VX-950-TiDP24-C124: A Phase I Trial to Investigate the Potential Pharmacokinetic Interactions Between Telaprevir and Darunavir/Ritonavir and Between Telaprevir and Fosamprenavir/Ritonavir at Steady-state. - Full Text View

Purpose

The primary objectives are to determine the effect of steady-state DRV/rtv 600/100 mg twice daily (b.i.d.) on the steady-state pharmacokinetics of telaprevir 750 mg every (q) 8h and 1125 mg q12h and vice versa;- to determine the effect at steady-state of fAPV/rtv 700/100 mg b.i.d. on the steady-state pharmacokinetics of telaprevir 750 mg q8h and 1125 mg q 12h and vice versa; to determine the steady-state pharmacokinetics of telaprevir 750 mg q8h versus telaprevir 1125 mg q12h, alone and during coadministration of either steady-state DRV/rtv 600/100 mg b.i.d or fAPV/rtv 700/100 mg b.i.d.

Condition	Intervention	Phase
Hepatitis C Telaprevir HIV	Drug: Telaprevir; Darunavir; Ritonavir; Fosamprenavir	Phase 1


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Crossover Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase I, Open-label, Randomized, 2-way Crossover Trial in 40 Healthy Subjects to Investigate the Potential Pharmacokinetic Interactions Between Telaprevir and Darunavir/Ritonavir and Between Telaprevir and Fosamprenavir/Ritonavir at Steady-state.

Resource links provided by NLM:

MedlinePlus related topics: Drug Reactions

Drug Information available for: Ritonavir Darunavir Fosamprenavir Fosamprenavir sodium Fosamprenavir calcium Telaprevir Darunavir ethanolate

U.S. FDA Resources

Further study details as provided by Tibotec BVBA:

Primary Outcome Measures:

Effect of steady-state DRV/rtv 600/100 mg b.i.d. and steady-state of fAPV/rtv 700/100 mg on the steady-state PK of telaprevir 750 mg q8h and 1125 mg q12h and vice versa. Steady-state PK on telaprevir 750 mg q8h and 1125 mg q12h alone.

Secondary Outcome Measures:

The secondary objective is to determine the short-term safety and tolerability of coadministration of telaprevir and DRV/rtv, and telaprevir and fAPV/rtv.


Enrollment:	40
Study Start Date:	June 2008
Study Completion Date:	October 2008
Primary Completion Date:	October 2008 (Final data collection date for primary outcome measure)

Detailed Description:

This is a Phase I, open-label, randomized (patients are assigned different treatments based on chance), 2-way crossover trial in 2 panels of healthy subjects to investigate the effect of steady-state darunavir/ritonavir (DRV/rtv) 600/100 mg b.i.d. (twice a day) or fosamprenavir/ritonavir (fAPV/rtv) 700/100 mg b.i.d. on the steady state pharmacokinetics (study of the bodily absorption, distribution, metabolism, and excretion of drugs) of telaprevir 750 mg q 8h and 1125 mg q12h, and vice versa.Telaprevir is being investigated for the treatment of HCV infection.The trial will enroll 40 subjects, divided over 2 panels of 20 subjects each. Subjects in Panel 1 will receive Treatments A and B, and subjects in Panel 2 will receive Treatments C and D, in a randomized order. In both panels, treatments will be separated by a washout period of at least 13 days. In Panel 1, Treatment A, subjects will receive telaprevir 750 mg q8h on Days 1 to 10, and telaprevir 1125 mg q12h on Days 11 to 13 with a morning dose on Day 14. In Panel 1, Treatment B, subjects will receive DRV/rtv 600/100 mg b.i.d. on Days 1 to 23, with an additional morning dose on Day 24, with coadministration of telaprevir 750 mg q8h on Days 11 to 20, and 1125 mg q12h on Days 21 to 23 with a morning dose on Day 24. In Panel 2, Treatment C, subjects will receive telaprevir 750 mg q 8h on Days 1 to 10, and telaprevir 1125 mg q12h on Days 11 to 13 with a morning dose on Day 14. In Panel 2, Treatment D, subjects will receive fAPV/rtv 700/100 mg b.i.d. on Days 1 to 23, with an additional morning dose on Day 24, with coadministration of telaprevir 750 mg q8h on Days 11 to 20, and 1125 mg q12h on Days 21 to 23 with a morning dose on Day 24. All intakes of study medication will be under fed conditions. Pharmacokinetic profiles of telaprevir and VRT-127394 (Rdiastereomer of telaprevir) will be measured up to 8 hours after intake of the morning dose on Day 10 of Treatments A and C and on Day 20 of Treatments B and D, and up to 12 hours after intake of the morning dose of Day 14 of Treatments A and C and on Day 24 of Treatments B and D. During Treatment B, pharmacokinetic profiles of DRV and ritonavir will be measured up to 12 hours after intake of the morning dose on Day 10, Day 20 and Day 24. During Treatment D, pharmacokinetic profiles of amprenavir and ritonavir will be measured up to 12 hours after intake of the morning dose on Day 10, Day 20 and Day 24. Safety and tolerability evaluations will be recorded at regular intervals throughout the trial period. Group A/C: telaprevir 750 mg each 8 hrs on Days 1-10, and telaprevir 1125 mg each 12hrs on Days 11-13 with a morning dose on Day 14. Group B: DRV/rtv 600/100 mg 2/day on Days 1-23 + morning dose on Day 24 + telaprevir 750 mg each 8 hrs on Days 11-20, and 1125 mg each 12hrs on Days 21 to 23 + morning dose on Day 24. Group D: fAPV/rtv 700/100 mg 2/day on Days 1-23 + morning dose on Day 24, + telaprevir 750 mg each 8hrs Days 11-20, and 1125 mg each 12hrs on Days 21-23 + morning dose on Day 24.

Eligibility


Ages Eligible for Study:	18 Years to 55 Years (Adult)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Females in menopause for at least 3 years or surgically sterilized
Nonsmoking or smoking no more than 10 cigarettes, or 2 cigars, or 2 pipes per day for at least 3 months prior to screening
Normal weight at screening as defined by a body mass index (BMI) of 18 to 30 kg/m2, extremes included
Able to comply with protocol requirements
Healthy on the basis of a medical evaluation that reveals the absence of any clinically relevant abnormality and includes a physical examination, medical history, ECG, vital signs, and the results of blood biochemistry, blood coagulation and hematology tests and a urinalysis carried out at screening.

Exclusion Criteria:

Subjects must not have a history of any illness that, in the opinion of the investigator or the subject's general practitioner, might confound the results of the study or pose an additional risk in administering trial drug(s) to the subject
Subjects should currently not use prescription medication. Subjects should stop any short-duration courses of prescription medication at least 14 days before the screening visit. Potential subjects should not stop any chronic, prescribed medication being taken at the direction of a physician, without obtaining agreement from that physician
Subjects should not have regular treatment with over-the-counter medications. Subjects should stop over-the-counter medications on the date of the screening visit but no less than 7 days prior to the first administration of study medication (Day 1 of Session I). Potential subjects should not stop any chronic, over-the-counter medication being taken at the direction of a physician, without obtaining agreement from that physician
Subjects should not consumeherbal medications or dietary supplements and grapefruit or grapefruit juice, apple juice, or orange juice within 14 days before the first administration of study medication (Day 1 of Session I)
Subjects should not have a history of drug or alcohol abuse or addiction within 2 years prior to dosing, or who test positive for alcohol or drugs such as amphetamine, barbiturates, benzodiazepines, cocaine, cannabinoids, opioids, metamphetamine and methadone during the screening period
Subject should not have participated in a clinical study involving administration of an investigational drug within 3 months or 5 half lives (whichever is longer) prior to the screening visit.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00775125

Sponsors and Collaborators

Tibotec BVBA

Investigators


Study Director:	Tibotec-Virco Virology BVBA Clinical Trial	Tibotec BVBA

More Information


ClinicalTrials.gov Identifier:	NCT00775125 History of Changes
Other Study ID Numbers:	CR015208
Study First Received:	October 16, 2008
Last Updated:	December 16, 2010
Health Authority:	USA: FOOD AND DRUG ADMINISTRATION - CENTER FOR DRUG EVALUATION AND RESEARCH

Keywords provided by Tibotec BVBA:


VX-950-TiDP24-C124 VX-950-C124 HCV DDI telaprevir darunavir	ritonavir fosamprenavir interaction pharmacokinetics steady-state

Additional relevant MeSH terms:


Hepatitis C Hepatitis, Viral, Human Virus Diseases Flaviviridae Infections RNA Virus Infections Hepatitis Liver Diseases Digestive System Diseases Ritonavir Darunavir Fosamprenavir	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

ClinicalTrials.gov processed this record on September 29, 2016