Effect of BI 201335 Mediated UGT1A1 (Uridine-diphosphate-glucuronosyltransferases) Inhibition in Healthy Volunteers

July 17, 2014 updated by: Boehringer Ingelheim

An Open Label Fixed Sequence Phase I Study to Investigate the Effect of BI 201335 Mediated UGT1A1 Inhibition on the Multiple Oral Dose Pharmacokinetics of Raltegravir (Isentress®) in Healthy Male and Female Volunteers

Study to investigate the effect of UGT1A1 inhibition by single and multiple oral doses of BI 201335 on the single and multiple oral dose pharmacokinetics of raltegravir and to investigate safety and tolerability.

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.
24

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

21 years to 50 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Healthy males and females
  • Age ranging ≥ 21 and ≤ 50 years
  • Body mass index (BMI) ≥ 18.5 and ≤ 29.9 kg/m2
  • Willing to complete all study-related activities including genotyping
  • Volunteers give their written informed consent prior to admission to the study

Exclusion Criteria:

  • Any finding of the medical examination (including blood pressure, pulse rate and ECG (Electrocardiogram)) deviating from normal and of clinical relevance
  • Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders, clinically relevant electrolyte disturbances
  • Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
  • History of photosensitivity or recurrent rash
  • History of orthostatic hypotension, fainting spells or blackouts
  • Chronic or clinically relevant acute infections
  • History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator
  • Intake of drugs with a long half-life (> 24:00 hours) within at least one month or less than ten half-lives of the respective drug before enrolment in the study or during the study (with the exception of hormonal contraceptives)
  • Use of any drugs which might influence the results of the trial up to 7 days prior to enrolment in the trial or during the trial
  • Participation in another trial with an investigational drug (within two months prior to administration or during the trial)
  • Smoker (> 10 cigarettes or > 3 cigars of > 3 pipes/day)
  • Inability to refrain from smoking on trial days
  • Alcohol abuse (> 60 g/day)
  • Drug abuse
  • Blood donation (> 100 mL within four weeks prior to administration or during the trial)
  • Any laboratory value outside the reference range if indicative of underlying disease or poor health
  • Excessive physical activities within the last week before the trial or during the trial
  • Hypersensitivity to treatment medication and/or related drugs of these classes
  • A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTcF, or QTcB interval >450 ms)
  • Vulnerable subjects (that is persons kept in detention)
  • The subject is not able to understand and comply with protocol requirements, instructions and protocol-stated restrictions

  • For Female Subjects:

    • Pregnancy
    • Positive pregnancy test
    • Lactation period
    • No adequate contraception: females participating in the study must be either (1) of non-childbearing potential (e.g. surgically sterilized or postmenopausal with no menstrual bleeding for at least 2 years prior the study), or (2) using one of the following contraceptive methods plus condom during the course of the study and up to one month (i.e. one complete menstrual cycle) after the last administration of the study drug (whichever is longer): implants of levonorgestrel or injectable progestogen, oral contraceptive - combined or progestogen only, intrauterine device (IUD)- any IUD with published data showing that the lowest expected failure rate is less than 1% per year (not all IUDs meet this criteria)

  • For Male Subjects:

    • No adequate contraception: (1) surgically sterilized or (2) or use a condom plus another form of contraception (e.g. spermicide, IUD, birth control pills taken by female partner, diaphragm with spermicide). Male subjects must not father a child from administration of the first dose and up to 3 months after the last dose of study medication

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: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

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: BI 201335 NA

400 mg raltegravir (bid) from day 1-14 and once on day 15;

240 mg BI 201335 NA (bid) from day 7-14 with a loading dose of 480 mg in the morning of day 6 and once on day 15
Drug: Raltegravir
Drug: BI 201335 NA

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
Steady-state Cmax,ss (maximum measured concentration) of raltegravir and raltegravir glucuronide
Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 hours post-dose on day 5, 7 and 15
Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 hours post-dose on day 5, 7 and 15
Steady-state AUC0-12h,ss (Area under the concentration-time curve) of raltegravir and raltegravir glucuronide
Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 hours post-dose on day 5, 7 and 15
Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 hours post-dose on day 5, 7 and 15
C12h,ss of raltegravir and raltegravir glucuronide
Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 hours post-dose on day 5, 7 and 15
Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 hours post-dose on day 5, 7 and 15

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
Number of patients with abnormal findings in physical examination
Time Frame: Baseline and within 7-14 days after last treatment
Baseline and within 7-14 days after last treatment
Number of patients with clinically significant changes in vital signs (blood pressure, pulse rate)
Time Frame: Baseline and days 1, 5, 6, 7, 15 and within 7-14 days after last treatment
Baseline and days 1, 5, 6, 7, 15 and within 7-14 days after last treatment
Number of patients with adverse events
Time Frame: up to 7 - 14 days after last treatment
up to 7 - 14 days after last treatment
Number of patients with abnormal findings in 12-lead ECG (electrocardiogram)
Time Frame: Baseline, days 1, 5, 6, 7, 15 and within 7-14 days after last treatment
Baseline, days 1, 5, 6, 7, 15 and within 7-14 days after last treatment
Number of patients with abnormal changes in laboratory tests (hematology, clinical chemistry, urine analysis)
Time Frame: Baseline, days 1, 2, 5, 6, 7, 8, 10, 12, 14, 15, 16 and within 7-14 days after last treatment
Baseline, days 1, 2, 5, 6, 7, 8, 10, 12, 14, 15, 16 and within 7-14 days after last treatment
Assessment of tolerability by investigator on a 4-point scale
Time Frame: within 7-14 days after last treatment
within 7-14 days after last treatment
Cmax,ss of BI 201335 ZW
Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 hours post-dose on day 7 and 15
Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 hours post-dose on day 7 and 15
C12h,ss of BI 201335 ZW
Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 hours post-dose on day 7 and 15
Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 hours post-dose on day 7 and 15
AUC0-12,ss of BI 201335 ZW
Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 hours post-dose on day 7 and 15
Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 hours post-dose on day 7 and 15
tmax,ss (Time from dosing to the maximum measured concentration) of BI 201335 ZW
Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 hours post-dose on day 7 and 15
Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 hours post-dose on day 7 and 15
CL/F0-12,ss (Total apparent clearance) of BI 201335 ZW
Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 hours post-dose on day 7 and 15
Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 hours post-dose on day 7 and 15
V/F0-12,ss (Apparent volume of distribution) of BI 201335 ZW
Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 hours post-dose on day 7 and 15
Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 hours post-dose on day 7 and 15
tmax,ss of raltegravir and raltegravir glucuronide
Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 hours post-dose on day 5, 7 and 15
Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 hours post-dose on day 5, 7 and 15
CL/F0-12,ss of raltegravir
Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 hours post-dose on day 5, 7 and 15
Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 hours post-dose on day 5, 7 and 15
V/F0-12,ss of raltegravir
Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 hours post-dose on day 5, 7 and 15
Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 hours post-dose on day 5, 7 and 15
t1/2 of raltegravir and raltegravir glucuronide
Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 hours post-dose on day 5, 7 and 15
Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 hours post-dose on day 5, 7 and 15
Ae (Amount of analyte eliminated in urine) of raltegravir and raltegravir glucuronide
Time Frame: pre-dose and 0-4, 4-8, 8-12 hours post-dose on day 5, 7, 15
pre-dose and 0-4, 4-8, 8-12 hours post-dose on day 5, 7, 15
CLR (Renal clearance) of raltegravir and raltegravir glucuronide
Time Frame: pre-dose and 0-4, 4-8, 8-12 hours post-dose on day 5, 7, 15
pre-dose and 0-4, 4-8, 8-12 hours post-dose on day 5, 7, 15
fe (Fraction of analyte eliminated in urine) of raltegravir and raltegravir glucuronide
Time Frame: pre-dose and 0-4, 4-8, 8-12 hours post-dose on day 5, 7, 15
pre-dose and 0-4, 4-8, 8-12 hours post-dose on day 5, 7, 15

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.
January 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.
March 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).
July 2, 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.
July 7, 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.
July 8, 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.
July 18, 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.
July 17, 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.
July 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.
  • 1220.9

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