Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication Amlodipine besylate is a calcium channel blocker and may be used alone or in combination with other antihypertensive and antianginal agents for the treatment of: • Hypertension ( 1.1 ) o Amlodipine besylate tablets are indicated for the treatment of hypertension, to lower blood pressure.
Also known as Azilsartan medoxomil, Edarbi, TAK-491CLD, Azilsartan medoxomil (TAK-491), chlorthalidone, Norvasc
TAK-491 · 20 trials · 4 indications
The change in trough clinic sitting SBP measured at Week 8 relative to baseline. The trough is the average of the non-missing values of 3 serial trough sitting SBP measurements. Blood pressure was measured using a validated, automated device after the participant had been sitting for at least 5 minutes. Week 8 blood pressure was measured approximately 24 hours after the previous day's dose.
The change in trough clinic sitting systolic blood pressure measured at week 6 relative to baseline. The trough is the average of the non-missing values of 3 serial trough sitting systolic blood pressure measurements. Blood pressure was measured using a validated, automated device after the participant had been sitting for at least 5 minutes. Week 6 blood pressure was measured approximately 24 hours after the previous day's dose. An analysis of covariance (ANCOVA) model, with treatment group as a fixed effect and Baseline sitting clinic systolic blood pressure as a covariate was used for analysis.
The change between trough systolic blood pressure measured at final visit or Week 8 relative to baseline. Systolic blood pressure is the arithmetic mean of the 3 trough sitting systolic blood pressure measurements.
An AE is any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have a causal relationship with this treatment. A serious AE is defined as any untoward medical occurrence that resulted in death, was life threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability or incapacity, led to a congenital anomaly/birth defect or was an important medical event that may have required intervention to prevent any of items above.
The change in sitting trough clinic systolic blood pressure measured at week 12 or final visit relative to baseline. Trough blood pressure is the average of the non-missing values of the 3 serial trough sitting systolic blood pressure measurements.
An adverse event is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product without regard to causality.
The change in trough systolic blood pressure measured at week 8 or final visit relative to baseline. Systolic blood pressure is the average of the 3 serial trough sitting systolic blood pressure measurements.
The change in sitting trough clinic systolic blood pressure measured at each week indicated including final visit relative to baseline. Systolic blood pressure is the average of the 3 serial trough sitting systolic blood pressure measurements.
The change in trough systolic blood pressure measured at final visit or week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The trough is the average of all measurements recorded from 22 to 24 hours after dosing.
The change in trough systolic blood pressure measured at final visit or week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The trough is the average of all measurements recorded from 22 to 24 hours after dosing.
The change in 24-hour mean systolic blood pressure measured at week 6 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 24-hour mean is the average of all measurements recorded for 24 hours after dosing.
The change in mean trough clinic sitting systolic blood pressure measured at final visit or week 24 relative to baseline. Systolic blood pressure is the arithmetic mean of the 3 trough sitting systolic blood pressure measurements.
The change in 24-hour mean systolic blood pressure measured at week 24 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 24-hour mean is the average of all measurements recorded for 24 hours after dosing.
Treatment-emergent adverse events are defined as any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product reported from first dose of study drug through 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug.
Treatment-emergent adverse events are defined as any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product reported from first dose of study drug through 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug.
The change in sitting clinic diastolic blood pressure measured at final visit or week 32 from Double-blind Baseline/Week 26. Diastolic blood pressure is the arithmetic mean of the 3 trough sitting diastolic blood pressure measurements. Each participant's blood pressure at the Final Visit/Week 26 of the open-label phase represented their Baseline blood pressure for the double-blind reversal phase.
The change in sitting clinic diastolic blood pressure measured at final visit or week 8 relative to baseline. Diastolic blood pressure is the arithmetic mean of the 3 trough sitting diastolic blood pressure measurements.
| Arm | Type | Description |
|---|---|---|
| Azilsartan medoxomil 40 mg | EXPERIMENTAL | Run-in Period: azilsartan medoxomil 40 mg placebo-matching tablets, azilsartan medoxomil 80 mg placebo-matching tablets, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for 2 weeks prior to the start of the treatment period. Treatment Period: azilsartan medoxomil 40 mg tablets, orally, once daily, azilsartan medoxomil 80 mg placebo-matching tablets, orally, once daily, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for up to 8 weeks. |
| Azilsartan medoxomil 80 mg | EXPERIMENTAL | Run-in Period: azilsartan medoxomil 40 mg placebo-matching tablets, azilsartan medoxomil 80 mg placebo-matching tablets, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for 2 weeks prior to the start of the treatment period. Treatment Period: azilsartan medoxomil 80 mg tablets, orally, once daily, azilsartan medoxomil 40 mg placebo-matching tablets, orally, once daily, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for up to 8 weeks. |
| Valsartan 160 mg | ACTIVE_COMPARATOR | Run-in Period: azilsartan medoxomil 40 mg placebo-matching tablets, azilsartan medoxomil 80 mg placebo-matching tablets, and valsartan two 80 mg placebo-matching capsules, orally, once daily, for 2 weeks prior to the start of the treatment period. Treatment Period: valsartan two 80 mg capsules, orally, once daily, azilsartan medoxomil 40 mg placebo-matching tablets, orally, once daily, and azilsartan medoxomil 80 mg placebo-matching tablets, orally, once daily, for up to 8 weeks. |
| Placebo | PLACEBO_COMPARATOR | Azilsartan medoxomil placebo-matching tablets, orally, once daily for 6 weeks. |
| Azilsartan medoxomil + chlorthalidone 40/12.5 mg | EXPERIMENTAL | Azilsartan 40 mg and chlorthalidone 12.5 mg combination tablets, orally, once daily for up to 8 weeks. |
| Azilsartan medoxomil + chlorthalidone 40/25 mg | EXPERIMENTAL | Azilsartan medoxomil 40 mg and chlorthalidone 25 mg combination tablets, orally, once daily for up to 8 weeks. |
| Azilsartan Medoxomil + Chlorthalidone | EXPERIMENTAL | United States and Europe: Azilsartan medoxomil 20 mg plus chlorthalidone 12.5 mg fixed dose combination tablets, titrated up to azilsartan medoxomil 40 mg plus chlorthalidone 25 mg orally, once daily for up to 52 weeks. |
| Olmesartan Medoxomil + Hydrochlorothiazide | ACTIVE_COMPARATOR | United States: Olmesartan medoxomil 20 mg plus hydrochlorothiazide 12.5 mg fixed dose combination tablets, titrated up to olmesartan medoxomil 40 mg plus hydrochlorothiazide 25 mg orally, once daily for up to 52 weeks. Europe: Olmesartan medoxomil 20 mg plus hydrochlorothiazide 12.5 mg fixed dose combination tablets, titrated up to olmesartan medoxomil 20 mg plus hydrochlorothiazide 25 mg orally, once daily for up to 52 weeks. |
| Azilsartan Medoxomil 20-40mg/Chlorthalidone 12.5-25mg QD | EXPERIMENTAL | - |
| Azilsartan Medoxomil 40-80mg/Chlorthalidone 12.5-25mg QD | EXPERIMENTAL | - |
| Olmesartan Medoxomil 20-40mg/Hydrochlorothiazide 12.5-25mg QD | ACTIVE_COMPARATOR | - |
| Azilsartan Medoxomil and Chlorthalidone | EXPERIMENTAL | Azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablet, orally, once daily for up to 52 weeks. For participants who did not achieve target blood pressure by Week 4, titration to a maximum dose of azilsartan medoxomil 80 mg and chlorthalidone 25 mg. |
| Olmesartan Medoxomil and Hydrochlorothiazide QD | ACTIVE_COMPARATOR | Participants in the United States: Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablet, orally, once daily for up to 52 weeks. For participants who did not achieve target blood pressure by Week 4, titration to a maximum dose of Olmesartan medoxomil 40 mg and hydrochlorothiazide 25 mg. Participants in Europe: Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablet, orally, once daily for up to 52 weeks. For participants who did not achieve target blood pressure by Week 4, titration to a maximum dose of Olmesartan medoxomil 20 mg and hydrochlorothiazide 25 mg. |
| Azilsartan Medoxomil 20-40mg plus Chlorthalidone 12.5-25 mg QD | EXPERIMENTAL | (dependant on blood pressure) |
| Azilsartan Medoxomil 40-80mg plus Chlorthalidone 12.5-25 mg QD | EXPERIMENTAL | (dependant on blood pressure) |
| Azilsartan Medoxomil 40 mg/Chlorthalidone 12.5 mg QD | EXPERIMENTAL | - |
| Azilsartan Medoxomil 40 mg + Hydrochlorothiazide 12.5 mg QD | EXPERIMENTAL | - |
| Azilsartan medoxomil 20 mg/chlorthalidone 12.5 mg QD | EXPERIMENTAL | - |
| Azilsartan medoxomil 20 mg/chlorthalidone 25 mg QD | EXPERIMENTAL | - |
| Azilsartan medoxomil 40 mg/chlorthalidone 25 mg QD | EXPERIMENTAL | - |
| Azilsartan medoxomil 80 mg/chlorthalidone 12.5 mg QD | EXPERIMENTAL | - |
| Azilsartan medoxomil 80 mg/chlorthalidone 25 mg QD | EXPERIMENTAL | - |
| Chlorthalidone 12.5 mg QD | ACTIVE_COMPARATOR | - |
| Chlorthalidone 25 mg QD | ACTIVE_COMPARATOR | - |
| Azilsartan medoxomil 20 mg QD | EXPERIMENTAL | - |
| Azilsartan medoxomil 40 mg QD | EXPERIMENTAL | - |
| Azilsartan medoxomil 80 mg QD | EXPERIMENTAL | - |
| Valsartan 320 mg QD | ACTIVE_COMPARATOR | - |
| Olmesartan 40 mg QD | ACTIVE_COMPARATOR | - |
| Placebo QD | PLACEBO_COMPARATOR | - |
| Ramipril 10 mg QD | ACTIVE_COMPARATOR | - |
| Azilsartan Medoxomil 40 mg QD and Amlodipine 5 mg QD | EXPERIMENTAL | - |
| Azilsartan Medoxomil 80 mg QD and Amlodipine 5 mg QD | EXPERIMENTAL | - |
| Amlodipine 5 mg QD | ACTIVE_COMPARATOR | - |
| Azilsartan Medoxomil 40 mg QD and Chlorthalidone 25 mg QD | EXPERIMENTAL | - |
| Azilsartan Medoxomil 80 mg QD and Chlorthalidone 25 mg QD | EXPERIMENTAL | - |
| Azilsartan Medoxomil | EXPERIMENTAL | - |
| Azilsartan Medoxomil QD-Open Label Phase (Baseline - Week 26) | EXPERIMENTAL | - |
| Azilsartan Medoxomil QD - Double-Blind Phase (Week 26-32) | EXPERIMENTAL | - |
| Placebo QD - Double-Blind Phase (Week 26- 32) | PLACEBO_COMPARATOR | - |
| Azilsartan Medoxomil 5 mg QD | EXPERIMENTAL | - |
| Azilsartan Medoxomil 10 mg QD | EXPERIMENTAL | - |
| Olmesartan 20 mg QD | ACTIVE_COMPARATOR | - |
| TAK-491 40 mg (Open Label) | EXPERIMENTAL | TAK-491 40 milligram (mg), tablet, orally, once daily on Day 1 and Days 4 to 10 as an open-label treatment. |
| TAK-491 80 mg (Open-label) | EXPERIMENTAL | TAK-491 80 mg, tablet, orally, once daily on Day 1 and Days 4 to 10 as an open-label treatment. |
| TAK-491 40 mg (Double-blind) | EXPERIMENTAL | TAK-491 40 mg, tablet, orally, once daily and TAK-491 80 mg placebo-matching tablet, orally, once daily on Day 1 and Days 4 to 10 in double-blind manner. |
| TAK-491 80 mg (Double-blind) | EXPERIMENTAL | TAK-491 80 mg, tablet, orally, once daily and TAK-491 40 mg placebo-matching tablet, orally, once daily on Day 1 and Days 4 to 10 in double-blind manner. |
| Name | Type | Description |
|---|---|---|
| Azilsartan medoxomil | DRUG | Azilsartan medoxomil tablets |
| Valsartan | DRUG | Valsartan 80 mg capsules |
| Azilsartan medoxomil Placebo | DRUG | Azilsartan medoxomil placebo-matching tablets |
| Valsartan Placebo | DRUG | Valsartan placebo-matching capsules |
| Azilsartan medoxomil/placebo | DRUG | Azilsartan medoxomil and placebo to chlorthalidone combination tablets |
| Azilsartan medoxomil - chlorthalidone | DRUG | Azilsartan medoxomil and chlorthalidone fixed dose combination tablets |
| Azilsartan medoxomil and chlorthalidone | DRUG | Fixed-dose combination tablets. |
| Olmesartan medoxomil and hydrochlorothiazide | DRUG | Fixed-dose combination tablets. |
| Olmesartan medoxomil-hydrochlorothiazide | DRUG | Olmesartan medoxomil 20 mg/hydrochlorothiazide 12.5 mg, tablets, orally, and Azilsartan medoxomil and chlorthalidone placebo-matching tablets, orally, once daily for 8 weeks. If participant does not achieve target blood pressure at Week 4, then the dosage will be increased to olmesartan medoxomil 40 mg/hydrochlorothiazide 25 mg, tablets, orally, once daily for the remaining 4 weeks. |
| Azilsartan medoxomil and hydrochlorothiazide | DRUG | Azilsartan medoxomil 40 mg, tablets, orally, once daily and hydrochlorothiazide 12.5 mg, tablets, orally, once daily for up to 10 weeks. For participants who do not achieve target blood pressure by Week 6, the dose of hydrochlorothiazide will be increased for the remaining 4 weeks of treatment. |
| Chlorthalidone | DRUG | Azilsartan medoxomil placebo and chlorthalidone 12.5 mg combination tablets, orally, once daily for up to 8 weeks |
| Olmesartan | DRUG | Olmesartan 20 mg, tablets and matching placebo comparator, orally, once daily for two weeks. Increased to Olmesartan 40 mg, tablets and matching placebo comparator, orally, once daily for up to four weeks. |
| Placebo | DRUG | Matching placebo, orally, once daily for up to six weeks. |
| Ramipril | DRUG | Ramipril 2.5 mg, tablets, orally, once daily for two weeks; then increased to 10 mg, tablets, orally, once daily for up to 22 weeks. |
| Azilsartan Medoxomil and amlodipine | DRUG | Azilsartan Medoxomil 40 mg, tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks. |
| Amlodipine | DRUG | Azilsartan medoxomil placebo-matching tablets, orally, once daily and amlodipine 5 mg, tablets, orally, once daily for up to 6 weeks. |
| Azilsartan medoxomil with or without add-on chlorthalidone | DRUG | Azilsartan medoxomil 40 mg, tablets, orally, once daily for four weeks; increased to azilsartan medoxomil 80 mg, tablets, orally, once daily for remainder of 56-week treatment period, if tolerated. Additional antihypertensive medications added, beginning with chlorthalidone 25 mg, once-daily, if target blood pressure not achieved. |
| Azilsartan medoxomil with or without add-on hydrochlorothiazide | DRUG | Azilsartan medoxomil 40 mg, tablets, orally, once daily for four weeks; increased to azilsartan medoxomil 80 mg, tablets, orally, once daily for remainder of 56-week treatment period, if tolerated. Additional antihypertensive medications added, beginning with hydrochlorothiazide 12.5 to 25 mg, once-daily, if target blood pressure not achieved. |
| Azilsartan medoxomil and olmesartan | DRUG | Azilsartan medoxomil 20 mg, tablets, azilsartan medoxomil 40 mg placebo-matching tablets, azilsartan medoxomil 80 mg placebo-matching tablets and olmesartan 40 mg placebo-matching tablets, orally, for up to 6 weeks. |
| Azilsartan medoxomil, with or without chlorthalidone and other non-angiotensin II receptor blocker antihypertensive medications. | DRUG | Azilsartan medoxomil at the final dose received during the open-label phase: (20 mg, 40 mg or 80 mg), tablets, orally, once daily with or without chlorthalidone 25 mg, tablets, orally once daily and other non-ARB antihypertensive medications (if currently taking), for 6 weeks/Week 32. |
| TAK-491 | DRUG | TAK-491 tablets |
| TAK-491 placebo | DRUG | TAK-491 placebo-matching tablets |
Inclusion Criteria: 1. Is treated with antihypertensive therapy and has a post-washout mean sitting clinic systolic blood pressure (SBP) ≥150 and ≤180 mm Hg on Day 1; or the participant has not received antihypertensive treatment within 28 days prior to Screening and has a mean sitting clinic SBP ≥...
TAK-491 is an investigational small molecule developed by Takeda Pharmaceutical Company Limited. It has been studied in a Phase 1 clinical trial in healthy Chinese participants. The specific therapeutic indication for TAK-491 has not been disclosed.
TAK-491 is being developed by Takeda Pharmaceutical Company Limited, which trades under the ticker TAK. Takeda is the sponsor of the clinical program for this asset.
TAK-491 is in Phase 1 clinical development. It is an investigational drug and has not been approved by the FDA or any other regulatory agency for any indication.
TAK-491 has been evaluated in one completed Phase 1 trial, NCT02541669, titled A Single- and Multiple-Dose Study of the Pharmacokinetics of TAK-491 in Healthy Chinese Participants. The trial enrolled 64 healthy volunteers in China and was randomized, double-blind, and placebo-controlled.
No, TAK-491 is not approved by the FDA. It remains an investigational drug in Phase 1 clinical development, with only one completed Phase 1 trial to date.