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The purpose of this study is to determine the effect of EFV (Efavirenz) and TDF (Tenofovir disoproxil fumarate) on the pharmacokinetics of TVR (Telaprevir) and to determine the effect of TVR on the pharmacokinetics of EFV and TDF. Pharmacokinetics means how the drug is absorbed into the bloodstream, distributed in the body and eliminated from the body. Furthermore, the short-term safety and tolerability of giving TVR, EFV and TDF together will be evaluated.
The trial will enroll 20 Healthy volunteers. All participants will receive 4 different treatments:
Treatment A: TVR every 8 hours alone for 6 days with an additional morning intake on Day 7. Treatment B: EFV + TDF once daily alone for 7 days. Treatment C: TVR every 8 hours + EFV once daily + TDF once daily for 7 days. Treatment D: TVR every 12 hours + EFV once daily + TDF once daily for 7 days.
All participants will start with Treatment A followed by a 7 or 8-day washout period. Subsequently, participants will start with Treatment B. At the end of Treatment B, participants will be randomized (this is assigned to one of the two sequences by chance) to continue without a washout period with Sequence 1 (Treatment C followed by D without a washout) or Sequence 2 (Treatment D followed by C without a washout). Participants will thus receive daily EFV and TDF for a total of 21 consecutive days, with addition of 2 different dosages of TVR for the last 14 days.
TVR will be taken with food, 30 minutes after the start of a meal. EFV and TDF should be taken on an empty stomach (2.5 hours after start of breakfast). Pharmacokinetic profiles of TVR and VRT-127394 (R-diastereomer of TVR) will be measured up to 8 hours after intake of the morning dose on Day 7 of Treatments A and C, and up to 12 hours after intake of the morning dose on Day 7 of Treatment D. Pharmacokinetic profiles of EFV and tenofovir will be measured up to 24 hours after intake on Day 7 of Treatments B, C, and D. Safety and tolerability evaluations will be recorded at regular intervals throughout the trial period. Treatment A: TVR every 8 hours alone for 6 days with an additional morning intake on Day 7. Treatment B: EFV + TDF once daily alone for 7 days. Treatment C: TVR every 8 hours + EFV once daily + TDF once daily for 7 days. Treatment D: TVR every 12 hours + EFV once daily + TDF once daily for 7 days.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Efavirenz; Tenofovir disoproxil fumarate; Telaprevir | Drug |
| Measure | Description | Time Frame |
|---|---|---|
| The primary objectives are to determine the effect of EFV and TDF on the pharmacokinetics of TVR and VRT-127394 and of TVR every 8h and every 12h on the pharmacokinetics of EFV and TDF. |
| Measure | Description | Time Frame |
|---|---|---|
| The secondary objective is to determine the short-term safety and tolerability of the coadministration of TVR, EFV and TDF. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Tibotec-Virco Virology BVBA Clinical Trial | Tibotec BVBA | Study Director |
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| ID | Term |
|---|---|
| D006526 | Hepatitis C |
| D000163 | Acquired Immunodeficiency Syndrome |
| D015658 | HIV Infections |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D006525 | Hepatitis, Viral, Human |
| D014777 | Virus Diseases |
| D018178 | Flaviviridae Infections |
| D012327 | RNA Virus Infections |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D015229 | Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012897 | Slow Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C098320 | efavirenz |
| D000068698 | Tenofovir |
| C486464 | telaprevir |
| ID | Term |
|---|---|
| D063065 | Organophosphonates |
| D009943 | Organophosphorus Compounds |
| D009930 | Organic Chemicals |
| D000225 | Adenine |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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