E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10038274 |
E.1.2 | Term | Refractory hypertension |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to determine if darusentan is effective in reducing SBP in subjects with RHTN, despite treatment with full doses of three or more antihypertensive drugs, including a diuretic. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives of this study are to examine the effect of darusentan on trough sitting DBP, mean 24-hour ambulatory blood pressure, percent of subjects meeting SBP goal, and eGFR, and to evaluate the safety and tolerability of the study drug in the subject population. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Subjects must be competent to provide written informed consent - Aged 35 to 80 years - Subjects must have resistant systolic hypertension consistent with current clinical guidelines for the treatment of hypertension. Subjects with diabetes and/or CKD must have an average sitting SBP of ≥130 mmHg and all other subjects must have an average sitting SBP ≥140 mmHg at Screening. - Subjects must be receiving, and adhering to, full doses of appropriate guideline-recommended antihypertensive drugs from three classes of antihypertensive agents, including a diuretic. - Subjects must have a BMI of 20 to 43 kg/m2, inclusive. If >43kg/m2, the subject must have an upper arm circumference <42 cm at Screening (Visit 1). - Subjects must have an Egfr of ≥ 30 MI/min/1.73m2 at Screening. - Female subjects must be of non-childbearing potential, i.e. documented post-menopausal (cessation of regular menstrual periods) for at least 2 years or surgically sterile (i.e., hysterectomy and/or bilateral oophorectomy). Post-menopausal female subjects who are not surgically sterile will be required to use a double-barrier method of birth control throughout study participation.
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E.4 | Principal exclusion criteria |
- Average sitting systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥110 mmHg - Serum ALT or AST ≥2X ULN - Subjects who have experienced myocardial infarction, unstable angina pectoris, or a cerebrovascular accident (CVA) within 6 month; or sick sinus syndrome or second or third degree atrioventricular block, atrial fibrillation or recurrent atrial tachyarrhythmia, recurrent ventricular tachycardia, or symptomatic bradycardia - Implanted pacemakers or implanted cardioverter defibrillator (ICD) - Subjects with a historical or current diagnosis of symptomatic or asymptomatic CHF, treated or untreated. - Hemodynamically significant valvular heart disease - Type I diabetes mellitus - Hemodialysis or peritoneal dialysis; or history of solid organ transplant (e.g., kidney, heart). - Diagnosis or recurrence of malignancy within the past 3 years - Subjects with sleep apnea are excluded, unless a post-treatment sleep study has confirmed treatment efficacy and there are no recordings of blood oxygen saturation (SpO2) <90% at any time during the testing period. - Subjects who perform alternating shift or night work - Subjects who have participated in a clinical study involving another investigational drug or device within 4 weeks prior to Screening - Use of thiazolidinedione (i.e., glitazone) class of anti-diabetic medications (e.g., rosiglitazone, pioglitazone; alone or in combination pills) at or within 4 weeks of Screening (Visit 1). Subjects should not initiate treatment with thiazolidinediones at any time during the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The co-primary endpoints are the change from baseline to Week 14 in trough sitting SBP and trough sitting DBP, as measured by sphygmomanometry. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 44 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |