A Study to Test How Healthy Men Tolerate Different Doses of BI 1595043

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Placebo; Drug: BI 1595043; Drug: Midazolam

• Registration Number: NCT04789304
• Lead Sponsor: Boehringer Ingelheim

Brief Summary

The primary objectives of this trial are to investigate safety and tolerability of BI 1595043 in healthy male subjects following administration of multiple rising doses over 14 days.

Secondary objectives are the exploration of pharmacokinetics (PK) of BI 1595043 after single and multiple dosing.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-03-08
• Study First Submitted QC: 2021-03-08
• Study First Posted: 2021-03-09
• Study Start: 2021-04-01
• Primary Completion: 2022-01-14
• Study Completion: 2022-01-14
• Status Verified: 2023-07
• Results First Submitted: 2023-07-05
• Results First Submitted QC: 2023-07-05
• Last Update Submitted: 2023-07-05
• Results First Posted: 2024-02-21
• Last Update Posted: 2024-02-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 30

Inclusion Criteria

• Healthy male subjects according to the assessment of the investigator, as based on a complete medical history including a physical examination, vital signs (blood pressure (BP), pulse rate (PR), body temperature), 12-lead electrocardiogram (ECG), and clinical laboratory tests

• Age of 18 to 50 years (inclusive)

• BMI of 18.5 to 29.9 kg/m2 (inclusive)

• Signed and dated written informed consent prior to admission to the study, in accordance with Good Clinical Practice (GCP) and local legislation

• Male subjects who meet any of the following criteria from at least 30 days before the first administration of trial medication until 30 days after trial completion:

  • Use of adequate contraception, i.e. use of condom (male subjects) plus any of the following methods (female partners): intrauterine device, hormonal contraception (e.g. implants, injectables, combined oral or vaginal contraceptives) that started at least 2 months prior to first drug administration to the male subject, or barrier method (e.g. diaphragm with spermicide), or surgically sterilised (including bilateral tubal occlusion, hysterectomy or bilateral oophorectomy), or postmenopausal, defined as at least 1 year of spontaneous amenorrhea
  • Sexually abstinent
  • Vasectomised (vasectomy at least 1 year prior to enrolment) in combination with a barrier method (i.e. condom) Unprotected sexual intercourse (i.e. without use of condom) with a pregnant female partner and sperm donation is not allowed throughout the study and until 30 days after trial completion

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 millimetre of mercury (mmHg), diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 45 to 90 beats per minute (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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
60 mg BI 1595043 + Midazolam	Midazolam	60 mg BI 1595043 + Midazolam. Dose group 3.
Placebo / Placebo + Midazolam	Placebo	Placebo matching BI 1595043. Patients included in the placebo arm corresponding to dose group 3, also received Midazolam.
15 mg BI 1595043	BI 1595043	15 milligram (mg) BI 1595043. Dose group 1.
30 mg BI 1595043	BI 1595043	30 mg BI 1595043. Dose group 2.
60 mg BI 1595043 + Midazolam	BI 1595043	60 mg BI 1595043 + Midazolam. Dose group 3.
Placebo / Placebo + Midazolam	Midazolam	Placebo matching BI 1595043. Patients included in the placebo arm corresponding to dose group 3, also received Midazolam.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Drug-related Adverse Events (AEs)	From first drug administration until end of trial examination, up to 30 days.	Percentage of participants with drug-related adverse events (AEs). The causal relationship of AEs to the investigational product was judged by the investigator. The investigator was asked to record a 'yes' if there was, in his/her judgement, a reasonable causal relationship between the investigational product administered and the AE or a 'no' if there was, in his/her judgement, no reasonable causal relationship between the investigational product administered and the AE.

Secondary Outcome Measures

Name	Time	Method
Area Under the Concentration-time Curve of BI 1595043 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUC0-τ,ss)	0.25 hours before and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 34, 48, 72, 96, 120 and 144 hours after the last dose of BI 1595043.	Area under the concentration-time curve of BI 1595043 in plasma at steady state over a uniform dosing interval τ (AUC0-τ,ss) after the last dose of BI 1595043.
Accumulation Ratio Based on Area Under the Concentration-time Curve of BI 1595043 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUC0-τ,ss) (RA, AUC)	0.25 hours before and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 34, 48, 72, 96, 120 and 144 hours after the last dose of BI 1595043.	Accumulation ratio based on area under the concentration-time curve of BI 1595043 in plasma at steady state over a uniform dosing interval τ (AUC0-τ,ss) (RA, AUC).; RA,AUC = AUC0-\\tau after last dose / AUC0-\\tau after first dose.
Maximum Measured Concentration of BI 1595043 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss)	0.25 hours before and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 34, 48, 72, 96, 120 and 144 hours after the last dose of BI 1595043.	Maximum measured concentration of BI 1595043 in plasma at steady state over a uniform dosing interval τ (Cmax,ss) after the last dose of BI 1595043.
Accumulation Ratio Based on Maximum Measured Concentration of BI 1595043 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss) (RA, Cmax)	0.25 hours before and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 34, 48, 72, 96, 120 and 144 hours after the last dose of BI 1595043.	Accumulation ratio based on maximum measured concentration of BI 1595043 in plasma at steady state over a uniform dosing interval τ (Cmax,ss) (RA, Cmax), after the last dose.; RA,Cmax = Cmax after last dose / Cmax after first dose.
Minimum Measured Concentration of BI 1595043 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmin,ss)	0.25 hours before and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 34, 48, 72, 96, 120 and 144 hours after the last dose of BI 1595043.	Minimum measured concentration of BI 1595043 in plasma at steady state over a uniform dosing interval τ (Cmin,ss) after the last dose of BI 1595043.

Trial Locations

Locations (1)

SGS Life Science Services - Clinical Research; 🇧🇪 Edegem, Belgium