Relative Bioavailability of Tipranavir (TPV)/Ritonavir (RTV) at Steady State Administered as Oral Solutions vs. Capsules in the Fed and Fasted State in Healthy Volunteers

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: TPV solution; Drug: TPV capsule; Drug: RTV capsule; Drug: RTV solution; Other: standard meal

• Registration Number: NCT02227017
• Lead Sponsor: Boehringer Ingelheim

Brief Summary

Study to establish the relative bioavailability of the TPV oral solution formulation (500 mg coadministered with RTV oral solution 200 mg) to the TPV capsule formulation (500 mg coadministered with RTV capsules 200 mg), with both treatments at steady-state under fasted and fed conditions in healthy male and female volunteers.

Detailed Description

Not available

Study Timeline

• Study Start: 2006-02
• Primary Completion: 2006-04
• Status Verified: 2014-08
• Study First Submitted: 2014-08-26
• Study First Submitted QC: 2014-08-26
• Last Update Submitted: 2014-08-26
• Study First Posted: 2014-08-27
• Last Update Posted: 2014-08-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 35

Inclusion Criteria

1. Male and female subjects 18 to 65 years of age inclusive

2. A Body Mass Index (BMI): ≥18.5 and ≤35 kg/m2

3. Signed informed consent prior to performance of any study procedures

4. Ability to swallow multiple large capsules without difficulty

5. Screening laboratory values within the normal range. Inclusion of any subject with an abnormal laboratory value was subject to approval by the BI trial clinical monitor

6. Acceptable medical history, physical examination, and 12-lead ECG at screening

7. Willingness to abstain from the following starting 5 days prior to administration of any study medication and up until the end of the study:

   • Grapefruit or grapefruit juice, red wine, Seville oranges, St. John's Wort and Milk Thistle

8. Willingness to abstain from the following starting 3 days prior to administration of any study medication up to the end of the study:

   • Garlic supplements and methylxanthine containing foods or drinks (including coffee, tea, cola, energy drinks, chocolate, etc.), apples and apple juice

9. Willingness to abstain from over-the-counter herbal medications for the duration of the study

10. Are non-smokers

11. Willingness to abstain from vigorous physical exercise during intensive pharmacokinetic days 10, 11, 14, 15

12. Reasonable probability for completion of the study

Exclusion Criteria

1. Participation in another trial with an investigational medicine within 2 months prior to Day 0 of this study

2. Female subjects of reproductive potential who:

   • Have a positive pregnancy test
   • Have not been using a barrier method of contraception for at least 3 months prior to participation in the study
   • Are not willing to use a reliable method of barrier contraception (such as diaphragm with spermicidal cream/jelly or condoms with spermicidal foam), during and 60 days after completion/termination of the trial
   • Are breast-feeding
   • Use any pharmacological contraceptive (including oral, patch or injectable contraceptives) within 1 month prior to Day 0 and for the duration of the study. Due to long half-life, subjects using Depo-Provera® within 6 months prior to Day 1 are excluded from participation in this study
   • Use of hormone replacement therapy within 1 month prior to Day 0 and anytime during the study

3. Use of any medication listed in Protocol within 30 days prior to Day 0 of this study

4. Administration of antibiotics within 15 days prior to Day 0 and anytime during the study

5. History of acute illness within 60 days prior to Day 0

   • Subjects will be excluded for acute illnesses that occurred more than 60 days prior to Day 0 if, in the opinion of the investigator, the subject did not qualify as a healthy volunteer

6. Serological evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV)

7. Serological evidence of exposure to HIV

8. Alcohol or substance abuse within 1 year prior to screening or during the study

9. Blood or plasma donations within 30 days prior to Day 0 or during the study

10. Subjects with a history of any illness or allergy that, in the opinion of the investigator, might have confounded the results of the study or pose additional risk in administering TPV, or RTV to the subject

11. Subjects who have taken (within 7 days prior to Day 0) any over-the-counter or prescription medication that, in the opinion of the investigator in consultation with the sponsor's clinical monitor, might have interfered with absorption, distribution, or metabolism of the study medications

12. Known hypersensitivity to sulphonamide class of drugs

13. Known hypersensitivity to TPV, RTV, or antiretroviral drugs (marketed or experimental use as part of clinical research studies)

14. Known elevated liver enzymes in past trials with any compound

15. Known allergy to nuts or nut products (A spoonful of peanut or hazelnut butter was taken immediately before administration of TPV or RTV oral solution, to help mask the taste of the solutions)

16. Inability to adhere to the protocol

17. Inability to consume a standard high-fat meal

18. Cautions or warnings in the package insert which, in the opinion of the investigator, constituted grounds for subject exclusion

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
TPV/RTV solutions fed	TPV solution	-
TPV/RTV solutions fed	standard meal	-
TPV/RTV capsules fed	standard meal	-
TPV/RTV capsules fasted	RTV capsule	-
TPV/RTV capsules fed	TPV capsule	-
TPV/RTV capsules fasted	TPV capsule	-
TPV/RTV solutions fasted	TPV solution	-
TPV/RTV solutions fasted	RTV solution	-
TPV/RTV solutions fed	RTV solution	-
TPV/RTV capsules fed	RTV capsule	-

Primary Outcome Measures

Name	Time	Method
Area under the concentration-time curve of TPV from time zero to 12 hours at steady state (AUC0-12)	up to 12 hours after drug administration

Secondary Outcome Measures

Name	Time	Method
Apparent clearance of the analyte in plasma at steady state following extravascular administration (CL/F)	up to 12 hours after drug administration
Number of subjects with clinically significant findings in laboratory tests	up to day 16
Area under the concentration-time curve of RTV from time zero to 12 hours at steady state (AUC0-12)	up to 12 hours after drug administration
Maximum measured concentration of the analyte in plasma at steady state (Cmax)	up to 12 hours after drug administration
Volume of distribution at steady state (Vd)	up to 12 hours after drug administration
Number of subjects with adverse events	up to day 16
Drug concentration in plasma after 12 hours at steady state (Cp12h)	up to 12 hours after drug administration	Drug concentration in plasma at last measurement (Cplast) if Cp12h is below limit of quantification (BLQ)
Terminal half life at steady state (t1/2)	up to 12 hours after drug administration
Number of subjects with clinically significant findings in vital signs	up to day 16	blood pressure, pulse rate
Number of subjects with clinically significant findings in ECG	up to day 16