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Completed

NCT Number: 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

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.

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Key information

Conditions

Age range

20 year–45 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 1

Primary location

SOUSEIKAI Sumida Hospital

Tokyo, Sumida-ku, 130-0004, Japan

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

BI 1323495

Drug

BI 1323495

Placebo

Drug

Placebo

Itraconazole

Drug

Itraconazole

Primary outcomes

  1. 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).

    Number of participants with drug-related adverse events (AEs) is reported for Single rising dose (SRD) and Multiple dose (MD) parts is reported.

  2. 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.

  3. 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.

Secondary outcomes

  1. 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.

  2. 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.

    The area under the concentration-time curve of BI 1323495 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is reported.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

    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.

  7. 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.

Sponsors and collaborators

Lead sponsor

Boehringer Ingelheim

Industry

Registry information

Official study title

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)

Important dates

Study start
2020
Primary completion
2021
Study completion
2021
First posted
Nov 6, 2020
Registry last updated
Mar 27, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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