A Phase 3, Double-blind, Placebo-controlled and Open-label Efficacy and Long-term Safety Study of Firibastat (QGC001) Administered Orally, Once Daily, for Up to 48 Weeks in Patients with Difficult-to-treat/Resistant Hypertensio
- Conditions
- Difficult to treat and Treatment-resistant high blood pressure10082206
- Registration Number
- NL-OMON52137
- Lead Sponsor
- Quantum Genomics
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 35
1. Able to understand and willing to provide written informed consent, and able
to comply with the study procedures and restrictions.
2. Adult men and women (at Screening). For all countries, age criteria must be
as per local regulations; eg, subjects in Canada must be aged >= 18 years or
>=19 years of age at Screening, as per the applicable.
Canadian provincial criteria
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 179 mmHg (inclusive) at Screening
(visit 1) while on their current chronic antihypertensive treatments.
• Have a successful ABPM measurement with a mean systolic daytime ABP >135 mmHg
after the Run-in Period while on their current chronic antihypertensive
treatments. An ABPM is successful if at least 21 daytime readings and 6
nighttime readings have been successfully recorded.
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 post dose.
Approved forms of contraception include intrauterine devices, intrauterine
hormone-releasing systems, bilateral tubal ligation, or hormonal intrauterine
devices, hormonal contraceptives (oral birth control pills, depo, patch, or
injectable) together with supplementary barrier methods such as condoms or
diaphragms with spermicidal gel or foam.
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 2B, Day 1).
1. Known or suspected secondary HTN (eg, hyperaldosteronism, renovascular HTN,
pheochromocytoma, Cushing*s disease).
2. Systolic AOBP >=180 mmHg or DBP >=110 mmHg at the Screening or Inclusion Visit
(Visit 2B, 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 any 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 <0.5 cm²/m²).
8.Subjects with severe symptomatic heart failure (New York Heart Association
[NYHA] Class III or Class IV).
9.History of acute coronary syndrome (non-ST elevation myocardial infarction
[MI], ST elevation MI, and unstable angina pectoris), stroke, or transient
ischemic attack within 6 months prior to Visit 2A, Day 0.
10. Known history of malabsorption syndrome, or has undergone gastrointestinal
surgery, including bariatric procedures that induce chronic malabsorption,
within 2 years of Screening.
11.Treatment with anti-obesity drugs or procedures 3 months prior to Screening
(ie, surgery, aggressive diet regimen, etc.), leading to unstable body weight.
12.Female who is breastfeeding, pregnant, or planning to become pregnant during
the study period.
13.Medical history of cancer (except for basal cell carcinoma) and/or treatment
for cancer within the last 3 years.
14.Shift workers who routinely sleep during the daytime and/or whose work hours
include midnight.
15.Subjects with moderate to severe hepatic impairment (Child-Pugh A, B, or C);
alanine aminotransferase (ALT), aspartate aminotransferase (AST), or alkaline
phosphatase (ALP) >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) <30 mL/min/1.73 m2, as
calculated using the Chronic Kidney Disease Epidemiology Collaboration
(CKD-EPI) formula (Levey AS, et al. 2009) at Screening.
17.History of any blood disorder, other than sickle cell trait, causing
hemolysis or unstable red blood cells (eg, malaria, babesiosis, hemolytic
anemia, thalassemia, sickle cell anemia).
18.Subjects with documented DI.
19.Subjects with Type 1 diabetes mellitus.
20.Subjects with Type 2 diabetes mellitus who:
• Are poorly controlled, defined as glycosylated hemoglobin A1c (HbA1c) >9% at
Screening; OR
• Are taking short-acting insulin. Use of a stable dose [>=12 weeks prior to
Screening] of the following medications, (or any combination of the following
medications) is permitted: glucagon like peptide 1 analog, metformin,
sulfonylurea, dipeptidyl peptidase-4 inhibitor, and single basal insulin,
sodium glucose co-transporter 2 (SGLT2) inhibitors and pioglitazone.
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 h
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary efficacy endpoint is the change from baseline in systolic AOBP at<br /><br>Week 12.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary efficacy endpoints: AOBP at every visit. 24-hour ambulatory BP after<br /><br>12 weeks (end of double-blind period [Period 1]). Biomarker NT-ProBNP,<br /><br>fibrinogen and hsCRP at Visit 2B, Day 1, and Visit 4B, Day 85 (±3 d).<br /><br>Proportion of subjects requiring an increase in the dose of current<br /><br>antihypertensive drugs or addition of another hypertensive drug during the<br /><br>open-label treatment periods (Periods 2 and 3) of the study.</p><br>