GMRx2_ACT: Efficacy and Safety of GMRx2 Compared to Dual Combinations for the Treatment of Hypertension

Sponsor
George Medicines PTY Limited (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04518293
Collaborator
(none)
1,500
85
4
25.1
17.6
0.7

Study Details

Study Description

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 dual combinations.

Condition or Disease Intervention/Treatment Phase
  • Drug: Telmisartan 20 mg/amlodipine 2.5 mg/indapamide 1.25 mg
  • Drug: telmisartan 40 mg/amlodipine 5 mg/indapamide 2.5 mg
  • Drug: Telmisartan 20 mg/amlodipine 2.5 mg .
  • Drug: telmisartan 40 mg/amlodipine 5 mg
  • Drug: Telmisartan 20 mg/indapamide 1.25 mg
  • Drug: telmisartan 40 mg/indapamide 2.5 mg
  • Drug: Amlodipine 2.5 mg/indapamide 1.25 mg
  • Drug: amlodipine 5 mg/indapamide 2.5 mg
Phase 3

Detailed Description

TRIAL DRUG:
GMRx2: Single pill combinations of telmisartan/amlodipine/indapamide Dose version 2:

telmisartan 20mg/amlodipine 2.5mg/indapamide 1.25mg Dose version 3: telmisartan 40mg/amlodipine 5 mg/indapamide 2.5mg INDICATION: Hypertension TRIAL DESIGN: International, multicenter, randomized, double-blind, active controlled, parallel-group.

OBJECTIVES: To investigate the efficacy and safety of GMRx2 compared to dual combinations

INTERVENTION:

Single-Blind Active Run-In Period. Enrolled participants will be asked to discontinue their current BP-lowering drug(s) and undergo a single-blind active run-in period for 4 weeks with GMRx2 dose version 2. Participants will be advised to take the capsule once daily in the morning at the same time (± 2 hours) before home BP measurement is performed.

Double-Blind Treatment Period. Participants still eligible after the run-in period will be allocated in a double-blind fashion to one of the following 4 randomized groups: GMRx2 dose version 2, or telmisartan20mg+amlodipine2.5mg, or telmisartan 20mg+indapamide 1.25mg, or amlodipine2.5mg+indapamide 1.25mg. At week 6 all doses will be doubled.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
1500 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
International, multicenter, randomized, double-blind, active-controlled, parallel group.International, multicenter, randomized, double-blind, active-controlled, parallel group.
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 Dual Combinations for the Treatment of Hypertension
Actual Study Start Date :
Jun 26, 2021
Anticipated Primary Completion Date :
Mar 31, 2023
Anticipated Study Completion Date :
Jul 31, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Triple - TAI

Telmisartan 20 mg/amlodipine 2.5 mg/indapamide 1.25 mg. At week 6 visit, forced up-titration to telmisartan 40 mg/amlodipine 5 mg/indapamide 2.5 mg

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

Drug: telmisartan 40 mg/amlodipine 5 mg/indapamide 2.5 mg
Signle pill

Active Comparator: Dual - TA

Telmisartan 20 mg/amlodipine 2.5 mg . At week 6 visit, forced up-titration to telmisartan 40 mg/amlodipine 5 mg

Drug: Telmisartan 20 mg/amlodipine 2.5 mg .
oral tablet

Drug: telmisartan 40 mg/amlodipine 5 mg
oral tablet

Active Comparator: Dual - TI

Telmisartan 20 mg/indapamide 1.25 mg. At week 6 visit, forced up-titration to telmisartan 40 mg/indapamide 2.5 mg

Drug: Telmisartan 20 mg/indapamide 1.25 mg
oral tablet

Drug: telmisartan 40 mg/indapamide 2.5 mg
oral tablet

Active Comparator: Dual - AI

Amlodipine 2.5 mg/indapamide 1.25 mg. At week 6 visit, forced up-titration to amlodipine 5 mg/indapamide 2.5 mg

Drug: Amlodipine 2.5 mg/indapamide 1.25 mg
oral tablet

Drug: amlodipine 5 mg/indapamide 2.5 mg
oral tablet

Outcome Measures

Primary Outcome Measures

  1. Difference in change in home SBP from baseline to week 12 [12 weeks]

Secondary Outcome Measures

  1. Difference in change in clinic seated mean SBP from baseline to Week 12 [12 weeks]

  2. Difference in change in clinic seated mean SBP from baseline to Week 6 [6 weeks]

  3. Difference in change in clinic seated mean DBP from baseline to Week 12 [12 weeks]

  4. Difference in change in clinic seated mean DBP from baseline to Week 6 [6 weeks]

  5. Percentage of participants with clinic seated mean SBP <140 and DBP <90 mmHg at Week 12 [12 weeks]

  6. Percentage of participants with clinic seated mean SBP <140 and DBP <90 mmHg at Week 6 [6 weeks]

  7. Percentage of participants with clinic seated mean SBP <130 and DBP <80 mmHg at Week 12 [12 weeks]

  8. Percentage of participants with clinic seated mean SBP <130 and DBP <80 mmHg at Week 6 [6 weeks]

  9. Difference in change in home seated mean SBP from baseline to Week 6 [6 weeks]

  10. Difference in change in home seated mean DBP from baseline to Week 12 [12 weeks]

  11. Difference in change in home seated mean DBP from baseline to Week 6 [6 weeks]

  12. Difference in change in trough home seated mean SBP from baseline to week 12 [12 weeks]

  13. Difference in change in trough home seated mean SBP from baseline to Week 6 [6 weeks]

  14. Percentage of participants with home seated mean SBP <135 and DBP <85 mmHg at Week 12 [12 weeks]

  15. Percentage of participants with home seated mean SBP <135 and DBP <85 mmHg at Week 6 [6 weeks]

  16. Percentage of participants with home seated mean SBP <130 and DBP <80 mmHg at Week 12 [12 weeks]

  17. Percentage of participants with home seated mean SBP <130 and DBP <80 mmHg at Week 6 [6 weeks]

Other Outcome Measures

  1. Safety Outcomes [12 weeks]

    Percentage of participants discontinued trial medication due to AE/SAE from baseline to week 12

  2. Safety Outcomes [6 weeks]

    Percentage of participants discontinued trial medication due to AE/SAE from baseline to Week 6

  3. Safety Outcomes [12 weeks]

    Percentage of participants with an SAE from baseline to Week 12

  4. Safety Outcomes [6 weeks]

    Percentage of participants with SAE from baseline to Week 6

  5. Safety Outcomes [12 weeks]

    Percentage of participants with symptomatic hypotension from baseline to Week 12

  6. Safety Outcomes [6 weeks]

    Percentage of participants with symptomatic hypotension from baseline to Week 6

  7. Safety Outcomes [12 weeks]

    Percentage of participants with serum sodium concentration below 135 mmol/l at Week 12

  8. Safety Outcomes [6 weeks]

    Percentage of participants with serum sodium concentration below 135 mmol/l at Week 6

  9. Safety Outcomes [12 weeks]

    Percentage of participants with serum sodium concentration above 145 mmol/l at Week 12

  10. Safety Outcomes [6 weeks]

    Percentage of participants with serum sodium concentration above 145 mmol/l at Week 6

  11. Safety Outcomes [12 weeks]

    Percentage of participants with serum potassium concentration below 3.5 mmol/l at Week 12

  12. Safety Outcomes [6 weeks]

    Percentage of participants with serum potassium concentration below 3.5 mmol/l at Week 6

  13. Safety Outcomes [12 weeks]

    Percentage of participants with serum potassium concentration above 5.5 mmol/l at Week 12

  14. Safety Outcomes [6 weeks]

    Percentage of participants with serum potassium concentration above 5.5 mmol/l at Week 6

  15. Safety Outcomes [12 weeks]

    Percentage of participants with eGFR drop of over 30% from baseline to Week 12

  16. Safety Outcomes [6 weeks]

    Percentage of participants with eGFR drop of over 30% from baseline to Week 6

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

At screening visit

  1. Provided signed consent to participate in the trial.

  2. Adult of age ≥18 years.

  3. Attended automated clinic seated mean SBP (average of last 2 measurements calculated by the device):

150-179 mmHg on 0 blood pressure (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 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: ≥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 (i.e. accepting measures outside of the recommended 0600-1000 and 1800-2200 periods as long as they are in the am or pm, respectively).

At week 12 (for optional open-label extension)

  1. Provided signed informed consent.

  2. completed randomized treatment and willing to continue GMRx2-based regimen for up to 12 months.

Exclusion Criteria:

At screening visit

  1. Receiving 4 or more BP-lowering drugs.

  2. receiving any BP lowering drugs for indications other than hypertension e.g. heart failure

  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 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 there has been no episode in the last 3 months, while patient with a 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 a known secondary cause of hypertension, such as primary aldosteronism, renal artery stenosis, pheochromocytoma, or Cushing's syndrome.

  11. Current/history of substantially uncontrolled diabetes (HbA1c > 11.0%) within last three months.

  12. Current/history of end-stage renal disease or anuria or estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m2.

  13. Electrolyte levels that would be regarded as contraindications for any of the potential treatment arms e.g. serum sodium <132mmol/l or >148mmol/l serum potassium <3.1 mmol/l or >5.6 mmol/l.

  14. Current/history of aspartate aminotransferase (AST) or alanine aminotransferase (ALT)

3 times the upper limit of normal range within 6 months.

  1. 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.

  2. Arm circumference that is too large (>55 cm) or too small (<20 cm) to allow accurate measurement of BP.

  3. 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.

  4. 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).

  5. 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.

  6. Individuals working >2 nightshifts per week.

  7. Participated in any investigative drug or device trial within the previous 30 days.

  8. History of alcohol or drug abuse within 12 months.

At randomization visit

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

  3. 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 or low in clinic only; for example, the clinical relevance of 'whitecoat hypertension' is uncertain.

  4. High or low home diastolic BP (DBP) levels. The exact levels of DBP is not specified, reflecting clinical uncertainty of the implications of 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.

  5. 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.

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

At week 12 (for optional open-label extension)

  1. contraindication to open-label GMRx2-ased BP-lowering treatment.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Elite Clinical Studies Phoenix Arizona United States 85018
2 Healthlines Research Scottsdale Arizona United States 85260
3 Quality of Life Medical & Research Associates Tucson Arizona United States 85712
4 Valiance Clinical Research S. Gate California United States 90280
5 Valiance Clinical Research Tarzana California United States 91356
6 Clinical Research of Brandon Brandon Florida United States 33511
7 Inpatient Research Clinic Hialeah Florida United States 33013
8 Multi-Speciality Research Associates Lake City Florida United States 32055
9 Suncoast Research Group Miami Florida United States 33135
10 New Horizon Research Center Miami Florida United States 33165
11 Ocala Research Institute Ocala Florida United States 34471
12 Suncoast Research Associates Saint Petersburg Florida United States 33173
13 Accel Research Saint Petersburg Florida United States 33709
14 Precision Research Center Tampa Florida United States 33603
15 Meridian Clinical Research Savannah Georgia United States 31406
16 Buckhead Primary Care Research Snellville Georgia United States 30078
17 Loyola University Maywood Illinois United States 60153
18 Meridian Clinical Research Baton Rouge Louisiana United States 70809
19 Meridian Clinical Research Endwell New York United States 13760
20 Javarra Research Charlotte North Carolina United States 28210
21 East Carolina University Greenville North Carolina United States 27834
22 The University of Tennessee Health Science Center Memphis Tennessee United States 38105
23 ACRC Trials - Southwest Medical Village Austin Texas United States 78735
24 ACRC Trials - Premier Family Physicians Austin Texas United States 78746
25 ACRC Trials - Family Medicine Associates of Texas Carlton Texas United States 75010
26 Synergy Groups Medical Houston Texas United States 77036
27 Synergy Groups Medical Houston Texas United States 77087
28 Synergy Groups Medical Missouri City Texas United States 77459
29 North Hills Medical Research North Richland Hills Texas United States 76180
30 ACRC Trials - Village Health Partners Plano Texas United States 75093
31 Meridian Clinical Research Portsmouth Virginia United States 23703
32 Castle Hill Medical Centre Castle Hill New South Wales Australia 2154
33 Princess Alexandra Hospital - Hypertension Unit Brisbane Queensland Australia 4102
34 Hudson Institute of Medical Research Clayton Victoria Australia 3168
35 Barwon Health, Geelong University Hospital Geelong Victoria Australia 3220
36 Curtin University Bentley Western Australia Australia 6102
37 Royal Perth Hospital Perth Western Australia Australia 6000
38 EDUMED, s.r.o Broumov Kralovehradsky Czechia 550 01
39 EDUMED, s.r.o Jaroměř Kralovehradsky Czechia 551 01
40 Private Cardiologic Ambulance, Medicus Services s.r.o Brandýs Nad Labem Stredocesky Czechia 250 01
41 Middlemore Clinical Trials Otahuhu Auckland New Zealand 2025
42 Gisborne Hospital Gisborne New Zealand 4040
43 Medical University of Gdansk Gdańsk Gdansk Poland 80-214
44 Futuremeds Wrocław Wroclaw Poland 50-088
45 Pratia Katowice Medical Centre Katowice Poland 40-081
46 ETG Network Skierniewice Poland 96-100
47 Clinical Medicine Academic & Research Centre Colombo Sri Lanka 10-01000
48 Clinical Medicine Academic & Research Centre Colombo Sri Lanka 10-01000
49 Institute of Cardiology, National Hospital of Sri Lanka Colombo Sri Lanka 10-01000
50 Institute of Cardiology, National Hospital of Sri Lanka Colombo Sri Lanka 10-01000
51 Institute of Cardiology, National Hospital of Sri Lanka Colombo Sri Lanka 10-01000
52 Institute of Cardiology, National Hospital of Sri Lanka Colombo Sri Lanka 10-01000
53 Colombo South Teaching Hospital Dehiwala Sri Lanka 10350
54 Karapitiya Teaching Hospital Galle Sri Lanka 80000
55 Jafna Teaching Hospital Jaffna Sri Lanka 40000
56 Kandy National Hospital Kandy Sri Lanka 20000
57 Kurunegala Teaching Hospital Kurunegala Sri Lanka 60000
58 Negombo District General Hospital Negombo Sri Lanka 11500
59 Sri Jayawardenapura General Hospital Nugegoda Sri Lanka 10250
60 Colombo North Teaching Hospital Ragama Sri Lanka 11010
61 Steploe Medical Centre Soham Cambridgeshire United Kingdom CB7 5JD
62 Ashfields Primary Care Centre Sandbach Cheshire United Kingdom CW11 1EQ
63 Newquay Medical Newquay Cornwall United Kingdom TR7 1RU
64 Royal Primary care Ashgate Chesterfield Derbyshire United Kingdom S40 4AA
65 Carmel Medical Practice Darlington Durham United Kingdom DL3 8SQ
66 PRC Leciester Leicester East Midlands United Kingdom LE5 4PW
67 Portmill Surgery Hitchin Herts. United Kingdom SG49TH
68 Layton Medical Centre Blackpool Lancashire United Kingdom FY3 7EN
69 Waterloo Medical Centre Blackpool Lancashire United Kingdom FY4 3AD
70 Burbage Surgery Hinckley Leicestershire United Kingdom LE10 2SE
71 Belmont Health Centre Harrow London United Kingdom HA3 7LT
72 The Adam Practice Upton Poole United Kingdom BH165PW
73 Heart of bath Medical Partnership Bath Somerset United Kingdom BA2 3HT
74 West Walk Surgery Bristol Somerset United Kingdom BS37 4AX
75 Tyntesfield Medical Group Nailsea Somerset United Kingdom BS48 1BZ
76 Clifton Medical centre Rotherham South Yorkshire United Kingdom S65 1DA
77 Ely Bridge Cardiff Wales United Kingdom CV32 4RA
78 Atherstone Surgery Atherstone Warwickshire United Kingdom CV9 1EU
79 Lakeside Surgery Coventry West Midlands United Kingdom CV3 6NF
80 Sherbourne Medical Centre Leamington Spa West Midlands United Kingdom CV324RA
81 Hathaway Surgery Chippenham Wiltshire United Kingdom SN14 6GT
82 Rowden Surgery Chippenham Wiltshire United Kingdom SN15 2SB
83 Trowbridge Health Centre Trowbridge Wiltshire United Kingdom BA14 8LW
84 Bart's NHS Trust London United Kingdom EC1M6BO
85 Ecclesfield group Practice Sheffield United Kingdom S35 9XQ

Sponsors and Collaborators

  • George Medicines PTY Limited

Investigators

  • Principal Investigator: Anthony Rodgers, Professor, The George Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
George Medicines PTY Limited
ClinicalTrials.gov Identifier:
NCT04518293
Other Study ID Numbers:
  • GMRx2-HTN-2020-ACT1
First Posted:
Aug 19, 2020
Last Update Posted:
Aug 22, 2022
Last Verified:
Aug 1, 2022
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Aug 22, 2022