Efficacy and Safety of GMRx2 Compared to Placebo for the Treatment of Hypertension

NCT04518306 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: GMRx2-HTN-2020-PCT1
• Study Type: interventional
• Target: 755
• Locations: 5 countries
• Sites: 47

Brief Summary

Recent hypertension guidelines recommend combination therapy as initial treatment for many or most patients. Several trials suggest triple low-dose combination therapy may be highly effective in terms of achieving blood pressure control without increasing adverse effects. This trial is designed to investigate the efficacy and safety of GMRx2 in participants with high blood pressure compared to placebo.

Conditions

Hypertension

Outcome Measures

Primary Outcomes (1)

• Difference in Change in Home Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 4

  Each blood pressure (BP) measurement consisted of valid SBP values (ie. SBP\>60 mmHg and \<250 mmHg). BP values were summarized using descriptive statistics, including actual values and changes from randomization to Week 4, by timepoint and treatment groups.

  Randomization to Week 4

Secondary Outcomes (9)

• Difference in Change in Clinic Seated Mean Mean Systolic Blood Pressure (SBP) From Randomization to Week 4

  Randomization to Week 4

• Difference in Change in Clinic Seated Mean Diastolic Blood Pressure (DBP) From Randomization to Week 4

  Randomization to Week 4

• Percentage of Participants With Clinic Seated Mean Systolic Blood Pressure (SBP) <140 and DBP <90 mmHg at Week 4

  At Week 4

• Percentage of Participants With Clinic Seated Mean Systolic Blood Pressure (SBP) <130 and Diastolic Blood Pressure (DBP) <80 mmHg at Week 4

  At Week 4

• Difference in Change in Home Seated Mean Diastolic Blood Pressure (DBP) From Randomization to Week 4

  Randomization to Week 4

Other Outcomes (11)

• Percentage of Participants Discontinued Trial Medication Due to Adverse Event (AE) or a Serious Adverse Event (SAE) From Randomization to Week 4

  Randomization to Week 4

• Percentage of Participants With an Serious Adverse Event (SAE) From Randomization to Week 4

  Randomization to Week 4

• Percentage of Participants With Symptomatic Hypotension From Randomization to Week 4

  Randomization to Week 4

Study Arms (3)

Triple ¼ (GMRx2)

EXPERIMENTAL

Telmisartan 10 mg/amlodipine 1.25 mg/indapamide 0.625 mg

Drug: Telmisartan 10 mg/amlodipine 1.25 mg/indapamide 0.625 mg

Triple ½ (GMRx2)

ACTIVE COMPARATOR

Telmisartan 20 mg/amlodipine 2.5 mg/indapamide 1.25 mg

Drug: Telmisartan 20 mg/amlodipine 2.5 mg/indapamide 1.25 mg

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Telmisartan 10 mg/amlodipine 1.25 mg/indapamide 0.625 mg DRUG

Oral tablets

Triple ¼ (GMRx2)

Telmisartan 20 mg/amlodipine 2.5 mg/indapamide 1.25 mg DRUG

Oral tablets

Triple ½ (GMRx2)

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At screening visit:
• Provided signed consent to participate in the trial.
• Adult aged ≥18 years.
• Low calculated CV risk according to local guidelines such that pharmacological BP-lowering treatment is not mandatory: e.g. Pooled Cohorts Equation 10-years ASCVD risk \<10% in the USA.
• Likely diagnosis of hypertension, defined as one or more of:
• automated SBP at this clinic visit according to trial methods (see Appendix 2) of ≥130mmHg on no BP lowering medicines or ≥120mmHg on 1 BP lowering medicine that will be stopped at this visit, OR
• documentation in last 6 months of office SBP ≥ 140 mmHg and/or DBP ≥ 90mmHg on no BP lowering medicines or SBP ≥ 130 mmHg and/or DBP ≥ 85mmHg on 1 BP lowering medicine that will be stopped at this visit, OR
• documentation in last 6 months of home SBP ≥ 130 mmHg and/or DBP ≥ 80mmHg on no BP lowering medicines or SBP ≥ 120 mmHg and/or DBP ≥ 75mmHg on 1 BP lowering medicine that will be stopped at this visit, OR
• documentation in last 6 months of ambulatory daytime SBP ≥ 130 mmHg and/or DBP ≥ 80mmHg on no BP lowering medicines or SBP ≥ 120 mmHg and/or DBP ≥ 75mmHg on 1 BP lowering medicine that will be stopped at this visit
• No contraindication to trial medications, including 2-weeks placebo run-in and 4-weeks randomized treatment period with GMRx2 (dose version 1 or 2) or placebo.
• At randomization visit:
• Home seated mean SBP 130-154 mmHg in the week before the randomization visit.
• Adherence of 80-120% to placebo run-in.
• Tolerated placebo run-in.
• 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. 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.

You may not qualify if:

• At screening visit:
• Receiving 2 or more BP-lowering drugs.
• Clinic seated mean SBP ≥160 mmHg and/or DBP ≥100 mmHg.
• 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. Acceptable methods of birth control include hormonal prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double-barrier method (e.g. condoms, diaphragm, or cervical cap with spermicidal foam, cream, or gel), or male partner sterilization. Contraception should be used for at least 1 month before the screening visit and until the end of trial participation.
• Not suitable for participation in a clinical trial according to local ethical or regulatory requirements related to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).
• Contraindication, including hypersensitivity (e.g. anaphylaxis or angioedema), to any of the 3 trial medications.
• Current/history of transient ischemic attack, stroke, or hypertensive encephalopathy.
• Current/history of acute coronary syndrome, unstable angina, myocardial infarction, percutaneous transluminal coronary revascularization, or coronary artery bypass graft.
• Current/history of New York Heart Association class III and IV congestive heart failure.
• Current/history of a known secondary cause of hypertension, such as primary aldosteronism, renal artery stenosis, pheochromocytoma, or Cushing's syndrome.
• Current/history of substantially uncontrolled diabetes (HbA1c \> 11.0%) within last three months.
• Current/history of end-stage renal disease or anuria or estimated glomerular filtration rate (eGFR) \<60 ml/min/1.73m2.
• Current/history of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>3 times the upper limit of normal range within 6 months.
• 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' well-being.
• Arm circumference that is too large (\>55 cm) or too small (\<20 cm) to allow accurate measurement of BP.

Sponsors & Collaborators

• George Medicines PTY Limited: lead

Study Sites (47)

Elite Clinical Studies

Phoenix, Arizona, 85018, United States

Location

Headlands Research

Scottsdale, Arizona, 85260, United States

Location

Quality of Life Medical & Research Centers, LLC

Tucson, Arizona, 85712, United States

Location

Valiance Clinical Research

South Gate, California, 90280, United States

Location

Valiance Clinical Research

Tarzana, California, 91356, United States

Location

Clinical Research of Brandon

Brandon, Florida, 33511, United States

Location

Inpatient Research Clinic

Hialeah, Florida, 33013, United States

Location

Suncoast Research Group

Miami, Florida, 33135, United States

Location

New Horizon Research Center

Miami, Florida, 33165, United States

Location

Ocala Research Institute

Ocala, Florida, 34471, United States

Location

Altus Research, Inc

Palm Beach, Florida, 33461, United States

Location

Suncoast Research Associates

St. Petersburg, Florida, 33173, United States

Location

Accel Research

St. Petersburg, Florida, 33709, United States

Location

Precision Clinical Research

Sunrise, Florida, 33351, United States

Location

Precision Research Center

Tampa, Florida, 33603, United States

Location

Buckhead Primary Care Research

Snellville, Georgia, 30078, United States

Location

Meridian Clinical Research

Baton Rouge, Louisiana, 70809, United States

Location

The University of Tennessee Health Science Center

Memphis, Tennessee, 38105, United States

Location

Synergy Groups Medical

Houston, Texas, 77036, United States

Location

Synergy Groups Medical

Houston, Texas, 77087, United States

Location

Synergy Groups Medical

Missouri City, Texas, 77459, United States

Location

North Hills Medical Research

North Richland Hills, Texas, 76180, United States

Location

Meridian Clinical Research

Portsmouth, Virginia, 23703, United States

Location

Castle Hill Medical Centre

Castle Hill, New South Wales, 2154, Australia

Location

Hudson Institute of Medical Research

Clayton, Victoria, 3168, Australia

Location

Barwon Health, Geelong University Hospital

Geelong, Victoria, 3220, Australia

Location

Curtin University

Bentley, Western Australia, 6102, Australia

Location

Royal Perth Hospital

Perth, Western Australia, 6000, Australia

Location

University of Abuja Teaching Hospital

Gwagwalada, Federal Capital Territory, 902101, Nigeria

Location

Aminu Kano Teaching Hospital

Kano, Nigeria

Location

Institute of Cardiology, National Hospital of Sri Lanka

Colombo, 10-01000, Sri Lanka

Location

Colombo South Teaching Hospital

Dehiwala, 10350, Sri Lanka

Location

Karapitiya Teaching Hospital

Galle, 80000, Sri Lanka

Location

Jafna Teaching Hospital

Jaffna, 40000, Sri Lanka

Location

Kandy National Hospital

Kandy, 20000, Sri Lanka

Location

Kurunegala Teaching Hospital

Kurunegala, 60000, Sri Lanka

Location

Colombo North Teaching Hospital

Ragama, 11010, Sri Lanka

Location

Steploe Medical Centre

Soham, Cambridgeshire, CB7 5JD, United Kingdom

Location

Newquay Medical

Newquay, Cornwall, TR7 1RU, United Kingdom

Location

Burbage Surgery

Hinckley, Leicestershire, LE10 2SE, United Kingdom

Location

Belmont Health Centre

Harrow, London, HA3 7LT, United Kingdom

Location

West Walk Surgery

Bristol, Somerset, BS37 4AX, United Kingdom

Location

Brockwood Medical Practice

Betchworth, Surrey, RH3 7NJ, United Kingdom

Location

Lakeside Surgery

Coventry, West Midlands, CV3 6NF, United Kingdom

Location

Trowbridge Health Centre

Trowbridge, Wiltshire, BA14 8LW, United Kingdom

Location

Abbeywell Surgery

Romsey, SO51 8EN, United Kingdom

Location

Albany House Medical Centre

Wellingborough, NN8 4RW, United Kingdom

Location

Related Publications (2)

• Salam A, de Silva HA, Ojji D, de Silva AP, Galappatthy G, Lakshman P, Kumanan T, Mayurathan G, Pereira T, Rahuman M, Ranasinghe G, Rasnayake L, Uluwattage W, Constantine GR, Kandeepan T, Sani MU, Kumar A, Pant R, Cushman WC, Di Tanna GL, Grobbee D, Narkiewicz K, Oparil S, Poulter NR, Schlaich MP, Schutte AE, Spiering W, Williams B, Wright JT Jr, Gianacas C, Shanthakumar M, Liu X, Freed R, Whelton PK, Rodgers A. Long-Term Efficacy and Safety of a Novel Low-Dose Triple Single-Pill Combination for the Treatment of Hypertension. Glob Heart. 2025 Oct 31;20(1):102. doi: 10.5334/gh.1481. eCollection 2025.

  PMID: 41180852 DERIVED

• Rodgers A, Salam A, Schutte AE, Cushman WC, de Silva HA, Di Tanna GL, Grobbee D, Narkiewicz K, Ojji DB, Poulter NR, Schlaich MP, Oparil S, Spiering W, Williams B, Wright JT Jr, Gutierez A, Sanni A, Lakshman P, McMullen D, Ranasinghe G, Gianacas C, Shanthakumar M, Liu X, Wang N, Whelton P. Efficacy and Safety of a Novel Low-Dose Triple Single-Pill Combination Compared With Placebo for Initial Treatment of Hypertension. J Am Coll Cardiol. 2024 Dec 10;84(24):2393-2403. doi: 10.1016/j.jacc.2024.08.025. Epub 2024 Aug 31.

  PMID: 39217570 DERIVED

MeSH Terms

Conditions

Hypertension

Interventions

Telmisartan; Amlodipine; Indapamide

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Sulfonamides; Amides; Sulfones; Sulfur Compounds; Indoles

Results Point of Contact

• Title: Anthony Rodgers (Principal Investigator)
• Organization: George Medicines Pty Limited

arodgers@georgeinstitute.org

+44 7983 578 290

Study Officials

• Anthony Rodgers, Professor

  The George Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: International, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial.

Study Record Dates

• First Submitted: August 15, 2020
• First Posted: August 19, 2020
• Study Start: June 14, 2021
• Primary Completion: September 19, 2023
• Study Completion: October 18, 2023
• Last Updated: June 3, 2025
• Results First Posted: June 3, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (10); NG (2); AU (5); SR (7); US (23)