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

Phase 2
Completed
Conditions
Hypertension
Interventions
Drug: placebo
Registration Number
NCT00422461
Lead Sponsor
Pfizer
Brief Summary

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

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
135
Inclusion Criteria
  1. Males and/or Females of non-childbearing potential between 18 and 70 years of age
  2. History of mild to moderate hypertension
Exclusion Criteria
  1. Type 1 or 2 diabetes on prescribed medications
  2. Secondary, severe, or malignant hypertension
  3. History of a significant cardiovascular event within the last 12 months of enrollment

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Placeboplacebo-
PF-00489791 20 mg titrated to 40 mgPF-00489791-
PF-00489791 4 mgPF-00489791-
PF-00489791 10 mgPF-00489791-
Primary Outcome Measures
NameTimeMethod
Change From Baseline in Mean Daytime Systolic Blood Pressure (SBP) as Measured by Ambulatory Blood Pressure Monitoring (ABPM) at Day 28From 08:00 to 16:00 hours on Baseline (Day 0, 1 day prior to first double-blind dose of study drug) and 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.

Secondary Outcome Measures
NameTimeMethod
Change From Baseline in Cuff SBP and DBP at Day 28Baseline (pre dose value on Day 1 of treatment), 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.

Change From Baseline in Mean Daytime Diastolic Blood Pressure (DBP) as Measured by ABPM at Day 28From 08:00 to 16:00 hours on Baseline (Day 0, 1 day prior to first double-blind dose of study drug) and 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.

Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28Over 24 hours on Baseline (Day 0, 1 day prior to first double-blind dose of study drug), 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.

Number of Participants With Clinically Significant Laboratory AbnormalitiesDay 1 up to 14 days after last dose of study drug (maximum up to 42 days)

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.

Change From Baseline in Heart Rate at Baseline, Day 1, 7, 14, 21, 28 and 31Baseline (pre dose value on Day 1 of treatment), Day 1, 7, 14, 21, 28, 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.

Change From Baseline in Mean 24-Hour SBP and DBP as Measured by ABPM at Day 28Over 24 hours on Baseline (Day 0, 1 day prior to first double-blind dose of study drug) and 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.

Change From Baseline in Cuff Mean Arterial Pressure (MAP) at Day 28Baseline (pre dose value on Day 1 of treatment), 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.

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)Day 1 up to 14 days after last dose of study drug (maximum up to 42 days)

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.

Number of Participants With Clinically Significant Electrocardiogram (ECG) FindingsDay 1 up to 14 days after last dose of study drug (maximum up to 42 days)

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.

Change From Baseline in Cuff SBP and DBP at Day 31Baseline (pre dose value on Day 1 of treatment), 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.

Trial Locations

Locations (20)

Orange County Research Center

🇺🇸

Tustin, California, United States

Riser Medical Associates

🇺🇸

Picayune, Mississippi, United States

Piedmont Medical Research Associates

🇺🇸

Winston-Salem, North Carolina, United States

Andres Patron, DO, PA

🇺🇸

Pembroke Pines, Florida, United States

Triangle Medical Research Associates

🇺🇸

Raleigh, North Carolina, United States

Twin Cities Clinical Research

🇺🇸

Brooklyn Center, Minnesota, United States

Volunteer Research Group

🇺🇸

Knoxville, Tennessee, United States

Chase Medical Research, LLC

🇺🇸

Waterbury, Connecticut, United States

National Research Institute

🇺🇸

Los Angeles, California, United States

Apex Research Institute

🇺🇸

Santa Ana, California, United States

Jacksonville Center for Clinical Research

🇺🇸

Jacksonville, Florida, United States

Medical Research Associates of Charlotte, Inc

🇺🇸

Charlotte, North Carolina, United States

Sterling Research Group limited

🇺🇸

Cincinnati, Ohio, United States

Triangle Medical Research Associates, LLC

🇺🇸

Cary, North Carolina, United States

Commonwealth Biomedical Research, LLC

🇺🇸

Madisonville, Kentucky, United States

Midwest Internists Clinical Research, P.C.

🇺🇸

Saint Louis, Missouri, United States

New Orleans Center for Clinical Research

🇺🇸

Knoxville, Tennessee, United States

Triangle Medical Research

🇺🇸

Raleigh, North Carolina, United States

Clinical Research Associates Incorporated

🇺🇸

Nashville, Tennessee, United States

University of Connecticut Health Center

🇺🇸

Farmington, Connecticut, United States

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