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Efficacy and Safety of GMRx2 Compared to Placebo for the Treatment of Hypertension (GMRx2_PCT)

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ClinicalTrials.gov Identifier: NCT04518306
Recruitment Status : Completed
First Posted : August 19, 2020
Last Update Posted : December 19, 2023
Sponsor:
Information provided by (Responsible Party):
George Medicines PTY Limited

Study Description
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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.

Condition or disease Intervention/treatment Phase
Hypertension Drug: Telmisartan 10 mg/amlodipine 1.25 mg/indapamide 0.625 mg Drug: Telmisartan 20 mg/amlodipine 2.5 mg/indapamide 1.25 mg Drug: Placebo Phase 3

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 295 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: International, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Efficacy and Safety of GMRx2 (a Single Pill Combination Containing Telmisartan/Amlodipine/Indapamide) Compared to Placebo for the Treatment of Hypertension
Actual Study Start Date : June 6, 2021
Actual Primary Completion Date : September 18, 2023
Actual Study Completion Date : October 18, 2023

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Triple ¼ (GMRx2)
Telmisartan 10 mg/amlodipine 1.25 mg/indapamide 0.625 mg
 Drug: Telmisartan 10 mg/amlodipine 1.25 mg/indapamide 0.625 mg
Oral tablets
Active Comparator: Triple ½ (GMRx2)
Telmisartan 20 mg/amlodipine 2.5 mg/indapamide 1.25 mg
 Drug: Telmisartan 20 mg/amlodipine 2.5 mg/indapamide 1.25 mg
Oral tablets
Placebo Comparator: Placebo
Placebo
 Drug: Placebo
Placebo


Outcome Measures
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Primary Outcome Measures :
  1. Difference in change in home seated SBP from baseline to Week 4 [ Time Frame: 4 weeks ]

Secondary Outcome Measures :
  1. Difference in change in clinic seated mean SBP from baseline to Week 4 [ Time Frame: 4 weeks ]
  2. Difference in change in clinic seated mean DBP from baseline to Week 4 [ Time Frame: 4 weeks ]
  3. Percentage of participants with clinic seated mean SBP <140 and DBP <90 mmHg at Week 4 [ Time Frame: 4 weeks ]
  4. Percentage of participants with clinic seated mean SBP <130 and DBP <80 mmHg at Week 4 [ Time Frame: 4 weeks ]
  5. Difference in change in home seated mean DBP from baseline to Week 4 [ Time Frame: 4 weeks ]
  6. Difference in change in trough home seated mean SBP from baseline to week 4 [ Time Frame: 4 weeks ]
  7. Difference in change in trough home seated mean DBP from baseline to week 4 [ Time Frame: 4 weeks ]
  8. Percentage of participants with home seated mean SBP <135 and DBP <85 mmHg at Week 4 [ Time Frame: 4 weeks ]
  9. Percentage of participants with home seated mean SBP <130 and DBP <80 mmHg at Week 4 [ Time Frame: 4 weeks ]

Other Outcome Measures:
  1. Primary Safety Outcome [ Time Frame: 4 weeks ]
    Percentage of participants discontinued trial medication due to AE/SAE from baseline to Week 4

  2. Secondary Safety Outcome 1 [ Time Frame: 4 weeks ]
    Percentage of participants with an SAE from baseline to Week 4

  3. Secondary Safety Outcome 2 [ Time Frame: 4 weeks ]
    Percentage of participants with symptomatic hypotension from baseline to Week 4

  4. Secondary Safety Outcome 3 [ Time Frame: 4 weeks ]
    Percentage of participants with serum sodium concentration below 135 mmol/l at Week 4

  5. Secondary Safety Outcome 4 [ Time Frame: 4 weeks ]
    Percentage of participants with serum sodium concentration above 145 mmol/l at Week 4

  6. Secondary Safety Outcome 5 [ Time Frame: 4 weeks ]
    Percentage of participants with serum potassium concentration below 3.5 mmol/l at Week 4

  7. Secondary Safety Outcome 6 [ Time Frame: 4 weeks ]
    Percentage of participants with serum potassium concentration above 5.5 mmol/l at Week 4

  8. Secondary Safety Outcome 7 [ Time Frame: 4 weeks ]
    Percentage of participants with eGFR drop of over 30% from baseline to Week 4

  9. Secondary Safety Outcome 8 [ Time Frame: 4 weeks ]
    Percentage of participants with serum sodium <135mmol/l or >145 mmol/l, and/or serum potassium <3.5 mmol/l or >5.5mmol/l at week 4

  10. Secondary Safety Outcome 9 [ Time Frame: 4 weeks ]
    Percentage of participants with postural hypotension at Week 4

  11. Secondary Safety Outcome 10 [ Time Frame: 4 weeks ]
    Percentage of participants with postural hypertension at Week 4


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

At screening visit:

  1. Provided signed consent to participate in the trial.
  2. Adult aged ≥18 years.
  3. 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.

  4. 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
  5. 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:

  1. Home seated mean SBP 130-154 mmHg in the week before the randomization visit.
  2. Adherence of 80-120% to placebo run-in.
  3. Tolerated placebo run-in.
  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. 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.

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04518306


Locations
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Sponsors and Collaborators
George Medicines PTY Limited
Investigators
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Principal Investigator: Anthony Rodgers, Professor The George Institute
More Information
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Responsible Party: George Medicines PTY Limited
ClinicalTrials.gov Identifier: NCT04518306    
Other Study ID Numbers: GMRx2-HTN-2020-PCT1
First Posted: August 19, 2020    Key Record Dates
Last Update Posted: December 19, 2023
Last Verified: December 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: No If the sponsor receives a request for study data, then such requests will be reviewed by sponsor following completion of regulatory submissions and review, and with support from members of the GMRX2 steering committee who will advise on the scientific merit and integrity of the proposed analysis.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hypertension
Vascular Diseases
Cardiovascular Diseases
Amlodipine
Telmisartan
Indapamide
Antihypertensive Agents
Calcium Channel Blockers
Membrane Transport Modulators
 Molecular Mechanisms of Pharmacological Action
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Vasodilator Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Diuretics
Natriuretic Agents
Sodium Chloride Symporter Inhibitors