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

Healthy Clinical Trial

Official 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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04619251
• Other study ID #: 1405-0003
• Status: Completed
• Phase: Phase 1
• Start date: November 13, 2020
• Est. completion date: August 3, 2021

Study information

• Verified date: March 2024
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 74
• Est. completion date: August 3, 2021
• Est. primary completion date: July 30, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• BI 1323495
BI 1323495
• Placebo
Placebo
• Itraconazole
Itraconazole

Locations

Country	Name	City	State
Japan	SOUSEIKAI Sumida Hospital	Tokyo, Sumida-ku

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	SRD and MD Part: Number of Participants With Drug-related Adverse Events (AEs)	Number of participants with drug-related adverse events (AEs) is reported for Single rising dose (SRD) and Multiple dose (MD) parts is reported.	Up to 7 days (for SRD part), up to 17 days (for MD part).
Primary	DDI Part: Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-8)	The area under the concentration-time curve of BI 1323495 in plasma over the time interval from 0 extrapolated to infinity (AUC0-8) 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).
Primary	DDI Part: Maximum Measured Concentration of BI 1323495 in Plasma (Cmax)	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	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)	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).
Secondary	SRD Part: Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-8)	The area under the concentration-time curve of BI 1323495 in plasma over the time interval from 0 extrapolated to infinity (AUC0-8) 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.
Secondary	SRD Part: Maximum Measured Concentration of BI 1323495 in Plasma (Cmax)	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.
Secondary	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)	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.	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.
Secondary	MD Part: Maximum Measured Concentration of BI 1323495 in Plasma (Cmax) After First Dose	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.
Secondary	MD Part: Area Under the Concentration-time Curve of BI 1323495 in Plasma at Steady State Over a Uniform Dosing Interval t (AUCt,ss) After Last Dose Administration.	Area under the concentration-time curve of BI 1323495 in plasma at steady state over a uniform dosing interval t (AUCt,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.
Secondary	MD Part: Maximum Measured Concentration of BI 1323495 in Plasma at Steady State Over a Uniform Dosing Interval t (Cmax,ss)	Maximum measured concentration of BI 1323495 in plasma (Cmax,ss) at steady state over a uniform dosing interval t 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.

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