QTc Study of Rosi XR in Healthy Volunteers

GlaxoSmithKline (GSK)

Status and phase: Withdrawn; Phase 1

Conditions: Alzheimer's Disease

Treatments: Drug: Rosi XR; Drug: Moxifloxacin; Other: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT00884533

111802

Details and patient eligibility

About

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.

Full 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.

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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0 participants in 3 patient groups, including a placebo group

Group 1

Experimental group

Description:

Group 1 - placebo on Day -1, rosi XR 8mg from Days 1-20, rosi XR 20mg on Day 21

Treatment:

Drug: Rosi XR

Other: Placebo

Group 3

Placebo Comparator group

Description:

Placebo on Day -1, Days 1-20 and Day 21

Treatment:

Other: Placebo

Group 2

Active Comparator group

Description:

Placebo for Day -1, placebo on Days 1-20 and moxifloxacin active comparator 400 mg on Day 21

Treatment:

Drug: Moxifloxacin

Other: Placebo