Phase I Study in Healthy Male Subjects Comparing QGC001 to Placebo

Essential Hypertension Clinical Trial

Official title:

A Phase I, Double-blind, Placebo-controlled, Ascending Single-dose, Safety, Tolerability and Pharmacokinetic Study of QGC001 in Healthy Male Subjects.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01900171
• Other study ID #: QGC001/1QG1
• Status: Completed
• Phase: Phase 1
• First received: June 26, 2013
• Last updated: July 11, 2013
• Start date: February 2012
• Est. completion date: May 2012

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
• Study type: Interventional

Clinical Trial Summary

QGC001/1QG1 is a Phase I "first time in man" study aiming to determine the overall safety and tolerability of single ascending oral doses of QGC001 in healthy male subjects compared to placebo, as well as the pharmacokinetics of QGC001 and its metabolite EC33 and the pharmacodynamic properties of QGC001 (effects on the renin-angiotensin-aldosterone system, blood pressure and heart rate) in healthy male subjects.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: May 2012
• Est. primary completion date: May 2012
• 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.

• 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 11 days	Yes
Primary	Blood pressure		up to 11 days	Yes
Primary	Heart rate		up to 11 days	Yes
Primary	Body temperature		up to 11 days	Yes
Primary	12-lead ECG		up to 11 days	Yes
Primary	Red blood cell count		up to 11 days	Yes
Primary	Haemoglobin		up to 11 days	Yes
Primary	Haematocrit		up to 11 days	Yes
Primary	White blood cell count with differential		up to 11 days	Yes
Primary	Platelet count		up to 11 days	Yes
Primary	Plasma sodium		up to 11 days	Yes
Primary	Plasma potassium		up to 11 days	Yes
Primary	Plasma calcium		up to 11 days	Yes
Primary	Plasma total bilirubin		up to 11 days	Yes
Primary	Plasma conjugated bilirubin		up to 11 days	Yes
Primary	Plasma Aspartate Amino Transferase (ASAT)		up to 11 days	Yes
Primary	Plasma Alanine Amino Transferase (ALAT)		up to 11 days	Yes
Primary	Plasma Gamma Glutamyl Transferase (GGT)		up to 11 days	Yes
Primary	Plasma alkaline phosphatases		up to 11 days	Yes
Primary	Plasma total protein		up to 11 days	Yes
Primary	Plasma Creatine PhosphoKinase (CPK)		up to 11 days	Yes
Primary	Plasma creatinine		up to 11 days	Yes
Primary	Plasma glucose		up to 11 days	Yes
Primary	Plasma cholesterol		up to 11 days	Yes
Primary	Plasma triglycerides		up to 11 days	Yes
Primary	Urinary pH		up to 11 days	Yes
Primary	Urinary protein		up to 11 days	Yes
Primary	Urinary glucose		up to 11 days	Yes
Primary	Urinary leukocytes		up to 11 days	Yes
Primary	Urinary nitrites		up to 11 days	Yes
Primary	Urinary ketones		up to 11 days	Yes
Primary	Urinary blood		up to 11 days	Yes
Secondary	Maximum observed plasma concentration (Cmax) of QGC001		H0, H 0.5, H1, H1.5, H2, H3, H4, H5, H6, H9, H12, H24 and H48 post-dose	No
Secondary	Time at which Cmax is observed (tmax) of QGC001		H0, H 0.5, H1, H1.5, H2, H3, H4, H5, H6, H9, H12, H24 and H48 post-dose	No
Secondary	Elimination rate constant (?z) of QGC001		H0, H 0.5, H1, H1.5, H2, H3, H4, H5, H6, H9, H12, H24 and H48 post-dose	No
Secondary	Terminal half-life (t1/2,z) of QGC001		H0, H 0.5, H1, H1.5, H2, H3, H4, H5, H6, H9, H12, H24 and H48 post-dose	No
Secondary	Area Under the Concentration-time curve (AUClast and AUC0-8) of QGC001		H0, H 0.5, H1, H1.5, H2, H3, H4, H5, H6, H9, H12, H24 and H48 post-dose	No
Secondary	Maximum observed plasma concentration (MRCmax) of metabolic ratios		H0, H 0.5, H1, H1.5, H2, H3, H4, H5, H6, H9, H12, H24 and H48 post-dose	No
Secondary	Area Under the Concentration-time curve (MRAUC) of metabolic ratios		H0, H 0.5, H1, H1.5, H2, H3, H4, H5, H6, H9, H12, H24 and H48 post-dose	No
Secondary	Cumulative amount eliminated (Ae)		H-12 to H0 pre-dose and H0- H6, H6-H12 and H12-H24 post-dose	No
Secondary	Fraction recovered (Fe)		H-12 to H0 pre-dose and H0- H6, H6-H12 and H12-H24 post-dose	No
Secondary	Renal clearance (CLR)		H-12 to H0 pre-dose and H0- H6, H6-H12 and H12-H24 post-dose	No
Secondary	Plasma renin	Determination of renin in blood samples. In dose groups 1 and 2, no pharmacodynamic evaluations will be done.	H-1 pre-dose and H2, H4 and H9 post-dose	No
Secondary	Plasma aldosterone	Determination of aldosterone in blood samples. In dose groups 1 and 2, no pharmacodynamic evaluations will be done.	H-1 pre-dose and H2, H4 and H9 post-dose	No
Secondary	Plasma cortisol	Determination of cortisol in blood samples. In dose groups 1 and 2, no pharmacodynamic evaluations will be done.	H-1 pre-dose and H2, H4 and H9 post-dose	No
Secondary	Plasma copeptin	Determination of copeptin in blood samples (if possible, will be determined later). In dose groups 1 and 2, no pharmacodynamic evaluations will be done.	H-1 pre-dose and H2, H4 and H9 post-dose	No
Secondary	Urinary aldosterone	Aldosterone analysis in urine samples. In dose groups 1 and 2, no pharmacodynamic evaluations will be done.	H-12 to H0 pre-dose, H0-H6, H6-H12 and H12-H24 post-dose	No
Secondary	Urinary cortisol	Cortisol analysis in urine samples. In dose groups 1 and 2, no pharmacodynamic evaluations will be done.	H-12 to H0 pre-dose, H0-H6, H6-H12 and H12-H24 post-dose	No
Secondary	Urinary creatinin	Creatinin analysis in urine samples. In dose groups 1 and 2, no pharmacodynamic evaluations will be done.	H-12 to H0 pre-dose, H0-H6, H6-H12 and H12-H24 post-dose	No