Assessment of the Effect of BI 201335 on the QT Interval in Healthy Female and Male Subjects

Study Overview
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Brief Summary
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To demonstrate that BI 201335 does not prolong the QT interval more than placebo. To assess the tolerability of 1200 mg of BI 201335 as single dose in female subjects (double-blind, randomised, placebo-controlled) before inclusion of female subjects in the cross-over part of the trial.

Official Title
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Assessment of the Effect of 480 mg and 1200 mg of BI 201335 as Single Dose on the QT Interval in Healthy Female and Male Subjects. A Randomised, Placebo Controlled, Double-blind, Four-way Crossover Phase-I-study With Moxifloxacin as Positive Control

Conditions
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Healthy

Intervention / Treatment
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* Drug: BI 201335 low dose
* Drug: BI 201335 placebo
* Drug: Moxifloxacin
* Drug: BI 201335 high dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy caucasian males and females, 18 to 50 years of age Body mass index (BMI) ranging from 18.5 to 29.9 kg/m2 (BMI calculation: weight in kilograms divided by the square of height in meters) Signed written informed consent prior to admission to the study in accordance with Good Clinical Practice and the local legislation Exclusion Criteria: Any finding of the medical examination (including blood pressure, pulse rate and electrocardiogram (ECG)) deviating from normal and of clinical relevance Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders History of orthostatic hypotension, fainting spells or blackouts Chronic or relevant acute infections History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator Intake of drugs with a long half-life (> 24 hours) within at least one month or less than 10 half-lives of the respective drug before enrolment in the study or during the study Use of any drugs which might influence the results of the trial up to 7 days prior to enrolment in the study or during the study Participation in another trial with an investigational drug (≤ 30 days prior to administration or during the trial) Heavy smoker (> 10 cigarettes or > 3 cigars of > 3 pipes/day) Inability to refrain from smoking on trial days Alcohol abuse (> 60 g/day) Drug abuse Blood donation (≥ 100 mL within four weeks prior to administration or during the trial) Any deviation of a laboratory value that is considered to be of clinical relevance Excessive physical activities within the last week before the trial or during the trial Hypersensitivity to BI 201335, moxifloxacin or related drugs of these classes Homozygous genotype status for Gilbert polymorphisms (Uridine diphosphate (UDP)-glucuronosyl transferase 1A1 (UGT1A1)*28, *60) Heart rate at screening of > 85 bpm or < 40 bpm Any screening ECG value outside of the reference range of clinical relevance including, but not limited to pulse rate (PR) interval > 220 ms, QRS interval > 115 ms, QTcB (QT interval, corrected for heart rate according to Bazett's formula) > 470 ms, or QT (uncorrected) > 470 ms For Female subjects Pregnancy Positive pregnancy test No adequate contraception (adequate contraception e.g. sterilisation, intrauterine pressure , oral contraceptives). Females, who are not surgically sterile will be asked to additionally use barrier contraception methods (e.g. condom, diaphragm with spermicide) Inability to maintain this adequate contraception during the whole study period from the time of screening until one month after the last intake Lactation period

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: BI 201335 placebo<br>crossover part | Drug: BI 201335 placebo<br> <br> |
| Experimental: BI 201335 low dose<br>crossover part | Drug: BI 201335 low dose<br> <br> |
| Experimental: BI 201335 high dose<br>crossover part | Drug: BI 201335 high dose<br> <br> |
| Active Comparator: Moxifloxacin<br>crossover part | Drug: Moxifloxacin<br> <br> |
| Experimental: BI 201335 or Placebo<br>tolerability part in female subjects | Drug: BI 201335 placebo<br> <br> Drug: BI 201335 high dose<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| QTcI interval (QT interval individually corrected for heart rate) |  | pre-dose and 3 to 8 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The mean value of QTcI changes from baseline between 2 h and 24 h after dosing |  | Pre dose and 2 to 24 hours post dosing | 
| The change from mean baseline of the QTcI at any point in time between 2 h and 24 h after dosing |  | Pre dose and 2 to 24 hours post dosing | 
| The time-matched changes versus placebo in QTcI at any point in time between 2 h and 24 h after dosing |  | Pre dose and 2 to 24 hours post dosing |