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

• Sponsor: George Medicines PTY Limited (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04518306
• Collaborator: (none)
• Enrollment: 250
• Locations: 30
• Arms: 3
• Anticipated Duration (Months): 23.8
• Patients Per Site: 8.3
• Patients Per Site Per Month: 0.4

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 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

• Study Type: Interventional
• Anticipated Enrollment: 250 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: International, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial.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: Jun 6, 2021
• Anticipated Primary Completion Date: Mar 31, 2023
• Anticipated Study Completion Date: May 31, 2023

Arms and Interventions

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

Primary Outcome Measures

1. Difference in change in home SBP from baseline to Week 4 [4 weeks]

Secondary Outcome Measures

1. Difference in change in clinic seated mean SBP from baseline to Week 4 [4 weeks]

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

3. Percentage of participants with clinic seated mean SBP <140 and DBP <90 mmHg at Week 4 [4 weeks]

4. Percentage of participants with clinic seated mean SBP <130 and DBP <80 mmHg at Week 4 [4 weeks]

5. Difference in change in home seated mean DBP from baseline to Week 4 [4 weeks]

6. Difference in change in trough home seated mean SBP from baseline to week 4 [4 weeks]

7. Difference in change in trough home seated mean DBP from baseline to week 4 [4 weeks]

8. Percentage of participants with home seated mean SBP <135 and DBP <85 mmHg at Week 4 [4 weeks]

9. Percentage of participants with home seated mean SBP <130 and DBP <80 mmHg at Week 4 [4 weeks]

Other Outcome Measures

1. Safety Outcomes [4 weeks]

   Percentage of participants discontinued trial medication due to AE/SAE from baseline to Week 4

2. Safety Outcomes [4 weeks]

   Percentage of participants with an SAE from baseline to Week 4

3. Safety Outcomes [4 weeks]

   Percentage of participants with symptomatic hypotension from baseline to Week 4

4. Safety Outcomes [4 weeks]

   Percentage of participants with serum sodium concentration below 135 mmol/l at Week 4

5. Safety Outcomes [4 weeks]

   Percentage of participants with serum sodium concentration above 145 mmol/l at Week 4

6. Safety Outcomes [4 weeks]

   Percentage of participants with serum potassium concentration below 3.5 mmol/l at Week 4

7. Safety Outcomes [4 weeks]

   Percentage of participants with serum potassium concentration above 5.5 mmol/l at Week 4

8. Safety Outcomes [4 weeks]

   • Percentage of participants with eGFR drop of over 30% from baseline to Week 4

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 aged ≥18 years.

3. Low predicted CV risk, such that short-term treatment with placebo is clinically acceptable: e.g. atherosclerotic CV disease risk of <10% over 10-years as assessed by the Pooled Cohorts equation; or similar equation as recommended by local guidelines.

4. Clinic attended automated seated mean SBP (average of last 2 measurements calculated by the BP monitor);

• 140-159 mmHg on no treatment, or,

• 130-149 mmHg on 1 BP-lowering drug.

1. Any contraindication to trial medications, including 2-week placebo run-in and 4-week trial medication 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: ≥3 days in the week before the randomization visit and ≥1 day per week during the preceding weeks.

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:

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

4. 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.

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.

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 Centers, LLC	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	Suncoast Research Group	Miami	Florida	United States	33135
9	New Horizon Research Center	Miami	Florida	United States	33165
10	Ocala Research Institute	Ocala	Florida	United States	34471
11	Suncoast Research Associates	Saint Petersburg	Florida	United States	33173
12	Accel Research	Saint Petersburg	Florida	United States	33709
13	Precision Clinical Research	Sunrise	Florida	United States	33351
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	The University of Tennessee Health Science Center	Memphis	Tennessee	United States	38105
20	Synergy Groups Medical	Houston	Texas	United States	77036
21	Synergy Groups Medical	Houston	Texas	United States	77087
22	Synergy Groups Medical	Missouri City	Texas	United States	77459
23	North Hills Medical Research	North Richland Hills	Texas	United States	76180
24	Meridian Clinical Research	Portsmouth	Virginia	United States	23703
25	Castle Hill Medical Centre	Castle Hill	New South Wales	Australia	2154
26	Princess Alexandra Hospital	Brisbane	Queensland	Australia	4102
27	Hudson Institute of Medical Research	Clayton	Victoria	Australia	3168
28	Barwon Health, Geelong University Hospital	Geelong	Victoria	Australia	3220
29	Curtin University	Bentley	Western Australia	Australia	6102
30	Royal Perth Hospital	Perth	Western Australia	Australia	6000

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: NCT04518306
• Other Study ID Numbers: GMRx2-HTN-2020-PCT1
• First Posted: Aug 19, 2020
• Last Update Posted: Aug 22, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Hypertension; Amlodipine; Telmisartan; Indapamide

Study Results

No Results Posted as of Aug 22, 2022