TMC114-TiDP3-C176 - A Study in Healthy Volunteers Investigating the Bioequivalence Between Two Commercially Available 400-mg Tablets to One New 800-mg Tablet of Darunavir (DRV) in the Presence of Low-dose Ritonavir Under Fed and Fasted Conditions

A Phase I, Open-label, Randomized, 2-panel, 2-way Crossover Pivotal Bioequivalence Trial Between the Commercially Available 400-mg Tablet Formulation (F030) and the 800-mg Tablet Formulation of Darunavir (G002), in the Presence of Low-dose Ritonavir Under Fasted and Fed Conditions

In this study participants will be given 800 mg darunavir, either as one 800-mg tablet formulation (G002), or as two commercially available 400-mg tablets formulation (F030), to evaluate the effect between both, in the presence of low-dose ritonavir under fasted and fed conditions.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Darunavir (DRV); Drug: ritonavir

Detailed Description

Darunavir (DRV, formerly known as TMC114) is an inhibitor of human immunodeficiency virus (HIV) protease. This study is designed to establish the bioequivalence of a commercially available 400-mg tablet formulation (F030) to one 800-mg tablet formulation of DRV (G002) in the presence of low-dose ritonavir under fasted and fed conditions. This is a Phase I, open-label (both participant and investigator know the name of the medication given at certain moment), randomized (study medication is assigned by chance), 2-panel, 2-way crossover study in healthy volunteers to assess the bioequivalence of DRV following administration of 2 tablet strengths (in the presence of low-dose ritonavir) under fasted and fed conditions. A total of 124 participants will participate in this study. Participants will be divided into 2 panels; 80 participants in Panel 1 (fasted) and 44 in Panel 2 (fed). In Panel 1, during 2 subsequent sessions, each participant will receive 2 treatments under fasted conditions, meaning Treatment A, a single oral 800-mg dose of DRV formulated as the 400-mg commercially available tablet F030 and Treatment B, a single oral 800-mg dose of DRV formulated as the 800-mg tablet formulation G002. In Panel 2, the same design as Panel 1 will be followed but under fed conditions, and where the 2 treatments, respectively, will be called Treatments C and D. In both panels, participants will receive ritonavir 100 mg once a day on Days 1 to 5. Ritonavir will be administered under fed conditions in both panels except for the morning intake on Day 3 in Panel 2 where it will be administered under fasting conditions. A washout period of at least 7 days between subsequent treatments will be observed. Safety (blood and urine tests, blood pressure, pulse, electrocardiogram, and physical examination) and tolerability evaluations will be recorded at regular intervals throughout the trial. Panel 1 (fasted condition) and Panel 2 (fed condition): a single dose of 800 mg DRV on Day 3 and 100 mg ritonavir once daily from Day 1 to 5. DRV will be formulated as the commercially available 400-mg tablet formulation (F030) or as the investigational 800-mg tablet formulation (G002). Ritonavir will be used as the commercially available melt-extrusion tablet containing ritonavir eq. 100 mg.

• Study Type: Interventional
• Enrollment (Actual): 128
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy based on a medical evaluation including medical history, physical examination, blood tests and electrocardiogram
• Body Mass Index of 18.0 to 30.0 kg/m² and non-smoker or smoking no more than 10 cigarettes, or 2 cigars, or 2 pipes per day for at least 3 months
• Women must be postmenopausal for at least 2 years or be surgically sterile or be not heterosexually active for the duration of the study or have a vasectomized partner
• Men must agree to use a highly effective method of birth control.

Exclusion Criteria:

• Infection with Hepatitis A, B, or C virus
• infection with HIV
• Women who are pregnant or breastfeeding
• History of, or any current medical condition which could impact the safety of the participant in the study
• Previously participated in a multiple-dose study with DRV.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 001; Darunavir (DRV) 2x400-mg DRV tablet or 800-mg tablet on Day 3	Drug: Darunavir (DRV); 2x400-mg DRV tablet or 800-mg tablet
Experimental: 002; ritonavir 100-mg once daily on Day 1 to Day 5	Drug: ritonavir; on Day 3

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Plasma concentrations of 100-mg ritonavir after a multiple oral dose on Days 1 to 5 in healthy volunteers in fed or fasted conditions	measured on Day 1 to Day 6
Plasma concentrations of Darunavir (DRV) after a single oral dose of 800-mg DRV on Day 3 in healthy volunteers in fed or fasted conditions	measured on Day 1
Plasma concentrations of DRV after a single oral dose of 800-mg DRV on Day 3 in healthy volunteers in fed or fasted conditions	measured on Day 3 to Day 6

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of all adverse events by treatment group	Measured from Day 1 until end of trial
Blood tests	Measured from Day 1 until end of trial
Measurements of blood pressure	Measured from Day 1 until end of trial
Measurements of pulse	Measured from Day 1 until end of trial
Measurements of electrocardiograms	Measured from Day 1 until end of trial

Collaborators and Investigators

• Sponsor: Tibotec Pharmaceuticals, Ireland

Publications and helpful links

General Publications

• Kakuda TN, Leopold L, Timmers M, Van De Casteele T, Hillewaert V, Tomaka FL, Hoetelmans RM. Bioavailability and bioequivalence of a darunavir 800-mg tablet formulation compared with the 400-mg tablet formulation. Int J Clin Pharmacol Ther. 2014 Sep;52(9):805-16. doi: 10.5414/cp202066.

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Study Completion (Actual): May 1, 2011

Study Registration Dates

• First Submitted: February 3, 2011
• First Submitted That Met QC Criteria: March 3, 2011
• First Posted (Estimate): March 4, 2011

Study Record Updates

• Last Update Posted (Estimate): February 6, 2014
• Last Update Submitted That Met QC Criteria: February 5, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: Healthy volunteers; HIV; TMC114; TMC114-C176; DRV
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ritonavir; Darunavir
• Other Study ID Numbers: CR017776; TMC114-TiDP3-C176