Study to investigate the efficacy of QGC001 in patients affected by high blood pressure.
- Conditions
- Hyperactivity of the brain renin-angiotensin system participates to the development and maintenance of essential HypertensionMedDRA version: 18.0Level: PTClassification code 10015488Term: Essential hypertensionSystem Organ Class: 10047065 - Vascular disordersTherapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2014-003071-37-FR
- Lead Sponsor
- Quantum Genomics
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 40
1. Male and female of non-childbearing potential patients (post-menopausal since at least 12 months or surgically sterilized) aged 18 to 75 years of age;
2. Body weight =50 kg with a body mass index (BMI) calculated as weight in kg/(height in m2) from 18 to 40 kg/m2 at screening;
3. A signed and dated informed consent form before any study-specific screening procedure is performed;
4. With a diagnosis of essential grade I or II hypertension defined as:
• a supine office systolic BP (SBP) of 140–159 mmHg or diastolic BP (DBP) of 90–99 mmHg who should have an additional clinical indication for antihypertensive treatment according to ESH guidelines after a 2-week placebo run-in period,
• or a supine office SBP of 160-179 mmHg or DBP of 100–109 mmHg after a 2-week placebo run-in period with a diagnosis of essential grade II hypertension;
5. The diagnosis of permanent hypertension will be confirmed by a mean SBP or DBP higher than 135 or 85 mmHg on daytime ambulatory blood pressure monitoring (ABPM) after a 2-week placebo run-in period;
6. Estimated glomerular filtration rate (Modification of Diet in Renal Disease (MDRD) formula) = 60 ml/min/1.73 m2.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 16
1. Any significant hepatic, renal, respiratory (e.g., asthma), gastrointestinal, endocrine (e.g., diabetes, dyslipidemia necessitating drug therapy), immunologic, dermatological, hematological, neurologic, psychiatric disease or history of any clinically important drug
allergy;
2. Acute disease state (e.g., vomiting, fever, diarrhea) within 7 days before study day 1;
3. History of transient ischemic accident (TIA) or cerebrovascular accident (CVA) during the 6 months prior to screening;
4. History of acute heart failure or heart failure (NYHA class II-IV) within the 6 months prior to screening;
5. History of myocardial infarction, unstable angina, coronary bypass or percutaneous coronary angioplasty during the 6 months prior to screening;
6. History of malignant tumor during the past 5 years;
7. Any medical or surgical disorder considered by the investigator as increasing the risks of participation in the study, or liable to prevent the patient from complying with the equirements of the study or from continuing the study to completion;
8. Any situation which, in the investigator's opinion, might compromise assessment of efficacy or of safety;
9. History of non-adherence to treatment;
10. History of drug abuse within 1 year before study day 1;
11. History of alcoholism within 1 year before day 1;
12. Positive serologic findings for human immunodeficiency virus (HIV) antibodies, hepatitis Bsurface antigen (HBsAg), and/or hepatitis C virus (HCV) antibodies;
13. Use of any investigational drug within 30 days before IMP administration;
14. Donation of blood (i.e., 500 ml) within 90 days before study day 1;
15. Known secondary hypertension;
16. Grade III hypertension;
17. Estimated glomerular filtration rate (MDRD formula) below 60 ml/min/1.73 m2;
18. Type I diabetes mellitus or uncontrolled type II diabetes mellitus (HbA1C = 10%);
19. Severe obesity (BMI = 40 kg/m2);
20. Arm circumference = 42 cm;
21. Atrial fibrillation;
22. Known hypersensitivity to drugs;
23. History of spontaneous or drug induced angioneurotic edema;
24. Use of any medication of the following medications within the four (4) weeks prior to dosing.
• Thyroid medication, statin therapy, oral antidiabetic drugs, estrogen replacement therapy and/or chronic low dose aspirin (75 mg/day) unless the patient has been on a stable maintenance dose for at least 3 months prior to screening.
• Anticoagulant treatments
• Cholestyramine resins.
• Treatment with oral, topical, inhaled, eye drop corticosteroids
• Treatment with class Ia, Ib and Ic or III anti-arrhythmics
• CNS drugs
• P-glycoprotein (P-gp) inhibitors (e.g., verapamil, quinidine, ritonavir),
• known cytochrome P450 inducers or inhibitors (eg, ketoconazole/CYP3A4,quinidine/CYP2D6, gemfibrozil/CYP2C8)
• Chronic use of nonsteroidal anti-inflammatory drugs (NSAIDS) or cyclooxygenase(COX)-2 inhibitors
• Vasodilators or vascular muscle relaxants prescribed for other conditions
25. Unlikely to cooperate in the study and/or poor compliance anticipated by the investigator,e.g., uncooperative attitude, inability to return for follow-up visit, and unlikelihood of completing the study;
26. Participation in another interventional study at the same time or within 3 months prior to the beginning of the present study;
27. Participant not affiliated with the French social security;
28. No written informed consent.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: • To assess the BP lowering effect of 4-week administration of QGC001 oral doses in patients with grade I or II essential hypertension compared to placebo.;Secondary Objective: •To assess the safety and tolerability of 4-week administration of QGC001 oral doses in patients with grade I or II essential hypertension compared to placebo <br>•To obtain preliminary PK information for QGC001 given as multiple oral doses<br>•To determine preliminary PD profile of QGC001 multiple oral doses on plasma and urine hormones, which will be compared to that of placebo.<br>;Primary end point(s): The primary efficacy endpoint will be comparison of change from baseline of daytime mean systolic blood pressure (SBP) as calculated from the ambulatory blood pressure measurement (ABPM) after 4 weeks of treatment of QGC001 or placebo.;Timepoint(s) of evaluation of this end point: Throughout the study
- Secondary Outcome Measures
Name Time Method