Clinical trial NCT02337283: 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)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2015-01-13
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: frequency [N(%)] of subjects with drug related adverse events (AEs)
timeFrame: up to 25 days after first drug administration
measure: AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point) only part II
timeFrame: up to 96 hours
measure: Cmax (maximum measured concentration of the analyte in plasma) only part II
timeFrame: up to 96 hours
Secondary outcomes:
measure: Cmax (maximum measured concentration of the analyte in plasma)
timeFrame: up to 72 hours after first dose
measure: AUCt,ss (area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval t)
timeFrame: up to 216 hours after last dose
measure: Cmax,ss (maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval t)
timeFrame: up to 216 hours after last dose
measure: AUC0-infinity (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) only part II
timeFrame: up to 96 hours
measure: AUCt 0-24(area under the concentration-time curve of the analyte in plasma over a uniform dosing interval t after administration of the first dose)
timeFrame: up to 72 hours after first dose
Other outcomes:
Locations:
city: Mannheim
country: Germany
facility: 1346.2.1 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: 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.