- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02182375
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
Study Type
Interventional
Enrollment (Actual)
24
Phase
- 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
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 |
Intervention / Treatment |
---|---|
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 |
What is the study measuring?
Primary Outcome Measures
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
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
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
January 1, 2010
Primary Completion (ACTUAL)
March 1, 2010
Study Registration Dates
First Submitted
July 2, 2014
First Submitted That Met QC Criteria
July 7, 2014
First Posted (ESTIMATE)
July 8, 2014
Study Record Updates
Last Update Posted (ESTIMATE)
July 18, 2014
Last Update Submitted That Met QC Criteria
July 17, 2014
Last Verified
July 1, 2014
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 1220.9
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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