for MAD	No
Secondary	Fraction recovered (Fe)	Cohorts SAD 1 to 4 and MAD 1 to 3.	up to 2 days for SAD and FI, up to 8 days for MAD	No
Secondary	Renal clearance (CLR)	Cohorts SAD 1 to 4 and MAD 1 to 3.	up to 2 days for SAD and FI, up to 8 days for MAD	No
Secondary	Plasma renin	Determination of renin in blood samples. Cohorts SAD 1 to 3 and MAD 1 to 3.	up to 2 days for SAD and FI, up to 8 days for MAD	No
Secondary	Plasma aldosterone	Determination of aldosterone in blood samples. Cohorts SAD 1 to 3 and MAD 1 to 3.	up to 2 days for SAD and FI, up to 8 days for MAD	No
Secondary	Plasma cortisol	Determination of cortisol in blood samples. Cohorts SAD 1 to 3 and MAD 1 to 3.	up to 2 days for SAD and FI, up to 8 days for MAD	No
Secondary	Plasma copeptin	Determination of copeptin in blood samples. Cohorts SAD 1 to 3 and MAD 1 to 3.	up to 2 days for SAD and FI, up to 8 days for MAD	No
Secondary	Urinary aldosterone	Aldosterone analysis in urine samples. Cohorts SAD 1 to 3 and MAD 1 to 3.	up to 2 days for SAD and FI, up to 8 days for MAD	No
Secondary	Urinary cortisol	Cortisol analysis in urine samples. Cohorts SAD 1 to 3 and MAD 1 to 3.	up to 2 days for SAD and FI, up to 8 days for MAD	No
Secondary	Urinary sodium	Sodium analysis in urine samples. Cohorts SAD 1 to 3 and MAD 1 to 3.	up to 2 days for SAD and FI, up to 8 days for MAD	No
Secondary	Urinary potassium	Potassium analysis in urine samples. Cohorts SAD 1 to 3 and MAD 1 to 3.	up to 2 days for SAD and FI, up to 8 days for MAD	No
Secondary	Urinary creatinine	Creatinine analysis in urine samples. Cohorts SAD 1 to 3 and MAD 1 to 3.	up to 2 days for SAD and FI, up to 8 days for MAD	No
Secondary	Systolic and Diastolic Blood Pressure	Cohorts MAD 1 to 3.	up to 8 days for MAD	No
Secondary	Heart Rate	Cohorts MAD 1 to 3.	up to 8 days for MAD	No