Hypertension
Conditions
Keywords
Hypertension, African American, aliskiren, hydrochlorothiazide, systolic blood pressure, diastolic blood pressure, amlodipine, stage 2
Brief summary
The purpose of the study is to evaluate the efficacy and safety of a fixed dose combination of aliskiren HCTZ versus amlodipine in African American patients with Stage 2 hypertension.
Interventions
DRUGAliskiren Hydrochlorothiazide (HCTZ): 8 weeks
Aliskiren HCTZ (150/12.5 mg) for 1 week followed by forced titration to Aliskiren HCTZ (300/25 mg) for remaining 7 weeks
DRUGAmlodipine: 8 weeks
Amlodipine 5 mg for 1 week followed by forced titration to Amlodipine 10 mg for remaining 7 weeks
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients who are eligible and able to participate in the study, and who give written informed consent before any assessment is performed. * Men or women 18 years and older of African American background; self identified * Patients with stage 2 hypertension. Patients must have a MSSBP ≥ 160 mmHg and \< 200 mmHg at Visit 5 (randomization)
Exclusion criteria
* Office blood pressure measured by cuff (MSSBP ≥ 200 mmHg and/or MSDBP ≥ 110 mmHg) at any visit. * Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives whichever is longer. * History of hypersensitivity to any of the study drugs or to drugs belonging to the same therapeutic class (CCBs or thiazide diuretics) as the study drugs. * Long QT syndrome or QTc \> 450 msec for males and \> 470 msec for females at screening. * History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases. * Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (\> 5 mIU/mL) * Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant. including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS they are using two birth control methods. The two methods can be a double barrier method or a barrier method plus a hormonal method. 1. Adequate barrier methods of contraception include: diaphragm, condom (by the partner), intrauterine device (copper or hormonal), sponge or spermicide. Hormonal contraceptives include any marketed contraceptive agent that includes an estrogen and/or a progestational agent. Reliable contraception should be maintained throughout the study and for 7 days after study drug discontinuation. 2. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum FSH levels \> 40 mIU/mL \[and estradiol \< 20 pg/mL\] or have had surgical bilateral oophorectomy (with or without hysterectomy) at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment. * History or evidence of a secondary form of hypertension. * Known Keith-Wagener Grade III or IV hypertensive retinopathy. * History of cerebrovascular accident, transient ischemic cerebral attack (TIA), heart failure (NYHA Class II-IV), myocardial infarction, coronary bypass surgery, or any percutaneous coronary intervention (PCI) in the last 12 months. * Current angina pectoris requiring pharmacological therapy. * Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Sitting Systolic Blood Pressure (MSSBP) After 8 Weeks of Treatment | Baseline and 8 weeks | To assess the change from baseline in MSSBP after 8 weeks of treatment with an aliskiren HCTZ-based treatment regimen (aliskiren HCTZ 150/12.5 mg, 300/25 mg) versus an amlodipine-based treatment regimen (amlodipine 5 mg, 10 mg) in African American patients with stage 2 hypertension. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Sitting Diastolic Blood Pressure (MSDBP) After 8 Weeks of Treatment | Baseline and 8 weeks | To assess the change from baseline in mean sitting diastolic blood pressure (MSDBP) after 8 weeks of treatment with an aliskiren HCTZ-based treatment regimen (aliskiren HCTZ 150/12.5 mg, 300/25 mg) versus an amlodipine-based treatment regimen (amlodipine 5 mg, 10 mg) in African American patients with stage 2 hypertension. |
| Change in Mean Sitting Pulse Pressure (MSPP) After 8 Weeks of Treatment | Baseline and 8 weeks | To compare the change from baseline in mean sitting pulse pressure (MSPP) after 8 weeks of treatment with an aliskiren HCTZ-based treatment regimen (aliskiren HCTZ 150/12.5 mg, 300/25 mg) versus an amlodipine-based treatment regimen (amlodipine 5 mg, 10 mg) in African American patients with stage 2 hypertension. |
| Percentage of Responders After 8 Weeks of Treatment. | 8 weeks | To compare the percentage of responders after 8 weeks of treatment with an aliskiren HCTZ based treatment regimen (aliskiren HCTZ 150/12.5 mg, 300/25 mg) versus an amlodipine-based treatment regimen (amlodipine 5 mg, 10 mg) in African American patients with stage 2 hypertension: \[ Responders were defined as patients with MSSBP \< 140 mm Hg or a decrease from baseline ≥ 20 mm Hg at 1st response. A response was counted when a patient first achieved MSSBP \< 140 mm Hg or a decrease from baseline ≥ 20 mm Hg.\] |
| Percentage of Participants Achieving BP Control After 8 Weeks of Treatment | 8 weeks | To compare the percentage of patients achieving BP control (\<140/90 mm Hg) after 8 weeks of treatment with an aliskiren HCTZ-based treatment regimen (aliskiren HCTZ 150/12.5 mg, 300/25 mg) versus an amlodipine-based treatment regimen (amlodipine 5 mg, 10 mg) in African American patients with stage 2 hypertension. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aliskiren HCTZ Aliskiren HCTZ (150/12.5 mg) for 1 week followed by forced titration to Aliskiren HCTZ (300/25 mg) for remaining 7 weeks | 166 |
| Amlodipine Amlodipine 5 mg for 1 week followed by forced titration to Amlodipine 10 mg for remaining 7 weeks | 166 |
| Total | 332 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 12 | 6 |
| Overall Study | Lost to Follow-up | 0 | 2 |
| Overall Study | Patient Withdrew Consent | 8 | 8 |
| Overall Study | Protocol Deviation | 1 | 1 |
| Overall Study | Unsatisfactory Therapeutic Effect | 4 | 0 |
Baseline characteristics
| Characteristic | Total | Amlodipine | Aliskiren HCTZ |
|---|---|---|---|
| Age, Continuous | 52.6 years STANDARD_DEVIATION 11.41 | 53.1 years STANDARD_DEVIATION 11.56 | 52.0 years STANDARD_DEVIATION 11.27 |
| Age, Customized < 65 years | 284 participants | 143 participants | 141 participants |
| Age, Customized ≥ 65 years | 48 participants | 23 participants | 25 participants |
| Sex: Female, Male Female | 176 Participants | 91 Participants | 85 Participants |
| Sex: Female, Male Male | 156 Participants | 75 Participants | 81 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 166 | 0 / 166 |
| serious Total, serious adverse events | 5 / 166 | 3 / 166 |
Outcome results
Primary
Change in Mean Sitting Systolic Blood Pressure (MSSBP) After 8 Weeks of Treatment
To assess the change from baseline in MSSBP after 8 weeks of treatment with an aliskiren HCTZ-based treatment regimen (aliskiren HCTZ 150/12.5 mg, 300/25 mg) versus an amlodipine-based treatment regimen (amlodipine 5 mg, 10 mg) in African American patients with stage 2 hypertension.
Time frame: Baseline and 8 weeks
Population: The intent-to-treat (ITT) population consisted of all randomized patients who received at least one dose of study medication and had at least one valid post-baseline assessment of the primary efficacy variable. Last observation carried forward (LOCF) method was used for replacing missing values with post-baseline assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aliskiren HCTZ | Change in Mean Sitting Systolic Blood Pressure (MSSBP) After 8 Weeks of Treatment | Baseline | 168.2 mm Hg | Standard Deviation 8.49 |
| Aliskiren HCTZ | Change in Mean Sitting Systolic Blood Pressure (MSSBP) After 8 Weeks of Treatment | Week 8 | 138.8 mm Hg | Standard Deviation 18.21 |
| Aliskiren HCTZ | Change in Mean Sitting Systolic Blood Pressure (MSSBP) After 8 Weeks of Treatment | Change from baseline to Week 8 | -29.4 mm Hg | Standard Deviation 17.95 |
| Amlodipine | Change in Mean Sitting Systolic Blood Pressure (MSSBP) After 8 Weeks of Treatment | Baseline | 168.1 mm Hg | Standard Deviation 7.99 |
| Amlodipine | Change in Mean Sitting Systolic Blood Pressure (MSSBP) After 8 Weeks of Treatment | Week 8 | 139.1 mm Hg | Standard Deviation 14.45 |
| Amlodipine | Change in Mean Sitting Systolic Blood Pressure (MSSBP) After 8 Weeks of Treatment | Change from baseline to Week 8 | -29.0 mm Hg | Standard Deviation 13.17 |
Secondary
Change in Mean Sitting Diastolic Blood Pressure (MSDBP) After 8 Weeks of Treatment
To assess the change from baseline in mean sitting diastolic blood pressure (MSDBP) after 8 weeks of treatment with an aliskiren HCTZ-based treatment regimen (aliskiren HCTZ 150/12.5 mg, 300/25 mg) versus an amlodipine-based treatment regimen (amlodipine 5 mg, 10 mg) in African American patients with stage 2 hypertension.
Time frame: Baseline and 8 weeks
Population: The intent-to-treat (ITT) population consisted of all randomized patients who received at least one dose of study medication and had at least one valid post-baseline assessment of the primary efficacy variable. Last observation carried forward (LOCF) method was used for replacing missing values with post-baseline assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aliskiren HCTZ | Change in Mean Sitting Diastolic Blood Pressure (MSDBP) After 8 Weeks of Treatment | Baseline | 96.0 mm Hg | Standard Deviation 9.76 |
| Aliskiren HCTZ | Change in Mean Sitting Diastolic Blood Pressure (MSDBP) After 8 Weeks of Treatment | Week 8 | 86.0 mm Hg | Standard Deviation 12.02 |
| Aliskiren HCTZ | Change in Mean Sitting Diastolic Blood Pressure (MSDBP) After 8 Weeks of Treatment | Change from Baseline to Week 8 | -10.0 mm Hg | Standard Deviation 11.08 |
| Amlodipine | Change in Mean Sitting Diastolic Blood Pressure (MSDBP) After 8 Weeks of Treatment | Baseline | 95.0 mm Hg | Standard Deviation 8.86 |
| Amlodipine | Change in Mean Sitting Diastolic Blood Pressure (MSDBP) After 8 Weeks of Treatment | Week 8 | 84.0 mm Hg | Standard Deviation 9.72 |
| Amlodipine | Change in Mean Sitting Diastolic Blood Pressure (MSDBP) After 8 Weeks of Treatment | Change from Baseline to Week 8 | -11.0 mm Hg | Standard Deviation 9.81 |
Secondary
Change in Mean Sitting Pulse Pressure (MSPP) After 8 Weeks of Treatment
To compare the change from baseline in mean sitting pulse pressure (MSPP) after 8 weeks of treatment with an aliskiren HCTZ-based treatment regimen (aliskiren HCTZ 150/12.5 mg, 300/25 mg) versus an amlodipine-based treatment regimen (amlodipine 5 mg, 10 mg) in African American patients with stage 2 hypertension.
Time frame: Baseline and 8 weeks
Population: The intent-to-treat (ITT) population consisted of all randomized patients who received at least one dose of study medication and had at least one valid post-baseline assessment of the primary efficacy variable. Last observation carried forward (LOCF) method was used for replacing missing values with post-baseline assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aliskiren HCTZ | Change in Mean Sitting Pulse Pressure (MSPP) After 8 Weeks of Treatment | Baseline | 72.2 mm Hg | Standard Deviation 12.1 |
| Aliskiren HCTZ | Change in Mean Sitting Pulse Pressure (MSPP) After 8 Weeks of Treatment | Week 8 | 52.7 mm Hg | Standard Deviation 14.91 |
| Aliskiren HCTZ | Change in Mean Sitting Pulse Pressure (MSPP) After 8 Weeks of Treatment | Change from Baseline to Week 8 | -19.4 mm Hg | Standard Deviation 13.73 |
| Amlodipine | Change in Mean Sitting Pulse Pressure (MSPP) After 8 Weeks of Treatment | Baseline | 73.1 mm Hg | Standard Deviation 11.59 |
| Amlodipine | Change in Mean Sitting Pulse Pressure (MSPP) After 8 Weeks of Treatment | Week 8 | 55.1 mm Hg | Standard Deviation 12.13 |
| Amlodipine | Change in Mean Sitting Pulse Pressure (MSPP) After 8 Weeks of Treatment | Change from Baseline to Week 8 | -18.0 mm Hg | Standard Deviation 11.2 |
Secondary
Percentage of Participants Achieving BP Control After 8 Weeks of Treatment
To compare the percentage of patients achieving BP control (\<140/90 mm Hg) after 8 weeks of treatment with an aliskiren HCTZ-based treatment regimen (aliskiren HCTZ 150/12.5 mg, 300/25 mg) versus an amlodipine-based treatment regimen (amlodipine 5 mg, 10 mg) in African American patients with stage 2 hypertension.
Time frame: 8 weeks
Population: The intent-to-treat (ITT) population consisted of all randomized patients who received at least one dose of study medication and had at least one valid post-baseline assessment of the primary efficacy variable.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aliskiren HCTZ | Percentage of Participants Achieving BP Control After 8 Weeks of Treatment | 63.6 Cumulative percentage of participants |
| Amlodipine | Percentage of Participants Achieving BP Control After 8 Weeks of Treatment | 62.3 Cumulative percentage of participants |
Secondary
Percentage of Responders After 8 Weeks of Treatment.
To compare the percentage of responders after 8 weeks of treatment with an aliskiren HCTZ based treatment regimen (aliskiren HCTZ 150/12.5 mg, 300/25 mg) versus an amlodipine-based treatment regimen (amlodipine 5 mg, 10 mg) in African American patients with stage 2 hypertension: \[ Responders were defined as patients with MSSBP \< 140 mm Hg or a decrease from baseline ≥ 20 mm Hg at 1st response. A response was counted when a patient first achieved MSSBP \< 140 mm Hg or a decrease from baseline ≥ 20 mm Hg.\]
Time frame: 8 weeks
Population: The intent-to-treat (ITT) population consisted of all randomized patients who received at least one dose of study medication and had at least one valid post-baseline assessment of the primary efficacy variable.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aliskiren HCTZ | Percentage of Responders After 8 Weeks of Treatment. | 84.6 Cumulative percentage of responders |
| Amlodipine | Percentage of Responders After 8 Weeks of Treatment. | 90.7 Cumulative percentage of responders |