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

NCT01052883 | Completed Phase 1

• 1 other identifier: CR016903
• Study Type: interventional
• Target: 32
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

HIV Infections

Keywords

TMC114-TiDP3-C182; TMC114-C182; TMC114; HIV; HIV Infections

Outcome Measures

Primary Outcomes (1)

• Plasma levels of DRV 800 mg new formulation compared with 2x400 mg commercial formulation in fed and fasted conditions and in presence of low dose rtv

  Plasma levels of DRV in each session at 15 timepoints and plasma levels of rtv after intake on Day 3 at 13 timepoints

Secondary Outcomes (1)

• The short-term safety and tolerability of darunavir following administration of a single 800 mg dose of darunavir in the presence of low-dose ritonavir

  9 weeks (this includes treatment, washout and follow up period and is excluding screening period of maximum 21 days before first medication intake)

Study Arms (4)

1

EXPERIMENTAL

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 \[Treatment B\]

Drug: DRV commercial formulation/ DRV new formulation/ rtv 100mg tab

2

EXPERIMENTAL

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

3

EXPERIMENTAL

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

4

EXPERIMENTAL

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

Interventions

DRV commercial formulation/ DRV new formulation/ rtv 100mg tab DRUG

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 \[Treatment D\]

3

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Non-smoking, or smoking no more than 10 cigarettes, or 2 cigars, or 2 pipes per day for at least 3 months prior to selection
• Normal weight as defined by a Body Mass Index (BMI, weight in kg divided by the square of height in meters) of 18.0 to 30.0 kg/m2, extremes included
• Use of effective non hormonal birth control methods, or willing to continue practicing these birth control methods for at least 30 days after the end of the treatment period for female volunteers of childbearing potential
• Negative serum pregnancy test and will not be breast feeding at screening
• 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, electrocardiogram (ECG), vital signs, and the results of blood biochemistry, blood coagulation, and hematology tests and a urinalysis carried out at screening

You may not qualify if:

• Positive HIV 1 or HIV 2 test at screening
• Hepatitis A, B or C infection at screening
• History of significant skin disease such as, but not limited to rash or eruptions, food allergy or psoriasis
• Allergy, hypersensitivity or intolerance to DRV and rtv
• History of allergy to drugs such as, but not limited to, sulphonamides and penicillins

Sponsors & Collaborators

• Tibotec Pharmaceuticals, Ireland: lead

Related Publications (1)

• 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.

  PMID: 25109510 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Ritonavir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Tibotec Pharmaceuticals Clinical Trial

  Tibotec Pharmaceutical Limited

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2010
• First Posted: January 20, 2010
• Study Start: March 1, 2010
• Primary Completion: June 1, 2010
• Study Completion: July 1, 2010
• Last Updated: September 4, 2013

Record last verified: 2013-09