MedPath

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

Registration Number
NCT04518306
Lead Sponsor
George Medicines PTY Limited
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.

Detailed Description

TRIAL DRUG:

GMRx2: single pill combination of telmisartan/amlodipine/indapamide Dose version 1: telmisartan 10 mg/amlodipine 1.25 mg/indapamide 0.625 mg Dose version 2: telmisartan 20 mg/amlodipine 2.5 mg/indapamide 1.25 mg I NDICATION: Hypertension

TRIAL TITLE:

Efficacy and safety of GMRx2 compared to placebo for the treatment of hypertension.

OBJECTIVES:

To investigate the efficacy and safety of GMRx2 compared to placebo for the treatment of hypertension.

INTERVENTION:

A 2-week single-blind placebo run-in will be followed by a 4-week double-blind period with randomization to GMRx2 dose version 1, GMRx2 dose version 2 or placebo.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
295
Inclusion Criteria

Not provided

Exclusion Criteria

At screening visit:

  1. Receiving 2 or more BP-lowering drugs.
  2. Clinic seated mean SBP ≥160 mmHg and/or DBP ≥100 mmHg.
  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. 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.
  4. 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).
  5. Contraindication, including hypersensitivity (e.g. anaphylaxis or angioedema), to any of the 3 trial medications.
  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/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 substantially 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) <60 ml/min/1.73m2.
  12. Current/history of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3 times the upper limit of normal range within 6 months.
  13. 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.
  14. Arm circumference that is too large (>55 cm) or too small (<20 cm) to allow accurate measurement of BP.
  15. Currently taking or might need during the trial, a concomitant treatment which is known to interact significantly with the trial medication: digoxin, lithium, diabetics receiving aliskiren, moderate and strong CYP3A4 inhibitors [e.g. ritonavir, ketoconazole, diltiazem], simvastatin >20 mg/day, immunosuppressants.
  16. 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 Error! Reference source not found.).
  17. 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.
  18. Individuals working >2-night shifts per week.
  19. Participated in any investigational drug or device trial within the previous 30 days.
  20. History of alcohol or drug abuse within 12 months.

At randomization visit:

  1. Unable to adhere to the trial procedures during the run-in period.

  2. Any of the following which in the investigator's judgment may compromise the safety of the participant if randomized to the trial medications:

    1. High or low clinic BP levels even in the light of the values for home BP that are available for that participant. The exact levels of BP are not specified, since there is clinical uncertainty as to the relevance of BP levels which are high/low in clinic only; for example the clinical relevance of 'whitecoat hypertension' is uncertain.
    2. High or low home DBP levels. The exact levels of DBP are not specified, reflecting clinical uncertainty of for example isolated diastolic hypertension. However, home DBP values of >99 mmHg may typically be considered as requiring treatment intensification, and such participants would not be suitable for randomization.
  3. Any abnormal laboratory value which 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.

  4. Fulfilling any of the exclusion criteria mentioned for the screening visit, when verified again at randomization visit.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Triple ½ (GMRx2)Telmisartan 20 mg/amlodipine 2.5 mg/indapamide 1.25 mgTelmisartan 20 mg/amlodipine 2.5 mg/indapamide 1.25 mg
Triple ¼ (GMRx2)Telmisartan 10 mg/amlodipine 1.25 mg/indapamide 0.625 mgTelmisartan 10 mg/amlodipine 1.25 mg/indapamide 0.625 mg
PlaceboPlaceboPlacebo
Primary Outcome Measures
NameTimeMethod
Difference in change in home seated SBP from baseline to Week 44 weeks
Secondary Outcome Measures
NameTimeMethod
Difference in change in trough home seated mean DBP from baseline to week 44 weeks
Difference in change in clinic seated mean DBP from baseline to Week 44 weeks
Percentage of participants with clinic seated mean SBP <140 and DBP <90 mmHg at Week 44 weeks
Percentage of participants with home seated mean SBP <135 and DBP <85 mmHg at Week 44 weeks
Percentage of participants with clinic seated mean SBP <130 and DBP <80 mmHg at Week 44 weeks
Difference in change in clinic seated mean SBP from baseline to Week 44 weeks
Percentage of participants with home seated mean SBP <130 and DBP <80 mmHg at Week 44 weeks
Difference in change in home seated mean DBP from baseline to Week 44 weeks
Difference in change in trough home seated mean SBP from baseline to week 44 weeks

Trial Locations

Locations (43)

Buckhead Primary Care Research

🇺🇸

Snellville, Georgia, United States

Valiance Clinical Research

🇺🇸

Tarzana, California, United States

Albany House Medical Centre

🇬🇧

Wellingborough, United Kingdom

North Hills Medical Research

🇺🇸

North Richland Hills, Texas, United States

Ocala Research Institute

🇺🇸

Ocala, Florida, United States

Synergy Groups Medical

🇺🇸

Missouri City, Texas, United States

Castle Hill Medical Centre

🇦🇺

Castle Hill, New South Wales, Australia

Clinical Research of Brandon

🇺🇸

Brandon, Florida, United States

Kurunegala Teaching Hospital

🇱🇰

Kurunegala, Sri Lanka

Suncoast Research Associates

🇺🇸

Saint Petersburg, Florida, United States

Newquay Medical

🇬🇧

Newquay, Cornwall, United Kingdom

Belmont Health Centre

🇬🇧

Harrow, London, United Kingdom

Lakeside Surgery

🇬🇧

Coventry, West Midlands, United Kingdom

Altus Research, Inc

🇺🇸

Palm Beach, Florida, United States

Accel Research

🇺🇸

Saint Petersburg, Florida, United States

Precision Clinical Research

🇺🇸

Sunrise, Florida, United States

Royal Perth Hospital

🇦🇺

Perth, Western Australia, Australia

Karapitiya Teaching Hospital

🇱🇰

Galle, Sri Lanka

Kandy National Hospital

🇱🇰

Kandy, Sri Lanka

Abbeywell Surgery

🇬🇧

Romsey, United Kingdom

Curtin University

🇦🇺

Bentley, Western Australia, Australia

Colombo North Teaching Hospital

🇱🇰

Ragama, Sri Lanka

Burbage Surgery

🇬🇧

Hinckley, Leicestershire, United Kingdom

Headlands Research

🇺🇸

Scottsdale, Arizona, United States

West Walk Surgery

🇬🇧

Bristol, Somerset, United Kingdom

Quality of Life Medical & Research Centers, LLC

🇺🇸

Tucson, Arizona, United States

The University of Tennessee Health Science Center

🇺🇸

Memphis, Tennessee, United States

Steploe Medical Centre

🇬🇧

Soham, Cambridgeshire, United Kingdom

Aminu Kano Teaching Hospital

🇳🇬

Kano, Nigeria

Institute of Cardiology, National Hospital of Sri Lanka

🇱🇰

Colombo, Sri Lanka

Colombo South Teaching Hospital

🇱🇰

Dehiwala, Sri Lanka

Barwon Health, Geelong University Hospital

🇦🇺

Geelong, Victoria, Australia

University of Abuja Teaching Hospital

🇳🇬

Gwagwalada, Federal Capital Territory, Nigeria

Jafna Teaching Hospital

🇱🇰

Jaffna, Sri Lanka

Brockwood Medical Practice

🇬🇧

Betchworth, Surrey, United Kingdom

Trowbridge Health Centre

🇬🇧

Trowbridge, Wiltshire, United Kingdom

Hudson Institute of Medical Research

🇦🇺

Clayton, Victoria, Australia

Elite Clinical Studies

🇺🇸

Phoenix, Arizona, United States

Inpatient Research Clinic

🇺🇸

Hialeah, Florida, United States

Suncoast Research Group

🇺🇸

Miami, Florida, United States

New Horizon Research Center

🇺🇸

Miami, Florida, United States

Precision Research Center

🇺🇸

Tampa, Florida, United States

Meridian Clinical Research

🇺🇸

Portsmouth, Virginia, United States

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