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Study to investigate the effects of steady-state TPV/r (500 mg/100 mg BID) on the single-dose and steady-state pharmacokinetics of Atazanavir (300 mg QD) co-administered with Ritonavir (100 mg). To investigate the effects of single-dose and steady-state Atazanavir (300 mg) on the steady-state pharmacokinetics of Tipranavir and Ritonavir.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TAZ/RTV - TPV/RTV - TPV/RTV+TAZ | Experimental | Days 1-9: single dose TAZ/RTV Days 16-23: morning and evening dose TPV/RTV Days 24-32: TPV/RTV + TAZ |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tipranavir | Drug | TPV |
| |
| Ritonavir |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum plasma concentration | up to day 33 | |
| Drug concentration in plasma at 12 hr after administration for Tipranavir (TPV) and Ritonavir (RTV) | 12 hours after drug administration | |
| Drug concentration in plasma at 24 hr after administration for Atazanavir (TAZ) | 24 hours after drug administration | |
| Area under plasma concentration time curve from 0-12 hours (AUC0-12h) for TPV and RTV | up to 12 hours after drug administration | |
| AUC0-24h for TAZ | up to 24 hours after drug administration |
| Measure | Description | Time Frame |
|---|---|---|
| Time from dosing to the maximum concentration | up to day 33 | |
| Elimination half-life | up to day 33 | |
| Oral clearance |
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Inclusion Criteria:
Male and female subjects between 18 and 60 years of age inclusive
A Body Mass Index (BMI) between 18 and 29 kg/m2
Signed informed consent prior to trial participation
Ability to swallow multiple large capsules without difficulty
Acceptable laboratory values that indicate adequate baseline organ function at screening visit:
Acceptable medical history, physical examination, and 12-lead ECG at screening
Willingness to abstain from the following starting 2 weeks 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
Willingness to abstain from alcohol starting 3 days prior to administration of any study medication up to the end of the study
Willingness to abstain from the following starting 3 days prior to pharmacokinetic (PK) sampling:
- Garlic supplements and Methylxanthine containing foods or drinks (including coffee, tea, cola, energy drinks, chocolate, etc.)
Willingness to abstain from over-the-counter herbal medications for the duration of the study
Must be a non-smoker
Willingness to abstain from vigorous physical exercise during intensive PK Days 1, 9, 23, 24 and 32
Reasonable probability for completion of the study
Exclusion Criteria:
Female subjects of reproductive potential who:
Participation in another trial with an investigational medicine within 2 months prior to Day 0 of this study
Use of any medication listed in the protocol within 30 days prior to Day 0 of this study
Use of 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 of Depo-Provera within six months prior to Day 0 will be excluded from participation in this study
Use of hormone replacement therapy within 1 month prior to Day 0 and anytime during the 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
o 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 does not qualify as a healthy volunteer
Have serological evidence of hepatitis B or C virus
Have 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 confound the results of the study or pose additional risk in administering Tipranavir, Ritonavir or Atazanavir to the subject
Subjects with pre-existing heart conduction abnormalities
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 clinical monitor, might interfere with absorption, distribution, or metabolism of the study medications
Known hypersensitivity to sulphonamide class of drugs
Inability to adhere to the protocol
Cautions or warnings in the Ritonavir and Atazanavir package insert which, in the opinion of the investigator, constitute grounds for subject exclusion
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| Drug |
RTV |
|
| Atazanavir | Drug | TAZ |
|
| up to day 33 |
| Volume of distribution | up to day 33 |
| Number of patients with adverse events | up to day 33 |
| ID | Term |
|---|---|
| C107201 | tipranavir |
| D019438 | Ritonavir |
| D000069446 | Atazanavir Sulfate |
| ID | Term |
|---|---|
| D013844 | Thiazoles |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011725 | Pyridines |
| D009842 | Oligopeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
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