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

NCT02249416 | Completed Phase 1

• 1 other identifier: 1182.37
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

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

Conditions

Healthy

Outcome Measures

Primary Outcomes (4)

• Area under the concentration-time curve of the analyte in plasma from zero time to 12 hours (AUC0-12)

  Up to 12 h after drug administration

• Maximum plasma concentration (Cmax)

  Up to 24 h after drug administration

• Drug concentration in plasma at 6 hours after drug administration (Cp6h)

  Up to 6 h after drug administration

• Drug concentration in plasma at 12 hours after drug administration (Cp12h)

  Up to 12 h after drug administration

Secondary Outcomes (11)

• Maximum plasma concentration at steady state (Cmax ss)

  Up to 24 h after drug administration

• Trough plasma concentration (Cmin)

  Up to 24 h after drug administration

• Mean residence time (MRT)

  Up to 24 h after drug administration

• Terminal half life (t1/2)

  Up to 24 h after drug administration

• Time of maximum concentration (tmax)

  Up to 24 h after drug administration

Study Arms (2)

TPV/RTV low + ZDV

EXPERIMENTAL

Drug: Tipranavir (TPV) low; Drug: Ritonavir (RTV) low; Drug: Zidovudine

TPV/RTV high + ZDV

EXPERIMENTAL

Drug: Tipranavir (TPV) high; Drug: Ritonavir (RTV) high; Drug: Zidovudine

Interventions

Tipranavir (TPV) low DRUG

TPV/RTV low + ZDV

Ritonavir (RTV) low DRUG

Norvir®

TPV/RTV low + ZDV

Tipranavir (TPV) high DRUG

Retrovir®

TPV/RTV high + ZDV

Ritonavir (RTV) high DRUG

TPV/RTV high + ZDV

Zidovudine DRUG

TPV/RTV high + ZDV; TPV/RTV low + ZDV

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Boehringer Ingelheim: lead

MeSH Terms

Interventions

tipranavir; Ritonavir; Zidovudine

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thymidine; Pyrimidine Nucleosides; Pyrimidines; Dideoxynucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2014
• First Posted: September 25, 2014
• Study Start: November 1, 2001
• Primary Completion: February 1, 2002
• Last Updated: September 25, 2014

Record last verified: 2014-09