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

Hypertension Clinical Trial

— GMRx2_PCT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04518306
• Other study ID #: GMRx2-HTN-2020-PCT1
• Status: Completed
• Phase: Phase 3
• Start date: June 6, 2021
• Est. completion date: October 18, 2023

Study information

• Verified date: December 2023
• 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 placebo.

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 information / eligibility

• Status: Completed
• Enrollment: 295
• Est. completion date: October 18, 2023
• Est. primary completion date: September 18, 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 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.

Related Conditions & MeSH terms

• Hypertension

Intervention

Drug:
• Telmisartan 10 mg/amlodipine 1.25 mg/indapamide 0.625 mg
Oral tablets
• Telmisartan 20 mg/amlodipine 2.5 mg/indapamide 1.25 mg
Oral tablets
• Placebo
Placebo

Locations

Country	Name	City	State
Australia	Curtin University	Bentley	Western Australia
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
Nigeria	University of Abuja Teaching Hospital	Gwagwalada	Federal Capital Territory
Nigeria	Aminu Kano Teaching Hospital	Kano
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	Colombo North Teaching Hospital	Ragama
United Kingdom	Brockwood Medical Practice	Betchworth	Surrey
United Kingdom	West Walk Surgery	Bristol	Somerset
United Kingdom	Lakeside Surgery	Coventry	West Midlands
United Kingdom	Belmont Health Centre	Harrow	London
United Kingdom	Burbage Surgery	Hinckley	Leicestershire
United Kingdom	Newquay Medical	Newquay	Cornwall
United Kingdom	Abbeywell Surgery	Romsey
United Kingdom	Steploe Medical Centre	Soham	Cambridgeshire
United Kingdom	Trowbridge Health Centre	Trowbridge	Wiltshire
United Kingdom	Albany House Medical Centre	Wellingborough
United States	Meridian Clinical Research	Baton Rouge	Louisiana
United States	Clinical Research of Brandon	Brandon	Florida
United States	Inpatient Research Clinic	Hialeah	Florida
United States	Synergy Groups Medical	Houston	Texas
United States	Synergy Groups Medical	Houston	Texas
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	Altus Research, Inc	Palm Beach	Florida
United States	Elite Clinical Studies	Phoenix	Arizona
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	Headlands Research	Scottsdale	Arizona
United States	Buckhead Primary Care Research	Snellville	Georgia
United States	Precision Clinical Research	Sunrise	Florida
United States	Precision Research Center	Tampa	Florida
United States	Valiance Clinical Research	Tarzana	California
United States	Quality of Life Medical & Research Centers, LLC	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
George Medicines PTY Limited

Countries where clinical trial is conducted

United States,  Australia,  Nigeria,  Sri Lanka,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Primary Safety Outcome	Percentage of participants discontinued trial medication due to AE/SAE from baseline to Week 4	4 weeks
Other	Secondary Safety Outcome 1	Percentage of participants with an SAE from baseline to Week 4	4 weeks
Other	Secondary Safety Outcome 2	Percentage of participants with symptomatic hypotension from baseline to Week 4	4 weeks
Other	Secondary Safety Outcome 3	Percentage of participants with serum sodium concentration below 135 mmol/l at Week 4	4 weeks
Other	Secondary Safety Outcome 4	Percentage of participants with serum sodium concentration above 145 mmol/l at Week 4	4 weeks
Other	Secondary Safety Outcome 5	Percentage of participants with serum potassium concentration below 3.5 mmol/l at Week 4	4 weeks
Other	Secondary Safety Outcome 6	Percentage of participants with serum potassium concentration above 5.5 mmol/l at Week 4	4 weeks
Other	Secondary Safety Outcome 7	Percentage of participants with eGFR drop of over 30% from baseline to Week 4	4 weeks
Other	Secondary Safety Outcome 8	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	4 weeks
Other	Secondary Safety Outcome 9	Percentage of participants with postural hypotension at Week 4	4 weeks
Other	Secondary Safety Outcome 10	Percentage of participants with postural hypertension at Week 4	4 weeks
Primary	Difference in change in home seated SBP from baseline to Week 4		4 weeks
Secondary	Difference in change in clinic seated mean SBP from baseline to Week 4		4 weeks
Secondary	Difference in change in clinic seated mean DBP from baseline to Week 4		4 weeks
Secondary	Percentage of participants with clinic seated mean SBP <140 and DBP <90 mmHg at Week 4		4 weeks
Secondary	Percentage of participants with clinic seated mean SBP <130 and DBP <80 mmHg at Week 4		4 weeks
Secondary	Difference in change in home seated mean DBP from baseline to Week 4		4 weeks
Secondary	Difference in change in trough home seated mean SBP from baseline to week 4		4 weeks
Secondary	Difference in change in trough home seated mean DBP from baseline to week 4		4 weeks
Secondary	Percentage of participants with home seated mean SBP <135 and DBP <85 mmHg at Week 4		4 weeks
Secondary	Percentage of participants with home seated mean SBP <130 and DBP <80 mmHg at Week 4		4 weeks