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

Hypertension Clinical Trial

— GMRx2_ACT  

Official title:

Efficacy and Safety of GMRx2 (a Single Pill Combination Containing Telmisartan/Amlodipine/Indapamide) Compared to Dual Combinations for the Treatment of Hypertension

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04518293
• Other study ID #: GMRx2-HTN-2020-ACT1
• Status: Completed
• Phase: Phase 3
• Start date: June 26, 2021
• Est. completion date: September 1, 2023

Study information

• Verified date: April 2024
• Source: George Medicines PTY Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1385
• Est. completion date: September 1, 2023
• Est. primary completion date: August 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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):

140-179 mmHg on 0 blood pressure (BP)-lowering drugs, or 130-170 mmHg on 1 BP-lowering drug, or 120-160 mmHg on 2 BP-lowering drugs, or 110-150 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.

15. 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.

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

17. 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.

18. 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).

19. 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.

20. Individuals working >2 nightshifts per week.

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

22. 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:

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

2. 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.

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.

Related Conditions & MeSH terms

• Hypertension

Intervention

Drug:
• Telmisartan 20 mg/amlodipine 2.5 mg/indapamide 1.25 mg
Single pill
• telmisartan 40 mg/amlodipine 5 mg/indapamide 2.5 mg
Signle pill
• Telmisartan 20 mg/amlodipine 2.5 mg .
oral tablet
• telmisartan 40 mg/amlodipine 5 mg
oral tablet
• Telmisartan 20 mg/indapamide 1.25 mg
oral tablet
• telmisartan 40 mg/indapamide 2.5 mg
oral tablet
• Amlodipine 2.5 mg/indapamide 1.25 mg
oral tablet
• amlodipine 5 mg/indapamide 2.5 mg
oral tablet

Locations

Country	Name	City	State
Australia	Curtin University	Bentley	Western Australia
Australia	Princess Alexandra Hospital - Hypertension Unit	Brisbane	Queensland
Australia	Castle Hill Medical Centre	Castle Hill	New South Wales
Australia	Hudson Institute of Medical Research	Clayton	Victoria
Australia	Barwon Health, Geelong University Hospital	Geelong	Victoria
Australia	Royal Perth Hospital	Perth	Western Australia
Czechia	Private Cardiologic Ambulance, Medicus Services s.r.o	Brandýs Nad Labem	Stredocesky
Czechia	EDUMED, s.r.o	Broumov	Kralovehradsky
Czechia	EDUMED, s.r.o	Jaromer	Kralovehradsky
New Zealand	Gisborne Hospital	Gisborne
New Zealand	Middlemore Clinical Trials	Otahuhu	Auckland
Poland	Medical University of Gdansk	Gdansk	Gdansk
Poland	Medical University of Gdansk	Gdansk
Poland	Pratia Katowice Medical Centre	Katowice
Poland	Pratia Katowice Medical Centre	Katowice
Poland	Nowodworskie Medical Center	Nowy Dwór Mazowiecki
Poland	Medical Center Pratia Poznan	Poznan
Poland	ETG Network	Skierniewice
Poland	ETG Network	Skierniewice
Poland	The Medical University of Warsaw	Warsaw
Poland	EMC Instytut Medyczny S.A	Wroclaw
Poland	Futuremeds	Wroclaw
Poland	Futuremeds	Wroclaw	Wroclaw
Sri Lanka	Clinical Medicine Academic & Research Centre	Colombo
Sri Lanka	Institute of Cardiology, National Hospital of Sri Lanka	Colombo
Sri Lanka	Colombo South Teaching Hospital	Dehiwala
Sri Lanka	Karapitiya Teaching Hospital	Galle
Sri Lanka	Jafna Teaching Hospital	Jaffna
Sri Lanka	Kandy National Hospital	Kandy
Sri Lanka	Kurunegala Teaching Hospital	Kurunegala
Sri Lanka	Negombo District General Hospital	Negombo
Sri Lanka	Sri Jayawardenapura General Hospital	Nugegoda
Sri Lanka	Colombo North Teaching Hospital	Ragama
United Kingdom	Atherstone Surgery	Atherstone	Warwickshire
United Kingdom	Heart of bath Medical Partnership	Bath	Somerset
United Kingdom	Layton Medical Centre	Blackpool	Lancashire
United Kingdom	Waterloo Medical Centre	Blackpool	Lancashire
United Kingdom	West Walk Surgery	Bristol	Somerset
United Kingdom	Ely Bridge	Cardiff	Wales
United Kingdom	Royal Primary care Ashgate	Chesterfield	Derbyshire
United Kingdom	Hathaway Surgery	Chippenham	Wiltshire
United Kingdom	Rowden Surgery	Chippenham	Wiltshire
United Kingdom	Lakeside Surgery	Coventry	West Midlands
United Kingdom	Carmel Medical Practice	Darlington	Durham
United Kingdom	Belmont Health Centre	Harrow	London
United Kingdom	Burbage Surgery	Hinckley	Leicestershire
United Kingdom	Portmill Surgery	Hitchin	Herts.
United Kingdom	Sherbourne Medical Centre	Leamington Spa	West Midlands
United Kingdom	PRC Leciester	Leicester	East Midlands
United Kingdom	Bart's NHS Trust	London
United Kingdom	Tyntesfield Medical Group	Nailsea	Somerset
United Kingdom	Newquay Medical	Newquay	Cornwall
United Kingdom	Clifton Medical centre	Rotherham	South Yorkshire
United Kingdom	Ashfields Primary Care Centre	Sandbach	Cheshire
United Kingdom	Ecclesfield group Practice	Sheffield
United Kingdom	Steploe Medical Centre	Soham	Cambridgeshire
United Kingdom	Trowbridge Health Centre	Trowbridge	Wiltshire
United Kingdom	The Adam Practice	Upton	Poole
United States	ACRC Trials - Premier Family Physicians	Austin	Texas
United States	ACRC Trials - Southwest Medical Village	Austin	Texas
United States	Meridian Clinical Research	Baton Rouge	Louisiana
United States	Clinical Research of Brandon	Brandon	Florida
United States	ACRC Trials - Family Medicine Associates of Texas	Carlton	Texas
United States	Javarra Research	Charlotte	North Carolina
United States	Meridian Clinical Research	Endwell	New York
United States	East Carolina University	Greenville	North Carolina
United States	Inpatient Research Clinic	Hialeah	Florida
United States	Synergy Groups Medical	Houston	Texas
United States	Synergy Groups Medical	Houston	Texas
United States	Multi-Speciality Research Associates	Lake City	Florida
United States	Loyola University	Maywood	Illinois
United States	The University of Tennessee Health Science Center	Memphis	Tennessee
United States	New Horizon Research Center	Miami	Florida
United States	Suncoast Research Group	Miami	Florida
United States	Synergy Groups Medical	Missouri City	Texas
United States	North Hills Medical Research	North Richland Hills	Texas
United States	Ocala Research Institute	Ocala	Florida
United States	Elite Clinical Studies	Phoenix	Arizona
United States	ACRC Trials - Village Health Partners	Plano	Texas
United States	Meridian Clinical Research	Portsmouth	Virginia
United States	Valiance Clinical Research	S. Gate	California
United States	Accel Research	Saint Petersburg	Florida
United States	Suncoast Research Associates	Saint Petersburg	Florida
United States	Meridian Clinical Research	Savannah	Georgia
United States	Headlands Research	Scottsdale	Arizona
United States	Buckhead Primary Care Research	Snellville	Georgia
United States	Precision Research Center	Tampa	Florida
United States	Valiance Clinical Research	Tarzana	California
United States	Quality of Life Medical & Research Associates	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
George Medicines PTY Limited

Countries where clinical trial is conducted

United States,  Australia,  Czechia,  New Zealand,  Poland,  Sri Lanka,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Percentage of participants discontinued trial medication due to AE/SAE from baseline to week 12	Safety Outcomes	12 weeks
Other	Percentage of participants discontinued trial medication due to AE/SAE from baseline to Week 6	Safety Outcomes	6 weeks
Other	Percentage of participants with an SAE from baseline to Week 12	Safety Outcomes	12 weeks
Other	Percentage of participants with SAE from baseline to Week 6	Safety Outcomes	6 weeks
Other	Percentage of participants with symptomatic hypotension from baseline to Week 12	Safety Outcomes	12 weeks
Other	Percentage of participants with symptomatic hypotension from baseline to Week 6	Safety Outcomes	6 weeks
Other	Percentage of participants with serum sodium concentration below 135 mmol/l at Week 12	Safety Outcomes	12 weeks
Other	Percentage of participants with serum sodium concentration below 135 mmol/l at Week 6	Safety Outcomes	6 weeks
Other	Percentage of participants with serum sodium concentration above 145 mmol/l at Week 12	Safety Outcomes	12 weeks
Other	Percentage of participants with serum sodium concentration above 145 mmol/l at Week 6	Safety Outcomes	6 weeks
Other	Percentage of participants with serum potassium concentration below 3.5 mmol/l at Week 12	Safety Outcomes	12 weeks
Other	Percentage of participants with serum potassium concentration below 3.5 mmol/l at Week 6	Safety Outcomes	6 weeks
Other	Percentage of participants with serum potassium concentration above 5.5 mmol/l at Week 12	Safety Outcomes	12 weeks
Other	Percentage of participants with serum potassium concentration above 5.5 mmol/l at Week 6	Safety Outcomes	6 weeks
Other	Percentage of participants with eGFR drop of over 30% from baseline to Week 12	Safety Outcomes	12 weeks
Other	Percentage of participants with eGFR drop of over 30% from baseline to Week 6	Safety Outcomes	6 weeks
Primary	Difference in change in home SBP from baseline to week 12		12 weeks
Secondary	Difference in change in clinic seated mean SBP from baseline to Week 12		12 weeks
Secondary	Difference in change in clinic seated mean SBP from baseline to Week 6		6 weeks
Secondary	Difference in change in clinic seated mean DBP from baseline to Week 12		12 weeks
Secondary	Difference in change in clinic seated mean DBP from baseline to Week 6		6 weeks
Secondary	Percentage of participants with clinic seated mean SBP <140 and DBP <90 mmHg at Week 12		12 weeks
Secondary	Percentage of participants with clinic seated mean SBP <140 and DBP <90 mmHg at Week 6		6 weeks
Secondary	Percentage of participants with clinic seated mean SBP <130 and DBP <80 mmHg at Week 12		12 weeks
Secondary	Percentage of participants with clinic seated mean SBP <130 and DBP <80 mmHg at Week 6		6 weeks
Secondary	Difference in change in home seated mean SBP from baseline to Week 6		6 weeks
Secondary	Difference in change in home seated mean DBP from baseline to Week 12		12 weeks
Secondary	Difference in change in home seated mean DBP from baseline to Week 6		6 weeks
Secondary	Difference in change in trough home seated mean SBP from baseline to week 12		12 weeks
Secondary	Difference in change in trough home seated mean SBP from baseline to Week 6		6 weeks
Secondary	Percentage of participants with home seated mean SBP <135 and DBP <85 mmHg at Week 12		12 weeks
Secondary	Percentage of participants with home seated mean SBP <135 and DBP <85 mmHg at Week 6		6 weeks
Secondary	Percentage of participants with home seated mean SBP <130 and DBP <80 mmHg at Week 12		12 weeks
Secondary	Percentage of participants with home seated mean SBP <130 and DBP <80 mmHg at Week 6		6 weeks