Phase 3
Completed N=395
A Study to Evaluate the Effectiveness and Safety of a Fixed Dose Combination of Azilsartan Medoxomil and Chlorthalidone in Patients With High Blood Pressure Who do Not Achieve Target Blood Pressure Following Treatment With Azilsartan Medoxomil Alone
Source: ClinicalTrials.gov NCT01456169 ↗Enrolled (actual)
395
Serious AEs
0.5%
Results posted
Apr 2014
Primary outcomePrimary: Change From Baseline to Week 8 in Trough, Sitting, Clinic Systolic Blood Pressure — 150.7; 149.8; 149.8; -6.4 mm Hg — p=<0.001
Summary
The purpose of this study is to evaluate the efficacy and safety of the fixed dose combinations of azilsartan medoxomil plus chlorthalidone (40/12.5 and 40/25 mg), once daily, in participants with grades 2 or 3 essential hypertension who do not reach target blood pressure following treatment with 40 mg azilsartan medoxomil monotherapy after 4 weeks.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline to Week 8 in Trough, Sitting, Clinic Systolic Blood Pressure |
150.7; 149.8; 149.8; -6.4; -15.8; -21.1 | <0.001 sig |
| SECONDARY Change From Baseline to Week 8 in Trough, Sitting, Clinic Diastolic Blood Pressure |
89.8; 87.7; 88.8; -3.2; -7.7; -10.3 | — |
| SECONDARY Change From Baseline to Week 8 in Trough Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring |
143.1; 140.2; 142.0; -2.5; -14.0; -16.6 | — |
| SECONDARY Change From Baseline to Week 8 in Trough Diastolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring |
86.4; 83.6; 86.0; -2.2; -8.8; -9.4 | — |
| SECONDARY Change From Baseline to Week 8 in the 24-hour Mean Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring |
138.0; 137.0; 138.2; -2.3; -14.7; -18.1 | — |
| SECONDARY Change From Baseline to Week 8 in the 24-hour Mean Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring |
81.9; 80.3; 82.5; -1.6; -8.5; -10.1 | — |
| SECONDARY Change From Baseline to Week 8 in the Mean Daytime Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring |
141.5; 141.1; 141.9; -2.4; -15.3; -18.2 | — |
| SECONDARY Change From Baseline to Week 8 in the Mean Daytime Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring |
84.9; 83.6; 85.7; -1.7; -8.9; -10.1 | — |
| SECONDARY Change From Baseline to Week 8 in the Mean Nighttime Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring |
127.3; 124.2; 126.3; -2.2; -12.7; -17.3 | — |
| SECONDARY Change From Baseline to Week 8 in the Mean Nighttime Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring |
73.2; 70.6; 72.9; -1.6; -7.2; -9.8 | — |
| SECONDARY Change From Baseline to Week 8 in the Mean Systolic Blood Pressure 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring |
141.6; 141.8; 142.3; -2.3; -15.4; -18.2 | — |
| SECONDARY Change From Baseline to Week 8 in the Mean Diastolic Blood Pressure 0 to 12 Hours After Dosing, as Measured by Ambulatory Blood Pressure Monitoring |
85.2; 84.2; 86.0; -1.6; -8.9; -10.1 | — |
| SECONDARY Percentage of Participants Who Achieve a Target Clinic Systolic Blood Pressure at Week 8 |
35.3; 62.7; 77.8 | — |
| SECONDARY Percentage of Participants Who Achieve a Target Clinic Diastolic Blood Pressure at Week 8 |
60.2; 81.0; 85.9 | — |
| SECONDARY Percentage of Participants Who Achieve Both Clinic Systolic and Diastolic Blood Pressure Targets at Week 8 |
30.8; 59.5; 74.1 | — |
Eligibility Criteria
Inclusion Criteria
At Screening
- The participant has grade 2-3 essential hypertension which is not adequately controlled, as defined by mean, trough, sitting, clinic systolic blood pressure (SBP):
- ≥160 to ≤180 mm Hg in participants who have not received any antihypertensive medication in the 14 days prior to Visit 1.
- ≥150 to ≤170 mm Hg in participants taking 1 antihypertensive medication at Visit 1.
- ≥140 to ≤160 mm Hg in participants taking 2 antihypertensive medications at Visit 1.
- The participant has clinical laboratory test results (clinical chemistry, hematology, and complete urinalysis) within the reference range for the testing laboratory or the investigator does not consider the results to be clinically relevant for precluding entry in to the study in this hypertensive population.
- The participant is willing to discontinue current antihypertensive medications.
- In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
- The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
- Male or female adult, at least 18 years of age.
- A female of childbearing potential who is sexually active with a nonsterilized male partner agrees to routinely use adequate contraception from signing of the informed consent through 30 days after the last study drug dose. NOTE: Women NOT of childbearing potential are defined as those who have been surgically sterilized (hysterectomy, bilateral oophorectomy, tubal ligation [performed more than one 1 year prior to Screening]) or who are postmenopausal (defined as at least 1 year since last regular menses).
Post-placebo run-in:
- The participant must have a post-placebo run-in, 24-hour mean SBP by ambulatory blood pressure monitoring (ABPM) of 140-175 mm Hg inclusive, and a clinic SBP measurement of 160 to 190 mm Hg inclusive (determined by the mean of 3 sitting, trough, measurements on Day -29) to qualify for entry in to the 4 week single-blind TAK-491 40 mg monotherapy treatment period.
Post-4 week, single-blind TAK-491 40 mg monotherapy treatment:
- The participant does not achieve target blood pressure (defined as clinic SBP ≥140 mm Hg as determined by the mean of 3 sitting, trough, measurements) following 4 weeks single-blind treatment with TAK-491 40 mg monotherapy at Day -1, prior to randomization to double-blind treatment.
Exclusion Criteria
At Screening
- The participant has clinic diastolic blood pressure (DBP) >110 mm Hg.
- The participant's 3 SBP measurements differ by more than 15 mm Hg (confirmed by a second set of three measurements).
- The participant has received any investigational compound within 30 days prior to Screening or is currently participating in another investigational study. NOTE: Participants participating in observational studies (per local definition) may enter Screening provided that the last intervention or invasive procedure was >30 days prior to Visit 1.
- The participant has been randomized/enrolled in a previous TAK-491 or TAK-491CLD study. NOTE: This criterion does not apply to participants who entered screening or placebo run-in in another TAK-491 or TAK-491CLD study but were not randomized/enrolled.
- The participant is a study site employee or is in a dependent relationship with a study site employee who is involved in conduct of this study (e.g., spouse, parent, child, sibling) or may consent under duress.
- The participant is currently treated with more than 2 antihypertensive medications.
- The participant works a night (third) shift (defined as 11 PM [2300] to 7 AM [0700]).
- The participant has an upper arm circumference 42 cm.
- The participant has secondary hypertension of any etiology (e.g., renovascular disease, pheochromocytoma, Cushing's syndrome).
- The participant has any hi
Data sourced from ClinicalTrials.gov (NCT01456169). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.