Hypertension
Conditions
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 (BP) 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.
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 approximately the same time each day. For days on which BP is being measured, the capsule should be taken directly after the morning home BP measurement. 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 telmisartan 20mg+amlodipine2.5mg, or telmisartan 20mg+indapamide 1.25mg, or amlodipine 2.5mg+indapamide 1.25mg. At week 6 all doses will be doubled.
Interventions
DRUGamlodipine 5 mg/indapamide 2.5 mg
oral tablet
DRUGAmlodipine 2.5 mg/indapamide 1.25 mg
oral tablet
Single pill
DRUGtelmisartan 40 mg/amlodipine 5 mg/indapamide 2.5 mg
Single pill
DRUGTelmisartan 20 mg/amlodipine 2.5 mg
oral tablet
DRUGtelmisartan 40 mg/amlodipine 5 mg
oral tablet
DRUGTelmisartan 20 mg/indapamide 1.25 mg
oral tablet
DRUGtelmisartan 40 mg/indapamide 2.5 mg
oral tablet
Sponsors
George Medicines PTY Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
International, multicenter, randomized, double-blind, active-controlled, parallel group.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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 systolic blood pressure (SBP) (average of last 2 measurements calculated by the device): 140-179 mmHg on 0 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: in the week before randomization, at least 6 measures (e.g. ≥2 sets of triplicate measures, ≥3 sets of duplicate 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 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 (\<15-24 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. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in Change in Home Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 12 | Week 12 | The primary outcome measure is difference in change in average home SBP for GMRx2 vs each dual combination evaluated from randomization to Week 12. The change in home SBP from randomization for all treatment arms was measured using least squares (LS) mean change. The pairwise comparisons between GMRx2 and dual treatments in change in home SBP were estimated using LS means difference and are described in the statistical analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Difference in Change in Clinic Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 6 | Week 6 | Difference in change in average clinic SBP for GMRx2 vs each dual combination was evaluated from randomization to Week 6. |
| Difference in Change in Clinic Seated Mean Diastolic Blood Pressure (DBP) From Randomization to Week 12 | Week 12 | Difference in change in average clinic DBP for GMRx2 vs each dual combination was evaluated from randomization to Week 12. |
| Difference in Change in Clinic Seated Mean Diastolic Blood Pressure (DBP) From Randomization to Week 6 | Week 6 | Difference in change in average clinic DBP for GMRx2 vs each dual combination was evaluated from randomization to Week 6. |
| Percentage of Participants With Clinic Seated Mean Systolic Blood Pressure (SBP) <140 and Diastolic Blood Pressure (DBP) <90 mmHg at Week 12 | Week 12 | The percentage of participants achieving averaged clinic SBP \<140 mmHg and DBP \<90 mmHg at Week 12 was evaluated. |
| Percentage of Participants With Clinic Seated Mean Systolic Blood Pressure (SBP) <140 and Diastolic Blood Pressure (DBP) <90 mmHg at Week 6 | Week 6 | The percentage of participants achieving averaged clinic SBP \<140 mmHg and DBP \<80 mmHg at Week 6 was evaluated. |
| Percentage of Participants With Clinic Seated Mean Systolic Blood Pressure (SBP) <130 and Diastolic Blood Pressure (DBP) <80 mmHg at Week 12 | Week 12 | The percentage of participants achieving averaged clinic SBP \<130 mmHg and DBP \<80 mmHg at Week 12 was evaluated. |
| Percentage of Participants With Clinic Seated Mean Systolic Blood Pressure (SBP) <130 and Diastolic Blood Pressure (DBP) <80 mmHg at Week 6 | Week 6 | The percentage of participants achieving averaged clinic SBP \<130 mmHg and DBP \<80 mmHg at Week 6 was evaluated. |
| Difference in Change in Home Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 6 | Week 6 | Difference in change in average home SBP for GMRx2 vs each dual combination was evaluated from randomization to Week 6. |
| Difference in Change in Home Seated Mean Diastolic Blood Pressure (DBP) From Randomization to Week 12 | Week 12 | Difference in change in average home DBP for GMRx2 vs each dual combination was evaluated from randomization to Week 12. |
| Difference in Change in Home Seated Mean Diastolic Blood Pressure (DBP) From Randomization to Week 6 | Week 6 | Difference in change in average home DBP for GMRx2 vs each dual combination was evaluated from randomization to Week 6. |
| Difference in Change in Trough Home Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 12 | Week 12 | Difference in change in trough home SBP for GMRx2 vs each dual combination was evaluated from randomization to Week 12. Trough values were measured before morning dose of the study medication. |
| Difference in Change in Trough Home Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 6 | Week 6 | Difference in change in trough home SBP for GMRx2 vs each dual combination was evaluated from randomization to Week 6. Trough values were measured before morning dose of the study medication. |
| Percentage of Participants With Home Seated Mean Systolic Blood Pressure (SBP) <135 and Diastolic Blood Pressure (DBP) <85 mmHg at Week 12 | Week 12 | The percentage of participants achieving averaged home SBP \<135 mmHg and DBP \<85 mmHg at week 12 was calculated. |
| Percentage of Participants With Home Seated Mean Systolic Blood Pressure (SBP) <135 and Diastolic Blood Pressure (DBP) <85 mmHg at Week 6 | Week 6 | The percentage of participants achieving averaged home SBP \<135 mmHg and DBP \<85 mmHg at Week 6 was evaluated. |
| Percentage of Participants With Home Seated Mean Systolic Blood Pressure (SBP) <130 and Diastolic Blood Pressure (DBP) <80 mmHg at Week 12 | Week 12 | The percentage of participants achieving averaged home SBP \<130 mmHg and DBP \<80 mmHg at Week 12 was evaluated. |
| Percentage of Participants With Home Seated Mean Systolic Blood Pressure (SBP) <130 and Diastolic Blood Pressure (DBP) <80 mmHg at Week 6 | Week 6 | The percentage of participants achieving averaged home SBP \<130 mmHg and DBP \<80 mmHg at Week 6 was evaluated. |
| Difference in Change in Clinic Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 12 | Week 12 | Difference in change in average clinic SBP for GMRx2 vs each dual combination was evaluated from randomization to Week 12. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Discontinued Trial Medication Due to Adverse Event (AE)/Serious Adverse Event (SAE) From Randomization to Week 6 | Week 6 | The secondary safety outcome is the proportion of participants who discontinued trial medication due to AE/SAE from randomization to follow-up at Week 6. |
| Percentage of Participants With a Serious Adverse Event (SAE) From Randomization to Week 12 | At Week 12 | The secondary safety outcome is the proportion of participants with at least one SAE from randomization to follow-up at Week 12. |
| Percentage of Participants With Serious Adverse Event (SAE) From Randomization to Week 6 | Week 6 | The secondary safety outcome is the proportion of participants with at least one SAE from randomization to follow-up at Week 6. |
| Percentage of Participants With Symptomatic Hypotension From Randomization to Week 12 | Week 12 | The secondary safety outcome is the proportion of participants who experienced at least one symptomatic hypotension episode from randomization to follow-up at Week 12. |
| Percentage of Participants With Symptomatic Hypotension From Randomization to Week 6 | Week 6 | The secondary safety outcome is the proportion of participants who experienced at least one symptomatic hypotension episode from randomization to follow-up at Week 6. |
| Percentage of Participants With Serum Sodium Concentration Below 135 mmol/l at Week 12 | Week 12 | The secondary safety outcome is the proportion of participants with serum sodium \<135 mmol/L at follow-up Week 12. |
| Percentage of Participants With Serum Sodium Concentration Below 135 mmol/l at Week 6 | Week 6 | The secondary safety outcome is the proportion of participants with serum sodium \<135 mmol/L at follow-up Week 6. |
| Percentage of Participants With Serum Sodium Concentration Above 145 mmol/l at Week 12 | Week 12 | The secondary safety outcome is the proportion of participants with serum sodium \>145 mmol/L at follow-up Week 12. |
| Percentage of Participants With Serum Sodium Concentration Above 145 mmol/l at Week 6 | Week 6 | The secondary safety outcome is the proportion of participants with serum sodium \>145 mmol/L at follow-up Week 6. |
| Percentage of Participants With Serum Potassium Concentration Below 3.5 mmol/l at Week 12 | Week 12 | The secondary safety outcome is the proportion of participants with serum potassium concentration \<3.5 mmol/L at follow-up Week 12. |
| Percentage of Participants With Serum Potassium Concentration Below 3.5 mmol/l at Week 6 | Week 6 | The secondary safety outcome is the proportion of participants with serum potassium concentration below 3.5 mmol/l at follow-up Week 6. |
| Percentage of Participants With Serum Potassium Concentration Above 5.5 mmol/l at Week 12 | Week 12 | The secondary safety outcome is proportion of participants with serum potassium concentration \>5.5 mmol/l at follow-up Week 12. |
| Percentage of Participants With Serum Potassium Concentration Above 5.5 mmol/l at Week 6 | Week 6 | The secondary safety outcome is proportion of participants with serum potassium concentration \>5.5 mmol/L at follow-up Week 6. |
| Percentage of Participants With Estimated Glomerular Filtration Rate (eGFR) Drop of Over 30% From Randomization to Week 12 | Week 12 | The secondary safety outcome was the proportion of participants with an eGFR drop of over 30% from randomization to follow-up at Week 12. |
| Percentage of Participants With Estimated Glomerular Filtration Rate (eGFR) Drop of Over 30% From Randomization to Week 6 | Week 6 | The secondary safety outcome is the proportion of participants with an eGFR drop of over 30% from randomization to follow-up at Week 6. |
| 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 Follow-up Week 12 | Week 12 | The secondary safety outcome is the proportion of participants with serum sodium \<135mmol/L or \>145 mmol/L, and/or serum potassium \<3.5 mmol/L or \>5.5mmol/L at follow-up Week 12. |
| Percentage of Participants With Serum Sodium <135 mmol/L or >145 mmol/L, and/or Serum Potassium <3.5 mmol/L or >5.5 mmol/L at Week 6 | Week 6 | The secondary safety outcome is proportion of participants with serum sodium \<135 mmol/L or \>145 mmol/L, and/or serum potassium \<3.5 mmol/L or \>5.5 mmol/L at follow-up Week 6. |
| Percentage of Participants With Orthostatic Hypotension at Week 6 | Week 6 | The secondary safety outcome is the proportion of participants with orthostatic hypotension at follow-up Week 6. |
| Percentage of Participants With Orthostatic Hypotension at Week 12 | Week 12 | The secondary safety outcome is the proportion of participants with orthostatic hypotension at follow-up Week 12. |
| Percentage of Participants With Orthostatic Hypertension at Week 6 | Week 6 | The secondary safety outcome is the proportion of participants with orthostatic hypertension at follow-up Week 6. |
| Percentage of Participants With Orthostatic Hypertension at Week 12 | Week 12 | The secondary safety outcome is the proportion of participants with orthostatic hypertension at follow-up Week 12. |
| Percentage of Participants Discontinued Trial Medication Due to Adverse Event (AE)/Serious Adverse Event (SAE) From Randomization to Week 12 | Week 12 | The primary safety outcome is the proportion of participants who discontinued trial medication due to an AE or SAE from randomization to follow-up at Week 12. |
Countries
Australia, Czechia, New Zealand, Poland, Sri Lanka, United Kingdom, United States
Participant flow
Recruitment details
This trial was conducted at 83 study centers across 7 countries (Australia \[6\], Czech Republic \[2\], Great Britain \[25\], New Zealand \[2\], Poland \[9\], Sri Lanka \[14\], and USA \[25\]).
Participants by arm
| Arm | Count |
|---|---|
| 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
Telmisartan 20 mg/amlodipine 2.5 mg/indapamide 1.25 mg: Single pill
telmisartan 40 mg/amlodipine 5 mg/indapamide 2.5 mg: Single pill | 551 |
| Dual - TA Telmisartan 20 mg/amlodipine 2.5 mg. At week 6 visit, forced up-titration to telmisartan 40 mg/amlodipine 5 mg
Telmisartan 20 mg/amlodipine 2.5 mg: oral tablet
telmisartan 40 mg/amlodipine 5 mg: oral tablet | 282 |
| Dual - TI Telmisartan 20 mg/indapamide 1.25 mg. At week 6 visit, forced up-titration to telmisartan 40 mg/indapamide 2.5 mg
Telmisartan 20 mg/indapamide 1.25 mg: oral tablet
telmisartan 40 mg/indapamide 2.5 mg: oral tablet | 276 |
| 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
Amlodipine 2.5 mg/indapamide 1.25 mg: oral tablet
amlodipine 5 mg/indapamide 2.5 mg: oral tablet | 276 |
| Total | 1,385 |
Baseline characteristics
| Characteristic | GMRx2 | Total | Dual - AI | Dual - TI | Dual - TA |
|---|---|---|---|---|---|
| Age, Continuous | 59.1 Years STANDARD_DEVIATION 11.28 | 59.0 Years STANDARD_DEVIATION 11.12 | 58.9 Years STANDARD_DEVIATION 11.32 | 59.2 Years STANDARD_DEVIATION 10.29 | 58.7 Years STANDARD_DEVIATION 11.41 |
| Alcohol Currently drink alcohol once a week or more | 179 Participants | 481 Participants | 105 Participants | 96 Participants | 101 Participants |
| Alcohol Not currently drinking | 372 Participants | 904 Participants | 171 Participants | 180 Participants | 181 Participants |
| Body Mass Index (BMI) | 28.87 Kg/m^2 STANDARD_DEVIATION 5.688 | 28.86 Kg/m^2 STANDARD_DEVIATION 5.761 | 28.82 Kg/m^2 STANDARD_DEVIATION 6.022 | 29.05 Kg/m^2 STANDARD_DEVIATION 5.686 | 28.68 Kg/m^2 STANDARD_DEVIATION 5.735 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 63 Participants | 159 Participants | 35 Participants | 30 Participants | 31 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 487 Participants | 1224 Participants | 241 Participants | 246 Participants | 250 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants |
| Height | 164.72 cm STANDARD_DEVIATION 11.054 | 164.46 cm STANDARD_DEVIATION 11.204 | 163.84 cm STANDARD_DEVIATION 11.702 | 164.54 cm STANDARD_DEVIATION 11.566 | 164.47 cm STANDARD_DEVIATION 10.659 |
| Hypertension Status at Screening Office BP<140/90 mmHg | 197 Participants | 489 Participants | 104 Participants | 96 Participants | 92 Participants |
| Hypertension Status at Screening Office BP≥140/90 mmHg | 354 Participants | 896 Participants | 172 Participants | 180 Participants | 190 Participants |
| Number of Prior BP Treatments at Screening 0 | 65 Participants | 144 Participants | 24 Participants | 28 Participants | 27 Participants |
| Number of Prior BP Treatments at Screening 1 | 193 Participants | 473 Participants | 87 Participants | 83 Participants | 110 Participants |
| Number of Prior BP Treatments at Screening 2 | 217 Participants | 555 Participants | 121 Participants | 112 Participants | 105 Participants |
| Number of Prior BP Treatments at Screening 3 | 76 Participants | 213 Participants | 44 Participants | 53 Participants | 40 Participants |
| Pre-Screening 12-Lead ECG Any other abnormalities | 120 Participants | 277 Participants | 52 Participants | 48 Participants | 57 Participants |
| Pre-Screening 12-Lead ECG Atrial fibrillation | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Pre-Screening 12-Lead ECG Missing | 29 Participants | 67 Participants | 14 Participants | 13 Participants | 11 Participants |
| Pre-Screening 12-Lead ECG Normal | 402 Participants | 1041 Participants | 210 Participants | 215 Participants | 214 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 272 Participants | 673 Participants | 134 Participants | 132 Participants | 135 Participants |
| Race (NIH/OMB) Black or African American | 30 Participants | 70 Participants | 16 Participants | 13 Participants | 11 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 9 Participants | 1 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 246 Participants | 631 Participants | 125 Participants | 128 Participants | 132 Participants |
| Region of Enrollment Australia | 54 Participants | 130 Participants | 25 Participants | 25 Participants | 26 Participants |
| Region of Enrollment Czechia | 4 Participants | 11 Participants | 2 Participants | 3 Participants | 2 Participants |
| Region of Enrollment New Zealand | 8 Participants | 20 Participants | 4 Participants | 4 Participants | 4 Participants |
| Region of Enrollment Poland | 4 Participants | 9 Participants | 1 Participants | 2 Participants | 2 Participants |
| Region of Enrollment Sri Lanka | 260 Participants | 646 Participants | 127 Participants | 128 Participants | 131 Participants |
| Region of Enrollment United Kingdom | 138 Participants | 351 Participants | 68 Participants | 72 Participants | 73 Participants |
| Region of Enrollment United States | 83 Participants | 218 Participants | 49 Participants | 42 Participants | 44 Participants |
| Sex: Female, Male Female | 276 Participants | 712 Participants | 148 Participants | 143 Participants | 145 Participants |
| Sex: Female, Male Male | 275 Participants | 673 Participants | 128 Participants | 133 Participants | 137 Participants |
| Smoking Current smoker | 28 Participants | 72 Participants | 15 Participants | 14 Participants | 15 Participants |
| Smoking Ex-smoker | 92 Participants | 266 Participants | 50 Participants | 64 Participants | 60 Participants |
| Smoking Never | 431 Participants | 1047 Participants | 211 Participants | 198 Participants | 207 Participants |
| Weight | 79.09 Kg STANDARD_DEVIATION 20.714 | 78.75 Kg STANDARD_DEVIATION 20.565 | 78.03 Kg STANDARD_DEVIATION 20.859 | 79.38 Kg STANDARD_DEVIATION 20.623 | 78.19 Kg STANDARD_DEVIATION 19.995 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 859 | 0 / 551 | 0 / 282 | 0 / 276 | 0 / 276 |
| other Total, other adverse events | 136 / 859 | 306 / 551 | 139 / 282 | 142 / 276 | 136 / 276 |
| serious Total, serious adverse events | 15 / 859 | 22 / 551 | 11 / 282 | 14 / 276 | 8 / 276 |
Outcome results
Primary
Difference in Change in Home Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 12
The primary outcome measure is difference in change in average home SBP for GMRx2 vs each dual combination evaluated from randomization to Week 12. The change in home SBP from randomization for all treatment arms was measured using least squares (LS) mean change. The pairwise comparisons between GMRx2 and dual treatments in change in home SBP were estimated using LS means difference and are described in the statistical analysis.
Time frame: Week 12
Population: Analysis was performed on all participants who had been randomized. Participants were analyzed in the treatment group to which they had been randomized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| GMRx2 | Difference in Change in Home Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 12 | -4.0 mmHg | Standard Error 0.45 |
| Dual - TA | Difference in Change in Home Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 12 | 1.4 mmHg | Standard Error 0.6 |
| Dual - TI | Difference in Change in Home Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 12 | -1.5 mmHg | Standard Error 0.51 |
| Dual - AI | Difference in Change in Home Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 12 | 0.4 mmHg | Standard Error 0.62 |
Comparison: The LS means (LSM) difference (95% CI) in home seated SBP reduction was calculated between GMRx2 and dual-TA arms.p-value: <0.000195% CI: [-6.774, -4.107]MIANALYZE procedure
Comparison: The LSM difference (95% CI) in home SBP reduction was calculated between GMRx2 and dual-TI arms.p-value: <0.000195% CI: [-3.723, -1.251]MIANALYZE procedure
Comparison: The LSM difference (95% CI) in home SBP reduction was calculated between GMRx2 and dual-AI arms.p-value: <0.000195% CI: [-5.758, -3.091]MIANALYZE procedure
Secondary
Difference in Change in Clinic Seated Mean Diastolic Blood Pressure (DBP) From Randomization to Week 12
Difference in change in average clinic DBP for GMRx2 vs each dual combination was evaluated from randomization to Week 12.
Time frame: Week 12
Population: Analysis was performed on all participants who had been randomized. Participants were analyzed in the treatment group to which they had been randomized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| GMRx2 | Difference in Change in Clinic Seated Mean Diastolic Blood Pressure (DBP) From Randomization to Week 12 | -3.4 mmHg | Standard Error 0.42 |
| Dual - TA | Difference in Change in Clinic Seated Mean Diastolic Blood Pressure (DBP) From Randomization to Week 12 | 0.4 mmHg | Standard Error 0.52 |
| Dual - TI | Difference in Change in Clinic Seated Mean Diastolic Blood Pressure (DBP) From Randomization to Week 12 | 0.2 mmHg | Standard Error 0.56 |
| Dual - AI | Difference in Change in Clinic Seated Mean Diastolic Blood Pressure (DBP) From Randomization to Week 12 | 1.1 mmHg | Standard Error 0.61 |
Comparison: The LSM difference (95% CI) in clinic DBP reduction was calculated between GMRx2 and dual-TA arms.p-value: <0.000195% CI: [-4.692, -2.757]Mixed Models Analysis
Comparison: The LSM difference (95% CI) in clinic DBP reduction was calculated between GMRx2 and dual-TI arms.p-value: <0.000195% CI: [-4.897, -2.128]Mixed Models Analysis
Comparison: The LSM difference (95% CI) in clinic DBP reduction was calculated between GMRx2 and dual-AI arms.p-value: <0.000195% CI: [-5.812, -3.189]Mixed Models Analysis
Secondary
Difference in Change in Clinic Seated Mean Diastolic Blood Pressure (DBP) From Randomization to Week 6
Difference in change in average clinic DBP for GMRx2 vs each dual combination was evaluated from randomization to Week 6.
Time frame: Week 6
Population: Analysis was performed on all participants who had been randomized. Participants were analyzed in the treatment group to which they had been randomized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| GMRx2 | Difference in Change in Clinic Seated Mean Diastolic Blood Pressure (DBP) From Randomization to Week 6 | -0.7 mmHg | Standard Error 0.38 |
| Dual - TA | Difference in Change in Clinic Seated Mean Diastolic Blood Pressure (DBP) From Randomization to Week 6 | 1.7 mmHg | Standard Error 0.57 |
| Dual - TI | Difference in Change in Clinic Seated Mean Diastolic Blood Pressure (DBP) From Randomization to Week 6 | 1.6 mmHg | Standard Error 0.57 |
| Dual - AI | Difference in Change in Clinic Seated Mean Diastolic Blood Pressure (DBP) From Randomization to Week 6 | 3.1 mmHg | Standard Error 0.57 |
Comparison: The LSM difference (95% CI) in clinic DBP reduction was calculated between GMRx2 and dual-TA arms.p-value: <0.000195% CI: [-3.392, -1.469]Mixed Models Analysis
Comparison: The LSM difference (95% CI) in clinic DBP reduction was calculated between GMRx2 and dual-TI arms.p-value: <0.000195% CI: [-3.371, -1.201]Mixed Models Analysis
Comparison: The LSM difference (95% CI) in clinic DBP reduction was calculated between GMRx2 and dual-AI arms.p-value: <0.000195% CI: [-4.882, -2.664]Mixed Models Analysis
Secondary
Difference in Change in Clinic Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 12
Difference in change in average clinic SBP for GMRx2 vs each dual combination was evaluated from randomization to Week 12.
Time frame: Week 12
Population: Analysis was performed on all participants who had been randomized. Participants were analyzed in the treatment group to which they had been randomized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| GMRx2 | Difference in Change in Clinic Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 12 | -5.5 mmHg | Standard Error 0.55 |
| Dual - TA | Difference in Change in Clinic Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 12 | 0.1 mmHg | Standard Error 0.85 |
| Dual - TI | Difference in Change in Clinic Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 12 | -1.2 mmHg | Standard Error 1.02 |
| Dual - AI | Difference in Change in Clinic Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 12 | 0.9 mmHg | Standard Error 0.86 |
Comparison: The LSM difference (95% CI) in clinic SBP reduction was calculated between GMRx2 between dual-TA arms.p-value: <0.000195% CI: [-7.307, -3.902]Mixed Models Analysis
Comparison: The LSM difference (95% CI) in clinic SBP reduction was calculated between GMRx2 and dual-TI arms.p-value: 0.000595% CI: [-6.718, -1.933]Mixed Models Analysis
Comparison: The LSM difference (95% CI) in clinic SBP reduction was calculated between GMRx2 and dual-AI arms.p-value: <0.000195% CI: [-7.984, -4.68]Mixed Models Analysis
Secondary
Difference in Change in Clinic Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 6
Difference in change in average clinic SBP for GMRx2 vs each dual combination was evaluated from randomization to Week 6.
Time frame: Week 6
Population: Analysis was performed on all participants who had been randomized. Participants were analyzed in the treatment group to which they had been randomized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| GMRx2 | Difference in Change in Clinic Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 6 | -0.8 mmHg | Standard Error 0.5 |
| Dual - TA | Difference in Change in Clinic Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 6 | 4.2 mmHg | Standard Error 0.88 |
| Dual - TI | Difference in Change in Clinic Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 6 | 2.7 mmHg | Standard Error 0.96 |
| Dual - AI | Difference in Change in Clinic Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 6 | 4.5 mmHg | Standard Error 1.02 |
Comparison: The LSM difference (95% CI) in clinic SBP reduction was calculated between GMRx2 and dual-TA arms.p-value: <0.000195% CI: [-6.703, -3.317]Mixed Models Analysis
Comparison: The LSM difference (95% CI) in clinic SBP reduction was calculated between GMRx2 and dual-TI arms.p-value: 0.000295% CI: [-5.293, -1.7]Mixed Models Analysis
Comparison: The LSM difference (95% CI) in clinic SBP reduction was calculated between GMRx2 and dual-AI arms.p-value: <0.000195% CI: [-7.251, -3.444]Mixed Models Analysis
Secondary
Difference in Change in Home Seated Mean Diastolic Blood Pressure (DBP) From Randomization to Week 12
Difference in change in average home DBP for GMRx2 vs each dual combination was evaluated from randomization to Week 12.
Time frame: Week 12
Population: Analysis was performed on all participants who had been randomized. Participants were analyzed in the treatment group to which they had been randomized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| GMRx2 | Difference in Change in Home Seated Mean Diastolic Blood Pressure (DBP) From Randomization to Week 12 | -2.9 mmHg | Standard Error 0.28 |
| Dual - TA | Difference in Change in Home Seated Mean Diastolic Blood Pressure (DBP) From Randomization to Week 12 | 0.5 mmHg | Standard Error 0.32 |
| Dual - TI | Difference in Change in Home Seated Mean Diastolic Blood Pressure (DBP) From Randomization to Week 12 | -0.8 mmHg | Standard Error 0.35 |
| Dual - AI | Difference in Change in Home Seated Mean Diastolic Blood Pressure (DBP) From Randomization to Week 12 | 0.7 mmHg | Standard Error 0.45 |
Comparison: The LSM difference (95% CI) in home DBP reduction was calculated between GMRx2 and dual-TA arms.p-value: <0.000195% CI: [-4.069, -2.632]Mixed Models Analysis
Comparison: The LSM difference (95% CI) in home DBP reduction was calculated between GMRx2 and dual-TI arms.p-value: <0.000195% CI: [-2.998, -1.2]Mixed Models Analysis
Comparison: The LSM difference (95% CI) in home DBP reduction was calculated between GMRx2 and dual-AI arms.p-value: <0.000195% CI: [-4.617, -2.649]Mixed Models Analysis
Secondary
Difference in Change in Home Seated Mean Diastolic Blood Pressure (DBP) From Randomization to Week 6
Difference in change in average home DBP for GMRx2 vs each dual combination was evaluated from randomization to Week 6.
Time frame: Week 6
Population: Analysis was performed on all participants who had been randomized. Participants were analyzed in the treatment group to which they had been randomized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| GMRx2 | Difference in Change in Home Seated Mean Diastolic Blood Pressure (DBP) From Randomization to Week 6 | -0.7 mmHg | Standard Error 0.29 |
| Dual - TA | Difference in Change in Home Seated Mean Diastolic Blood Pressure (DBP) From Randomization to Week 6 | 2.5 mmHg | Standard Error 0.39 |
| Dual - TI | Difference in Change in Home Seated Mean Diastolic Blood Pressure (DBP) From Randomization to Week 6 | 1.3 mmHg | Standard Error 0.4 |
| Dual - AI | Difference in Change in Home Seated Mean Diastolic Blood Pressure (DBP) From Randomization to Week 6 | 2.5 mmHg | Standard Error 0.41 |
Comparison: The LSM difference (95% CI) in home DBP reduction was calculated between GMRx2 and dual-TA arms.p-value: <0.000195% CI: [-4.137, -2.908]Mixed Models Analysis
Comparison: The LSM difference (95% CI) in home DBP reduction was calculated between GMRx2 and dual-TI arms.p-value: <0.000195% CI: [-2.803, -1.376]Mixed Models Analysis
Comparison: The LSM difference (95% CI) in home DBP reduction was calculated between GMRx2 and dual-AI arms.p-value: <0.000195% CI: [-4.446, -2.713]Mixed Models Analysis
Secondary
Difference in Change in Home Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 6
Difference in change in average home SBP for GMRx2 vs each dual combination was evaluated from randomization to Week 6.
Time frame: Week 6
Population: Analysis was performed on all participants who had been randomized. Participants were analyzed in the treatment group to which they had been randomized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| GMRx2 | Difference in Change in Home Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 6 | -0.9 mmHg | Standard Error 0.4 |
| Dual - TA | Difference in Change in Home Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 6 | 5.2 mmHg | Standard Error 0.57 |
| Dual - TI | Difference in Change in Home Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 6 | 2.1 mmHg | Standard Error 0.49 |
| Dual - AI | Difference in Change in Home Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 6 | 4.2 mmHg | Standard Error 0.56 |
Comparison: The LSM difference (95% CI) in home SBP reduction was calculated between GMRx2 and dual-TA arms.p-value: <0.000195% CI: [-7.086, -5.144]Mixed Models Analysis
Comparison: The LSM difference (95% CI) in home SBP reduction was calculated between GMRx2 and dual-TI arms.p-value: <0.000195% CI: [-4.06, -1.932]Mixed Models Analysis
Comparison: The LSM difference (95% CI) in home SBP reduction was calculated between GMRx2 and dual-AI arms.p-value: <0.000195% CI: [-6.274, -3.912]Mixed Models Analysis
Secondary
Difference in Change in Trough Home Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 12
Difference in change in trough home SBP for GMRx2 vs each dual combination was evaluated from randomization to Week 12. Trough values were measured before morning dose of the study medication.
Time frame: Week 12
Population: Analysis was performed on all participants who had been randomized. Participants were analyzed in the treatment group to which they had been randomized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| GMRx2 | Difference in Change in Trough Home Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 12 | -4.0 mmHg | Standard Error 0.48 |
| Dual - TA | Difference in Change in Trough Home Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 12 | 1.6 mmHg | Standard Error 0.59 |
| Dual - TI | Difference in Change in Trough Home Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 12 | -2.1 mmHg | Standard Error 0.58 |
| Dual - AI | Difference in Change in Trough Home Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 12 | -0.2 mmHg | Standard Error 0.63 |
Comparison: The LSM difference (95% CI) in trough (i.e. before morning dose) home SBP reduction was calculated between GMRx2 and dual-TA arms.p-value: <0.000195% CI: [-6.983, -4.169]Mixed Models Analysis
Comparison: The LSM difference (95% CI) in trough (i.e. before morning dose) home SBP reduction was calculated between GMRx2 and dual-TI arms.p-value: 0.004395% CI: [-3.218, -0.607]Mixed Models Analysis
Comparison: The LSM difference (95% CI) in trough (i.e. before morning dose) home SBP reduction was calculated between GMRx2 and dual-AI arms.p-value: <0.000195% CI: [-5.214, -2.274]Mixed Models Analysis
Secondary
Difference in Change in Trough Home Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 6
Difference in change in trough home SBP for GMRx2 vs each dual combination was evaluated from randomization to Week 6. Trough values were measured before morning dose of the study medication.
Time frame: Week 6
Population: Analysis was performed on all participants who had been randomized. Participants were analyzed in the treatment group to which they had been randomized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| GMRx2 | Difference in Change in Trough Home Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 6 | -0.9 mmHg | Standard Error 0.41 |
| Dual - TA | Difference in Change in Trough Home Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 6 | 5.3 mmHg | Standard Error 0.66 |
| Dual - TI | Difference in Change in Trough Home Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 6 | 1.8 mmHg | Standard Error 0.61 |
| Dual - AI | Difference in Change in Trough Home Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 6 | 3.5 mmHg | Standard Error 0.57 |
Comparison: The LSM difference (95% CI) in trough (i.e. before morning dose) home SBP reduction was calculated between GMRx2 and dual-TA arms.p-value: <0.000195% CI: [-7.324, -5.168]Mixed Models Analysis
Comparison: The LSM difference (95% CI) in trough (i.e. before morning dose) home SBP reduction was calculated between GMRx2 and dual-TI arms.p-value: <0.000195% CI: [-3.941, -1.507]Mixed Models Analysis
Comparison: The LSM difference (95% CI) in trough (i.e. before morning dose) home SBP reduction was calculated between GMRx2 and dual-AI arms.p-value: <0.000195% CI: [-5.489, -3.368]Mixed Models Analysis
Secondary
Percentage of Participants With Clinic Seated Mean Systolic Blood Pressure (SBP) <130 and Diastolic Blood Pressure (DBP) <80 mmHg at Week 12
The percentage of participants achieving averaged clinic SBP \<130 mmHg and DBP \<80 mmHg at Week 12 was evaluated.
Time frame: Week 12
Population: Analysis was performed on all participants who had been randomized. Participants were analyzed in the treatment group to which they had been randomized.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GMRx2 | Percentage of Participants With Clinic Seated Mean Systolic Blood Pressure (SBP) <130 and Diastolic Blood Pressure (DBP) <80 mmHg at Week 12 | 218 Participants |
| Dual - TA | Percentage of Participants With Clinic Seated Mean Systolic Blood Pressure (SBP) <130 and Diastolic Blood Pressure (DBP) <80 mmHg at Week 12 | 65 Participants |
| Dual - TI | Percentage of Participants With Clinic Seated Mean Systolic Blood Pressure (SBP) <130 and Diastolic Blood Pressure (DBP) <80 mmHg at Week 12 | 76 Participants |
| Dual - AI | Percentage of Participants With Clinic Seated Mean Systolic Blood Pressure (SBP) <130 and Diastolic Blood Pressure (DBP) <80 mmHg at Week 12 | 59 Participants |
Comparison: The difference between GMRx2 and TA at Week 12 was estimated using Generalized Estimating Equation.p-value: <0.000195% CI: [9.707, 22.837]Wald test
Comparison: The difference between GMRx2 and TI at Week 12 was estimated using Generalized Estimating Equation.p-value: 0.000495% CI: [4.982, 18.658]Wald test
Comparison: The difference between GMRx2 and AI at Week 12 was estimated using Generalized Estimating Equation.p-value: <0.000195% CI: [11.412, 24.432]Wald test
Secondary
Percentage of Participants With Clinic Seated Mean Systolic Blood Pressure (SBP) <130 and Diastolic Blood Pressure (DBP) <80 mmHg at Week 6
The percentage of participants achieving averaged clinic SBP \<130 mmHg and DBP \<80 mmHg at Week 6 was evaluated.
Time frame: Week 6
Population: Analysis was performed on all participants who had been randomized. Participants were analyzed in the treatment group to which they had been randomized.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GMRx2 | Percentage of Participants With Clinic Seated Mean Systolic Blood Pressure (SBP) <130 and Diastolic Blood Pressure (DBP) <80 mmHg at Week 6 | 167 Participants |
| Dual - TA | Percentage of Participants With Clinic Seated Mean Systolic Blood Pressure (SBP) <130 and Diastolic Blood Pressure (DBP) <80 mmHg at Week 6 | 56 Participants |
| Dual - TI | Percentage of Participants With Clinic Seated Mean Systolic Blood Pressure (SBP) <130 and Diastolic Blood Pressure (DBP) <80 mmHg at Week 6 | 59 Participants |
| Dual - AI | Percentage of Participants With Clinic Seated Mean Systolic Blood Pressure (SBP) <130 and Diastolic Blood Pressure (DBP) <80 mmHg at Week 6 | 50 Participants |
Comparison: The difference between GMRx2 and TA at Week 6 was estimated using Generalized Estimating Equation.p-value: 0.000795% CI: [3.993, 16.433]Wald test
Comparison: The difference between GMRx2 and TI at Week 6 was estimated using Generalized Estimating Equation.p-value: 0.004695% CI: [2.337, 15.058]Wald test
p-value: <0.000195% CI: [5.792, 18.073]Wald test
Secondary
Percentage of Participants With Clinic Seated Mean Systolic Blood Pressure (SBP) <140 and Diastolic Blood Pressure (DBP) <90 mmHg at Week 12
The percentage of participants achieving averaged clinic SBP \<140 mmHg and DBP \<90 mmHg at Week 12 was evaluated.
Time frame: Week 12
Population: Analysis was performed on all participants who had been randomized. Participants were analyzed in the treatment group to which they had been randomized.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GMRx2 | Percentage of Participants With Clinic Seated Mean Systolic Blood Pressure (SBP) <140 and Diastolic Blood Pressure (DBP) <90 mmHg at Week 12 | 407 Participants |
| Dual - TA | Percentage of Participants With Clinic Seated Mean Systolic Blood Pressure (SBP) <140 and Diastolic Blood Pressure (DBP) <90 mmHg at Week 12 | 173 Participants |
| Dual - TI | Percentage of Participants With Clinic Seated Mean Systolic Blood Pressure (SBP) <140 and Diastolic Blood Pressure (DBP) <90 mmHg at Week 12 | 167 Participants |
| Dual - AI | Percentage of Participants With Clinic Seated Mean Systolic Blood Pressure (SBP) <140 and Diastolic Blood Pressure (DBP) <90 mmHg at Week 12 | 146 Participants |
Comparison: The difference between GMRx2 and TA at Week 12 was estimated using Generalized Estimating Equation.p-value: 0.000395% CI: [5.63, 19.487]Wald test
Comparison: The difference between GMRx2 and TI at Week 12 was estimated using Generalized Estimating Equation.p-value: 0.000195% CI: [6.392, 20.394]Wald test
Comparison: The difference between GMRx2 and AI at Week 12 was estimated using Generalized Estimating Equation.p-value: <0.000195% CI: [13.812, 28.013]Wald test
Secondary
Percentage of Participants With Clinic Seated Mean Systolic Blood Pressure (SBP) <140 and Diastolic Blood Pressure (DBP) <90 mmHg at Week 6
The percentage of participants achieving averaged clinic SBP \<140 mmHg and DBP \<80 mmHg at Week 6 was evaluated.
Time frame: Week 6
Population: Analysis was performed on all participants who had been randomized. Participants were analyzed in the treatment group to which they had been randomized.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GMRx2 | Percentage of Participants With Clinic Seated Mean Systolic Blood Pressure (SBP) <140 and Diastolic Blood Pressure (DBP) <90 mmHg at Week 6 | 346 Participants |
| Dual - TA | Percentage of Participants With Clinic Seated Mean Systolic Blood Pressure (SBP) <140 and Diastolic Blood Pressure (DBP) <90 mmHg at Week 6 | 148 Participants |
| Dual - TI | Percentage of Participants With Clinic Seated Mean Systolic Blood Pressure (SBP) <140 and Diastolic Blood Pressure (DBP) <90 mmHg at Week 6 | 151 Participants |
| Dual - AI | Percentage of Participants With Clinic Seated Mean Systolic Blood Pressure (SBP) <140 and Diastolic Blood Pressure (DBP) <90 mmHg at Week 6 | 122 Participants |
Comparison: The difference between GMRx2 and TA at Week 6 was estimated using Generalized Estimating Equation.p-value: 0.004495% CI: [3.044, 17.535]Wald test
Comparison: The difference between GMRx2 and TI at Week 6 was estimated using Generalized Estimating Equation.p-value: 0.026295% CI: [0.804, 15.373]Wald test
Comparison: The difference between GMRx2 and AI at Week 6 was estimated using Generalized Estimating Equation.p-value: <0.000195% CI: [11.201, 25.746]Wald test
Secondary
Percentage of Participants With Home Seated Mean Systolic Blood Pressure (SBP) <130 and Diastolic Blood Pressure (DBP) <80 mmHg at Week 12
The percentage of participants achieving averaged home SBP \<130 mmHg and DBP \<80 mmHg at Week 12 was evaluated.
Time frame: Week 12
Population: Analysis was performed on all participants who had been randomized. Participants were analyzed in the treatment group to which they had been randomized.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GMRx2 | Percentage of Participants With Home Seated Mean Systolic Blood Pressure (SBP) <130 and Diastolic Blood Pressure (DBP) <80 mmHg at Week 12 | 308 Participants |
| Dual - TA | Percentage of Participants With Home Seated Mean Systolic Blood Pressure (SBP) <130 and Diastolic Blood Pressure (DBP) <80 mmHg at Week 12 | 109 Participants |
| Dual - TI | Percentage of Participants With Home Seated Mean Systolic Blood Pressure (SBP) <130 and Diastolic Blood Pressure (DBP) <80 mmHg at Week 12 | 121 Participants |
| Dual - AI | Percentage of Participants With Home Seated Mean Systolic Blood Pressure (SBP) <130 and Diastolic Blood Pressure (DBP) <80 mmHg at Week 12 | 91 Participants |
Comparison: The difference between GMRx2 and TA at Week 12 was estimated using Generalized Estimating Equation.p-value: <0.000195% CI: [9.902, 24.286]Wald test
Comparison: The difference between GMRx2 and TI at Week 12 was estimated using Generalized Estimating Equation.p-value: 0.00195% CI: [4.632, 19.293]Wald test
Comparison: The difference between GMRx2 and AI at Week 12 was estimated using Generalized Estimating Equation.p-value: <0.000195% CI: [15.622, 29.796]Wald test
Secondary
Percentage of Participants With Home Seated Mean Systolic Blood Pressure (SBP) <130 and Diastolic Blood Pressure (DBP) <80 mmHg at Week 6
The percentage of participants achieving averaged home SBP \<130 mmHg and DBP \<80 mmHg at Week 6 was evaluated.
Time frame: Week 6
Population: Analysis was performed on all participants who had been randomized. Participants were analyzed in the treatment group to which they had been randomized.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GMRx2 | Percentage of Participants With Home Seated Mean Systolic Blood Pressure (SBP) <130 and Diastolic Blood Pressure (DBP) <80 mmHg at Week 6 | 247 Participants |
| Dual - TA | Percentage of Participants With Home Seated Mean Systolic Blood Pressure (SBP) <130 and Diastolic Blood Pressure (DBP) <80 mmHg at Week 6 | 74 Participants |
| Dual - TI | Percentage of Participants With Home Seated Mean Systolic Blood Pressure (SBP) <130 and Diastolic Blood Pressure (DBP) <80 mmHg at Week 6 | 90 Participants |
| Dual - AI | Percentage of Participants With Home Seated Mean Systolic Blood Pressure (SBP) <130 and Diastolic Blood Pressure (DBP) <80 mmHg at Week 6 | 79 Participants |
Comparison: The difference between GMRx2 and TA at Week 6 was estimated using Generalized Estimating Equation.p-value: <0.000195% CI: [11.579, 25.124]Wald test
Comparison: The difference between GMRx2 and TI at Week 6 was estimated using Generalized Estimating Equation.p-value: 0.000595% CI: [4.963, 19.123]Wald test
Comparison: The difference between GMRx2 and AI at Week 6 was estimated using Generalized Estimating Equation.p-value: <0.000195% CI: [9.06, 22.914]Wald test
Secondary
Percentage of Participants With Home Seated Mean Systolic Blood Pressure (SBP) <135 and Diastolic Blood Pressure (DBP) <85 mmHg at Week 12
The percentage of participants achieving averaged home SBP \<135 mmHg and DBP \<85 mmHg at week 12 was calculated.
Time frame: Week 12
Population: Analysis was performed on all participants who had been randomized. Participants were analyzed in the treatment group to which they had been randomized.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GMRx2 | Percentage of Participants With Home Seated Mean Systolic Blood Pressure (SBP) <135 and Diastolic Blood Pressure (DBP) <85 mmHg at Week 12 | 398 Participants |
| Dual - TA | Percentage of Participants With Home Seated Mean Systolic Blood Pressure (SBP) <135 and Diastolic Blood Pressure (DBP) <85 mmHg at Week 12 | 162 Participants |
| Dual - TI | Percentage of Participants With Home Seated Mean Systolic Blood Pressure (SBP) <135 and Diastolic Blood Pressure (DBP) <85 mmHg at Week 12 | 176 Participants |
| Dual - AI | Percentage of Participants With Home Seated Mean Systolic Blood Pressure (SBP) <135 and Diastolic Blood Pressure (DBP) <85 mmHg at Week 12 | 155 Participants |
Comparison: The difference between GMRx2 and TA at Week 12 was estimated using Generalized Estimating Equation.p-value: <0.000195% CI: [7.749, 21.824]Wald test
Comparison: The difference between GMRx2 and TI at Week 12 was estimated using Generalized Estimating Equation.p-value: 0.014695% CI: [1.58, 15.501]Wald test
Comparison: The difference between GMRx2 and AI at Week 12 was estimated using Generalized Estimating Equation.p-value: <0.000195% CI: [8.953, 23.171]Wald test
Secondary
Percentage of Participants With Home Seated Mean Systolic Blood Pressure (SBP) <135 and Diastolic Blood Pressure (DBP) <85 mmHg at Week 6
The percentage of participants achieving averaged home SBP \<135 mmHg and DBP \<85 mmHg at Week 6 was evaluated.
Time frame: Week 6
Population: Analysis was performed on all participants who had been randomized. Participants were analyzed in the treatment group to which they had been randomized.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GMRx2 | Percentage of Participants With Home Seated Mean Systolic Blood Pressure (SBP) <135 and Diastolic Blood Pressure (DBP) <85 mmHg at Week 6 | 346 Participants |
| Dual - TA | Percentage of Participants With Home Seated Mean Systolic Blood Pressure (SBP) <135 and Diastolic Blood Pressure (DBP) <85 mmHg at Week 6 | 126 Participants |
| Dual - TI | Percentage of Participants With Home Seated Mean Systolic Blood Pressure (SBP) <135 and Diastolic Blood Pressure (DBP) <85 mmHg at Week 6 | 155 Participants |
| Dual - AI | Percentage of Participants With Home Seated Mean Systolic Blood Pressure (SBP) <135 and Diastolic Blood Pressure (DBP) <85 mmHg at Week 6 | 123 Participants |
Comparison: The difference between GMRx2 and TA at Week 6 was estimated using Generalized Estimating Equation.p-value: <0.000195% CI: [10.778, 25.226]Wald test
Comparison: The difference between GMRx2 and TI at Week 12 was estimated using Generalized Estimating Equation.p-value: 0.067495% CI: [-0.613, 13.926]Wald test
Comparison: The difference between GMRx2 and AI at Week 12 was estimated using Generalized Estimating Equation.p-value: <0.000195% CI: [10.839, 25.392]Wald test
Other Pre-specified
Percentage of Participants Discontinued Trial Medication Due to Adverse Event (AE)/Serious Adverse Event (SAE) From Randomization to Week 12
The primary safety outcome is the proportion of participants who discontinued trial medication due to an AE or SAE from randomization to follow-up at Week 12.
Time frame: Week 12
Population: Analysis was done on the safety set which included all participants who had taken at least one dose of study treatment, including during Period 1 single-blind run-in. For the analysis of the safety outcomes, participants were analyzed in the treatment group that was received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GMRx2 | Percentage of Participants Discontinued Trial Medication Due to Adverse Event (AE)/Serious Adverse Event (SAE) From Randomization to Week 12 | 11 Participants |
| Dual - TA | Percentage of Participants Discontinued Trial Medication Due to Adverse Event (AE)/Serious Adverse Event (SAE) From Randomization to Week 12 | 3 Participants |
| Dual - TI | Percentage of Participants Discontinued Trial Medication Due to Adverse Event (AE)/Serious Adverse Event (SAE) From Randomization to Week 12 | 4 Participants |
| Dual - AI | Percentage of Participants Discontinued Trial Medication Due to Adverse Event (AE)/Serious Adverse Event (SAE) From Randomization to Week 12 | 4 Participants |
Comparison: The Risk difference (95% CI) in percentage of participants discontinuing trial medication due to AE/SAE at Week 12 was calculated between GMRx2 and dual-TA arms.95% CI: [-1.529, 2.768]
Comparison: The Risk difference (95% CI) in percentage of participants discontinuing trial medication due to AE/SAE at Week 12 was calculated between GMRx2 and dual-TI arms.95% CI: [-2.098, 2.475]
Comparison: The Risk difference (95% CI) in percentage of participants discontinuing trial medication due to AE/SAE at Week 12 was calculated between GMRx2 and dual-AI arms.95% CI: [-2.098, 2.475]
Other Pre-specified
Percentage of Participants Discontinued Trial Medication Due to Adverse Event (AE)/Serious Adverse Event (SAE) From Randomization to Week 6
The secondary safety outcome is the proportion of participants who discontinued trial medication due to AE/SAE from randomization to follow-up at Week 6.
Time frame: Week 6
Population: Analysis was done on the safety set which included all participants who had taken at least one dose of study treatment, including during Period 1 single-blind run-in. For the analysis of the safety outcomes, participants were analyzed in the treatment group that was received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GMRx2 | Percentage of Participants Discontinued Trial Medication Due to Adverse Event (AE)/Serious Adverse Event (SAE) From Randomization to Week 6 | 5 Participants |
| Dual - TA | Percentage of Participants Discontinued Trial Medication Due to Adverse Event (AE)/Serious Adverse Event (SAE) From Randomization to Week 6 | 3 Participants |
| Dual - TI | Percentage of Participants Discontinued Trial Medication Due to Adverse Event (AE)/Serious Adverse Event (SAE) From Randomization to Week 6 | 1 Participants |
| Dual - AI | Percentage of Participants Discontinued Trial Medication Due to Adverse Event (AE)/Serious Adverse Event (SAE) From Randomization to Week 6 | 3 Participants |
Other Pre-specified
Percentage of Participants With a Serious Adverse Event (SAE) From Randomization to Week 12
The secondary safety outcome is the proportion of participants with at least one SAE from randomization to follow-up at Week 12.
Time frame: At Week 12
Population: Analysis was done on the safety set which included all participants who had taken at least one dose of study treatment, including during Period 1 single-blind run-in. For the analysis of the safety outcomes, participants were analyzed in the treatment group that was received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GMRx2 | Percentage of Participants With a Serious Adverse Event (SAE) From Randomization to Week 12 | 17 Participants |
| Dual - TA | Percentage of Participants With a Serious Adverse Event (SAE) From Randomization to Week 12 | 6 Participants |
| Dual - TI | Percentage of Participants With a Serious Adverse Event (SAE) From Randomization to Week 12 | 7 Participants |
| Dual - AI | Percentage of Participants With a Serious Adverse Event (SAE) From Randomization to Week 12 | 6 Participants |
Other Pre-specified
Percentage of Participants With Estimated Glomerular Filtration Rate (eGFR) Drop of Over 30% From Randomization to Week 12
The secondary safety outcome was the proportion of participants with an eGFR drop of over 30% from randomization to follow-up at Week 12.
Time frame: Week 12
Population: Analysis was done on the safety set which included all participants who had taken at least one dose of study treatment, including during Period 1 single-blind run-in. For the analysis of the safety outcomes, participants were analyzed in the treatment group that was received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GMRx2 | Percentage of Participants With Estimated Glomerular Filtration Rate (eGFR) Drop of Over 30% From Randomization to Week 12 | 8 Participants |
| Dual - TA | Percentage of Participants With Estimated Glomerular Filtration Rate (eGFR) Drop of Over 30% From Randomization to Week 12 | 3 Participants |
| Dual - TI | Percentage of Participants With Estimated Glomerular Filtration Rate (eGFR) Drop of Over 30% From Randomization to Week 12 | 1 Participants |
| Dual - AI | Percentage of Participants With Estimated Glomerular Filtration Rate (eGFR) Drop of Over 30% From Randomization to Week 12 | 1 Participants |
Comparison: The Risk difference (95% CI) in percentage of participants with eGFR drop of over 30% at Week 12 was calculated between GMRx2 and dual-TA arms.95% CI: [-2.014, 2.087]
Comparison: The Risk difference (95% CI) in percentage of participants with eGFR drop of over 30% at Week 12 was calculated between GMRx2 and dual-TI arms.95% CI: [-1.015, 2.633]
Comparison: The Risk difference (95% CI) in percentage of participants with eGFR drop of over 30% at Week 12 was calculated between GMRx2 and dual-AI arms.95% CI: [-1.015, 2.633]
Other Pre-specified
Percentage of Participants With Estimated Glomerular Filtration Rate (eGFR) Drop of Over 30% From Randomization to Week 6
The secondary safety outcome is the proportion of participants with an eGFR drop of over 30% from randomization to follow-up at Week 6.
Time frame: Week 6
Population: Analysis was done on the safety set which included all participants who had taken at least one dose of study treatment, including during Period 1 single-blind run-in. For the analysis of the safety outcomes, participants were analyzed in the treatment group that was received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GMRx2 | Percentage of Participants With Estimated Glomerular Filtration Rate (eGFR) Drop of Over 30% From Randomization to Week 6 | 5 Participants |
| Dual - TA | Percentage of Participants With Estimated Glomerular Filtration Rate (eGFR) Drop of Over 30% From Randomization to Week 6 | 3 Participants |
| Dual - TI | Percentage of Participants With Estimated Glomerular Filtration Rate (eGFR) Drop of Over 30% From Randomization to Week 6 | 4 Participants |
| Dual - AI | Percentage of Participants With Estimated Glomerular Filtration Rate (eGFR) Drop of Over 30% From Randomization to Week 6 | 3 Participants |
Comparison: The Risk difference (95% CI) in percentage of participants with eGFR drop of over 30% at Week 6 was calculated between GMRx2 and dual-TA arms.95% CI: [-2.501, 1.385]
Comparison: The Risk difference (95% CI) in percentage of participants with eGFR drop of over 30% at Week 6 was calculated between GMRx2 and dual-TI arms.95% CI: [-3.078, 1.108]
Comparison: The Risk difference (95% CI) in percentage of participants with eGFR drop of over 30% at Week 6 was calculated between GMRx2 and dual-AI arms.95% CI: [-2.571, 1.37]
Other Pre-specified
Percentage of Participants With Orthostatic Hypertension at Week 12
The secondary safety outcome is the proportion of participants with orthostatic hypertension at follow-up Week 12.
Time frame: Week 12
Population: Analysis was done on the safety set which included all participants who had taken at least one dose of study treatment, including during Period 1 single-blind run-in. For the analysis of the safety outcomes, participants were analyzed in the treatment group that was received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GMRx2 | Percentage of Participants With Orthostatic Hypertension at Week 12 | 112 Participants |
| Dual - TA | Percentage of Participants With Orthostatic Hypertension at Week 12 | 57 Participants |
| Dual - TI | Percentage of Participants With Orthostatic Hypertension at Week 12 | 66 Participants |
| Dual - AI | Percentage of Participants With Orthostatic Hypertension at Week 12 | 57 Participants |
Comparison: The Risk difference (95% CI) in percentage of participants with orthostatic hypertension at Week 12 was calculated between GMRx2 and dual-TA arms.p-value: 0.969195% CI: [-6.063, 5.859]Wald test
Comparison: The Risk difference (95% CI) in percentage of participants with orthostatic hypertension at Week 12 was calculated between GMRx2 and dual-TI arms.p-value: 0.245495% CI: [-10.018, 2.462]Wald test
Comparison: The Risk difference (95% CI) in percentage of participants with orthostatic hypertension at Week 12 was calculated between GMRx2 and dual-AI arms.p-value: 0.91395% CI: [-6.583, 5.488]Wald test
Other Pre-specified
Percentage of Participants With Orthostatic Hypertension at Week 6
The secondary safety outcome is the proportion of participants with orthostatic hypertension at follow-up Week 6.
Time frame: Week 6
Population: Analysis was done on the safety set which included all participants who had taken at least one dose of study treatment, including during Period 1 single-blind run-in. For the analysis of the safety outcomes, participants were analyzed in the treatment group that was received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GMRx2 | Percentage of Participants With Orthostatic Hypertension at Week 6 | 119 Participants |
| Dual - TA | Percentage of Participants With Orthostatic Hypertension at Week 6 | 69 Participants |
| Dual - TI | Percentage of Participants With Orthostatic Hypertension at Week 6 | 57 Participants |
| Dual - AI | Percentage of Participants With Orthostatic Hypertension at Week 6 | 66 Participants |
Comparison: The Risk difference (95% CI) in percentage of participants with orthostatic hypertension at Week 6 was calculated between GMRx2 and dual-TA arms.p-value: 0.354895% CI: [-9.316, 3.215]Wald test
Comparison: The Risk difference (95% CI) in percentage of participants with orthostatic hypertension at Week 6 was calculated between GMRx2 and dual-TI arms.p-value: 0.752995% CI: [-5.356, 6.8]Wald test
Comparison: The Risk difference (95% CI) in percentage of participants with orthostatic hypertension at Week 6 was calculated between GMRx2 and dual-AI arms.p-value: 0.456395% CI: [-8.791, 3.772]Wald test
Other Pre-specified
Percentage of Participants With Orthostatic Hypotension at Week 12
The secondary safety outcome is the proportion of participants with orthostatic hypotension at follow-up Week 12.
Time frame: Week 12
Population: Analysis was done on the safety set which included all participants who had taken at least one dose of study treatment, including during Period 1 single-blind run-in. For the analysis of the safety outcomes, participants were analyzed in the treatment group that was received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GMRx2 | Percentage of Participants With Orthostatic Hypotension at Week 12 | 28 Participants |
| Dual - TA | Percentage of Participants With Orthostatic Hypotension at Week 12 | 14 Participants |
| Dual - TI | Percentage of Participants With Orthostatic Hypotension at Week 12 | 21 Participants |
| Dual - AI | Percentage of Participants With Orthostatic Hypotension at Week 12 | 20 Participants |
Comparison: The Risk difference (95% CI) in percentage of participants with orthostatic hypotension at Week 12 was calculated between GMRx2 and dual-TA arms.p-value: 0.941595% CI: [-3.657, 3.222]Wald test
Comparison: The Risk difference (95% CI) in percentage of participants with orthostatic hypotension at Week 12 was calculated between GMRx2 and dual-TI arms.p-value: 0.171995% CI: [-6.799, 1.019]Wald test
Comparison: The Risk difference (95% CI) in percentage of participants with orthostatic hypotension at Week 12 was calculated between GMRx2 and dual-AI arms.p-value: 0.234295% CI: [-6.38, 1.326]Wald test
Other Pre-specified
Percentage of Participants With Orthostatic Hypotension at Week 6
The secondary safety outcome is the proportion of participants with orthostatic hypotension at follow-up Week 6.
Time frame: Week 6
Population: Analysis was done on the safety set which included all participants who had taken at least one dose of study treatment, including during Period 1 single-blind run-in. For the analysis of the safety outcomes, participants were analyzed in the treatment group that was received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GMRx2 | Percentage of Participants With Orthostatic Hypotension at Week 6 | 27 Participants |
| Dual - TA | Percentage of Participants With Orthostatic Hypotension at Week 6 | 14 Participants |
| Dual - TI | Percentage of Participants With Orthostatic Hypotension at Week 6 | 20 Participants |
| Dual - AI | Percentage of Participants With Orthostatic Hypotension at Week 6 | 15 Participants |
Comparison: The Risk difference (95% CI) in percentage of participants with orthostatic hypotension at Week 6 was calculated between GMRx2 and dual-TA arms.p-value: 0.967795% CI: [-3.825, 3.019]Wald test
Comparison: The Risk difference (95% CI) in percentage of participants with orthostatic hypotension at Week 6 was calculated between GMRx2 and dual-TI arms.p-value: 0.195295% CI: [-6.55, 1.125]Wald test
Comparison: The Risk difference (95% CI) in percentage of participants with orthostatic hypotension at Week 6 was calculated between GMRx2 and dual-AI arms.p-value: 0.745395% CI: [-4.428, 2.642]Wald test
Other Pre-specified
Percentage of Participants With Serious Adverse Event (SAE) From Randomization to Week 6
The secondary safety outcome is the proportion of participants with at least one SAE from randomization to follow-up at Week 6.
Time frame: Week 6
Population: Analysis was done on the safety set which included all participants who had taken at least one dose of study treatment, including during Period 1 single-blind run-in. For the analysis of the safety outcomes, participants were analyzed in the treatment group that was received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GMRx2 | Percentage of Participants With Serious Adverse Event (SAE) From Randomization to Week 6 | 12 Participants |
| Dual - TA | Percentage of Participants With Serious Adverse Event (SAE) From Randomization to Week 6 | 4 Participants |
| Dual - TI | Percentage of Participants With Serious Adverse Event (SAE) From Randomization to Week 6 | 4 Participants |
| Dual - AI | Percentage of Participants With Serious Adverse Event (SAE) From Randomization to Week 6 | 6 Participants |
Other Pre-specified
Percentage of Participants With Serum Potassium Concentration Above 5.5 mmol/l at Week 12
The secondary safety outcome is proportion of participants with serum potassium concentration \>5.5 mmol/l at follow-up Week 12.
Time frame: Week 12
Population: Analysis was done on the safety set which included all participants who had taken at least one dose of study treatment, including during Period 1 single-blind run-in. For the analysis of the safety outcomes, participants were analyzed in the treatment group that was received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GMRx2 | Percentage of Participants With Serum Potassium Concentration Above 5.5 mmol/l at Week 12 | 5 Participants |
| Dual - TA | Percentage of Participants With Serum Potassium Concentration Above 5.5 mmol/l at Week 12 | 0 Participants |
| Dual - TI | Percentage of Participants With Serum Potassium Concentration Above 5.5 mmol/l at Week 12 | 0 Participants |
| Dual - AI | Percentage of Participants With Serum Potassium Concentration Above 5.5 mmol/l at Week 12 | 1 Participants |
Comparison: The Risk difference (95% CI) in percentage of participants with serum potassium concentration above 5.5 mmol/l at Week 12 was calculated between GMRx2 and dual-TA arms.95% CI: [-0.863, 2.231]
Comparison: The Risk difference (95% CI) in percentage of participants with serum potassium concentration above 5.5 mmol/l at Week 12 was calculated between GMRx2 and dual-TI arms.95% CI: [-0.897, 2.231]
Comparison: The Risk difference (95% CI) in percentage of participants with serum potassium concentration above 5.5 mmol/l at Week 12 was calculated between GMRx2 and dual-AI arms.95% CI: [-1.494, 1.913]
Other Pre-specified
Percentage of Participants With Serum Potassium Concentration Above 5.5 mmol/l at Week 6
The secondary safety outcome is proportion of participants with serum potassium concentration \>5.5 mmol/L at follow-up Week 6.
Time frame: Week 6
Population: Analysis was done on the safety set which included all participants who had taken at least one dose of study treatment, including during Period 1 single-blind run-in. For the analysis of the safety outcomes, participants were analyzed in the treatment group that was received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GMRx2 | Percentage of Participants With Serum Potassium Concentration Above 5.5 mmol/l at Week 6 | 2 Participants |
| Dual - TA | Percentage of Participants With Serum Potassium Concentration Above 5.5 mmol/l at Week 6 | 1 Participants |
| Dual - TI | Percentage of Participants With Serum Potassium Concentration Above 5.5 mmol/l at Week 6 | 1 Participants |
| Dual - AI | Percentage of Participants With Serum Potassium Concentration Above 5.5 mmol/l at Week 6 | 0 Participants |
Comparison: The Risk difference (95% CI) in percentage of participants with serum potassium concentration above 5.5 mmol/l at Week 6 was calculated between GMRx2 and dual-TA arms.95% CI: [-1.931, 1.149]
Comparison: The Risk difference (95% CI) in percentage of participants with serum potassium concentration above 5.5 mmol/l at Week 6 was calculated between GMRx2 and dual-TI arms.95% CI: [-1.979, 1.143]
Comparison: The Risk difference (95% CI) in percentage of participants with serum potassium concentration above 5.5 mmol/l at Week 6 was calculated between GMRx2 and dual-AI arms.95% CI: [-1.374, 1.453]
Other Pre-specified
Percentage of Participants With Serum Potassium Concentration Below 3.5 mmol/l at Week 12
The secondary safety outcome is the proportion of participants with serum potassium concentration \<3.5 mmol/L at follow-up Week 12.
Time frame: Week 12
Population: Analysis was done on the safety set which included all participants who had taken at least one dose of study treatment, including during Period 1 single-blind run-in. For the analysis of the safety outcomes, participants were analyzed in the treatment group that was received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GMRx2 | Percentage of Participants With Serum Potassium Concentration Below 3.5 mmol/l at Week 12 | 37 Participants |
| Dual - TA | Percentage of Participants With Serum Potassium Concentration Below 3.5 mmol/l at Week 12 | 0 Participants |
| Dual - TI | Percentage of Participants With Serum Potassium Concentration Below 3.5 mmol/l at Week 12 | 13 Participants |
| Dual - AI | Percentage of Participants With Serum Potassium Concentration Below 3.5 mmol/l at Week 12 | 35 Participants |
Comparison: The Risk difference (95% CI) in percentage of participants with serum potassium concentration below 3.5 mmol/l at Week 12 was calculated between GMRx2 and dual-TA arms.95% CI: [4.196, 9.222]
Comparison: The Risk difference (95% CI) in percentage of participants with serum potassium concentration below 3.5 mmol/l at Week 12 was calculated between GMRx2 and dual-TI arms.95% CI: [-1.883, 5.257]
Comparison: The Risk difference (95% CI) in percentage of participants with serum potassium concentration below 3.5 mmol/l at Week 12 was calculated between GMRx2 and dual-AI arms.95% CI: [-10.979, -1.6]
Other Pre-specified
Percentage of Participants With Serum Potassium Concentration Below 3.5 mmol/l at Week 6
The secondary safety outcome is the proportion of participants with serum potassium concentration below 3.5 mmol/l at follow-up Week 6.
Time frame: Week 6
Population: Analysis was done on the safety set which included all participants who had taken at least one dose of study treatment, including during Period 1 single-blind run-in. For the analysis of the safety outcomes, participants were analyzed in the treatment group that was received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GMRx2 | Percentage of Participants With Serum Potassium Concentration Below 3.5 mmol/l at Week 6 | 27 Participants |
| Dual - TA | Percentage of Participants With Serum Potassium Concentration Below 3.5 mmol/l at Week 6 | 5 Participants |
| Dual - TI | Percentage of Participants With Serum Potassium Concentration Below 3.5 mmol/l at Week 6 | 10 Participants |
| Dual - AI | Percentage of Participants With Serum Potassium Concentration Below 3.5 mmol/l at Week 6 | 21 Participants |
Comparison: The Risk difference (95% CI) in percentage of participants with serum potassium concentration below 3.5 mmol/l at Week 6 was calculated between GMRx2 and dual-TA arms.95% CI: [0.123, 5.632]
Comparison: The Risk difference (95% CI) in percentage of participants with serum potassium concentration below 3.5 mmol/l at Week 6 was calculated between GMRx2 and dual-TI arms.95% CI: [-2.245, 4.134]
Comparison: The Risk difference (95% CI) in percentage of participants with serum potassium concentration below 3.5 mmol/l at Week 6 was calculated between GMRx2 and dual-AI arms.95% CI: [-6.968, 0.819]
Other Pre-specified
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 Follow-up Week 12
The secondary safety outcome is the proportion of participants with serum sodium \<135mmol/L or \>145 mmol/L, and/or serum potassium \<3.5 mmol/L or \>5.5mmol/L at follow-up Week 12.
Time frame: Week 12
Population: Analysis was done on the safety set which included all participants who had taken at least one dose of study treatment, including during Period 1 single-blind run-in. For the analysis of the safety outcomes, participants were analyzed in the treatment group that was received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GMRx2 | 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 Follow-up Week 12 | 105 Participants |
| Dual - TA | 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 Follow-up Week 12 | 24 Participants |
| Dual - TI | 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 Follow-up Week 12 | 44 Participants |
| Dual - AI | 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 Follow-up Week 12 | 57 Participants |
Comparison: The Risk difference (95% CI) in 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 12 was calculated between GMRx2 and dual-TA arms.95% CI: [5.422, 15.138]
Comparison: The Risk difference (95% CI) in 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 12 was calculated between GMRx2 and dual-TI arms.95% CI: [-2.776, 8.49]
Comparison: The Risk difference (95% CI) in 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 12 was calculated between GMRx2 and dual-AI arms.95% CI: [-7.807, 4.174]
Other Pre-specified
Percentage of Participants With Serum Sodium <135 mmol/L or >145 mmol/L, and/or Serum Potassium <3.5 mmol/L or >5.5 mmol/L at Week 6
The secondary safety outcome is proportion of participants with serum sodium \<135 mmol/L or \>145 mmol/L, and/or serum potassium \<3.5 mmol/L or \>5.5 mmol/L at follow-up Week 6.
Time frame: Week 6
Population: Analysis was done on the safety set which included all participants who had taken at least one dose of study treatment, including during Period 1 single-blind run-in. For the analysis of the safety outcomes, participants were analyzed in the treatment group that was received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GMRx2 | Percentage of Participants With Serum Sodium <135 mmol/L or >145 mmol/L, and/or Serum Potassium <3.5 mmol/L or >5.5 mmol/L at Week 6 | 79 Participants |
| Dual - TA | Percentage of Participants With Serum Sodium <135 mmol/L or >145 mmol/L, and/or Serum Potassium <3.5 mmol/L or >5.5 mmol/L at Week 6 | 25 Participants |
| Dual - TI | Percentage of Participants With Serum Sodium <135 mmol/L or >145 mmol/L, and/or Serum Potassium <3.5 mmol/L or >5.5 mmol/L at Week 6 | 26 Participants |
| Dual - AI | Percentage of Participants With Serum Sodium <135 mmol/L or >145 mmol/L, and/or Serum Potassium <3.5 mmol/L or >5.5 mmol/L at Week 6 | 44 Participants |
Comparison: The Risk difference (95% CI) in 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 6 was calculated between GMRx2 and dual-TA arms.95% CI: [0.531, 9.867]
Comparison: The Risk difference (95% CI) in 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 6 was calculated between GMRx2 and dual-TI arms.95% CI: [-0.136, 9.397]
Comparison: The Risk difference (95% CI) in 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 6 was calculated between GMRx2 and dual-AI arms.95% CI: [-7.299, 3.567]
Other Pre-specified
Percentage of Participants With Serum Sodium Concentration Above 145 mmol/l at Week 12
The secondary safety outcome is the proportion of participants with serum sodium \>145 mmol/L at follow-up Week 12.
Time frame: Week 12
Population: Analysis was done on the safety set which included all participants who had taken at least one dose of study treatment, including during Period 1 single-blind run-in. For the analysis of the safety outcomes, participants were analyzed in the treatment group that was received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GMRx2 | Percentage of Participants With Serum Sodium Concentration Above 145 mmol/l at Week 12 | 29 Participants |
| Dual - TA | Percentage of Participants With Serum Sodium Concentration Above 145 mmol/l at Week 12 | 15 Participants |
| Dual - TI | Percentage of Participants With Serum Sodium Concentration Above 145 mmol/l at Week 12 | 16 Participants |
| Dual - AI | Percentage of Participants With Serum Sodium Concentration Above 145 mmol/l at Week 12 | 13 Participants |
Comparison: The Risk difference (95% CI) in percentage of participants with serum sodium concentration above 145 mmol/l at Week 12 was calculated between GMRx2 and dual-TA arms.95% CI: [-3.911, 3.129]
Comparison: The Risk difference (95% CI) in percentage of participants with serum sodium concentration above 145 mmol/l at Week 12 was calculated between GMRx2 and dual-TI arms.95% CI: [-4.519, 2.744]
Comparison: The Risk difference (95% CI) in percentage of participants with serum sodium concentration above 145 mmol/l at Week 12 was calculated between GMRx2 and dual-AI arms.95% CI: [-3.228, 3.647]
Other Pre-specified
Percentage of Participants With Serum Sodium Concentration Above 145 mmol/l at Week 6
The secondary safety outcome is the proportion of participants with serum sodium \>145 mmol/L at follow-up Week 6.
Time frame: Week 6
Population: Analysis was done on the safety set which included all participants who had taken at least one dose of study treatment, including during Period 1 single-blind run-in. For the analysis of the safety outcomes, participants were analyzed in the treatment group that was received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GMRx2 | Percentage of Participants With Serum Sodium Concentration Above 145 mmol/l at Week 6 | 26 Participants |
| Dual - TA | Percentage of Participants With Serum Sodium Concentration Above 145 mmol/l at Week 6 | 14 Participants |
| Dual - TI | Percentage of Participants With Serum Sodium Concentration Above 145 mmol/l at Week 6 | 8 Participants |
| Dual - AI | Percentage of Participants With Serum Sodium Concentration Above 145 mmol/l at Week 6 | 15 Participants |
Comparison: The Risk difference (95% CI) in percentage of participants with serum sodium concentration above 145 mmol/l at Week 6 was calculated between GMRx2 and dual-TA arms.95% CI: [-3.993, 2.816]
Comparison: The Risk difference (95% CI) in percentage of participants with serum sodium concentration above 145 mmol/l at Week 6 was calculated between GMRx2 and dual-TI arms.95% CI: [-1.513, 4.517]
Comparison: The Risk difference (95% CI) in percentage of participants with serum sodium concentration above 145 mmol/l at Week 6 was calculated between GMRx2 and dual-TI arms.95% CI: [-4.596, 2.44]
Other Pre-specified
Percentage of Participants With Serum Sodium Concentration Below 135 mmol/l at Week 12
The secondary safety outcome is the proportion of participants with serum sodium \<135 mmol/L at follow-up Week 12.
Time frame: Week 12
Population: Analysis was done on the safety set which included all participants who had taken at least one dose of study treatment, including during Period 1 single-blind run-in. For the analysis of the safety outcomes, participants were analyzed in the treatment group that was received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GMRx2 | Percentage of Participants With Serum Sodium Concentration Below 135 mmol/l at Week 12 | 40 Participants |
| Dual - TA | Percentage of Participants With Serum Sodium Concentration Below 135 mmol/l at Week 12 | 9 Participants |
| Dual - TI | Percentage of Participants With Serum Sodium Concentration Below 135 mmol/l at Week 12 | 19 Participants |
| Dual - AI | Percentage of Participants With Serum Sodium Concentration Below 135 mmol/l at Week 12 | 10 Participants |
Comparison: The Risk difference (95% CI) in percentage of participants with serum sodium concentration below 135 mmol/l at Week 12 was calculated between GMRx2 and dual-TA arms.95% CI: [0.494, 7.116]
Comparison: The Risk difference (95% CI) in percentage of participants with serum sodium concentration below 135 mmol/l at Week 12 was calculated between GMRx2 and dual-TI arms.95% CI: [-3.927, 4.02]
Comparison: The Risk difference (95% CI) in percentage of participants with serum sodium concentration below 135 mmol/l at Week 12 was calculated between GMRx2 and dual-AI arms.95% CI: [-0.07, 6.764]
Other Pre-specified
Percentage of Participants With Serum Sodium Concentration Below 135 mmol/l at Week 6
The secondary safety outcome is the proportion of participants with serum sodium \<135 mmol/L at follow-up Week 6.
Time frame: Week 6
Population: Analysis was done on the safety set which included all participants who had taken at least one dose of study treatment, including during Period 1 single-blind run-in. For the analysis of the safety outcomes, participants were analyzed in the treatment group that was received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GMRx2 | Percentage of Participants With Serum Sodium Concentration Below 135 mmol/l at Week 6 | 26 Participants |
| Dual - TA | Percentage of Participants With Serum Sodium Concentration Below 135 mmol/l at Week 6 | 6 Participants |
| Dual - TI | Percentage of Participants With Serum Sodium Concentration Below 135 mmol/l at Week 6 | 8 Participants |
| Dual - AI | Percentage of Participants With Serum Sodium Concentration Below 135 mmol/l at Week 6 | 11 Participants |
Comparison: The Risk difference (95% CI) in percentage of participants with serum sodium concentration below 135 mmol/l at Week 6 was calculated between GMRx2 and dual-TA arms.95% CI: [-0.5, 5.136]
Comparison: The Risk difference (95% CI) in percentage of participants with serum sodium concentration below 135 mmol/l at Week 6 was calculated between GMRx2 and dual-TI arms.95% CI: [-1.513, 4.517]
Comparison: The Risk difference (95% CI) in percentage of participants with serum sodium concentration below 135 mmol/l at Week 6 was calculated between GMRx2 and dual-AI arms.95% CI: [-2.855, 3.633]
Other Pre-specified
Percentage of Participants With Symptomatic Hypotension From Randomization to Week 12
The secondary safety outcome is the proportion of participants who experienced at least one symptomatic hypotension episode from randomization to follow-up at Week 12.
Time frame: Week 12
Population: Analysis was done on the safety set which included all participants who had taken at least one dose of study treatment, including during Period 1 single-blind run-in. For the analysis of the safety outcomes, participants were analyzed in the treatment group that was received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GMRx2 | Percentage of Participants With Symptomatic Hypotension From Randomization to Week 12 | 32 Participants |
| Dual - TA | Percentage of Participants With Symptomatic Hypotension From Randomization to Week 12 | 5 Participants |
| Dual - TI | Percentage of Participants With Symptomatic Hypotension From Randomization to Week 12 | 11 Participants |
| Dual - AI | Percentage of Participants With Symptomatic Hypotension From Randomization to Week 12 | 4 Participants |
Other Pre-specified
Percentage of Participants With Symptomatic Hypotension From Randomization to Week 6
The secondary safety outcome is the proportion of participants who experienced at least one symptomatic hypotension episode from randomization to follow-up at Week 6.
Time frame: Week 6
Population: Analysis was done on the safety set which included all participants who had taken at least one dose of study treatment, including during Period 1 single-blind run-in. For the analysis of the safety outcomes, participants were analyzed in the treatment group that was received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GMRx2 | Percentage of Participants With Symptomatic Hypotension From Randomization to Week 6 | 15 Participants |
| Dual - TA | Percentage of Participants With Symptomatic Hypotension From Randomization to Week 6 | 3 Participants |
| Dual - TI | Percentage of Participants With Symptomatic Hypotension From Randomization to Week 6 | 1 Participants |
| Dual - AI | Percentage of Participants With Symptomatic Hypotension From Randomization to Week 6 | 2 Participants |