Comparison of the Effect of Tipranavir and Ritonavir or Tipranavir and Ritonavir on the Pharmacokinetic Characteristics of Zidovudine in Healthy Volunteers

Boehringer Ingelheim

Status and phase

Completed

Phase 1

Conditions

Healthy

Treatments

Drug: Ritonavir (RTV) high

Drug: Zidovudine

Drug: Tipranavir (TPV) low

Drug: Ritonavir (RTV) low

Drug: Tipranavir (TPV) high

Study type

Interventional

Funder types

Industry

Identifiers

NCT02249416

1182.37

Details and patient eligibility

About

The objective of this study was to characterize the effect of two dose combinations of tipranavir/ritonavir (TPV 500 mg/RTV 100 mg and TPV 750 mg/RTV 200 mg) administered twice daily on the pharmacokinetics (PK) of zidovudine (ZDV) and zidovudine-glucuronide (GZDV) as well as the effects of zidovudine on the pharmacokinetics of TPV/RTV

Enrollment

60 patients

Sex

All

Ages

18 to 60 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Ability and willingness to give written informed consent in accordance with institutional and federal guidelines and to comply with the investigational nature of the study and the related requirements
Healthy males or females between 18 and 60 years of age inclusive
A Body Mass Index between 18 and 35 kg/m2
Ability to swallow numerous large capsules without difficulty
Reasonable probability for completion of the study, in the opinion of the investigator
Acceptable laboratory values that indicate adequate baseline organ function are required at the time of screening. Laboratory values are considered to be acceptable if severity <= Grade 1 based on the ACTG DAIDS Grading Scale. All abnormal laboratory values > Grade 1 (e.g., CPK, amylase, triglycerides) are subject to approval by the BIPI clinical monitor
Acceptable medical history, physical examination, ECG, and Chest X-ray are required prior to entering the study
Willingness to abstain from alcohol for 48 hours prior to Study Day 0 and abstain from alcohol for the duration of the study. In addition, Cabernet Sauvignon must not have been ingested within 15 days prior to Day 0 (Visit 2)
Willingness to abstain from ingesting grapefruit and grapefruit juice within 15 days of Day 0, Visit 2 and for the duration of the study
Willingness to abstain from ingesting Seville oranges, garlic supplements, St. John's Wort, Milk Thistle, or methylxanthine-containing drinks or food (coffee, tea, cola, energy drinks, chocolate, etc.) within 72 hours of PK sampling days (Day 1 (Visit 3), Days 11-14 (Visits 5-8))
Willingness to abstain from use of tobacco products for the duration of the study
Urine drug screen negative for illegal non-prescription drugs
Negative HIV serology
Negative for Hepatitis B surface antigen and Hepatitis C

Exclusion criteria

Female subjects who are of reproductive potential who:
- Have a positive serum B-HCG at Visit 1 or 2 or,
- Have not been using a barrier contraceptive method for at least 3 months prior to Visit 3 (Day 1) or,
- Are not willing to use a reliable method of double-barrier contraception (such as diaphragm with spermicidal cream/jelly or condoms with spermicidal foam) during the trial and 30 days after completion / termination or,
- Are breast-feeding
Participation in another trial with an investigational medicine for 30 days prior to Day 0 (Visit 2)
Ingestion of any known enzyme altering drug (such as phenothiazines, cimetidine, barbiturates, ketoconazole, fluconazole, rifampin, steroids, and herbal medications for 30 days prior to Day 0 (Visit 2)
Ingestion of grapefruit, grapefruit juice, and Cabernet Sauvignon within 15 days prior to Day 0 (Visit 2)
Ingestion of Seville oranges, garlic supplements, St. John's Wort, Milk Thistle, or methylxanthine-containing drinks or food (coffee, tea, cola, energy drinks, chocolate, etc.) within 72 hours of PK sampling days [Day 1 (Visit 3), Days 11-14 (Visits 5-8)]
Ingestion of antibiotics within 10 days prior to Day 0 (Visit 2)
Inability to comply with investigator's instructions
History of gastrointestinal, hepatic, or renal disorders within 60 days
History of alcohol abuse
Current use of cigarettes defined as greater than 10 cigarettes per day
Blood or plasma donations within 30 days prior to Day 0 (Visit 2)
Subjects with a seated systolic blood pressure either <100 mm Hg or >150 mm Hg; resting heart rate either <50 beats/min or >90 beats/min
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 or ritonavir or zidovudine to the subject
Subjects who have had an acute illness within 2 weeks prior to Day 0 (Visit 2)
Subjects who are currently taking any over-the-counter drug within 7 days prior to Day 0, (Visit 2) or who are currently taking any prescription drug that, in the opinion of the investigator in consultation with the BIPI clinical monitor and pharmacokineticist, might interfere with either the absorption, distribution or metabolism of the test substances
Hypersensitivity to tipranavir, ritonavir, or zidovudine