Efficacy and safety of GMRx2 compared to dual combinations for the treatment of high blood pressure

Phase 1

• Conditions: Hypertension; MedDRA version: 20.0Level: PTClassification code 10020772Term: HypertensionSystem Organ Class: 10047065 - Vascular disorders; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2020-004196-40-PL
• Lead Sponsor: George Medicines Pty Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-11-23
• Last Update Posted: 8 October 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 1500

Inclusion Criteria

At screening visit
1. Provided signed consent to participate in the trial.
2. Adult of age =18 years.
3. Clinic attended automated seated mean SBP (average of the last 2 of 3 measurements):
150-179 mmHg on 0 BP-lowering drugs, or 140-170 mmHg on 1 BP-lowering drug, or 130-160 mmHg on 2 BP-lowering drugs, or 120-150 mmHg on 3 BP-lowering drugs.
At randomization visit
1. Home seated mean SBP 120-154 mmHg in the week prior to the randomization visit.
2. Adherence of 80-120% to run-in medication.
3. Tolerated run-in medication.
4. Adherence to home BP monitoring schedule: =3 days in the week before the randomization visit and 1
day per week during the preceding weeks, with =2 measures in the specified morning and evening time periods on each day.

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 1000
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 500

Exclusion Criteria

At screening visit
1.Receiving 4 or more BP-lowering drugs.
2.Pregnant or had a positive pregnancy test or unwilling to undertake a pregnancy test during the trial and up to 30 days after the discontinuation of the trial medication or breastfeeding or of childbearing age and not using an acceptable method of contraception. Contraception should be used for at least 1 month before the screening visit and until the end of trial participation.
3.Meets any criteria of local ethical or regulatory requirements related To severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that would deem participation in a clinical trial unsuitable.
4.Contraindication, including hypersensitivity (e.g. anaphylaxis or angioedema), to the active run-in treatment or to any of the trial medication options in the four randomized groups.
5.Current/history of transient ischemic attack, stroke, or hypertensive encephalopathy.
6.Current/history of acute coronary syndrome, unstable angina, myocardial infarction, percutaneous transluminal coronary revascularization, or coronary artery bypass graft.
7.Current atrial fibrillation. Patients with a history of paroxysmal atrial fibrillation are potentially eligible as long as there has been no episode in the last 3 months, while patients with a history of persistent or permanent atrial fibrillation are not eligible.
8.Current/history of New York Heart Association class III and IV congestive heart failure.
9.Current/history of a known secondary cause of hypertension, such as primary aldosteronism, renal artery stenosis, pheochromocytoma, or Cushing's syndrome.
10.Current/history of severe uncontrolled diabetes (HbA1c > 11.0%) within last three months.
11.Current/history of end-stage renal disease or anuria or estimated glomerular filtration rate (eGFR) <60ml/min/1.73m2.
12.Electrolyte levels that would be regarded as contraindications for any of the potential treatment arms e.g. serum sodium <132mmol/l or >148 mmol/l or serum potassium <3.1 mmol/l or >5.6mmol/l.
13.Current/history of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3 times the upper limit of normal range within 6 months.
14.Current concomitant illness or physical impairment or mental condition that in the judgment of the investigator could interfere with the effective conduct of the trial or constitutes a significant risk to the participants’ safety or well-being.
15.Arm circumference that is too large (>55 cm) or too small (<20 cm) to allow accurate measurement of BP.
16.Currently taking or might need during the trial, a concomitant treatment which is known to interact with one or more of the trial medications: digoxin, lithium, diabetics receiving aliskiren, moderate and strong CYP3A4 inhibitors (e.g. ritonavir, ketoconazole, diltiazem], simvastatin >20 mg/day, immunosuppressants.
17.Might need treatment with drugs that are prohibited during the trial: other antihypertensive drugs, endothelin receptor antagonists, neprilysin inhibitors, or other drugs that may affect BP (see Appendix 5).
18.Current surgical or medical condition that might significantly alter the absorption, distribution, metabolism, or excretion of trial drugs such as prior major gastrointestinal tract surgery (e.g. gastrectomy, lap band, or bowel resection) or acute flare of inflammatory bowel disease within one year.
19.Individuals working >2 nightshifts per week.
20.Participated in any investigative drug or device trial within the previous 30 days.
21.History o

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Timepoint(s) of evaluation of this end point: Week 12;Main Objective: To assess the efficacy of GMRx2 for lowering BP compared to each of the three dual combinations of component drugs of GMRx2 at equivalent doses.;Secondary Objective: To assess the safety of GMRx2 compared to each of the three dual combinations of component drugs of GMRx2 at equivalent doses.;Primary end point(s): Difference in change in home seated mean SBP from randomization to Week 12.