Phase I Study in Healthy Male Subjects Comparing QGC001 to Placebo

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

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.

Study Overview

• Status: Completed
• Conditions: Essential Hypertension
• Intervention / Treatment: Drug: QGC001 [(3S,3'S)-4,4'-dithiobis (3-aminobutane-1-sulfonic acid)]; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Rueil-Malmaison, France, 92502
    • Biotrial PARIS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 10 mg of QGC001; Each dose of QGC001 was administered orally with 100 mL of sterile water for irrigation at 08:00 in the morning of Day 1.	Drug: QGC001 [(3S,3'S)-4,4'-dithiobis (3-aminobutane-1-sulfonic acid)]
Experimental: 50 mg of QGC001; Each dose of QGC001 was administered orally with 100 mL of sterile water for irrigation at 08:00 in the morning of Day 1.	Drug: QGC001 [(3S,3'S)-4,4'-dithiobis (3-aminobutane-1-sulfonic acid)]
Experimental: 125 mg of QGC001; Each dose of QGC001 was administered orally with 100 mL of sterile water for irrigation at 08:00 in the morning of Day 1.	Drug: QGC001 [(3S,3'S)-4,4'-dithiobis (3-aminobutane-1-sulfonic acid)]
Experimental: 250 mg of QGC001; Each dose of QGC001 was administered orally with 100 mL of sterile water for irrigation at 08:00 in the morning of Day 1.	Drug: QGC001 [(3S,3'S)-4,4'-dithiobis (3-aminobutane-1-sulfonic acid)]
Experimental: 500 mg of QGC001; Each dose of QGC001 was administered orally with 100 mL of sterile water for irrigation at 08:00 in the morning of Day 1.	Drug: QGC001 [(3S,3'S)-4,4'-dithiobis (3-aminobutane-1-sulfonic acid)]
Experimental: 750 mg of QGC001; Each dose of QGC001 was administered orally with 100 mL of sterile water for irrigation at 08:00 in the morning of Day 1.	Drug: QGC001 [(3S,3'S)-4,4'-dithiobis (3-aminobutane-1-sulfonic acid)]
Experimental: 1,000 mg of QGC001; Each dose of QGC001 was administered orally with 100 mL of sterile water for irrigation at 08:00 in the morning of Day 1.	Drug: QGC001 [(3S,3'S)-4,4'-dithiobis (3-aminobutane-1-sulfonic acid)]
Experimental: 1,250 mg of QGC001; Each dose of QGC001 was administered orally with 100 mL of sterile water for irrigation at 08:00 in the morning of Day 1.	Drug: QGC001 [(3S,3'S)-4,4'-dithiobis (3-aminobutane-1-sulfonic acid)]
Placebo Comparator: Placebo; The placebo was administered orally with 100 mL of sterile water for irrigation at 08:00 in the morning of Day 1.	Drug: Placebo; Contains magnesium stearate, silica dental type, anhydrous lactose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Adverse events	up to 11 days
Blood pressure	up to 11 days
Heart rate	up to 11 days
Body temperature	up to 11 days
12-lead ECG	up to 11 days
Red blood cell count	up to 11 days
Haemoglobin	up to 11 days
Haematocrit	up to 11 days
White blood cell count with differential	up to 11 days
Platelet count	up to 11 days
Plasma sodium	up to 11 days
Plasma potassium	up to 11 days
Plasma calcium	up to 11 days
Plasma total bilirubin	up to 11 days
Plasma conjugated bilirubin	up to 11 days
Plasma Aspartate Amino Transferase (ASAT)	up to 11 days
Plasma Alanine Amino Transferase (ALAT)	up to 11 days
Plasma Gamma Glutamyl Transferase (GGT)	up to 11 days
Plasma alkaline phosphatases	up to 11 days
Plasma total protein	up to 11 days
Plasma Creatine PhosphoKinase (CPK)	up to 11 days
Plasma creatinine	up to 11 days
Plasma glucose	up to 11 days
Plasma cholesterol	up to 11 days
Plasma triglycerides	up to 11 days
Urinary pH	up to 11 days
Urinary protein	up to 11 days
Urinary glucose	up to 11 days
Urinary leukocytes	up to 11 days
Urinary nitrites	up to 11 days
Urinary ketones	up to 11 days
Urinary blood	up to 11 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Elimination rate constant (λz) of QGC001		H0, H 0.5, H1, H1.5, H2, H3, H4, H5, H6, H9, H12, H24 and H48 post-dose
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
Area Under the Concentration-time curve (AUClast and AUC0-∞) of QGC001		H0, H 0.5, H1, H1.5, H2, H3, H4, H5, H6, H9, H12, H24 and H48 post-dose
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
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
Cumulative amount eliminated (Ae)		H-12 to H0 pre-dose and H0- H6, H6-H12 and H12-H24 post-dose
Fraction recovered (Fe)		H-12 to H0 pre-dose and H0- H6, H6-H12 and H12-H24 post-dose
Renal clearance (CLR)		H-12 to H0 pre-dose and H0- H6, H6-H12 and H12-H24 post-dose
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Quantum Genomics SA

Publications and helpful links

General Publications

• Khosla J, Aronow WS, Frishman WH. Firibastat: An Oral First-in-Class Brain Aminopeptidase A Inhibitor for Systemic Hypertension. Cardiol Rev. 2022 Jan-Feb 01;30(1):50-55. doi: 10.1097/CRD.0000000000000360.

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: June 26, 2013
• First Submitted That Met QC Criteria: July 11, 2013
• First Posted (Estimate): July 16, 2013

Study Record Updates

• Last Update Posted (Estimate): July 16, 2013
• Last Update Submitted That Met QC Criteria: July 11, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Essential Hypertension
• Other Study ID Numbers: QGC001/1QG1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No