NCT01052883

TMC114-TiDP3-C182 - A Study to Compare the Oral Bioavailability of a 800 mg Prototype Tablet Formulation of Darunivar (DRV) to That of the 400 mg Commercial Tablet Formulation in the Presence of Low Dose Ritonavir, Under Fasted and Fed Conditions

A Phase I, Open Label, Randomized, Single Dose, Crossover Study in Healthy Subjects to Compare the Oral Bioavailability of a Prototype Tablet Formulation of Darunavir 800mg(G002) to That of the Commercial 400mg(F030) Tablet Formulation Under Fed & Fasted Conditions, in Presence of Low-dose Ritonavir

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 32 (actual)
• Sponsor: Tibotec Pharmaceuticals, Ireland · Industry
• Sex: All
• Age: 18 Years – 55 Years
• Healthy volunteers: Accepted

Summary

The purpose of this study is to compare the drug levels of darunavir obtained after administration of a single administration of the 800 mg tablet (new formulation) to that following administration of two 400 mg commercial tablets formulation when administered under fed and fasted conditions to those also taking low-dose ritonavir. Darunavir is marketed for the treatment of HIV. The short-term safety and tolerability of darunavir following administration of a single 800 mg dose of darunavir given to healthy volunteers taking taking low-dose ritonavir will also be assessed.

Detailed description

This is an open label study, which means that all parties including the study doctor, the healthy volunteer and the sponsor will know at all times which treatment group the volunteer is in. This is a cross over trial, which means that every volunteer will be sequentially subjected to 2 different treatments. A total of 32 healthy volunteers will participate in this study. Volunteers will be divided over 2 panels of 16 volunteers each. Volunteers in Panel 1 will be randomly assigned to treatment sequence AB or BA. Volunteers in Panel 2 will be randomly assigned to treatment sequence CD or DC. During all treatment periods 100 mg ritonavir (rtv) will be dosed once daily on Day 1 to Day 5. In treatment A you will receive a single dose of darunavir (DRV) two 400 mg commercial formulation in the morning of day 3 after a standard breakfast. In treatment B you will receive a single dose of darunavir (DRV) 800 mg new formulation in the morning of Day 3 also under fed conditions. In treatment C you will receive a single dose of darunavir (DRV) two 400 mg commercial formulation in the morning of day 3 under fasted conditions. In treatment D you will receive a single dose of darunavir (DRV) 800 mg new formulation in the morning of day 3 also under fasted conditions. Treatment sessions are organized with 7 days between treatment periods. In each session, an extensive investigation of the levels of DRV and rtv in the blood circulation is planned. Levels of DRV will be assessed at 15 different time points, i.e. before administration of DRV 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 24, 48 and 72 hours after intake of DRV. Levels of rtv will be assessed at 13 different time points, i.e. before administration of rtv on Day 3, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9 and 12 hours after intake of rtv on day 3 and before administration of rtv on Day 4. Standard Safety assessments (blood biochemistry and hematology, urine analysis, ECG, pulse rate and blood pressure) will be performed on Day1, 3 and 6 in each Treatment period. Two 400 mg DRV commercial tablet formulation (F030) single dose on Day 3 of treatment A and C; 800 mg DRV new tablet formulation (G002) single dose on Day 3 of treatment B and D; 100 mg rtv capsule once daily on Day 1 to Day 5. All intake are oral.

Conditions

• HIV Infections

Interventions

Type	Name	Description
DRUG	DRV commercial formulation/ DRV new formulation/ rtv 100mg tab	DRV two 400 mg commercial formulation tablets in the morning of day 3 fasting + rtv 100 mg 1/day on Day 1-5 \[Treatment C\], then after 7 days off treatment start DRV 800 mg new formulation in the morning of day 3 fasting + rtv 100 mg 1/day on Day 1-5 \[Treatment D\]
DRUG	DRV commercial formulation/ DRV new formulation/ rtv 100mg tab	DRV 800 mg new formulation tablet/rtv 100mg tablet in the morning of Day 3 after food+ rtv 100 mg 1/day on Day 1-5 \[Treatment B\], then after 7 days off treatment start DRV two 400 mg commercial formulation tablets in the morning of day 3 after food + rtv 100 mg 1/day on Day 1-5 \[Treatment A\]
DRUG	DRV commercial formulation/ DRV new formulation/ rtv 100mg tab	DRV 800 mg new formulation in the morning of day 3 fasting + rtv 100 mg 1/day on Day 1-5 \[Treatment D\], then after 7 days off treatment start DRV two 400 mg commercial formulation tablets in the morning of day 3 fasting + rtv 100 mg 1/day on Day 1-5 \[Treatment C\]
DRUG	DRV commercial formulation/ DRV new formulation/ rtv 100mg tab	DRV two 400 mg commercial formulation tablets in the morning of day 3 after food + rtv 100 mg 1/day on Day 1-5 \[Treatment A\], then after 7 days off treatment start DRV 800 mg new formulation tablet in the morning of Day 3 after food + rtv 100 mg 1/day on Day 1-5 \[Treatment B\]

Timeline

• Start date: 2010-03-01
• Primary completion: 2010-06-01
• Completion: 2010-07-01
• First posted: 2010-01-20
• Last updated: 2013-09-04