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)

Boehringer Ingelheim96 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Healthy

Interventions

BI 425809DRUG

Tablets

Eligibility

Sex: ALLMin age: 18 YearsMax age: 50 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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

Time frame: 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.

Time frame: 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.

Time frame: 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 Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: Up to 528 hours. The details are described in description.

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)

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes