Pharmacokinetics of Tipranavir Soft Elastic Capsules (SEDDS) and Ritonavir and Their Effects on Cytochrome P-450 (3A4) in Healthy Volunteers

September 25, 2014 updated by: Boehringer Ingelheim

An Open-label, Parallel Group, Multiple-dose Investigation of the Pharmacokinetics of Tipranavir Soft Elastic Capsules SEDDS and Ritonavir Soft Gel Capsules and Their Effects on Cytochrome P-450 (3A4) Activity in Normal Healthy Volunteers

The objective of this study is to establish the tipranavir-ritonavir steady-state dose-exposure relationships when administered on a b.i.d. dosing regimen; to determine the effects of tipranavir (TPV) and ritonavir (RTV) on cytochrome P-450 (CYP3A4) activity; to establish the dependency of the TPV M1 metabolite on RTV co-administration. Additionally, the short-term safety and tolerance of this drug combination will be evaluated.

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.

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.
113

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 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male or female between 18 and 75 years of age inclusive
  • Female subjects of child-bearing potential are required to use a barrier contraceptive method for at least 3 months prior to administration of study medication, during study medication administration and for 30 days after the end of the study
  • Ability to swallow numerous large capsules without difficulty
  • A body mass index (BMI) between 19 and 29 kg/m2
  • Signed informed consent prior to trial participation
  • Reasonable probability for completion of the study
  • Acceptable screening laboratory values that indicate adequate baseline organ function are required at the time of screening. Laboratory values are considered to be acceptable if severity is no higher than Grade 1 based on the AIDS Clinical Trials Group (ACTG) Grading Scale. All laboratory values > Grade 1 are subject to approval by the BIPI clinical monitor
  • Acceptable medical history, physical examination, electrocardiogram, and chest X-ray are required prior to entering the treatment phase of the study
  • Willingness to abstain from alcohol for 48 hours prior to study Day 0 and abstain from alcohol for the duration of the study
  • Willingness to abstain from ingesting grapefruit or grapefruit juice for the duration of the study
  • Urine drug screen negative for drugs of abuse
  • Negative HIV serology
  • Negative for Hepatitis B surface antigen and Hepatitis C antibody

Exclusion Criteria:

  • Female subjects who:

    • have a positive serum pregnancy test at Visits 1 or 2 OR
    • are breastfeeding
  • Receipt of any other investigational medicine for 30 days prior to Day 0
  • Receipt of any known enzyme altering drug for 30 days prior to Day 0, grapefruit and grapefruit juice within 15 days prior to Day 0 and antibiotics within 10 days prior to Day 0
  • Excessive cigarette smoking, defined as greater than 10 cigarettes per day
  • Blood or plasma donation within 30 days prior to Day 0
  • Subjects with a seated systolic blood pressure either < 100 mg Hg or > 150 mm Hg; resting heart rate either < 50 beats/min or > 90 beats/min
  • Subjects with a history of any illness or allergy that, in the opinion of the investigator, might confound the results of the study or pose additional risk in administering tipranavir or ritonavir to the subject
  • Subjects who have had an acute illness within 2 weeks prior to Day 0
  • Subjects who are currently taking any over-the-counter drug within 7 days prior to Day 0, or who are currently taking any prescription drug that, in the opinion of the investigator in consultation with the BIPI medical monitor and pharmacokineticist, might interfere with either the absorption, distribution or metabolism of the test substances
  • Hypersensitivity to tipranavir, ritonavir or sulfonamide containing drugs
  • Evidence of active substance abuse that, in the investigator's opinion, could affect study adherence

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: Parallel 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: TPV/RTV Low 1
Drug: TPV low 1
Drug: Ritonavir high
Drug: Radiolabelled erythromycin
Experimental: TPV/RTV Low 2
Drug: Radiolabelled erythromycin
Drug: TPV low 2
Drug: RTV low
Experimental: TPV/RTV Low 3
Drug: Ritonavir high
Drug: Radiolabelled erythromycin
Drug: TPV low 2
Experimental: TPV/RTV Medium 1
Drug: Radiolabelled erythromycin
Drug: RTV low
Drug: TPV medium
Experimental: TPV/RTV Medium 2
Drug: Ritonavir high
Drug: Radiolabelled erythromycin
Drug: TPV medium
Experimental: TPV/RTV High 1
Drug: Radiolabelled erythromycin
Drug: RTV low
Drug: TPV high 1
Experimental: TPV/RTV High 2
Drug: Ritonavir high
Drug: Radiolabelled erythromycin
Drug: TPV high 1
Experimental: TPV/RTV High 3
Drug: Ritonavir high
Drug: Radiolabelled erythromycin
Drug: TPV high 2

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
Trough plasma concentration at steady state (Cmin,ss)
Time Frame: up to 24 hours
up to 24 hours
Maximum plasma concentration at steady state (Cmax,ss)
Time Frame: up to 24 hours
up to 24 hours
Time of maximum concentration (tmax)
Time Frame: up to 24 hours
up to 24 hours
Area under the plasma concentration time curve from 0 to 12 hours (AUC0-12)
Time Frame: up to 12 hours
up to 12 hours

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
Measure Description
Time Frame
Number of subjects with adverse events
Time Frame: up to 32 days
up to 32 days
Oral clearance (Cl/F)
Time Frame: up to 24 hours
up to 24 hours
Apparent terminal half life (t1/2)
Time Frame: up to 24 hours
up to 24 hours
Percent of erythromycin metabolized per hour
Time Frame: up to 24 hours
Erythromycin breath test (ERMBT)
up to 24 hours
Number of subjects with clinically significant findings in laboratory tests
Time Frame: up to 32 days
up to 32 days

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.
Boehringer Ingelheim

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.

Helpful Links

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.
October 1, 2000

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.
December 1, 2000

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).
September 25, 2014

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.
September 25, 2014

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.
September 29, 2014

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 29, 2014

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 25, 2014

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, 2014

More Information

Terms related to this study

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.
  • 1182.5

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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