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

September 3, 2013 updated by: Tibotec Pharmaceuticals, Ireland

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
32

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 1
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
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]
Experimental: 2
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 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]
Experimental: 3
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 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]
Experimental: 4
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 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]

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
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
Time Frame: Plasma levels of DRV in each session at 15 timepoints and plasma levels of rtv after intake on Day 3 at 13 timepoints
Plasma levels of DRV in each session at 15 timepoints and plasma levels of rtv after intake on Day 3 at 13 timepoints

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
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
Time Frame: 9 weeks (this includes treatment, washout and follow up period and is excluding screening period of maximum 21 days before first medication intake)
9 weeks (this includes treatment, washout and follow up period and is excluding screening period of maximum 21 days before first medication intake)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Tibotec Pharmaceuticals, Ireland

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2010

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2010

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2010

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 15, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 19, 2010

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 20, 2010

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 4, 2013

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 3, 2013

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CR016903

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