A Study Of Different Doses Of TBC3711 In Patients With Uncontrolled High Blood Pressure Already Taking Medications For High Blood Pressure.

Study Overview
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Brief Summary
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The study was to determine the safe and effective dose of TBC3711 in patients with uncontrolled high blood pressure while already taking blood pressure medications.

Detailed Description
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The study was stopped due to Pfizer (sponsor) decision that the compound would not be involved in any further clinical development for the indication of resistant hypertension on 05 August 2008. This decision was not based on any safety or efficacy concern.

Official Title
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A Phase 2 Multi-Centre, Randomised, Double-Blind, Placebo Controlled, Dose Ranging Study Of TBC3711 In Subjects With Resistant Hypertension

Conditions
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Resistant Hypertension

Intervention / Treatment
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* Drug: Placebo
* Drug: TBC3711
* Drug: TBC3711
* Drug: TBC3711
* Drug: TBC3711


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of resistant hypertension. A stable anti-hypertensive drug regimen for at least 30 days. Exclusion Criteria: Sustained blood pressure greater than or equal to 180/120 mmHg. Required use of thigh cuff for blood pressure readings. Uncontrolled diabetes mellitus.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: placebo<br> | Drug: Placebo<br>* placebo tablet once daily for 12 weeks<br>|
| Experimental: ARM 1<br> | Drug: TBC3711<br>* 10 mg tablets once daily for 10 weeks<br>|
| Experimental: ARM 2<br> | Drug: TBC3711<br>* 50 mg tablet once daily for 10 weeks<br>|
| Experimental: ARM 3<br> | Drug: TBC3711<br>* 100 mg tablet once daily for 10 weeks<br>|
| Experimental: ARM 4<br> | Drug: TBC3711<br>* 200 mg tablet once daily for 10 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Blood Pressure (BP) Increase | BP is the pressure of the blood within the arteries. It is produced primarily by the contraction of the heart muscle. BP measurement is recorded by 2 numbers: systolic BP (SBP, BP when heart is contracting; it is the maximum arterial pressure during contraction of left ventricle) and diastolic BP (DBP, BP when heart is relaxing; it is the minimum arterial pressure during relaxation and dilation of ventricles). Maximum increase was calculated by subtracting baseline value from each post-dose measurement and selecting maximum of these values. | Baseline (Pre-Dose on Day 1 of Week 2) up to Week 12 | 
| Weighted Mean (Area Under Effect Curve [AUEC]) Blood Pressure Change | AUEC was calculated as the positive area under the change from baseline curve for sitting and standing SBP and DBP to Week 12, estimated by the linear trapezoidal rule corrected for the pre-dose baseline value. In the event that post-dose values returned below baseline at or before Week 12, then AUEC was calculated by setting the negative values to zero and taking only the positive area into account. | Baseline (Pre-Dose on Day 1 of Week 2) up to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sitting Systolic Blood Pressure (SBP) | SBP is the BP (pressure exerted by circulating blood on the walls of blood vessels) when heart is contracting; it is the maximum arterial pressure during contraction of left ventricle of heart. A total of 3 measurements were performed and average was calculated at each time point in participant's non-dominant arm using appropriate-sized cuff (cuff bladder encircling at least 80 percent [%] of the arm) after participant sat for 5 minutes for the first measurement and 2 minutes for second and third measurements. The same arm was used throughout the study. | Pre-Dose and 2 hour Post-Dose on Baseline (Day 1 of Placebo Run-In Phase), Week 1, 2, 3, 4, 6, 8, 10 | 
| Standing Systolic Blood Pressure (SBP) | SBP is the BP (pressure exerted by circulating blood on the walls of blood vessels) when heart is contracting; it is the maximum arterial pressure during contraction of left ventricle of heart. A total of 3 measurements were performed and average was calculated at each time point in participant's non-dominant arm using appropriate-sized cuff (cuff bladder encircling at least 80% of the arm) after participant stood for 2 minutes. The same arm was used throughout the study. | Pre-Dose and 2 hour Post-Dose on Baseline (Day 1 of Placebo Run-In Phase), Week 1, 2, 3, 4, 6, 8, 10 | 
| Sitting Diastolic Blood Pressure (DBP) | DBP is the BP (pressure exerted by circulating blood on the walls of blood vessels) when heart is relaxing; it is the minimum arterial pressure during relaxation and dilation of ventricles of heart. A total of 3 measurements were performed and average was calculated at each time point in participant's non-dominant arm using appropriate-sized cuff (cuff bladder encircling at least 80% of the arm) after participant sat for 5 minutes for the first measurement and 2 minutes for second and third measurements. The same arm was used throughout the study. | Pre-Dose and 2 hour Post-Dose on Baseline (Day 1 of Placebo Run-In Phase), Week 1, 2, 3, 4, 6, 8, 10 | 
| Standing Diastolic Blood Pressure (DBP) | DBP is the BP (pressure exerted by circulating blood on the walls of blood vessels) when heart is relaxing; it is the minimum arterial pressure during relaxation and dilation of ventricles of heart. A total of 3 measurements were performed and average was calculated at each time point in participant's non-dominant arm using appropriate-sized cuff (cuff bladder encircling at least 80% of the arm) after participant stood for 2 minutes. The same arm was used throughout the study. | Pre-Dose and 2 hour Post-Dose on Baseline (Day 1 of Placebo Run-In Phase), Week 1, 2, 3, 4, 6, 8, 10 | 
| Change From Standing to Sitting Systolic Blood Pressure (SBP) at Week 10 | SBP is the BP (pressure exerted by circulating blood on the walls of blood vessels) when heart is contracting; it is the maximum arterial pressure during contraction of left ventricle of heart. A total of 3 measurements were performed and average was calculated at each time point in participant's non-dominant arm using appropriate-sized cuff (cuff bladder encircling at least 80% of the arm). The same arm was used throughout the study. | Pre-Dose and 2 hours Post-Dose on Week 10 | 
| Change From Standing to Sitting Diastolic Blood Pressure (DBP) at Week 10 | DBP is the BP (pressure exerted by circulating blood on the walls of blood vessels) when heart is relaxing; it is the minimum arterial pressure during relaxation and dilation of ventricles of heart. A total of 3 measurements were performed and average was calculated at each time point in participant's non-dominant arm using appropriate-sized cuff (cuff bladder encircling at least 80% of the arm). The same arm was used throughout the study. | Pre-Dose and 2 hours Post-Dose on Week 10 | 
| Change From Pre-Dose to Post-Dose in Systolic Blood Pressure (SBP) at Week 10 | SBP is the BP (pressure exerted by circulating blood on the walls of blood vessels) when heart is contracting; it is the maximum arterial pressure during contraction of left ventricle of heart. A total of 3 measurements were performed and average was calculated at each time point in participant's non-dominant arm using appropriate-sized cuff (cuff bladder encircling at least 80% of the arm). The same arm was used throughout the study. | Pre-Dose and 2 hours Post-Dose on Week 10 | 
| Change From Pre-Dose to Post-Dose in Diastolic Blood Pressure (DBP) at Week 10 | DBP is the BP (pressure exerted by circulating blood on the walls of blood vessels) when heart is relaxing; it is the minimum arterial pressure during relaxation and dilation of ventricles of heart. A total of 3 measurements were performed and average was calculated at each time point in participant's non-dominant arm using appropriate-sized cuff (cuff bladder encircling at least 80% of the arm). The same arm was used throughout the study. | Pre-Dose and 2 hours Post-Dose on Week 10 |