Clinical trial NCT01900171: Phase I Study in Healthy Male Subjects Comparing QGC001 to Placebo
Official title: A Phase I, Double-blind, Placebo-controlled, Ascending Single-dose, Safety, Tolerability and Pharmacokinetic Study of QGC001 in Healthy Male 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: 56
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Adverse events
timeFrame: up to 11 days
measure: Blood pressure
timeFrame: up to 11 days
measure: Heart rate
timeFrame: up to 11 days
measure: Body temperature
timeFrame: up to 11 days
measure: 12-lead ECG
timeFrame: up to 11 days
measure: Red blood cell count
timeFrame: up to 11 days
measure: Haemoglobin
timeFrame: up to 11 days
measure: Haematocrit
timeFrame: up to 11 days
measure: White blood cell count with differential
timeFrame: up to 11 days
measure: Platelet count
timeFrame: up to 11 days
measure: Plasma sodium
timeFrame: up to 11 days
measure: Plasma potassium
timeFrame: up to 11 days
measure: Plasma calcium
timeFrame: up to 11 days
measure: Plasma total bilirubin
timeFrame: up to 11 days
measure: Plasma conjugated bilirubin
timeFrame: up to 11 days
measure: Plasma Aspartate Amino Transferase (ASAT)
timeFrame: up to 11 days
measure: Plasma Alanine Amino Transferase (ALAT)
timeFrame: up to 11 days
measure: Plasma Gamma Glutamyl Transferase (GGT)
timeFrame: up to 11 days
measure: Plasma alkaline phosphatases
timeFrame: up to 11 days
measure: Plasma total protein
timeFrame: up to 11 days
measure: Plasma Creatine PhosphoKinase (CPK)
timeFrame: up to 11 days
measure: Plasma creatinine
timeFrame: up to 11 days
measure: Plasma glucose
timeFrame: up to 11 days
measure: Plasma cholesterol
timeFrame: up to 11 days
measure: Plasma triglycerides
timeFrame: up to 11 days
measure: Urinary pH
timeFrame: up to 11 days
measure: Urinary protein
timeFrame: up to 11 days
measure: Urinary glucose
timeFrame: up to 11 days
measure: Urinary leukocytes
timeFrame: up to 11 days
measure: Urinary nitrites
timeFrame: up to 11 days
measure: Urinary ketones
timeFrame: up to 11 days
measure: Urinary blood
timeFrame: up to 11 days
Secondary outcomes:
measure: Maximum observed plasma concentration (Cmax) of QGC001
timeFrame: H0, H 0.5, H1, H1.5, H2, H3, H4, H5, H6, H9, H12, H24 and H48 post-dose
measure: Time at which Cmax is observed (tmax) of QGC001
timeFrame: H0, H 0.5, H1, H1.5, H2, H3, H4, H5, H6, H9, H12, H24 and H48 post-dose
measure: Elimination rate constant (λz) of QGC001
timeFrame: H0, H 0.5, H1, H1.5, H2, H3, H4, H5, H6, H9, H12, H24 and H48 post-dose
measure: Terminal half-life (t1/2,z) of QGC001
timeFrame: H0, H 0.5, H1, H1.5, H2, H3, H4, H5, H6, H9, H12, H24 and H48 post-dose
measure: Area Under the Concentration-time curve (AUClast and AUC0-∞) of QGC001
timeFrame: H0, H 0.5, H1, H1.5, H2, H3, H4, H5, H6, H9, H12, H24 and H48 post-dose
measure: Maximum observed plasma concentration (MRCmax) of metabolic ratios
timeFrame: H0, H 0.5, H1, H1.5, H2, H3, H4, H5, H6, H9, H12, H24 and H48 post-dose
measure: Area Under the Concentration-time curve (MRAUC) of metabolic ratios
timeFrame: H0, H 0.5, H1, H1.5, H2, H3, H4, H5, H6, H9, H12, H24 and H48 post-dose
measure: Cumulative amount eliminated (Ae)
timeFrame: H-12 to H0 pre-dose and H0- H6, H6-H12 and H12-H24 post-dose
measure: Fraction recovered (Fe)
timeFrame: H-12 to H0 pre-dose and H0- H6, H6-H12 and H12-H24 post-dose
measure: Renal clearance (CLR)
timeFrame: H-12 to H0 pre-dose and H0- H6, H6-H12 and H12-H24 post-dose
measure: Plasma renin
timeFrame: H-1 pre-dose and H2, H4 and H9 post-dose
measure: Plasma aldosterone
timeFrame: H-1 pre-dose and H2, H4 and H9 post-dose
measure: Plasma cortisol
timeFrame: H-1 pre-dose and H2, H4 and H9 post-dose
measure: Plasma copeptin
timeFrame: H-1 pre-dose and H2, H4 and H9 post-dose
measure: Urinary aldosterone
timeFrame: H-12 to H0 pre-dose, H0-H6, H6-H12 and H12-H24 post-dose
measure: Urinary cortisol
timeFrame: H-12 to H0 pre-dose, H0-H6, H6-H12 and H12-H24 post-dose
measure: Urinary creatinin
timeFrame: H-12 to H0 pre-dose, H0-H6, H6-H12 and H12-H24 post-dose
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.