QTc Study of Rosi XR in Healthy Volunteers

This study has been withdrawn prior to enrollment.
(The whole project was terminated)
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00884533
First received: April 16, 2009
Last updated: May 14, 2009
Last verified: May 2009
  Purpose

This study is a randomised double blind, parallel group, and will evaluate the effects of repeat oral doses of RSG- XR for 21 days on the QTc interval compared to placebo in a population of healthy adult males and females.


Condition Intervention Phase
Alzheimer's Disease
Drug: Rosi XR
Other: Placebo
Drug: Moxifloxacin
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Study to Evaluate the Effect of Extended Release Rosiglitazone (RSG XR) on Cardiac Conduction as Compared to Placebo and a Single Oral Dose of Moxifloxacin

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Day 20 time-matched change from baseline in QTcI for RSG- XR 8mg and placebo [ Time Frame: Day 20 ] [ Designated as safety issue: Yes ]
  • Day 21 time-matched change from baseline in QTcI for RSG- XR 20mg, placebo and moxifloxacin 400mg [ Time Frame: Day 21 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Day 20 time-matched change from baseline in QTcF and QTcB for RSG XR 8mg and placebo. [ Time Frame: Day 20 ] [ Designated as safety issue: Yes ]
  • Day 21 time-matched change from baseline in QTcF and QTcB for RSG XR 20mg, placebo and moxifloxacin 400mg [ Time Frame: Day 21 ] [ Designated as safety issue: Yes ]
  • Tolerability of repeat doses of RSG- XR at 8 mg and a single oral dose of RSG- XR at 20 mg as assessed by 12-lead ECGs, vital signs, adverse events, and clinical laboratory tests. [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 216
Study Start Date: June 2009
Estimated Study Completion Date: August 2009
Estimated Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1
Group 1 - placebo on Day -1, rosi XR 8mg from Days 1-20, rosi XR 20mg on Day 21
Drug: Rosi XR
Rosi XR
Other: Placebo
Placebo
Placebo Comparator: Group 3
Placebo on Day -1, Days 1-20 and Day 21
Other: Placebo
Placebo
Active Comparator: Group 2
Placebo for Day -1, placebo on Days 1-20 and moxifloxacin active comparator 400 mg on Day 21
Other: Placebo
Placebo
Drug: Moxifloxacin
400mg single dose

Detailed Description:

An extended release (XR) formulation of rosiglitazone maleate (RSG), a new formulation of rosiglitazone, is being investigated as a treatment for patients with mild to moderate Alzheimer's disease (AD).

This study is a randomised double blind, parallel group, and will evaluate the effects of repeat oral doses of RSG- XR for 21 days (due to the long half-life of the main metabolite M10) on the QTc interval compared to placebo in a population of healthy adult males and females between 18 and 45 years of age. Moxifloxacin, a drug with well-quantified QTc prolongation, will be included as a positive control in order to validate the ability of the study to detect small changes in QTc.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy male and female volunteers aged between 18 and 45
  • Female of non child bearing potential or if of child bearing potential they must use adequate contraception for the duration of the study up until 14 days after the last dose
  • Body weight greater than or equal to 45 kg and BMI within the range 19 - 32 inclusive
  • Subjects must provide full written informed consent

Exclusion Criteria:

  • Cardiac conduction abnormalities
  • Any history of myocardial infarction, syncope, or cardiac arrhythmias or a history of uncontrolled hypertension or unstable heart disease
  • Subjects with a systolic blood pressure outside the range of 90 to 150 mmHg or diastolic blood pressure outside the range of 50 to 100 mmHg
  • Subjects with a personal or family history of QTc prolongation or unexplained cardiac arrest.
  • Has a history of illicit drug use or alcohol abuse within the past year or a positive pre-study test for alcohol, cotinine, or drugs of abuse at Screening or prior to the start of dosing
  • Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase values greater than 2.5 times the ULN, total bilirubin values >1.5 times the upper limit of normal (ULN), or history of severe hepatobiliary disease (e.g. hepatitis B or C, or cirrhosis, Child-Pugh Class B/C)
  • A positive test at Screening for Hepatitis B, Hepatitis C, or Human Immunodeficiency Virus (HIV)
  • Use of any agents that are known to inhibit or induce cytochrome CYP3A4 enzymes within 7 days prior to the first dose of study drug (including foods or supplements such as grapefruit-containing products, mustard greens, kale, kohlrabi, broccoli, collard greens, brussel sprouts, watercress, charbroiled meats or St. John's Wort
  • Use of any prescription or non-prescription drugs, in particular drugs known to inhibit or induce CYP2C8, vitamins (exceptions may be considered on a case-by-case basis with the GSK medical monitor), herbal and dietary supplements within fourteen days prior to the first dose of study drug
  • Lactating or pregnant females
  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: NCT00884533

Locations
United States, Kansas
GSK Investigational Site
Overland Park, Kansas, United States, 66211
United Kingdom
GSK Investigational Site
London, United Kingdom, SE1 1YR
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: Study Director, GSK
ClinicalTrials.gov Identifier: NCT00884533     History of Changes
Other Study ID Numbers: 111802
Study First Received: April 16, 2009
Last Updated: May 14, 2009
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by GlaxoSmithKline:
QTc
pharmacokinetics
rosiglitazone XR
cardiac conduction
healthy volunteers

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Rosiglitazone
Moxifloxacin
Norgestimate, ethinyl estradiol drug combination
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Contraceptives, Oral, Combined
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents

ClinicalTrials.gov processed this record on August 26, 2014