Effects of Tipranavir (TPV) and Ritonavir (RTV) on the Pharmacokinetic Characteristics of Tenofovir Disoproxil Fumarate in Healthy Volunteers

NCT02251145 | Completed Phase 1

• 1 other identifier: 1182.46
• Study Type: interventional
• Target: 49
• Locations: 0 countries
• Sites: N/A

Brief Summary

Study to characterise the effects of two dose combinations of tipranavir/ritonavir (TPV 500 mg/RTV 100 mg and TPV 750 mg/RTV 200 mg) administered BID, on the pharmacokinetics of tenofovir disoproxil fumarate as well as the effects of tenofovir disoproxil fumarate on the pharmacokinetics of tipranavir/ritonavir.

Conditions

Healthy

Outcome Measures

Primary Outcomes (5)

• Area under plasma concentration time curve from 0-24 hours (AUC0-24) for tenofovir

  up to 24 hours

• Area under plasma concentration time curve from 0-12hours (AUC0-12) for tipranavir/ritonavir

  up to 12 hours

• Maximum plasma concentration (Cmax)

  up to 24 hours

• Drug concentration in plasma at 12 hours after administration (C12h) for tenofovir

  up to 12 hours

• Drug concentration in plasma at 12 hours after administration (C12h) for tipranavir/ritonavir

  up to 12 hours

Secondary Outcomes (12)

• Maximum plasma concentration at steady state (Cmax,ss)

  up to 24 hours

• Trough plasma concentration at steady state (Cmin)

  up to 24 hours

• Mean residency time (MRT)

  up to 24 hours

• Apparent terminal half life (T1/2)

  up to 24 hours

• Time of maximum concentration (Tmax)

  up to 24 hours

Study Arms (2)

tipranavir/ritonavir low dose

EXPERIMENTAL

Drug: Tipranavir low dose; Drug: Ritonavir low dose; Drug: Tenofovir disoproxil fumarate

tipranavir/ritonavir high dose

EXPERIMENTAL

Drug: Tipranavir high dose; Drug: Ritonavir high dose; Drug: Tenofovir disoproxil fumarate

Interventions

Tipranavir low dose DRUG

tipranavir/ritonavir low dose

Tipranavir high dose DRUG

tipranavir/ritonavir high dose

Ritonavir low dose DRUG

tipranavir/ritonavir low dose

Ritonavir high dose DRUG

tipranavir/ritonavir high dose

Tenofovir disoproxil fumarate DRUG

tipranavir/ritonavir high dose; tipranavir/ritonavir low dose

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 regulatory 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 \>18.5 and \<30 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 \<= Grade1 based on the AIDS Clinical Trials Group (ACTG) Division of AIDS (DAIDS) Grading Scale. All abnormal laboratory values \> Grade 1 (e.g., creatine phosphokinase (CPK), amylase, triglycerides) are subject to approval by the BIPI clinical monitor. Cholesterol \<= 240mg/dL at the time of screening is necessary for study entry
• Acceptable medical history, physical examination and ECG 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, strawberries or strawberry extract, 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 pharmacokinetic (PK) sampling days
• 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 regular oral contraception (combined oestrogen and progestogen pill or progestogen only pill) for 3 months and a barrier contraceptive method for at least 30 days prior to Visit 3 (Day 1) or 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). Use of any other herbal/complementary treatment must be discussed in advance with the monitor and permission obtained prior to study entry
• Ingestion of grapefruit, grapefruit juice, and Cabernet Sauvignon within 15 days prior to Day 0 (Visit 2)
• Ingestion of Seville oranges, strawberries or strawberry extract, 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
• 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 or rolling/pipe tobacco equivalent
• Blood or plasma donations within 30 days prior to Day 0 (Visit 2)

Sponsors & Collaborators

• Boehringer Ingelheim: lead

MeSH Terms

Interventions

tipranavir; Ritonavir; Tenofovir

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Organophosphonates; Organophosphorus Compounds; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

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 25, 2014
• First Posted: September 29, 2014
• Study Start: May 1, 2002
• Primary Completion: June 1, 2002
• Last Updated: September 29, 2014

Record last verified: 2014-09