Electrophysiological Effects of Tipranavir Co-administered With Ritonavir on the QT Interval in Healthy Female and Male Subjects

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

To demonstrate that tipranavir (TPV) co-administered with ritonavir (RTV) does not affect the QT interval more than placebo co-administered with ritonavir

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: Moxifloxacin; Drug: TPV low; Drug: RTV; Drug: TPV high

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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
2. Age ≥ 18 and Age ≤ 55 years
3. BMI ≥ 18.5 and BMI ≤ 29.9 kg/m2 (Body Mass Index)
4. Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation

Exclusion Criteria:

1. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
2. Gastrointestinal tract surgery (except appendectomy)
3. Diseases of the central nervous system (such as epilepsy, seizures) or psychiatric disorders or neurological disorders
4. History of relevant orthostatic hypotension, fainting spells or blackouts.
5. Relevant acute, chronic or active chronic infections (e.g. hepatitis, HIV).
6. History of allergy/hypersensitivity (including drug allergies) that are deemed relevant to the trial as judged by the investigator
7. 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
8. 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
9. Participation in another trial with an investigational drug within two months prior to administration or during the trial
10. Smoker (more than 10 cigarettes/day or 3 cigars/day or 3 pipes/day)
11. Inability to refrain from smoking on trial days
12. Alcohol abuse (more than 60 g/day)
13. Drug abuse
14. 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)
15. Blood donation (more than 100 mL within four weeks prior to administration or during the trial)
16. History of any bleeding disorder or acute blood coagulation defect
17. Hypersensitivity to ritonavir, moxifloxacin and/or related drugs of these classes
18. History of Glucose-6-phosphate-deficiency
19. Excessive physical activities (within one week prior to trial or during the trial)
20. Any laboratory value outside the reference range that is of clinical relevance
21. A history of additional risk factors for torsade de pointes (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
22. Heart rate at screening of > 80 bpm or < 45 bpm
23. 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

24. Inability to comply with the dietary regimen of the study centre

    For female subjects:

25. Pregnancy
26. Positive pregnancy test
27. No adequate contraception (adequate contraception e.g. sterilisation, intrauterine pessary (IUP) or oral contraception not containing ethinyl estradiol)
28. Oral contraception containing ethinyl estradiol without the use of an additional barrier method
29. Hormone replacement containing ethinyl estradiol
30. Inability to maintain this adequate contraception during the whole study period
31. Lactation period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: low TPV/RTV	Drug: Moxifloxacin; Other Names: Avelox®; Drug: TPV low; Drug: RTV
Experimental: high TPV/RTV	Drug: Moxifloxacin; Other Names: Avelox®; Drug: RTV; Drug: TPV high
Experimental: Placebo/RTV	Drug: Placebo; Drug: Moxifloxacin; Other Names: Avelox®; Drug: RTV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: December 1, 2005
• Primary Completion (Actual): March 1, 2006

Study Registration Dates

• First Submitted: September 24, 2014
• First Submitted That Met QC Criteria: September 24, 2014
• First Posted (Estimate): September 25, 2014

Study Record Updates

• Last Update Posted (Estimate): September 25, 2014
• Last Update Submitted That Met QC Criteria: September 24, 2014
• Last Verified: September 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: 1182.60