Electrophysiological Effects of Tipranavir Co-administered With Ritonavir 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 tipranavir (TPV) co-administered with ritonavir (RTV) does not affect the QT interval more than placebo co-administered with ritonavir

Official Title
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Assessment of Electrophysiological Effects of Tipranavir Co-administered With Ritonavir Given b.i.d. for 2.5 Days on the QT Interval in Healthy Female and Male Subjects. A Double-blind, Randomised, Placebo Controlled, Two-way Crossover Study With a Positive Control (Moxifloxacin) and Parallel Dose Groups

Conditions
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Healthy

Intervention / Treatment
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* Drug: TPV low
* Drug: Placebo
* Drug: Moxifloxacin
* Drug: TPV high
* Drug: RTV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy female and male volunteers as determined by the results of screening according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs (BP, HR), 12-lead ECG, clinical laboratory tests Age ≥ 18 and Age ≤ 55 years BMI ≥ 18.5 and BMI ≤ 29.9 kg/m2 (Body Mass Index) Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation Exclusion Criteria: Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders Gastrointestinal tract surgery (except appendectomy) Diseases of the central nervous system (such as epilepsy, seizures) or psychiatric disorders or neurological disorders History of relevant orthostatic hypotension, fainting spells or blackouts. Relevant acute, chronic or active chronic infections (e.g. hepatitis, HIV). History of allergy/hypersensitivity (including drug allergies) that are 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 prior to administration or during the trial Use of drugs which might reasonably influence the results of the trial based on the knowledge at the time of protocol preparation within 10 days prior to administration or during the trial Participation in another trial with an investigational drug within two months prior to administration or during the trial Smoker (more than 10 cigarettes/day or 3 cigars/day or 3 pipes/day) Inability to refrain from smoking on trial days Alcohol abuse (more than 60 g/day) Drug abuse Veins unsuited for i.v. puncture on either arm (e.g. veins which are difficult to locate, access or puncture, veins with a tendency to rupture during or after puncture) Blood donation (more than 100 mL within four weeks prior to administration or during the trial) History of any bleeding disorder or acute blood coagulation defect Hypersensitivity to ritonavir, moxifloxacin and/or related drugs of these classes History of Glucose-6-phosphate-deficiency Excessive physical activities (within one week prior to trial or during the trial) Any laboratory value outside the reference range that is of clinical relevance A history of additional risk factors for torsade de pointes (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome) Heart rate at screening of > 80 bpm or < 45 bpm Any screening ECG value outside of the reference range of clinical relevance including, but not limited to PR interval > 240 ms, QRS interval > 120 ms, QTcB or QTcF > 450 ms, or QT (uncorrected) > 470 ms Inability to comply with the dietary regimen of the study centre For female subjects: Pregnancy Positive pregnancy test No adequate contraception (adequate contraception e.g. sterilisation, intrauterine pessary (IUP) or oral contraception not containing ethinyl estradiol) Oral contraception containing ethinyl estradiol without the use of an additional barrier method Hormone replacement containing ethinyl estradiol Inability to maintain this adequate contraception during the whole study period Lactation period

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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 |
| --- | --- |
| Experimental: low TPV/RTV<br> | Drug: TPV low<br> <br> Drug: Moxifloxacin<br> <br> * Other names: Avelox®;Drug: RTV<br> <br> |
| Experimental: high TPV/RTV<br> | Drug: Moxifloxacin<br> <br> * Other names: Avelox®;Drug: TPV high<br> <br> Drug: RTV<br> <br> |
| Experimental: Placebo/RTV<br> | Drug: Placebo<br> <br> Drug: Moxifloxacin<br> <br> * Other names: Avelox®;Drug: RTV<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in individually heart rate corrected QT interval length (QTcI) |  | baseline and 2 to 4 hours after drug administration on day3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in (QTcI) |  | baseline and 2 to 4 hours after drug administration on day 1 | 
| Change from baseline in (QTcI) |  | baseline and 1 to 12 hours after drug administration on day1 and 3 |