Clinical trial NCT01900184: Study of the Product QGC001 as a Single Dose and Multiple Doses Administered Orally to Healthy Adult Subjects
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Essential Hypertension
Lead sponsor: Quantum Genomics SA
Sponsor class: INDUSTRY
First posted: 2013-07-16
Enrollment: 69
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Adverse events
timeFrame: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
measure: Red blood cell count
timeFrame: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
measure: Haemoglobin
timeFrame: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
measure: Haematocrit
timeFrame: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
measure: White blood cell count with differential
timeFrame: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
measure: Platelet count
timeFrame: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
measure: Plasma sodium
timeFrame: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
measure: Plasma potassium
timeFrame: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
measure: Plasma calcium
timeFrame: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
measure: Plasma total bilirubin
timeFrame: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
measure: Plasma conjugated bilirubin
timeFrame: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
measure: Plasma Aspartate Amino Transferase (ASAT)
timeFrame: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
measure: Plasma Alanine Amino Transferase (ALAT)
timeFrame: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
measure: Plasma Gamma Glutamyl Transferase (GGT)
timeFrame: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
measure: Plasma alkaline phosphatases
timeFrame: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
measure: Plasma total protein
timeFrame: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
measure: Plasma Creatine PhosphoKinase (CPK)
timeFrame: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
measure: Plasma creatinine
timeFrame: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
measure: Plasma glucose
timeFrame: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
measure: Plasma cholesterol
timeFrame: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
measure: Plasma triglycerides
timeFrame: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
measure: Urinary pH
timeFrame: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
measure: Urinary protein
timeFrame: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
measure: Urinary glucose
timeFrame: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
measure: Urinary leukocytes
timeFrame: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
measure: Urinary nitrites
timeFrame: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
measure: Urinary ketones
timeFrame: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
measure: Urinary blood
timeFrame: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
measure: Weight assessment (kg)
timeFrame: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
measure: Body temperature (°C)
timeFrame: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
measure: Supine and orthostatic (systolic and diastolic) blood pressure
timeFrame: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
measure: Heart rate
timeFrame: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
measure: 12-lead ECG
timeFrame: up to 4 weeks for SAD, 5 weeks for FI and 6 weeks for MAD
Secondary outcomes:
measure: Maximum observed plasma concentration (Cmax) of QGC001
timeFrame: up to 3 days for SAD and FI, up to 9 days for MAD
measure: Time at which Cmax is observed (tmax) of QGC001
timeFrame: up to 3 days for SAD and FI, up to 9 days for MAD
measure: Elimination rate constant (λz) of QGC001
timeFrame: up to 3 days for SAD and FI, up to 9 days for MAD
measure: Terminal half-life (t1/2,z) of QGC001
timeFrame: up to 3 days for SAD and FI, up to 9 days for MAD
measure: Area Under the Concentration-time curve (AUClast and AUC0-∞) of QGC001
timeFrame: up to 3 days for SAD and FI, up to 9 days for MAD
measure: Maximum observed plasma concentration (MRCmax) of metabolic ratios
timeFrame: up to 3 days for SAD and FI, up to 9 days for MAD
measure: Area Under the Concentration-time curve (MRAUC) of metabolic ratios
timeFrame: up to 3 days for SAD and FI, up to 9 days for MAD
measure: Cumulative amount eliminated (Ae)
timeFrame: up to 2 days for SAD and FI, up to 8 days for MAD
measure: Fraction recovered (Fe)
timeFrame: up to 2 days for SAD and FI, up to 8 days for MAD
measure: Renal clearance (CLR)
timeFrame: up to 2 days for SAD and FI, up to 8 days for MAD
measure: Plasma renin
timeFrame: up to 2 days for SAD and FI, up to 8 days for MAD
measure: Plasma aldosterone
timeFrame: up to 2 days for SAD and FI, up to 8 days for MAD
measure: Plasma cortisol
timeFrame: up to 2 days for SAD and FI, up to 8 days for MAD
measure: Plasma copeptin
timeFrame: up to 2 days for SAD and FI, up to 8 days for MAD
measure: Urinary aldosterone
timeFrame: up to 2 days for SAD and FI, up to 8 days for MAD
measure: Urinary cortisol
timeFrame: up to 2 days for SAD and FI, up to 8 days for MAD
measure: Urinary sodium
timeFrame: up to 2 days for SAD and FI, up to 8 days for MAD
measure: Urinary potassium
timeFrame: up to 2 days for SAD and FI, up to 8 days for MAD
measure: Urinary creatinine
timeFrame: up to 2 days for SAD and FI, up to 8 days for MAD
measure: Systolic and Diastolic Blood Pressure
timeFrame: up to 8 days for MAD
measure: Heart Rate
timeFrame: up to 8 days for MAD
Other outcomes:
Locations:
city: Rueil-Malmaison
country: France
facility: Biotrial PARIS
Study officials:
References:
citation: 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.