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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Moxifloxacin; Drug: BI 201335 placebo; Drug: BI 201335 low dose; Drug: BI 201335 high dose

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: BI 201335 placebo; crossover part	Drug: BI 201335 placebo
EXPERIMENTAL: BI 201335 low dose; crossover part	Drug: BI 201335 low dose
EXPERIMENTAL: BI 201335 high dose; crossover part	Drug: BI 201335 high dose
ACTIVE_COMPARATOR: Moxifloxacin; crossover part	Drug: Moxifloxacin
EXPERIMENTAL: BI 201335 or Placebo; tolerability part in female subjects	Drug: BI 201335 placebo; Drug: BI 201335 high dose

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (ACTUAL): October 1, 2008

Study Registration Dates

• First Submitted: July 2, 2014
• First Submitted That Met QC Criteria: July 7, 2014
• First Posted (ESTIMATE): July 8, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): July 18, 2014
• Last Update Submitted That Met QC Criteria: July 17, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Moxifloxacin
• Other Study ID Numbers: 1220.16