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

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.

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.

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): 69
• 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: Yes
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 500 mg bid of QGC001; Each dose of QGC001 will be administered in solution with 200 mL of purified water.	Drug: QGC001 [(3S,3'S)-4,4'-dithiobis (3-aminobutane-1-sulfonic acid)]
Experimental: 750 mg bid of QGC001; Each dose of QGC001 will be administered in solution with 200 mL of purified water.	Drug: QGC001 [(3S,3'S)-4,4'-dithiobis (3-aminobutane-1-sulfonic acid)]
Experimental: 1,000 mg bid of QGC001; Each dose of QGC001 will be administered in solution with 200 mL of purified water.	Drug: QGC001 [(3S,3'S)-4,4'-dithiobis (3-aminobutane-1-sulfonic acid)]
Placebo Comparator: Placebo; The placebo will be administered in solution with 200 mL of purified water.	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 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Red blood cell count	up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Haemoglobin	up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Haematocrit	up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
White blood cell count with differential	up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Platelet count	up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Plasma sodium	up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Plasma potassium	up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Plasma calcium	up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Plasma total bilirubin	up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Plasma conjugated bilirubin	up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Plasma Aspartate Amino Transferase (ASAT)	up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Plasma Alanine Amino Transferase (ALAT)	up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Plasma Gamma Glutamyl Transferase (GGT)	up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Plasma alkaline phosphatases	up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Plasma total protein	up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Plasma Creatine PhosphoKinase (CPK)	up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Plasma creatinine	up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Plasma glucose	up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Plasma cholesterol	up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Plasma triglycerides	up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Urinary pH	up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Urinary protein	up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Urinary glucose	up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Urinary leukocytes	up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Urinary nitrites	up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Urinary ketones	up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Urinary blood	up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Weight assessment (kg)	up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Body temperature (°C)	up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Supine and orthostatic (systolic and diastolic) blood pressure	up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Heart rate	up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
12-lead ECG	up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Elimination rate constant (λz) 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
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
Area Under the Concentration-time curve (AUClast and AUC0-∞) 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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Systolic and Diastolic Blood Pressure	Cohorts MAD 1 to 3.	up to 8 days for MAD
Heart Rate	Cohorts MAD 1 to 3.	up to 8 days for MAD

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: December 1, 2012
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: June 27, 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: QGC001/1QG2