QTc Study of Rosi XR in Healthy Volunteers

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: Rosi XR
* Other: Placebo
* Drug: Moxifloxacin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Group 1 - placebo on Day -1, rosi XR 8mg from Days 1-20, rosi XR 20mg on Day 21 | Drug: Rosi XR<br>* Rosi XR<br>Other: Placebo<br>* Placebo<br>|
| Placebo Comparator: Group 3<br>Placebo on Day -1, Days 1-20 and Day 21 | Other: Placebo<br>* Placebo<br>|
| Active Comparator: Group 2<br>Placebo for Day -1, placebo on Days 1-20 and moxifloxacin active comparator 400 mg on Day 21 | Other: Placebo<br>* Placebo<br>Drug: Moxifloxacin<br>* 400mg single dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Day 20 time-matched change from baseline in QTcI for RSG- XR 8mg and placebo |  | Day 20 | 
| Day 21 time-matched change from baseline in QTcI for RSG- XR 20mg, placebo and moxifloxacin 400mg |  | Day 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Day 20 time-matched change from baseline in QTcF and QTcB for RSG XR 8mg and placebo. |  | Day 20 | 
| Day 21 time-matched change from baseline in QTcF and QTcB for RSG XR 20mg, placebo and moxifloxacin 400mg |  | Day 21 | 
| 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. |  | 21 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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QTc, pharmacokinetics, rosiglitazone XR, cardiac conduction, healthy volunteers