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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TPV/RTV capsules fed | Experimental |
| |
| TPV/RTV capsules fasted | Experimental |
| |
| TPV/RTV solutions fed | Active Comparator |
| |
| TPV/RTV solutions fasted | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TPV capsule | Drug |
| ||
| TPV solution |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Male and female subjects 18 to 65 years of age inclusive
A Body Mass Index (BMI): ≥18.5 and ≤35 kg/m2
Signed informed consent prior to performance of any study procedures
Ability to swallow multiple large capsules without difficulty
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
Acceptable medical history, physical examination, and 12-lead ECG at screening
Willingness to abstain from the following starting 5 days prior to administration of any study medication and up until the end of the study:
Willingness to abstain from the following starting 3 days prior to administration of any study medication up to the end of the study:
Willingness to abstain from over-the-counter herbal medications for the duration of the study
Are non-smokers
Willingness to abstain from vigorous physical exercise during intensive pharmacokinetic days 10, 11, 14, 15
Reasonable probability for completion of the study
Exclusion Criteria:
Participation in another trial with an investigational medicine within 2 months prior to Day 0 of this study
Female subjects of reproductive potential who:
Use of any medication listed in Protocol within 30 days prior to Day 0 of this study
Administration of antibiotics within 15 days prior to Day 0 and anytime during the study
History of acute illness within 60 days prior to Day 0
Serological evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV)
Serological evidence of exposure to HIV
Alcohol or substance abuse within 1 year prior to screening or during the study
Blood or plasma donations within 30 days prior to Day 0 or during the study
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
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
Known hypersensitivity to sulphonamide class of drugs
Known hypersensitivity to TPV, RTV, or antiretroviral drugs (marketed or experimental use as part of clinical research studies)
Known elevated liver enzymes in past trials with any compound
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)
Inability to adhere to the protocol
Inability to consume a standard high-fat meal
Cautions or warnings in the package insert which, in the opinion of the investigator, constituted grounds for subject exclusion
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| Drug |
|
| RTV capsule | Drug |
|
| RTV solution | Drug |
|
| standard meal | Other |
|
| Drug concentration in plasma after 12 hours at steady state (Cp12h) | Drug concentration in plasma at last measurement (Cplast) if Cp12h is below limit of quantification (BLQ) | up to 12 hours after drug administration |
| Apparent clearance of the analyte in plasma at steady state following extravascular administration (CL/F) | up to 12 hours after drug administration |
| Volume of distribution at steady state (Vd) | up to 12 hours after drug administration |
| Terminal half life at steady state (t1/2) | up to 12 hours after drug administration |
| Number of subjects with adverse events | up to day 16 |
| Number of subjects with clinically significant findings in vital signs | blood pressure, pulse rate | up to day 16 |
| Number of subjects with clinically significant findings in ECG | up to day 16 |
| Number of subjects with clinically significant findings in laboratory tests | up to day 16 |
| ID | Term |
|---|---|
| D019438 | Ritonavir |
| ID | Term |
|---|---|
| D013844 | Thiazoles |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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