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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier:
NCT01308658
First received: February 3, 2011
Last updated: February 5, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Healthy
Drug: Darunavir (DRV)
Drug: ritonavir
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Tibotec Pharmaceuticals, Ireland:

Primary Outcome Measures:
  • Plasma concentrations of 100-mg ritonavir after a multiple oral dose on Days 1 to 5 in healthy volunteers in fed or fasted conditions [ Time Frame: measured on Day 1 to Day 6 ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: measured on Day 1 ] [ Designated as safety issue: No ]
  • Plasma concentrations of DRV after a single oral dose of 800-mg DRV on Day 3 in healthy volunteers in fed or fasted conditions [ Time Frame: measured on Day 3 to Day 6 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence of all adverse events by treatment group [ Time Frame: Measured from Day 1 until end of trial ] [ Designated as safety issue: Yes ]
  • Blood tests [ Time Frame: Measured from Day 1 until end of trial ] [ Designated as safety issue: Yes ]
  • Measurements of blood pressure [ Time Frame: Measured from Day 1 until end of trial ] [ Designated as safety issue: Yes ]
  • Measurements of pulse [ Time Frame: Measured from Day 1 until end of trial ] [ Designated as safety issue: Yes ]
  • Measurements of electrocardiograms [ Time Frame: Measured from Day 1 until end of trial ] [ Designated as safety issue: Yes ]

Enrollment: 128
Study Start Date: January 2011
Study Completion Date: May 2011
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01308658

Locations
Germany
Berlin, Germany
Sponsors and Collaborators
Tibotec Pharmaceuticals, Ireland
Investigators
Study Director: Tibotec Pharmaceuticals Clinical Trial Tibotec Pharmaceutical Limited
  More Information

No publications provided

Responsible Party: Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier: NCT01308658     History of Changes
Other Study ID Numbers: CR017776, TMC114-TiDP3-C176
Study First Received: February 3, 2011
Last Updated: February 5, 2014
Health Authority: Ireland: Irish Agriculture and Food Development Authority

Keywords provided by Tibotec Pharmaceuticals, Ireland:
TMC114-C176
TMC114
DRV
HIV
Healthy volunteers

Additional relevant MeSH terms:
Ritonavir
Darunavir
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 18, 2014