Clinical trial NCT02249416: Comparison of the Effect of Tipranavir and Ritonavir or Tipranavir and Ritonavir on the Pharmacokinetic Characteristics of Zidovudine in Healthy Volunteers
Official title: A Single Center, Open-Label, Randomised, Parallel, Multiple Dose Comparison of the Effect of Tipranavir 500 mg and Ritonavir 100 mg or Tipranavir 750 mg and Ritonavir 200 mg Twice a Day for 11.5 Days on the Pharmacokinetic Characteristics of Zidovudine 300 mg in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-09-25
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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

Primary outcomes:
measure: Area under the concentration-time curve of the analyte in plasma from zero time to 12 hours (AUC0-12)
timeFrame: Up to 12 h after drug administration
measure: Maximum plasma concentration (Cmax)
timeFrame: Up to 24 h after drug administration
measure: Drug concentration in plasma at 6 hours after drug administration (Cp6h)
timeFrame: Up to 6 h after drug administration
measure: Drug concentration in plasma at 12 hours after drug administration (Cp12h)
timeFrame: Up to 12 h after drug administration
Secondary outcomes:
measure: Maximum plasma concentration at steady state (Cmax ss)
timeFrame: Up to 24 h after drug administration
measure: Trough plasma concentration (Cmin)
timeFrame: Up to 24 h after drug administration
measure: Mean residence time (MRT)
timeFrame: Up to 24 h after drug administration
measure: Terminal half life (t1/2)
timeFrame: Up to 24 h after drug administration
measure: Time of maximum concentration (tmax)
timeFrame: Up to 24 h after drug administration
measure: Oral clearance (CL/F)
timeFrame: Up to 24 h after drug administration
measure: Apparent volume of distribution during the terminal elimination phase (Vz/F)
timeFrame: Up to 24 h after drug administration
measure: Number of participants with clinically significant changes in vital signs
timeFrame: Up to day 14 after first drug administration
measure: Number of participants with abnormal findings in physical examination
timeFrame: Up to day 14 after first drug administration
measure: Number of participants with abnormal changes in clinical laboratory parameters
timeFrame: Up to day 14 after first drug administration
measure: Number of participants with Adverse Events
timeFrame: Up to day 14 after first drug administration
Other outcomes:
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Study officials:
References: