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

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)

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

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: placebo; Drug: PF-00489791; Drug: PF-00489791; Drug: PF-00489791

• Study Type: Interventional
• Enrollment (Actual): 135
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90057
      • National Research Institute
    • Santa Ana, California, United States, 92705
      • Apex Research Institute
    • Tustin, California, United States, 92780
      • Orange County Research Center
  • Connecticut
    • Farmington, Connecticut, United States, 06030-3940
      • University of Connecticut Health Center
    • Waterbury, Connecticut, United States, 06708
      • Chase Medical Research, LLC
  • Florida
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research
    • Pembroke Pines, Florida, United States, 33026
      • Andres Patron, DO, PA
  • Kentucky
    • Madisonville, Kentucky, United States, 42431
      • Commonwealth Biomedical Research, LLC
  • Minnesota
    • Brooklyn Center, Minnesota, United States, 55430
      • Twin Cities Clinical Research
  • Mississippi
    • Picayune, Mississippi, United States, 39466
      • Riser Medical Associates
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Midwest Internists Clinical Research, P.C.
  • North Carolina
    • Cary, North Carolina, United States, 27518
      • Triangle Medical Research Associates, LLC
    • Charlotte, North Carolina, United States, 28277
      • Medical Research Associates of Charlotte, Inc
    • Raleigh, North Carolina, United States, 27609
      • Triangle Medical Research Associates
    • Raleigh, North Carolina, United States, 27609
      • Triangle Medical Research
    • Winston-Salem, North Carolina, United States, 27103
      • Piedmont Medical Research Associates
  • Ohio
    • Cincinnati, Ohio, United States, 45246
      • Sterling Research Group limited
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • New Orleans Center for Clinical Research
    • Knoxville, Tennessee, United States, 37920
      • Volunteer Research Group
    • Nashville, Tennessee, United States, 37203
      • Clinical Research Associates Incorporated

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2007
• Primary Completion (Actual): January 28, 2008
• Study Completion (Actual): January 28, 2008

Study Registration Dates

• First Submitted: January 12, 2007
• First Submitted That Met QC Criteria: January 12, 2007
• First Posted (Estimate): January 17, 2007

Study Record Updates

• Last Update Posted (Actual): October 11, 2021
• Last Update Submitted That Met QC Criteria: September 13, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Humans; Randomized Controlled Trial; Clinical Trial; Cyclic Nucleotide Phosphodiesterases Type 5
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: A7331007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.