- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04619251
A Study in Healthy Japanese Men to Test How Different Doses of BI 1323495 Are Tolerated and How Itraconazole Influences the Amount of BI 1323495 in the Blood
Safety, Tolerability and Pharmacokinetics of Single Rising Oral Doses and Multiple Oral Doses of BI 1323495 Versus Placebo in Healthy Male Japanese Subjects Genotyped as Poor and Extensive Metabolizers of UGT2B17 (Single-blind, Randomised, Placebo-controlled [Within Dose Groups] Trial), Including an Investigation of Drug-drug Interaction With Itraconazole in Healthy Male Subjects Genotyped as Poor Metabolizers of UGT2B17 (an Open-label, Two-period, Fixed Sequence Trial)
The main objective of the single-rising dose (SRD) part and the multiple rising dose (MD) part is to investigate safety, tolerability, pharmacokinetics and pharmacodynamics (for MD part only) following single rising doses and multiple oral doses of BI 1323495 in healthy male Japanese subjects genotyped as poor metabolizers (PM) and extensive metabolizers (EM) of UGT2B17.
The main objective of the drug-drug interaction (DDI) part is to investigate the relative bioavailability of a single oral dose of BI 1323495 when given alone (treatment R) or in combination with itraconazole (treatment T) in healthy male subjects genotyped as PM of UGT2B17.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Tokyo, Sumida-ku, Japan, 130-0004
- Souseikai Sumida Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Healthy male subjects according to the assessment of the investigator, as based on a complete medical history, including a medical examination, vital signs (BP, PR), 12- lead ECG, and clinical laboratory tests
Japanese ethnicity, according to the following criteria:
--born in Japan, have lived outside of Japan <10 years, and have parents and grandparents who are Japanese
- Age of 20 to 45 years (inclusive) at screening
- BMI of 18.5 to 25.0 kg/m2 (inclusive) at screening
- Signed and dated written informed consent prior to admission to the trial, in accordance with Good Clinical Practice (GCP) and local legislation
- Subjects who agree to minimize the risk of making their partner pregnant by fulfilling any of the following criteria starting from the first administration of trial medication until 90 days after last administration of trial medication
- Use of adequate contraception, any of the following methods plus condom: intrauterine device, combined oral contraceptives that started at least 2 months prior to the first drug administration.
- Vasectomized (vasectomy at least 1 year prior to enrolment)
- Surgical sterilization (including bilateral tubal occlusion, hysterectomy or bilateral oophorectomy) of the subject's female partner
- Subjects genotyped as UGT2B17 poor metabolizers, i.e. carrying allele of UGT2B17 gene (*2/*2) (DDI part only)
Exclusion Criteria:
- Any finding in the medical examination (including BP, PR or ECG) deviating from normal and assessed as clinically relevant by the investigator
- Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg, diastolic blood pressure outside the range of 40 to 90 mmHg, or pulse rate outside the range of 40 to 99 bpm
- Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
- Any evidence of a concomitant disease assessed as clinically relevant by the investigator
- Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
- Cholecystectomy or other surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy or simple hernia repair)
- Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders
- History of relevant orthostatic hypotension, fainting spells, or blackouts
- Further exclusion criteria apply
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Sequential Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: SRD part: PM Subjects, BI1323495 10mg
Participants were administered on Day 1 a single oral dose of 10 milligram (mg) of BI 1323495 film-coated tablet together with about 240 milliliter (mL) of water.
A standardized meal was served 30 minutes (min) before drug administration.
One authorized employee of the trial site was witness of the administration of the trial medication.
|
BI 1323495
|
Experimental: SRD part: PM Subjects, BI1323495 30mg
Participants were administered on Day 1 a single oral dose of 30 milligram (mg) of BI 1323495 film-coated tablets together with about 240 milliliter (mL) of water. A standardized meal was served 30 minutes (min) before drug administration. One authorized employee of the trial site was witness of the administration of the trial medication. |
BI 1323495
|
Experimental: SRD part: PM Subjects, BI1323495 100mg
Participants were administered on Day 1 a single oral dose of 100 milligram (mg) of BI 1323495 film-coated tablets together with about 240 milliliter (mL) of water.
A standardized meal was served 30 minutes (min) before drug administration.
One authorized employee of the trial site was witness of the administration of the trial medication.
|
BI 1323495
|
Experimental: SRD part: EM Subjects, BI1323495 30mg
Participants were administered on Day 1 a single oral dose of 30 milligram (mg) of BI 1323495 film-coated tablets together with about 240 milliliter (mL) of water.
A standardized meal was served 30 minutes (min) before drug administration.
One authorized employee of the trial site was witness of the administration of the trial medication.
|
BI 1323495
|
Experimental: SRD part: EM Subjects, BI1323495 70mg
Participants were administered on Day 1 a single oral dose of 70 milligram (mg) of BI 1323495 film-coated tablets together with about 240 milliliter (mL) of water.
A standardized meal was served 30 minutes (min) before drug administration.
One authorized employee of the trial site was witness of the administration of the trial medication.
|
BI 1323495
|
Experimental: SRD part: EM Subjects, BI1323495 150mg
Participants were administered on Day 1 a single oral dose of 150 milligram (mg) of BI 1323495 film-coated tablets together with about 240 milliliter (mL) of water.
A standardized meal was served 30 minutes (min) before drug administration.
One authorized employee of the trial site was witness of the administration of the trial medication.
|
BI 1323495
|
Placebo Comparator: SRD part: Placebo
This arm comprises all placebo treated participants in trial part SRD, regardless of the dose group in which they were treated. Participants were randomized within each dose group in a 3:1 ratio (test treatment to placebo). Participants were administered on Day 1 a single oral dose of placebo film-coated tablet(s) together with about 240 milliliter (mL) of water. A standardized meal was served 30 minutes (min) before drug administration. One authorized employee of the trial site was witness of the administration of the trial medication. |
Placebo
|
Experimental: MD part: PM Subjects, BI1323495 30mg BID
Participants were administered from Day 1 to Day 10 two times per day (bid) an oral dose of 30 milligram (mg) of BI 1323495 film-coated tablets together with about 240 milliliter (mL) of water, At Day 11 participants were administered only a single dose in the morning.
Participants took a normal caloric meal 30 minutes (min) before drug administration.
Subjects fasted for 4 hours (h) after intake of morning dose.
Morning and evening dose were taken with a 12 h time interval approximately at the same time each day during the treatment phase.
One authorized employee of the trial site was witness of the administration of the trial medication.
|
BI 1323495
|
Experimental: MD part: PM Subjects, BI1323495 60mg QD
Participants were administered from Day 1 to Day 11 one time per day (qd) an oral dose of 60 milligram (mg) of BI 1323495 film-coated tablets together with about 240 milliliter (mL) of water.
Participants took a normal caloric meal 30 minutes (min) before drug administration.
Subjects fasted for 4 hours (h) after intake of morning dose.
One authorized employee of the trial site was witness of the administration of the trial medication.
|
BI 1323495
|
Placebo Comparator: MD part: Placebo
This arm comprises all placebo treated participants in trial part MD, regardless of the dose group in which they were treated.
Participants were randomized within each dose group in a 3:1 ratio (test treatment to placebo).
Participants were administered from Day 1 to Day 11 one time per day (qd) an oral dose of placebo film-coated tablets or two times per day (bid) an oral dose of placebo together with about 240 milliliter (mL) of water.
Participants took a normal caloric meal 30 minutes (min) before drug administration.
Subjects fasted for 4 hours (h) after intake of morning dose.
One authorized employee of the trial site was witness of the administration of the trial medication.
|
Placebo
|
Experimental: DDI part: PM Subjects, BI1323495 / BI1323495+ Itraconazole
Administration of BI 1323495 in treatment R and T were separated by at least 11 days. |
BI 1323495
Itraconazole
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
SRD and MD Part: Number of Participants With Drug-related Adverse Events (AEs)
Time Frame: Up to 7 days (for SRD part), up to 17 days (for MD part).
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Number of participants with drug-related adverse events (AEs) is reported for Single rising dose (SRD) and Multiple dose (MD) parts is reported.
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Up to 7 days (for SRD part), up to 17 days (for MD part).
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DDI Part: Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
Time Frame: Within 3 hours (h) before and 20min, 40min, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h, 24h, 34h, 47h, 71h, 95h, 119h, 143h, and 167h after start of BI 1323495 administration on both periods (1 and 2).
|
The area under the concentration-time curve of BI 1323495 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is reported.
The statistical model used for the analysis of this endpoint was an analysis of variance (ANOVA) on the logarithmic scale.
That is, the PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model.
This model included effects accounting for the following sources of variation: subject and treatment.
The effect 'subject' was considered as random, whereas the effect 'treatment' was considered as fixed.
These quantities were then back-transformed to the original scale.
|
Within 3 hours (h) before and 20min, 40min, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h, 24h, 34h, 47h, 71h, 95h, 119h, 143h, and 167h after start of BI 1323495 administration on both periods (1 and 2).
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DDI Part: Maximum Measured Concentration of BI 1323495 in Plasma (Cmax)
Time Frame: Within 3 hours (h) before and 20min, 40min, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h, 24h, 34h, 47h, 71h, 95h, 119h, 143h, and 167h after start of BI 1323495 administration on both periods (1 and 2).
|
Maximum measured concentration of BI 1323495 in plasma is reported.
The statistical model used for the analysis of this endpoint was an analysis of variance (ANOVA) on the logarithmic scale.
That is, the PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model.
This model included effects accounting for the following sources of variation: subject and treatment.
The effect 'subject' was considered as random, whereas the effect 'treatment' was considered as fixed.
These quantities were then back-transformed to the original scale.
|
Within 3 hours (h) before and 20min, 40min, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h, 24h, 34h, 47h, 71h, 95h, 119h, 143h, and 167h after start of BI 1323495 administration on both periods (1 and 2).
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
SRD Part: Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
Time Frame: Within 3 hours (h) before and 20min, 40min, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h, 24h, 34h, 48h, 72h, 96h after start of BI 1323495 administration. Additionally only in the PM group: at 120h, 144h, and 168h.
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The area under the concentration-time curve of BI 1323495 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is reported.
|
Within 3 hours (h) before and 20min, 40min, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h, 24h, 34h, 48h, 72h, 96h after start of BI 1323495 administration. Additionally only in the PM group: at 120h, 144h, and 168h.
|
SRD Part: Maximum Measured Concentration of BI 1323495 in Plasma (Cmax)
Time Frame: Within 3 hours (h) before and 20min, 40min, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h, 24h, 34h, 48h, 72h, 96h after start of BI 1323495 administration. Additionally only in the PM group: at 120h, 144h, and 168h.
|
Maximum measured concentration of BI 1323495 in plasma (Cmax) is reported.
|
Within 3 hours (h) before and 20min, 40min, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h, 24h, 34h, 48h, 72h, 96h after start of BI 1323495 administration. Additionally only in the PM group: at 120h, 144h, and 168h.
|
MD Part: Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval of 12 h After Administration of the First Dose (AUC0-12)
Time Frame: Within 3 hours (h) before and 20min, 40min, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h, after start of first dose BI 1323495 administration.
|
The area under the concentration-time curve of BI 1323495 in plasma over the time interval of 12 h after administration of the first dose (AUC0-12) is reported.
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Within 3 hours (h) before and 20min, 40min, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h, after start of first dose BI 1323495 administration.
|
MD Part: Maximum Measured Concentration of BI 1323495 in Plasma (Cmax) After First Dose
Time Frame: Within 3 hours (h) before and 20min, 40min, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h, after start of first dose BI 1323495 administration.
|
Maximum measured concentration of BI 1323495 in plasma (Cmax) after first dose is reported.
|
Within 3 hours (h) before and 20min, 40min, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h, after start of first dose BI 1323495 administration.
|
MD Part: Area Under the Concentration-time Curve of BI 1323495 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss) After Last Dose Administration.
Time Frame: Within 15 minutes (min) before and 20min, 40min, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h and 24h (only for the 60mg qd administration) after last dose administration.
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Area under the concentration-time curve of BI 1323495 in plasma at steady state over a uniform dosing interval τ (AUCτ,ss) after last dose administration is reported.
T for 30 mg bid is 12h, for 60 mg qd is 24h.
|
Within 15 minutes (min) before and 20min, 40min, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h and 24h (only for the 60mg qd administration) after last dose administration.
|
MD Part: Maximum Measured Concentration of BI 1323495 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss)
Time Frame: Within 15 minutes (min) before and 20min, 40min, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h and 24h (only for the 60mg qd administration) after last dose administration.
|
Maximum measured concentration of BI 1323495 in plasma (Cmax,ss) at steady state over a uniform dosing interval τ is reported.
T for 30 mg bid is 12h, for 60 mg qd is 24h.
|
Within 15 minutes (min) before and 20min, 40min, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h and 24h (only for the 60mg qd administration) after last dose administration.
|
DDI Part: Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
Time Frame: Within 3 hours (h) before and 20min, 40min, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h, 24h, 34h, 47h, 71h, 95h, 119h, 143h, and 167h after start of BI 1323495 administration on both periods (1 and 2).
|
The area under the concentration-time curve BI 1323495 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) is reported.
The statistical model used for the analysis of this endpoint was an analysis of variance (ANOVA) on the logarithmic scale.
That is, the PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model.
This model included effects accounting for the following sources of variation: subject and treatment.
The effect 'subject' was considered as random, whereas the effect 'treatment' was considered as fixed.
These quantities were then back-transformed to the original scale.
|
Within 3 hours (h) before and 20min, 40min, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h, 24h, 34h, 47h, 71h, 95h, 119h, 143h, and 167h after start of BI 1323495 administration on both periods (1 and 2).
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 Enzyme Inhibitors
- Hormone Antagonists
- Antifungal Agents
- Steroid Synthesis Inhibitors
- 14-alpha Demethylase Inhibitors
- Itraconazole
Other Study ID Numbers
- 1405-0003
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions:1. studies in products where Boehringer Ingelheim is not the license holder; 2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; 3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization).
For more details refer to: https://www.mystudywindow.com/msw/datasharing
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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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