Study to Investigate Dose Proportionality of the Fixed Dose Combination of COREG CR and Lisinopril. - Full Text View

Sponsor:	GlaxoSmithKline
Information provided by:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT00549510

Purpose

This will be an open-label, single-dose, non-randomized, five-period crossover study in healthy volunteers. The duration of the study will last up to eleven weeks from screening to follow-up. PK samples will be taken.

Condition	Intervention	Phase
Hypertension	Drug: COREG CR and lisinopril (FDC)	Phase I

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Crossover Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Non-randomized, Open-label, Single-dose, Crossover Study to Evaluate the Dose Proportionality of the Final Fixed Dose Combination Formulation of COREG CR™ and Lisinopril.

Resource links provided by NLM:

MedlinePlus related topics: High Blood Pressure

Drug Information available for: Carvedilol Lisinopril

U.S. FDA Resources

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:

Assessment of dose proportionality by comparison of PK parameters across dosing range Blood sampling over up to a 120 hour period post dose in all dosing sessions

Secondary Outcome Measures:

Characterization of PK, safety and tolerability Safety and tolerability will be assessed by clinical data from spontaneous Adverse Event reporting, nurse/physician observations, vital sign assessment, ECGs, and clinical laboratory tests
The pharmacokinetic parameters to be evaluated are the Tmax and t1/2 of carvedilol [R(+) and S(-)enantiomers] and Tmax and t1/2 of lisinopril

Enrollment:	29
Study Start Date:	October 2007
Study Completion Date:	December 2007
Primary Completion Date:	December 2007 (Final data collection date for primary outcome measure)

Intervention Details:

Other Name: COREG CR and lisinopril (FDC)

Eligibility

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

Criteria

Inclusion criteria:

Healthy volunteer 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 (whichever is longer) prior to first dose of study medication and until the end of the study. Treatment with any CYP2D6 inhibitors such as but not limited to quinidine, fluoxetine, paroxetine, duloxetine, and terbinofine at least 14 days or 5 half-lives (whichever is longer) prior to Day 1 of Session 1 and until the end of the study.
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.
Abnormalities 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 the estimated 550 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 heparin, heparin-induced thrombocytopenia, or sensitivity to any of the study medications or components thereof.
History of anaphylaxis or anaphalactoid reactions or severe allergic responses to drugs.
History of angioedema.
History of sensitivity to carvedilol, lisinopril, alpha-blockers, beta-blockers or ACE inhibitors
Unwillingness or inability to follow the procedures outlined in the protocol or inability to provide written informed consent.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00549510

Locations

United States, Texas
GSK Investigational Site
Austin, Texas, United States, 78744

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:	NCT00549510 History of Changes
Other Study ID Numbers:	CFD108407
Study First Received:	October 23, 2007
Last Updated:	October 13, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:

COREG CR,
lisinopril,
hypertension,
dose proportionality,
fixed dose combination (FDC)

Additional relevant MeSH terms:

Hypertension
Vascular Diseases
Cardiovascular Diseases
Carvedilol
Lisinopril
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Vasodilator Agents
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Cardiotonic Agents
Protective Agents

ClinicalTrials.gov processed this record on February 09, 2012