Phase I Study in Healthy Male Subjects Comparing QGC001 to Placebo

Study Overview
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Brief Summary
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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.

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

Conditions
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Essential Hypertension

Intervention / Treatment
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* Drug: QGC001 [(3S,3'S)-4,4'-dithiobis (3-aminobutane-1-sulfonic acid)]
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 10 mg of QGC001<br>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)]<br> <br> |
| Experimental: 50 mg of QGC001<br>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)]<br> <br> |
| Experimental: 125 mg of QGC001<br>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)]<br> <br> |
| Experimental: 250 mg of QGC001<br>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)]<br> <br> |
| Experimental: 500 mg of QGC001<br>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)]<br> <br> |
| Experimental: 750 mg of QGC001<br>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)]<br> <br> |
| Experimental: 1,000 mg of QGC001<br>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)]<br> <br> |
| Experimental: 1,250 mg of QGC001<br>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)]<br> <br> |
| Placebo Comparator: Placebo<br>The placebo was administered orally with 100 mL of sterile water for irrigation at 08:00 in the morning of Day 1. | Drug: Placebo<br>* Contains magnesium stearate, silica dental type, anhydrous lactose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |