Evaluation of Potential for Orthostatic Hypotension in Elderly Hypertensives
A Study to Evaluate the Potential Incidence of Orthostatic Hypotension in Elderly Hypertensive Patients Following Administration of a Combination of COREG CR and Lisinopril
1 other identifier
interventional
62
1 country
20
Brief Summary
This is a multi-center, double-blind, randomized, placebo-controlled, 2-session crossover study to evaluate the incidence of orthostatic hypotension in elderly hypertensive subjects following co-administration of carvedilol CR and lisinopril.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1 hypertension
Started Sep 2007
Typical duration for phase_1 hypertension
20 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 26, 2007
CompletedFirst Posted
Study publicly available on registry
July 30, 2007
CompletedStudy Start
First participant enrolled
September 25, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 3, 2008
CompletedStudy Completion
Last participant's last visit for all outcomes
June 3, 2008
CompletedAugust 9, 2017
August 1, 2017
8 months
July 26, 2007
August 8, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Assessment of orthostasis 6 hours post dose on day 1, 7, 8, 14 in each dosing session
6 hours post dose on day 1, 7, 8, 14 in each dosing session
To evaluate the incidence of orthostatic hypotension (defined as a decrease in SBP of ≥20 mmHg and/or a decrease in DBP of ≥10 mmHg in changing from the supine to the standing position) following co-administration of COREG CR and lisinopril
Up to Day 14
Secondary Outcomes (5)
Relationship of concentration of drug to events 6 hours post dose on day 1, 7, 8, 14 in each dosing session
6 hours post dose on day 1, 7, 8, 14 in each dosing session
Relationship of concentration of drug to events
6 hours post dose on day 1, 7, 8, 14 in each dosing session
To evaluate the safety and tolerability of the co-administration of COREG CR and lisinopril
Up to Day 24
To evaluate the relationship between the plasma concentrations of carvedilol and lisinopril and the occurrence of orthostatic hypotension following co-administration of COREG CR and lisinopril
6 hours post dose on day 1, 7, 8, 14 in each dosing session
To evaluate the effects of COREG CR on plasma renin activity
Up to Day 14
Study Arms (2)
Subjects receiving treatment sequence AB
EXPERIMENTALEligible subjects will receive treatment sequence AB; A= Placebo to match COREG CR 20 milligrams once daily plus lisinopril 10 milligrams once daily (Days 1-7). Placebo to match COREG CR 40 milligrams once daily plus lisinopril 10 milligrams once daily (Days 8-14). B=COREG CR 20 milligrams once daily plus lisinopril 10 milligrams once daily (Days 1-7). COREG CR 40 milligrams once daily plus lisinopril 10 milligrams once daily (Days 8-14).
Subjects receiving treatment sequence BA
EXPERIMENTALEligible subjects will receive treatment sequence BA; B=COREG CR 20 milligrams once daily plus lisinopril 10 milligrams once daily (Days 1-7). COREG CR 40 milligrams once daily plus lisinopril 10 milligrams once daily (Days 8-14). A= Placebo to match COREG CR 20 milligrams once daily plus lisinopril 10 milligrams once daily (Days 1-7). Placebo to match COREG CR 40 milligrams once daily plus lisinopril 10 milligrams once daily (Days 8-14).
Interventions
The carvedilol micropump (COREG) CR cpsules will be available with doses of 20 milligrams and 40 milligrams administered orally once daily.
Placebo capsules to match each dose level will be provided.
Lisinopril will be available as 10 milligrams tablets administered orally once daily.
Eligibility Criteria
You may qualify if:
- Males or females who are ≥ 65 years of age
- Body mass index (BMI) between 24 and 37 kg/m2 where: BMI = (weight in kg)/ (height in meters)2
- Subjects must have a documented history of essential hypertension and must be stable on treatment with an ACE inhibitor or angiotensin II receptor antagonist or renin antagonist and no more than one other antihypertensive medication at least 3 months before screening with a sitting SBP\<180 mmHg and DBP\<110 mmHg.
- All subjects must be able to be safely (in the opinion of the Investigator) withdrawn or down-titrated from all antihypertensive treatment(s) and transitioned to lisinopril 10 mg OD for the two-week run-in phase.
You may not qualify if:
- Any clinically relevant abnormality identified on the screening history, physical or laboratory examination, or any other medical condition or circumstance making the volunteer unsuitable for participation in the study
- Subject who metabolizes carvedilol poorly based on CYP2D6 genotype as determined at screening
- Subject has persistent hyperkalemia or history of hyperkalemia resulting from either Type IV RTA (renal tubular acidosis) or previous treatment with an ACE inhibitor, ARB or renin inhibitor.
- Subject has malignant (accelerated) hypertension, history of malignant hypertension, or history of secondary forms of hypertension
- Subject has advanced hypertensive retinopathy (Keith Wagner Grade IV)
- Subject has a history of hepatic impairment (characterized by prolonged prothrombin time/low concentrations of albumin) and/or renal insufficiency (subjects with an estimated CrCl ≤ 30 mL/min by Cockroft-Gault must be excluded). CrCL = \[140-ageCr\]\[weight/70\] x 0.85 (if female); Cr in mg/dL; Weight in kg
- Subject is being treated for diabetes mellitus
- Subject has a history of angioedema
- Subject has been under treatment with 3 or more antihypertensive medications. (NOTE: A combination drug containing two antihypertensive agents represents two antihypertensive medications.)
- Subject has been under treatment with HCTZ \> 12.5 mg/day
- Subject is receiving ongoing treatment or is anticipated to receive treatment with any of the following medications during the study:
- monoamine oxidase inhibitors (MAO)
- any Class I or III antiarrhythmic
- alpha-adrenergic receptor blockers
- beta-2-adrenergic agonists
- +26 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- GlaxoSmithKlinelead
Study Sites (20)
GSK Investigational Site
Anniston, Alabama, 36207, United States
GSK Investigational Site
Glendale, Arizona, 85308, United States
GSK Investigational Site
Anaheim, California, 92801, United States
GSK Investigational Site
Beverly Hills, California, 90211, United States
GSK Investigational Site
Long Beach, California, 90806, United States
GSK Investigational Site
Coral Gables, Florida, 33134, United States
GSK Investigational Site
Miami, Florida, 33169, United States
GSK Investigational Site
Sarasota, Florida, 34239, United States
GSK Investigational Site
West Palm Beach, Florida, 33409, United States
GSK Investigational Site
Boise, Idaho, 83704, United States
GSK Investigational Site
Indianapolis, Indiana, 46260, United States
GSK Investigational Site
Las Vegas, Nevada, 89119, United States
GSK Investigational Site
Hackensack, New Jersey, 07601, United States
GSK Investigational Site
Fargo, North Dakota, 58103, United States
GSK Investigational Site
Cleveland, Ohio, 44122, United States
GSK Investigational Site
Oklahoma City, Oklahoma, 73132, United States
GSK Investigational Site
Portland, Oregon, 97239, United States
GSK Investigational Site
Austin, Texas, 78704, United States
GSK Investigational Site
Houston, Texas, 77081, United States
GSK Investigational Site
San Antonio, Texas, 78229, United States
Related Publications (1)
GSK has submitted manuscripts of these study results to peer-reviewed scientific journals which were not accepted for publication. GSK is providing the attached study results summary with a conclusion.
BACKGROUND
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
GSK Clinical Trials
GlaxoSmithKline
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Purpose
- TREATMENT
- Intervention Model
- CROSSOVER
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 26, 2007
First Posted
July 30, 2007
Study Start
September 25, 2007
Primary Completion
June 3, 2008
Study Completion
June 3, 2008
Last Updated
August 9, 2017
Record last verified: 2017-08
Data Sharing
- IPD Sharing
- Will share
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.