HIV Clinical Trial
Official title:
A Phase I, Open-label Trial to Investigate the Pharmacokinetic Interaction Between TMC125 and Two Antifungal Agents (Fluconazole and Voriconazole), All at Steady-state in Healthy Subjects.
This is a Phase I, open-label, 3-period crossover trial to investigate the pharmacokinetic interaction (process by which a drug is absorbed, distributed, metabolised and eliminated by the body) between TMC125 and fluconazole, and between TMC125 and voriconazole.
In this Phase I, open-label, 3-period crossover trial the potential pharmacokinetic
interaction between TMC125 and fluconazole and between TMC125 and voriconazole will be
investigated. Fluconazole and voriconazole are triazole antifungal agents.
Fluconazole and voriconazole are inhibitors of CYP isoenzymes 2C19, 2C9 and CYP3A4.
Fluconazole is metabolized by the liver to a small extent. Approximately 80% of the
administered fluconazole dose appears in the urine in unchanged form. Voriconazole is
metabolized by CYP2C19, 2C9 and 3A4. TMC125 is also metabolized by CYP3A, 2C9 and 2C19.
Because of the effect of fluconazole and voriconazole on the metabolic pathways relevant for
TMC125 metabolism, concomitant administration of TMC125 and fluconazole or voriconazole
might increase TMC125 pharmacokinetics. Because of the effect of TMC125 on the metabolic
pathways relevant for voriconazole metabolism, concomitant administration of TMC125 and
voriconazole might also modify voriconazole pharmacokinetics. Since the elimination of
fluconazole is mainly via the kidneys, an effect of TMC125 on fluconazole pharmacokinetics
is not expected. The current trial aims to assess the 2-way pharmacokinetic interaction
between TMC125 and fluconazole, and between TMC125 and voriconazole, to provide dosing
recommendations for combined use in the treatment of HIV infected patients.In this trial the
pharmacokinetic interaction between TMC125 and fluconazole, and between TMC125 and
voriconazole, all at steady-state will be investigated in 18 healthy subjects. During the
first two sessions, each subject will receive 2 treatments (Treatments A and B) in a
randomized way. In Treatment A, 200 mg TMC125 twice a day. will be administered from Day 1
to Day 7 with an additional morning dose on Day 8. In Treatment B, 200 mg fluconazole once a
day in the morning will be administered from Day 1 to Day 16, co-administered with 200 mg
TMC125 twice a day from Day 9 to Day 16.
These sessions are followed by a third session, Treatment C, in which 400 mg voriconazole
twice a day will be administered on Day 1 and 200 mg voriconazole twice a day will be
administered from Day 2 to Day 15, with an additional morning dose on Day 16. From Day 9 to
Day 15, 200 mg TMC125 twice a day will be co-administered, with an additional morning dose
on Day 16. All TMC125 and fluconazole intakes will be under fed conditions, within 10
minutes after a meal. Voriconazole will be administered 1.5 hour before a meal. Between
subsequent treatment sessions, there will be a washout period of at least 2 weeks. Full
pharmacokinetic profiles will be determined for one dosing interval (12 hours) for TMC125 on
Day 8 of Treatment A and on Day 16 of Treatments B and C. For fluconazole, full
pharmacokinetic profiles will be determined for one dosing interval (24 hours) on Days 8 and
16 of Treatment B. For voriconazole, full pharmacokinetic profiles will be determined for
one dosing interval (12 hours) on Days 8 and 16 of Treatment C. Safety and tolerability will
be monitored continuously throughout the trial. Treatment A: 200 mg TMC125 twice daily,
orally from Day 1 to 7 and a morning dose on Day 8. Treatment B: 200 mg fluconazole once
daily, orally from Day 1 to 16, co-administered with 200 mg TMC125 twice daily from Day 9 to
16. Treatment C: 400 mg voriconazole twice daily, orally on Day 1 and 200 mg voriconazole
twice daily will be administered from Day 2 to 15, with a morning dose on Day 16. From Day 9
to 15, 200 mg TMC125 twice daily will be co-administered, with a morning dose on Day 16.
;
Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT06162897 -
Case Management Dyad
|
N/A | |
Completed |
NCT03999411 -
Smartphone Intervention for Smoking Cessation and Improving Adherence to Treatment Among HIV Patients
|
Phase 4 | |
Completed |
NCT02528773 -
Efficacy of ART to Interrupt HIV Transmission Networks
|
||
Active, not recruiting |
NCT05454839 -
Preferences for Services in a Patient's First Six Months on Antiretroviral Therapy for HIV in South Africa
|
||
Recruiting |
NCT05322629 -
Stepped Care to Optimize PrEP Effectiveness in Pregnant and Postpartum Women
|
N/A | |
Completed |
NCT02579135 -
Reducing HIV Risk Among Adolescents: Evaluating Project HEART
|
N/A | |
Active, not recruiting |
NCT01790373 -
Evaluating a Youth-Focused Economic Empowerment Approach to HIV Treatment Adherence
|
N/A | |
Not yet recruiting |
NCT06044792 -
The Influence of Primary HIV-1 Drug Resistance Mutations on Immune Reconstruction in PLWH
|
||
Completed |
NCT04039217 -
Antiretroviral Therapy (ART) Persistence in Different Body Compartments in HIV Negative MSM
|
Phase 4 | |
Active, not recruiting |
NCT04519970 -
Clinical Opportunities and Management to Exploit Biktarvy as Asynchronous Connection Key (COMEBACK)
|
N/A | |
Completed |
NCT04124536 -
Combination Partner HIV Testing Strategies for HIV-positive and HIV-negative Pregnant Women
|
N/A | |
Recruiting |
NCT05599581 -
Tu'Washindi RCT: Adolescent Girls in Kenya Taking Control of Their Health
|
N/A | |
Active, not recruiting |
NCT04588883 -
Strengthening Families Living With HIV in Kenya
|
N/A | |
Completed |
NCT02758093 -
Speed of Processing Training in Adults With HIV
|
N/A | |
Completed |
NCT02500446 -
Dolutegravir Impact on Residual Replication
|
Phase 4 | |
Completed |
NCT03805451 -
Life Steps for PrEP for Youth
|
N/A | |
Active, not recruiting |
NCT03902431 -
Translating the ABCS Into HIV Care
|
N/A | |
Completed |
NCT00729391 -
Women-Focused HIV Prevention in the Western Cape
|
Phase 2/Phase 3 | |
Recruiting |
NCT05736588 -
Elimisha HPV (Human Papillomavirus)
|
N/A | |
Recruiting |
NCT03589040 -
Darunavir and Rilpivirine Interactions With Etonogestrel Contraceptive Implant
|
Phase 2 |