A Dose Finding Study Of PF-00489791 In Patients With Mild To Moderate High Blood Pressure

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and blood pressure lowering effect of different doses of PF-00489791 in patients with mild to moderate high blood pressure

Official Title
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A PHASE 2, RANDOMIZED, PLACEBO-CONTROLLED, DOSE-RANGING STUDY OF PF-00489791 IN SUBJECTS WITH STAGE 1 AND 2 ESSENTIAL HYPERTENSION USING AMBULATORY BLOOD PRESSURE MONITORING (ABPM)

Conditions
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Hypertension

Intervention / Treatment
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* Drug: placebo
* Drug: PF-00489791
* Drug: PF-00489791
* Drug: PF-00489791


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and/or Females of non-childbearing potential between 18 and 70 years of age History of mild to moderate hypertension Exclusion Criteria: Type 1 or 2 diabetes on prescribed medications Secondary, severe, or malignant hypertension History of a significant cardiovascular event within the last 12 months of enrollment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: placebo<br>* placebo, oral, tablets, once daily, for 28 days<br>|
| Experimental: PF-00489791 20 mg titrated to 40 mg<br> | Drug: PF-00489791<br>* PF-00489791 20 mg titrated to 40 mg, oral, tablets, once daily, for 28 days<br>|
| Experimental: PF-00489791 4 mg<br> | Drug: PF-00489791<br>* PF-00489791 4 mg, oral, tablets, once daily, for 28 days<br>|
| Experimental: PF-00489791 10 mg<br> | Drug: PF-00489791<br>* PF-00489791 10 mg, oral, tablets, once daily, for 28 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean Daytime Systolic Blood Pressure (SBP) as Measured by Ambulatory Blood Pressure Monitoring (ABPM) at Day 28 | The ABPM device was automatically programmed to inflate at every 20 minutes from 05:00 until 21:59 hours and from 22:00 to 04:59 hours the device inflated every 60 minutes. 24-hour clock time was used. ABPM was performed in this study on Baseline, Day 1, 14 and 28. Mean daytime SBP was an average of SBP measurements taken between 08:00 and 16:00 hours by ABPM device on the specified time points. In this outcome measure change from baseline in mean daytime SBP at Day 28 is reported. | From 08:00 to 16:00 hours on Baseline (Day 0, 1 day prior to first double-blind dose of study drug) and Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean Daytime Diastolic Blood Pressure (DBP) as Measured by ABPM at Day 28 | The ABPM device was automatically programmed to inflate at every 20 minutes from 05:00 until 21:59 hours and from 22:00 to 04:59 hours the device inflated every 60 minutes. 24-hour clock time was used. ABPM was performed in this study on Baseline, Day 1, 14 and 28. Mean daytime DBP was an average of DBP measurements taken between 08:00 and 16:00 hours by ABPM device on the specified time points. In this outcome measure change from baseline in mean daytime DBP at Day 28 is reported. | From 08:00 to 16:00 hours on Baseline (Day 0, 1 day prior to first double-blind dose of study drug) and Day 28 | 
| Change From Baseline in Mean 24-Hour SBP and DBP as Measured by ABPM at Day 28 | The ABPM device was automatically programmed to inflate at every 20 minutes from 05:00 until 21:59 hours and from 22:00 to 04:59 hours the device inflated every 60 minutes. 24-hour clock time was used. ABPM was performed in this study on Baseline, Day 1, 14 and 28. Mean 24-hour SBP and DBP was an average of SBP and DBP measurements, respectively, taken for 24 hours by ABPM device respectively. In this outcome measure change from baseline in mean 24-hour SBP and DBP at Day 28 is reported. | Over 24 hours on Baseline (Day 0, 1 day prior to first double-blind dose of study drug) and Day 28 | 
| Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | The ABPM device was automatically programmed to inflate at every 20 minutes from 05:00 until 21:59 hours and from 22:00 to 04:59 hours the device inflated every 60 minutes. 24-hour clock time was used. ABPM was performed on Baseline, Day 1, 14 and 28. In this outcome measure maximum and minimum SBP and DBP values recorded by ABPM device over 24 hours on Baseline, Day 1, 14 and 28 are reported. | Over 24 hours on Baseline (Day 0, 1 day prior to first double-blind dose of study drug), Day 1, 14 and 28 | 
| Change From Baseline in Cuff SBP and DBP at Day 28 | At Baseline and Day 28 visit, sitting cuff SBP and DBP was measured with the participant's arm supported at the level of the heart. The participant sat with feet flat on the floor for 5 minutes before the first BP was obtained. The BP measurement was done in duplicate approximately 5 minutes apart. The mean of duplicate measurements was recorded. | Baseline (pre dose value on Day 1 of treatment), Day 28 | 
| Change From Baseline in Cuff SBP and DBP at Day 31 | At Baseline and Day 31 visit, sitting cuff SBP and DBP was measured with the participant's arm supported at the level of the heart. The participant sat with feet flat on the floor for 5 minutes before the first BP was obtained. The BP measurement was done in duplicate approximately 5 minutes apart. The mean of duplicate measurements was recorded. | Baseline (pre dose value on Day 1 of treatment), Day 31 | 
| Change From Baseline in Cuff Mean Arterial Pressure (MAP) at Day 28 | At Baseline and Day 28, sitting cuff MAP was measured with the participant's arm supported at the level of the heart. The participant sat with feet flat on the floor for 5 minutes before the first MAP was obtained. The MAP measurement was done in duplicate approximately 5 minutes apart. The mean of duplicate measurements was recorded. | Baseline (pre dose value on Day 1 of treatment), Day 28 | 
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs are events between first dose of study drug and up to 14 days after last dose that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and all non-SAEs. | Day 1 up to 14 days after last dose of study drug (maximum up to 42 days) | 
| Number of Participants With Clinically Significant Laboratory Abnormalities | Criteria for laboratory abnormalities included: hemoglobin, hematocrit, red blood cell count, total neutrophils, total protein, albumin: <0.8* limit of normal (LLN). Platelets: less than (<)0.5* LLN, greater than (>)1.75* upper limit of normal (ULN); white blood cell, glucose: <0.6*LLN, >1.5*ULN, lymphocytes: <0.8*LLN; >1.2*ULN; basophils, monocytes, eosinophils, total protein, albumin, uric acid: >1.2*ULN; aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase: >3.0*ULN; blood urea nitrogen, creatinine: >1.3*ULN; sodium: <0.95*LLN, >1.05*ULN; potassium, chloride, calcium: <0.9*LLN, >1.1*ULN; creatine kinase: > 2.0*ULN, > 3.0*ULN, >10.0*ULN; total bilirubin, direct bilirubin, indirect bilirubin:>1.5*ULN; urinalysis: urine pH: <4.5, >8, glucose, ketones, protein, blood/hemoglobin: >=1, RBC, WBC, epithelial cells: >=6, casts: >1, bacteria: >20. | Day 1 up to 14 days after last dose of study drug (maximum up to 42 days) | 
| Change From Baseline in Heart Rate at Baseline, Day 1, 7, 14, 21, 28 and 31 | Sitting heart rate was measured with the participant's arm supported at the level of the heart. The participant sat with feet flat on the floor for 5 minutes before the heart rate was measured. The heart rate was measured for a minimum of 30 seconds, and the average of two measurements was recorded. Heart rate was measured in beats per minute. | Baseline (pre dose value on Day 1 of treatment), Day 1, 7, 14, 21, 28, 31 | 
| Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings | Following ECG parameters were evaluated: QT interval, QTc interval, RR interval, PR interval, QRS complex and heart rate. Clinical significant ECG findings were determined by the investigator's discretion. | Day 1 up to 14 days after last dose of study drug (maximum up to 42 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Clinical Trial, Randomized Controlled Trial, Humans, Cyclic Nucleotide Phosphodiesterases Type 5