Date

2022-05-11

Protocol

Protocol changed

Item Changed

Intervention(s) planned

Previous Version

Study setting: National Hospital of Sri Lanka Colombo North Teaching Hospital Negombo District General Hospital Sri Jayewardenepura General Hospital Colombo South Teaching Hospital Kandy National Hospital Kurunegala Teaching Hospital Jaffna Teaching Hospital Karapitiya Teaching Hospital 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. Single-Blind Active Run-In Period: During the screening visit, 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) after home BP measurement is performed. Double-Blind Treatment Period: Following randomization, participants will be allocated in a double-blind fashion to one of 4 randomized group. 1. Group 1 (Triple therapy - TAI (GMRx2))-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. (N= 600) 2. Group 2 (dual therapy)- Telmisartan 20 mg/amlodipine 2.5 mg. At Week 6 visit, forced up-titration to telmisartan 40 mg/amlodipine 5 mg (N= 300) 3. Group 3 (dual therapy)- Telmisartan 20 mg/indapamide 1.25 mg. At Week 6 visit, forced up-titration to telmisartan 40 mg/indapamide 2.5 mg (N= 300) 4. Group 4 (dual therapy)- Amlodipine 2.5 mg/indapamide 1.25 mg. At Week 6 visit, forced up-titration to amlodipine 5 mg/indapamide 2.5 mg (N=300) Randomisation method: A central computer based randomization sequence will be generated. Stratification will be by trial site. Participants will be randomised in the ratio of 2:1:1:1. On the day of randomization visit, all participants will be prescribed and dispensed trial medication to be taken between the randomization and Week 6 visit (period 2). On the day of the Week 6 visit, all participants will be prescribed and dispensed trial medication (the same initial treatment but at double dose) to be taken between Week 6 and Week 12 visit (period 3). All participants will be up-titrated at Week 6, unless the investigator believes there is a specific contraindication for a particular participant, such as symptomatic hypotension or is asymptomatic with very low home or clinical BP levels (i.e. SBP <100 mmHg). If a participant is asymptomatic but is judged to be not suitable for dose doubling, then they should be continued on existing trial medication for the remaining 6 weeks. Participants should take trial medication once daily in the morning either before or after breakfast immediately after taking home BP measurement.

Next Version

Single-Blind Active Run-In Period During the screening visit, enrolled participants will be asked to discontinue all current BP-lowering drug(s) if applicable and enter a single-blind active run-in period for 4 weeks with GMRx2 dose version 2. Participants will be advised to take the run-in capsule once daily in the morning at approximately the same time each day. For days on which BP is being measured, the run-in capsule should be taken directly after the morning home BP measurement. Participants will be advised to take the capsule once daily in the morning at the same time (±2 hours) after home BP measurement is performed. Double-Blind Treatment Period The 4-week single-blind active run-in will be followed by a 12-week double-blind period with randomization to one of the following four treatment groups: Group 1 (Triple therapy - TAI (GMRx2))-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. (N= 600) 2. Group 2 (dual therapy)- Telmisartan 20 mg/amlodipine 2.5 mg. At Week 6 visit, forced up-titration to telmisartan 40 mg/amlodipine 5 mg (N= 300) 3. Group 3 (dual therapy)- Telmisartan 20 mg/indapamide 1.25 mg. At Week 6 visit, forced up-titration to telmisartan 40 mg/indapamide 2.5 mg (N= 300) 4. Group 4 (dual therapy)- Amlodipine 2.5 mg/indapamide 1.25 mg. At Week 6 visit, forced up-titration to amlodipine 5 mg/indapamide 2.5 mg (N=300) Participants will be randomised in the ration 2:1:1:1 On the day of randomization visit (W0), all participants will be prescribed and dispensed trial medication to be taken between the randomization and Week 6 visit (period 2). On the day of the Week 6 visit, all participants will be prescribed and dispensed trial medication (the same initial treatment but at double dose) to be taken between Week 6 and Week 12 visit (period 3). All participants will be up-titrated at Week 6, unless the investigator believes there is a specific contraindication for a particular participant, such as symptomatic hypotension or is asymptomatic with very low home or clinical BP levels (i.e. SBP <100 mmHg). If a participant is asymptomatic but is judged to be not suitable for dose doubling, then they should be continued on existing trial medication for the remaining 6 weeks. Participants should take trial medication once daily in the morning either before or after breakfast immediately after taking home BP measurement.