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Evaluation of Potential for Orthostatic Hypotension in Elderly Hypertensives

This study has been completed.
Information provided by:
GlaxoSmithKline Identifier:
First received: July 26, 2007
Last updated: October 14, 2010
Last verified: October 2010
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.

Condition Intervention Phase
Drug: carvedilol CR + lisinopril
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Study to Evaluate the Potential Incidence of Orthostatic Hypotension in Elderly Hypertensive Patients Following Administration of a Combination of Carvedilol CR and Lisinopril

Resource links provided by NLM:

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Assessment of orthostasis 6 hours post dose on day 1, 7, 8, 14 in each dosing session [ Time Frame: 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

Secondary Outcome Measures:
  • Relationship of concentration of drug to events 6 hours post dose on day 1, 7, 8, 14 in each dosing session
  • Relationship of concentration of drug to events [ Time Frame: 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
  • 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
  • To evaluate the effects of COREG CR on plasma renin activity

Enrollment: 40
Study Start Date: September 2007
Study Completion Date: June 2008
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)

Ages Eligible for Study:   65 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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
    • all antidepressants including SSRIs
    • lithium
    • medications known to be inhibitors/inducers of cytochrome P-450 2D6 should be discontinued for at least 14 days or 5 half-lives [which ever is longer] prior to the first day of the run-in period
  • Treatment with any over-the-counter medications , herbal and dietary supplements, as well as grapefruit-containing products within 7 days or 5 half-lives (whichever is longer) prior to first day of run-in period through the end of the study unless approved by the PI and GSK medical monitor. Standard vitamins and/or daily multi-vitamins are permitted, however herbal vitamins should be excluded.
  • Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the run-in period
  • Subject has mean sitting SBP ≥ 180 mmHg at the screening assessment (one set of repeat measurement is permitted as per approval by the medical monitor).
  • Documented history of low blood pressure within six months of screening visit (average sitting SBP < 110 mm Hg and/or DBP /< 50 mm Hg) or blood pressure below these values at time of screening (one set of repeat measurement is permitted as per approval by the medical monitor).
  • Orthostatic hypotension diagnosed at screening (orthostatic hypotension is defined as a reduction in systolic blood pressure of 20 mmHg or more and/or a reduction in diastolic blood pressure of 10 mmHg or more for standing vs. supine measurements)
  • Subject has any of the following conditions:

    • uncontrollable or symptomatic arrhythmias; unstable angina
    • sick sinus syndrome or second or third degree heart block (unless treated with a permanent, functioning pacemaker)
    • bradycardia (seated heart rate <55 bpm) (one repeat measurement is permitted as per approval by the medical monitor) ; history of myocardial infarction, or history of stroke within 1 year of screening.
    • subject is in, or has a history of atrial fibrillation
  • Any of the following abnormalities on 12-lead ECG during screening:

    • complete RBBB or LBBB
    • evidence of second- or third-degree AV block
    • pathological Q-waves (Q-wave wider than 0.04 sec or depth greater than 0.4-0.5 mV)
    • any other abnormalities that investigator feels could be of concern when patient is taking a β-adrenergic blocking agent
  • Donation of blood in excess of 500 mL within a 56-day period including the estimated 150 mL of blood to be drawn during this study
  • History of asthma, COPD and/or hypersensitivity to β -adrenergic blocking agents
  • History of sensitivity to carvedilol, lisinopril, alpha-blockers, beta-blockers or ACE inhibitors
  • History of sensitivity to any of the study medications or components thereof
  • History of anaphylaxis or anaphylactoid reactions or severe allergic responses to drugs
  • History of regular alcohol consumption exceeding 7 drinks/week for women or 14 drinks/week for men (1 drink = 5 ounces of wine or 12 ounces of beer or 1.5 ounces of hard liquor) within 6 months of screening
  • Unanticipated positive urine drug screen (UDS) at screening. Note: If the subject is taking a drug known to give a positive on the UDS, then this should be discussed with the medical monitor prior to sending the UDS. In this situation, with prior approval, a positive finding on the UDS will not be considered an exclusion
  • Positive for Hepatitis B surface antigen or HIV
  • Unwillingness or inability to follow the procedures outlined in the protocol or inability to provide written informed consent
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00508365

United States, Alabama
GSK Investigational Site
Anniston, Alabama, United States, 36207
United States, Arizona
GSK Investigational Site
Glendale, Arizona, United States, 85308
United States, California
GSK Investigational Site
Anaheim, California, United States, 92801
GSK Investigational Site
Long Beach, California, United States, 90806
United States, Florida
GSK Investigational Site
Coral Gables, Florida, United States, 33134
GSK Investigational Site
Miami, Florida, United States, 33169
GSK Investigational Site
Sarasota, Florida, United States, 34239
GSK Investigational Site
West Palm Beach, Florida, United States, 33409
United States, Idaho
GSK Investigational Site
Boise, Idaho, United States, 83704
United States, Indiana
GSK Investigational Site
Indianapolis, Indiana, United States, 46260
United States, Nevada
GSK Investigational Site
Las Vegas, Nevada, United States, 89119
United States, New Jersey
GSK Investigational Site
Hackensack, New Jersey, United States, 07601
United States, North Dakota
GSK Investigational Site
Fargo, North Dakota, United States, 58103
United States, Ohio
GSK Investigational Site
Cleveland, Ohio, United States, 44122
United States, Oklahoma
GSK Investigational Site
Oklahoma City, Oklahoma, United States, 73132
United States, Oregon
GSK Investigational Site
Portland, Oregon, United States, 97239
United States, Texas
GSK Investigational Site
Austin, Texas, United States, 78704
GSK Investigational Site
Houston, Texas, United States, 77081
GSK Investigational Site
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Study Director: GSK Clinical Trials, MD GlaxoSmithKline
  More Information

Responsible Party: Study Director, GSK Identifier: NCT00508365     History of Changes
Other Study ID Numbers: CFD109701 
Study First Received: July 26, 2007
Last Updated: October 14, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:

Additional relevant MeSH terms:
Hypotension, Orthostatic
Orthostatic Intolerance
Vascular Diseases
Cardiovascular Diseases
Primary Dysautonomias
Autonomic Nervous System Diseases
Nervous System Diseases
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Antihypertensive Agents
Vasodilator Agents
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Cardiotonic Agents
Protective Agents processed this record on October 21, 2016