Treatment of hypertension (HTN) in difficult-to-treat and/or treatment resistant patients
Conditions
Sponsors
Quantum Genomics
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Able to understand, and willing to provide written informed consent and able to comply with the study procedures and restrictions. 2. Men and women =18 years of age at Screening 3. Diagnosis of primary HTN for at least 6 months prior to Screening and: • Currently treated with 2 antihypertensive classes of drug (difficult-to-treat subjects), or currently treated with at least 3 antihypertensive classes of drug including a diuretic (treatment resistant subjects), at the MTDs of those medications (ie, the subject can tolerate the current dose of each medication but higher doses have caused or may worsen side effects), with no change in their antihypertensive regimen (drug dose or schedule) for at least 6 weeks and with medication adherence =80% during the Run-in Period. • Have a systolic AOBP between 140 mmHg and 180 mmHg (inclusive) at Screening while on their current chronic antihypertensive treatments. • Have a successful ABPM measurement according to the criteria in Section 6.2.2.1, with a mean systolic daytime ABP >135 mmHg after the Run-in Period while on their current chronic antihypertensive treatments. 4. Women of childbearing potential and nonsurgically sterile male subjects who are sexually active must agree to use an approved highly effective form of contraception from the time of informed consent until 30 days postdose. Approved forms of contraception include hormonal intrauterine devices, hormonal contraceptives (oral birth control pills, depo, patch, or injectable) together with supplementary double barrier methods such as condoms or diaphragms with spermicidal gel or foam. Note: The following categories define women who are NOT considered to be of childbearing potential: • Premenopausal women with 1 of the following: o Documented hysterectomy o Documented bilateral salpingectomy o Documented bilateral oophorectomy OR • Postmenopausal women, defined as having amenorrhea for at least 12 months without an alternative medical cause. 5. Women of childbearing potential must have a negative serum pregnancy test result at Screening and a negative urine pregnancy test result at the Inclusion Visit (Visit 2, Day 1). 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 402 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: 1. Known or suspected secondary HTN (eg, hyperaldosteronism, renovascular HTN, pheochromocytoma, Cushing's disease). 2. Automated office SBP >170 mmHg or DBP >110 mmHg at the Screening or Inclusion Visit (Visit 2, Day 1) and confirmed by a second measurement within 30 minutes to 1 hour. 3. Known hypertensive retinopathy (Keith-Wagener Grade 3 or Grade 4) and/or hypertensive encephalopathy. 4. Upper arm circumference that is outside the limits of the study provided BP cuff associated with either the ABPM and/or AOBP measurement device. 5. History of spontaneous or drug-induced angioedema. 6. History of drug-related allergy or hypersensitivity to any components of the IP (firibastat [QGC001] or placebo). 7. Known severe aortic stenosis (symptomatic or asymptomatic with valvular indexed surface 3×upper limit of normal (ULN), or a total bilirubin =1.5×ULN (unless secondary to Gilbert's syndrome), or direct bilirubin >ULN in subjects with Gilbert's syndrome at Screening. 16. Estimated glomerular filtration rate (eGFR) 9% at Screening; OR • Are taking short-acting insulin. Use of a stable dose(=12 weeks prior to Screening) of medications listed in Section 7.7.1 is permitted. 21. Routine or anticipated treatment with any systemic corticosteroid. Use of topical, inhaled, intra-articular, or nasal corticosteroids is permitted. 22. Clinical evidence of thyroid disease, thyroid hormone therapy that is not stable =4 weeks prior to Screening, or a thyroid-stimulating hormone (TSH) level 1.5×ULN at Screening. 23. History of alcohol or drug abuse (including opioid overuse/misuse) within the 3 months prior to Screening that would interfere with study participation or lead to decreased compliance to study procedures or IP intake in the investigator's opinion. 24. Participation in another clinical study involving an investigational drug within 30 days prior to Screening or plans to pa
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to assess the effects of administration of firibastat (QGC001) 500 mg oral (po) twice daily (bis in die [bid]) on blood pressure (BP) over 12 weeks in subjects with uncontrolled primary HTN despite being treated with at 2 classes of antihypertensive therapies, at the maximum tolerated doses (MTDs). The secondary objective is to assess the safety of firibastat (QGC001).;Secondary Objective: The secondary objective is to assess the safety of firibastat (QGC001).;Primary end point(s): The primary efficacy endpoint is the change in systolic AOBP.;Timepoint(s) of evaluation of this end point: From baseline to Week 12 (Visit 5, Day 84). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Change in diastolic AOBP from baseline to Week 12 (Visit 5, Day 84) • Change in systolic and diastolic AOBP from baseline to Week 4 (Visit 3, Day 28) and Week 8 (Visit 4, Day 56) • Change in mean 24-hour ambulatory SBP and DBP from baseline to Week 12 (Visit 5, Day 84) • Percentage of controlled subjects (defined as subjects with normalized AOBP, ie, <140/90 mmHg at Week 12 [Visit 5, Day 84]) (as per European Society of Cardiology [ESC]/European Society of Hypertension [ESH] guidelines) • Percentage of controlled subjects (defined as subjects with normalized AOBP, ie, <130/80 mmHg at Week 12 [Visit 5, Day 84]) (as per 2017 American College of Cardiology [ACC]/American Heart Association [AHA] guidelines) • Predictive factors for controlled subjects at Week 12 (Visit 5, Day 84) • Change from baseline in plasma concentrations of Biomarkers NT-ProBNP;Timepoint(s) of evaluation of this end point: From baseline to Week 12 (Visit 5, Day 84). | — |
Countries
Brazil, Bulgaria, Canada, Czechia, Czech Republic, France, Germany, Hungary, Mexico, Poland, Slovakia, Spain, United States
Contacts
Public ContactBruno Besse
Quantum Genomics
Outcome results
None listed