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A Study Investigating the Bioequivalence of the Fixed Dose Combination of COREG CR to COREG CR and ZESTRIL.

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00552708
First received: October 31, 2007
Last updated: October 13, 2010
Last verified: October 2010
  Purpose

This study will be a randomized study investigating the bioequivalence of COREG CR to its components, COREG and Lisinopril (ZESTRIL). PK samples will be obtained throughout the study to investigate the PK of COREG CR FDC to COREG and Lisinopril


Condition Intervention Phase
Hypertension
Drug: COREG CR
Drug: Lisinopril
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Randomized, Open-label, Single-dose, Crossover Study to Demonstrate the Bioequivalence of the Final Fixed Dose Combination (FDC) Formulation (COREG CR & Lisinopril) to COREG CR & ZESTRIL Employed in the Phase III Factorial Study

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • To establish bioequivalence of the final FDC product (80 mg carvedilol CR/10 mg lisinopril) relative to concomitant dosing of COREG CR (80 mg) and ZESTRIL (10 mg, over encapsulated)throughout the study [ Time Frame: throughout the study ]

Secondary Outcome Measures:
  • To further evaluate the pharmacokinetic profile of the final FDC product. To evaluate the safety and tolerability of single doses of the fixed dose combination at the highest dose strengths of each component throughout the study [ Time Frame: throughout the study ]
  • plasma levels of carvedilol to determine pharmacokinetic parameters.
  • plasma levels of lisinopril determine pharmacokinetic parameters.

Enrollment: 55
Study Start Date: September 2007
Study Completion Date: December 2007
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: COREG CR Drug: Lisinopril
    Other Names:
    • COREG CR
    • Lisinopril
  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Adult males and females of non-child bearing potential who are between 18 to 55 years of age, inclusively
  • Body weight > 60 kg (132 lbs) and body mass index (BMI) between 19 and 33

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.
  • Subjects who metabolize carvedilol poorly based on CYP2D6 genotyping as determined at screening.
  • Treatment with any prescription or non-prescription drugs (including vitamins, herbal and dietary supplements, as well as grapefruit-containing products) within 7 days or 5 half-lives prior to first dose of study medication and until the end of the study. Treatment with any prescription drugs that are CYP2D6 inhibitors within 14 days prior to the first dose of study medication until the end of the study. Excluded from this list is acetaminophen at doses of ≤ 2 grams/day.
  • Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding Day 1 of Session 1.
  • Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
  • 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.
  • Positive urine drug screen (UDS) including alcohol at screening. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
  • Urine Na/creatinine ratio < 0.1 meq/mg.
  • Positive for Hepatitis B surface antigen or HIV.
  • Women of child-bearing potential.
  • Resting heart rate of ≤ 50 beats per minute (bpm) at screening.
  • Any abnormalities as defined in the protocol on 12-lead ECG during screening
  • Documented history of low blood pressure (average SBP ≤ 110 mm Hg and/or DBP ≤50 mm Hg) or blood pressure below these values at time of screening.
  • Orthostatic hypotension diagnosed at screening (orthostatic hypotension will be 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.
  • Donation of blood in excess of 500 mL within a 56 day period, including ~478 mL of blood drawn during this study.
  • History of asthma, COPD and/or hypersensitivity to β-adrenergic blocking agents.
  • History of sensitivity to heparin, heparin- induced thrombocytopenia, or sensitivity to any of the study medications or components thereof.
  • History of anaphylaxis or anaphylactoid reactions or severe allergic responses to drugs.
  • History of angioedema.
  • Unwillingness or inability to follow the procedures outlined in the protocol or inability to provide written informed consent.
  • History of sensitivity to carvedilol, lisinopril, alpha-blockers, beta-blockers or ACE inhibitors.
  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 ClinicalTrials.gov identifier: NCT00552708

Locations
United States, Washington
GSK Investigational Site
Tacoma, Washington, United States, 98418
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials, MD GlaxoSmithKline
  More Information

No publications provided

Responsible Party: Study Director, GSK
ClinicalTrials.gov Identifier: NCT00552708     History of Changes
Other Study ID Numbers: CFD108412
Study First Received: October 31, 2007
Last Updated: October 13, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
COREG CR

Additional relevant MeSH terms:
Hypertension
Cardiovascular Diseases
Vascular Diseases
Carvedilol
Lisinopril
Adrenergic Agents
Adrenergic Antagonists
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists
Adrenergic beta-Antagonists
Angiotensin-Converting Enzyme Inhibitors
Antihypertensive Agents
Cardiotonic Agents
Cardiovascular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protease Inhibitors
Protective Agents
Therapeutic Uses
Vasodilator Agents

ClinicalTrials.gov processed this record on November 20, 2014