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-CZ
• Lead Sponsor: George Medicines Pty Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-11-12
• Last Update Posted: 30 January 2023

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 3 measurements):
140-179 mmHg on 0 BP-lowering drugs, or 130-170 mmHg on 1 BP-lowering drug, or 120-160 mmHg on 2 BP-lowering drugs, or 110-150 mmHg on 3 BP-lowering drugs.
Note: A single tablet containing 2 or 3 different BP lowering agents (i.e. a combination medication) is considered as 2 or 3 BP lowering drugs, respectively.
At randomization visit
1. Home seated mean SBP 110-154 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: in the week before randomization, at least 6 measures
(e.g. =2 sets of triplicate measures) including at least 1 morning and 1 evening each with =2 measures
5. Morning is defined as any measure in the am and evening as any measure in the pm. Morning and
evening do not have to be same day.
At week 12 (for optional open-label extension Period)
1. Provided signed informed consent.
2. Completed randomized treatment and willing to continue GMRx2-based regimen for up to 12 months.

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. Receiving any BP lowering drugs for indications other than hypertension
3. 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 (oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double-barrier method, or male partner sterilization). Contraception should be used for at least 1 month before the screening visit and until the end of trial participation.
4. Meets any criteria of local ethical or regulatory requirements related to severe acute respiratory syndrome SARS-CoV-2
5. Contraindication, including hypersensitivity, to the active run-in treatment or to any of the trial medication options in the four randomized groups.
6. Current/history of transient ischemic attack, stroke, or hypertensive encephalopathy.
7. Current/history of acute coronary syndrome, unstable angina, myocardial infarction, percutaneous transluminal coronary revascularization, or coronary artery bypass graft.
8. Current atrial fibrillation. Patients with a history of paroxysmal atrial fibrillation are potentially eligible as long as no episode in the last 3 months, while history of persistent or permanent atrial fibrillation are not eligible.
9. Current/history of New York Heart Association class III and IV congestive heart failure.
10. Current/history of cardiomyopathy or any other cardiovascular condition of sufficient severity to contraindicate the trial medications or require a contraindicated medication.
11. Current/history of a known secondary cause of hypertension, such as primary aldosteronism, renal artery stenosis, pheochromocytoma, or Cushing's syndrome.
12. Current/history of severe uncontrolled diabetes (HbA1c > 11.0% (> 97 mmol/mol)) within last 3 months.
13. Current/history of end-stage renal disease or anuria or current estimated glomerular filtration rate <60 ml/min/1.73m2
14. Current electrolyte levels that would be regarded as contraindications for any of the potential treatment arms (serum sodium <132mmol/l or >148 mmol/l or serum potassium <3.1 mmol/l or >5.6mmol/l).
15. Current/history of aspartate aminotransferase or alanine aminotransferase >3 x upper limit of normal range within 6 months.
16. 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 constitute a significant risk to the participants’ safety or well-being.
17. Arm circumference that is too large or too small for available cuffs. Upper limit is 55cm in all countries, while lower limit is 15cm or 24cm depending on available cuff sizes.
18. 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 (ritonavir, ketoconazole, diltiazem, simvastatin >20 mg/day, immunosuppressants.
19. Might need treatment with drugs that are prohibited during the trial (see Appendix 5).
20. 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 or acute flare of inflammator

Study & Design

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