Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Indapamide · 1 trial · 1 indication
24-hour ABPM device was programmed to take readings every 20 minutes during day (6 am- 9:59 pm) and every 30 minutes during night (10 pm-5:59 am). ABPM was considered adequate if: 1. the number of successful daytime readings were ≥33; 2. the number of successful nighttime readings were ≥11; 3. no more than 3 hours are not represented (i.e.,3 sections of 60 minutes where 0 valid readings were obtained). To summarize 24-hour ABPM, the hourly adjusted mean was calculated. Hourly adjusted mean was the average BP for each hour of the day. The 24-hour mean was the average of the hourly means. Least squares (LS) mean and standard error (SE) were calculated using a mixed model repeated measures (MMRM) approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for SBP assessed using ABPM, while participants were on and within 2 weeks after stopping any escape medication were censored for this endpoint.
24-hour ABPM device was programmed to take readings every 20 minutes during day (6 am- 9:59 pm) and every 30 minutes during night (10 pm-5:59 am). ABPM was considered adequate if: 1. the number of successful daytime readings were ≥33; 2. the number of successful nighttime readings were ≥11; 3. no more than 3 hours are not represented (i.e.,3 sections of 60 minutes where 0 valid readings were obtained). To summarize 24-hour ABPM, the hourly adjusted mean was calculated. Hourly adjusted mean was the average BP for each hour of the day. The 24-hour mean was the average of the hourly means. LS mean and SE were calculated using a MMRM approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for SBP assessed using ABPM, while participants were on and within 2 weeks after stopping any escape medication were censored for this endpoint.
24-hour ABPM device was programmed to take readings every 20 minutes during day (6 am- 9:59 pm) and every 30 minutes during night (10 pm-5:59 am). ABPM was considered adequate if: 1. the number of successful daytime readings were ≥33; 2. the number of successful nighttime readings were ≥11; 3. no more than 3 hours are not represented (i.e.,3 sections of 60 minutes where 0 valid readings were obtained). To summarize 24-hour ABPM, the hourly adjusted mean was calculated. Hourly adjusted mean was the average BP for each hour of the day. The 24-hour mean was average of the hourly means. LS mean and SE were calculated using a MMRM approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for SBP assessed using ABPM, while participants were on and within 2 weeks after stopping any escape medication were censored for this endpoint.
| Arm | Type | Description |
|---|---|---|
| Placebo (Add-on to Indapamide) | PLACEBO_COMPARATOR | Following a 4-week run-in treatment on indapamide, 2.5 milligrams (mg), orally, once daily (QD), eligible participants were randomized to receive placebo matched to zilebesiran as a subcutaneous (SC) injection on Day 1 of 6-month double-blind (DB) treatment period as add-on therapy to indapamide. Participants received protocol-assigned background medication for 6 months, after which it was discontinued. Thereafter, participants will receive zilebesiran once every 6 months (Q6M) during the open-label extension (OLE) period. Upon implementation of Amendment 3, the OLE period was closed. |
| Zilebesiran (Add-on to Indapamide) | EXPERIMENTAL | Following a 4-week run-in treatment on indapamide, 2.5 mg, orally, QD, eligible participants were randomized to receive zilebesiran 600 mg, as a SC injection on Day 1 of 6-month DB treatment period as add-on therapy to indapamide. Participants received protocol-assigned background medication for 6 months, after which it was discontinued. Thereafter, participants will receive zilebesiran, Q6M during the OLE period. Upon implementation of Amendment 3, the OLE period was closed. |
| Placebo (Add-on to Amlodipine) | PLACEBO_COMPARATOR | Following a 4-week run-in treatment on amlodipine, 5 mg, orally, QD, eligible participants were randomized to receive placebo matched to zilebesiran as a SC injection on Day 1 of 6-month DB treatment period as add-on therapy to amlodipine. Participants received protocol-assigned background medication for 6 months, after which it was discontinued. Thereafter, participants will receive zilebesiran Q6M during the OLE period. Upon implementation of Amendment 3, the OLE period was closed. |
| Zilebesiran (Add-on to Amlodipine) | EXPERIMENTAL | Following a 4-week run-in treatment on amlodipine, 5 mg, orally, QD, eligible participants were randomized to receive zilebesiran 600 mg, as a SC injection on Day 1 of 6-month DB treatment period as add-on therapy to amlodipine. Participants received protocol-assigned background medication for 6 months, after which it was discontinued. Thereafter, participants will receive zilebesiran, Q6M during the OLE period. Upon implementation of Amendment 3, the OLE period was closed. |
| Placebo (Add-on to Olmesartan) | PLACEBO_COMPARATOR | Following a 4-week run-in treatment on olmesartan, 40 mg, orally, QD, (or 20 mg, orally, QD for participants with creatinine clearance ≤60 milliliters per minute \[mL/min\] at screening enrolled at sites outside of the United States \[US\] consistent with local labeling), eligible participants were randomized to receive placebo matched to zilebesiran as a SC injection on Day 1 of 6-month DB treatment period as add-on therapy to olmesartan. Participants received protocol-assigned background medication for 6 months, after which it was discontinued. Thereafter, participants will receive zilebesiran Q6M during the OLE period. Upon implementation of Amendment 3, the OLE period was closed. |
| Zilebesiran (Add-on to Olmesartan) | EXPERIMENTAL | Following a 4-week run-in treatment on olmesartan, 40 mg, orally, QD, (or 20 mg, orally, QD for participants with creatinine clearance ≤60 mL/min at screening enrolled at sites outside of the US consistent with local labeling), eligible participants were randomized to receive zilebesiran 600 mg, as a SC injection on Day 1 of 6-month DB treatment period as add-on therapy to olmesartan. Participants received protocol-assigned background medication for 6 months, after which it was discontinued. Thereafter, participants will receive zilebesiran, Q6M during the OLE period. Upon implementation of Amendment 3, the OLE period was closed. |
| Name | Type | Description |
|---|---|---|
| Indapamide | DRUG | Indapamide administered orally |
| Amlodipine | DRUG | Amlodipine administered orally |
| Olmesartan | DRUG | Olmesartan administered orally |
| Placebo | DRUG | Placebo administered by SC injection |
| Zilebesiran | DRUG | Zilebesiran administered by SC injection |
Inclusion Criteria: * Office SBP at Screening as follows: 1. ≥155 mmHg and ≤180 mmHg for patients with untreated hypertension 2. ≥145 mmHg and ≤180 mmHg for patients on antihypertensive medications * 24-hour mean SBP ≥130 mmHg and ≤160 mmHg by ABPM after at least 4 weeks of run-in Exclusion C...
Indapamide is a small molecule being studied for the treatment of hypertension. It is currently in Phase 2 clinical development as an add-on therapy for patients whose blood pressure is not adequately controlled by a standard of care antihypertensive medication.
Indapamide is being developed by Alnylam Pharmaceuticals, Inc. (NASDAQ: ALNY). The company is conducting clinical trials to evaluate the drug as an add-on treatment for hypertension.
Indapamide is in Phase 2 clinical development. It is an investigational drug and has not been approved by regulatory authorities. One Phase 2 trial has been completed, and the drug is not currently in any active trials.
Indapamide was studied in the KARDIA-2 trial (NCT05103332), a Phase 2, randomized, double-blind, placebo-controlled study. The trial enrolled 663 participants with hypertension across the United States, Canada, Estonia, Germany, Latvia, Lithuania, Poland, and the United Kingdom.
Indapamide is not the same as zilebesiran. The KARDIA-2 trial evaluated zilebesiran as an add-on therapy to a standard of care antihypertensive medication, which may include indapamide. Indapamide is a separate drug being developed by Alnylam Pharmaceuticals.