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

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ClinicalTrials.gov Identifier: NCT02249416
Recruitment Status : Completed
First Posted : September 25, 2014
Last Update Posted : September 25, 2014
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

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

Condition or disease Intervention/treatment Phase
Healthy Drug: Tipranavir (TPV) low Drug: Ritonavir (RTV) low Drug: Tipranavir (TPV) high Drug: Ritonavir (RTV) high Drug: Zidovudine Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : November 2001
Actual Primary Completion Date : February 2002

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: TPV/RTV low + ZDV Drug: Tipranavir (TPV) low
Drug: Ritonavir (RTV) low
Norvir®

Drug: Zidovudine
Experimental: TPV/RTV high + ZDV Drug: Tipranavir (TPV) high
Retrovir®

Drug: Ritonavir (RTV) high
Drug: Zidovudine



Primary Outcome Measures :
  1. Area under the concentration-time curve of the analyte in plasma from zero time to 12 hours (AUC0-12) [ Time Frame: Up to 12 h after drug administration ]
  2. Maximum plasma concentration (Cmax) [ Time Frame: Up to 24 h after drug administration ]
  3. Drug concentration in plasma at 6 hours after drug administration (Cp6h) [ Time Frame: Up to 6 h after drug administration ]
  4. Drug concentration in plasma at 12 hours after drug administration (Cp12h) [ Time Frame: Up to 12 h after drug administration ]

Secondary Outcome Measures :
  1. Maximum plasma concentration at steady state (Cmax ss) [ Time Frame: Up to 24 h after drug administration ]
  2. Trough plasma concentration (Cmin) [ Time Frame: Up to 24 h after drug administration ]
  3. Mean residence time (MRT) [ Time Frame: Up to 24 h after drug administration ]
  4. Terminal half life (t1/2) [ Time Frame: Up to 24 h after drug administration ]
  5. Time of maximum concentration (tmax) [ Time Frame: Up to 24 h after drug administration ]
  6. Oral clearance (CL/F) [ Time Frame: Up to 24 h after drug administration ]
  7. Apparent volume of distribution during the terminal elimination phase (Vz/F) [ Time Frame: Up to 24 h after drug administration ]
  8. Number of participants with clinically significant changes in vital signs [ Time Frame: Up to day 14 after first drug administration ]
  9. Number of participants with abnormal findings in physical examination [ Time Frame: Up to day 14 after first drug administration ]
  10. Number of participants with abnormal changes in clinical laboratory parameters [ Time Frame: Up to day 14 after first drug administration ]
  11. Number of participants with Adverse Events [ Time Frame: Up to day 14 after first drug administration ]


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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Additional Information:
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Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT02249416     History of Changes
Other Study ID Numbers: 1182.37
First Posted: September 25, 2014    Key Record Dates
Last Update Posted: September 25, 2014
Last Verified: September 2014
Additional relevant MeSH terms:
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Ritonavir
Zidovudine
Tipranavir
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Antimetabolites
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors