Safety, Tolerability, and Pharmacokinetics of Multiple Rising Doses of BI 425809 Tablets for 12 Days to Young and Elderly Healthy Male and Female Volunteers and Comparison of Pharmacokinetics of a Single Oral Dose of BI 425809 (Morning Versus Evening)

Safety, Tolerability, and Pharmacokinetics of Multiple Rising Doses of BI 425809 Tablets Given Orally Once Daily for 12 Days to Young and Elderly Healthy Male and Female Volunteers (Randomised, Double-blind, Placebo-controlled Within Dose Groups Phase I Study)(Part 1) and Comparison of Pharmacokinetics of a Single Oral Dose of BI 425809 After Oral Administration in the Morning Versus Oral Administration in the Evening in Young Healthy Male and Female Volunteers (Randomised, Two-sequence, Open, Two Period, Two-way Cross Over) (Part 2)

The aim of the study is to investigate the safety, tolerability, and pharmacokinetics of multiple rising doses of BI 425809 tablets given orally once daily for 12 days to young and elderly healthy male and female volunteers and to compare single dose pharmacokinetics of BI 425809 given in the morning and in the evening.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: BI 425809

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Mannheim, Germany, 68167
    • CRS Clinical Research Services Mannheim GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion criteria:

• Healthy male or female subjects according to the investigator´s assessment, based on a complete medical history including a physical examination, vital signs (blood pressure (BP), pulse rate (PR), 12-lead electrocardiogram (ECG), and clinical laboratory tests
• age of 18 to 50 years (incl.) for young healthy volunteers or age of 65 to 80 years (incl.) for elderly healthy volunteers
• Body mass index (BMI) of 18.5 to 29.9 kg/m2 (incl.)
• Signed and dated written informed consent prior to admission to the study in accordance with good clinical practice (GCP) and local legislation

• Female subjects who meet any of the following criteria:

  1. Surgically sterilised
  2. Postmenopausal, defined as at least 1 year of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous levels of follicle stimulating hormone (FSH) above 40 U/L and estradiol below 30 ng/L is confirmatory)

Exclusion criteria:

• Any finding in the medical examination (including BP, PR or ECG) is deviating from normal and judged 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 50 to 90 mmHg in young subjects, and systolic blood pressure greater than 150 mmHg, diastolic blood pressure greater than 95 mmHg in elderly subjects, or pulse rate outside the range of 50 to 90 bpm
• Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
• Any evidence of a concomitant disease judged as clinically relevant by the investigator
• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
• Surgery of the gastrointestinal tract that could interfere with kinetics of the trial medication
• 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
• Chronic or relevant acute infections
• Further exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BI 425809 very low dose - part I; Part I only - very low dose tablet, oral administration with 240 ml water, over 14 days	Drug: BI 425809; Tablets; Other Names: Iclepertin
Placebo Comparator: Placebo - part I; Part I only - placebo tablet, oral administration with 240ml water, over 14 days	Drug: Placebo; Tablets
Experimental: BI 425809 low dose - part I; Part I - low dose tablet, oral administration with 240 ml water, over 14 days	Drug: BI 425809; Tablets; Other Names: Iclepertin
Experimental: BI 425809 medium dose - part I; Part I only - medium dose tablet, oral administration with 240 ml water, over 14 days	Drug: BI 425809; Tablets; Other Names: Iclepertin
Experimental: BI 425809 high dose -part I; Part I only - high dose tablet, oral administration with 240 ml water, over 14 days	Drug: BI 425809; Tablets; Other Names: Iclepertin
Experimental: BI 425809 low dose - part II; Part II - one low dose tablet on day 1 of visit 2 and 2a	Drug: BI 425809; Tablets; Other Names: Iclepertin
Experimental: BI 425809 very high dose -part I; Part I only - very high dose tablet, oral administration with 240 ml water, over 14 days	Drug: BI 425809; Tablets; Other Names: Iclepertin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects With Drug Related Adverse Events (AEs) in Part I	Percentage of subjects with drug related adverse events (AEs) in part I is reported	From first dose of study medication until 11 days after the last dose of study medication, up to 25 days
Area Under the Concentration-time Curve of the BI 425809 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) Part II	Area under the concentration-time curve of the BI 425809 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) part II is reported.	PK samples were taken at: 0, 0:30, 1, 2, 3, 3:30, 4, 4:30, 5, 6, 8, 10, 12, 24, 34, 48, 72, 96 hours after drug administration
Maximum Measured Concentration of the BI 425809 in Plasma (Cmax) Part II	Maximum measured concentration of the BI 425809 in plasma (Cmax) part II.	PK samples were taken at: 0, 0:30, 1, 2, 3, 3:30, 4, 4:30, 5, 6, 8, 10, 12, 24, 34, 48, 72, 96 hours after drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects With Drug Related Adverse Events (AEs) in Part II	Percentage of subjects with drug related adverse events (AEs) in part II is reported.	From first dose of study medication until 11 days after the last dose of study medication, up to 12 days
Area Under the Concentration-time Curve of the BI 425809 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC 0-infinity) Part II	Area under the concentration-time curve of the BI 425809 in plasma over the time interval from 0 extrapolated to infinity (AUC 0-infinity) part II. After single dosing in the morning as well as in the evening.	PK samples were taken at: 0, 0:30, 1, 2, 3, 3:30, 4, 4:30, 5, 6, 8, 10, 12, 24, 34, 48, 72, 96 hours after drug administration
Area Under the Concentration-time Curve of the BI 425809 in Plasma Over the Time Interval From 0 to 24 Hours (AUC0-24) Part I	Area under the concentration-time curve of the BI 425809 in plasma over the time interval from 0 to 24 hours (AUC0-24) part I. After the first dose.	PK plasma samples were taken at: 2 hours before drug administration and 0:30, 1, 2, 3, 3:30, 4, 4:30, 5, 6, 8, 10, 12, 24 hours after the drug administration in YH and EH population
Area Under the Concentration-time Curve of the BI 425809 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss) Part I	The AUC of BI 425809 in plasma at steady state over a dosing interval (AUCτ,ss) in Part I was evaluated for all arms achieving steady state. For the 75 mg twice-daily multiple-dose arm in young healthy subjects (YH), steady state was not achieved due to nonlinear pharmacokinetics; therefore, AUCτ,ss was not determined. Instead, AUCτ after the final dose (AUCτ,22) was calculated, representing AUC over one dosing interval (τ; dosing interval) after the last dose on Day 14 (22nd dose), not at steady state. PK sampling: 75 mg BID YH: 2 h pre-dose and 0:30, 1-6 h (including 30-minute time points), 8, 10, 12, 24-240 h, 264, 288, 312-324 h (including 30-minute time points), 336, 360, 384, 408, 432, 456, 480, 504, 528 h post-dose. Other arms: 0:30, 1-6 h (including 30-minute time points), 8, 10, 12, 24-240 h, 264-272 h (including 30-minute time points), 288, 360, 384, 408, 432, 456, 480, 504, and 528 h post-dose. Time points 264-272 h apply only to 25 mg multiple-dose arms in YH and EH.	Up to 528 hours. The details are described in description.
Maximum Measured Concentration of the BI 425809 in Plasma (Cmax) Part I	Maximum measured concentration of the BI 425809 in plasma (Cmax) part I. After the first dose.	PK plasma samples were taken at: 0:30, 1, 2, 3, 3:30, 4, 4:30, 5, 6, 8, 10, 12, 24, 34, 48 and 58 hours after drug administration.
Maximum Measured Concentration of the BI 425809 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss) Part I	Maximum measured plasma concentration of BI 425809 at steady state over a dosing interval (Cmax,ss) in Part I was evaluated for all treatment arms achieving steady state For the 75 mg twice-daily multiple-dose arm in young healthy subjects (YH), steady state was not achieved due to non-linear pharmacokinetics; therefore, Cmax,ss was not determined. Instead, Cmax after the final dose (Cmax,22) was calculated, representing the maximum observed concentration following the last dose on Day 14 (22nd dose), not at steady-state PK sampling: 75 mg BID YH: 2 h pre-dose and 0:30, 1-6 h (including 30-min time points), 8, 10, 12, 24-240 h, 264, 288, 312-324 h (including 30-min time points), 336, 360, 384, 408, 432, 456, 480, 504, 528 h post-dose Other arms: 0:30, 1-6 h (including 30-min time points), 8, 10, 12, 24-240 h, 264-272 h (including 30-min time points); 288, 360, 384, 408, 432, 456, 480, 504, and 528 h post-dose Time points 264-272 h apply only to 25 mg multiple-dose arms in YH and EH	Up to 528 hours. The details are described in description.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim
• Investigators: Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Publications and helpful links

General Publications

• Moschetti V, Schlecker C, Wind S, Goetz S, Schmitt H, Schultz A, Liesenfeld KH, Wunderlich G, Desch M. Multiple Rising Doses of Oral BI 425809, a GlyT1 Inhibitor, in Young and Elderly Healthy Volunteers: A Randomised, Double-Blind, Phase I Study Investigating Safety and Pharmacokinetics. Clin Drug Investig. 2018 Aug;38(8):737-750. doi: 10.1007/s40261-018-0660-2.

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2015
• Primary Completion (Actual): November 16, 2015
• Study Completion (Actual): November 16, 2015

Study Registration Dates

• First Submitted: January 9, 2015
• First Submitted That Met QC Criteria: January 9, 2015
• First Posted (Estimated): January 13, 2015

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: April 21, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nootropic Agents; BI 425809
• Other Study ID Numbers: 1346.2; 2014-004390-16 (EudraCT Number: EudraCT)