A Study in Healthy Japanese and Chinese Men to Test How Well Different Doses of BI 706321 Are Tolerated

Phase 1

Terminated

Conditions: Healthy

Interventions: Drug: Placebo
Drug: BI 706321

Registration Number: NCT05183360

Lead Sponsor: Boehringer Ingelheim

Brief Summary: Part I: The main objectives of this trial are to investigate safety, tolerability, and pharmacokinetics (PK) of BI 706321 in healthy Japanese male subjects following oral administration of multiple rising doses.

Part II: The main objectives of this trial are to investigate safety, tolerability, and pharmacokinetics (PK) of BI 706321 in healthy Chinese male subjects following oral administration of single dose.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: Male

Target Recruitment: 48

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) including body temperature, 12-lead electrocardiogram (ECG), and clinical laboratory tests at screening visit
Part I: Japanese ethnicity, according to the following criteria:

-- born in Japan, have lived outside of Japan <10 years
Part II: Chinese ethnicity including Taiwanese, according to the following criteria:

-- have parents and grandparents who are Chinese
Age of 20 to 45 years (inclusive) at screening visit
Body mass index (BMI) of 18.5 to 25.0kg/m2 (inclusive) at screening visit
Signed and dated written informed consent prior to admission to the study, in accordance with Good Clinical Practice (GCP) and local legislation
Willingness to comply with contraception requirements. Subjects who are sexually active must use adequate contraception methods throughout the trial and until three months after the last administration of trial medication. Adequate methods are:
- A vasectomy performed at least 1 year prior to screening and with medical assessment of the surgical success or
- Surgical sterilization, including bilateral tubal occlusion, hysterectomy or bilateral oophorectomy, of the subject's female partner or
- The use of condoms, if the female partner uses an adequate contraception method in addition, e.g., intrauterine device (IUD), or hormonal contraception, such as implants and injectables, combined with oral or vaginal contraceptives, that started at least 2 months prior to first drug administration, or barrier method, e.g., diaphragm with spermicide

Exclusion Criteria

Any finding in the medical examination (including BP, PR, body temperature or ECG) deviating from normal and assessed as clinically relevant by the investigator at screening visit
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 at screening visit
Any laboratory value outside the reference range that the investigator considers to be of clinical relevance at screening visit
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, per investigator judgement
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
Placebo Matching BI 706321 (Part I)	Placebo	This trial consisted of two parts: a single-dose part and a multiple-dose part. Single-Dose Part: On Day 1, after fasting for at least 10 hours overnight, participants received a single dose of placebo tablets matching BI 706321. Multiple-Dose Part: From Day 6 to Day 19, after fasting for at least 10 hours overnight, participants received a daily dose of placebo tablets matching BI 706321.
2 mg BI 706321 (Part I)	BI 706321	This trial consisted of two parts: a single-dose part and a multiple-dose part. Single-Dose Part: On Day 1, after fasting for at least 10 hours overnight, participants received a single dose of one 2 milligrams (mg) tablet BI 706321. Multiple-Dose Part: From Day 6 to Day 19, after fasting for at least 10 hours overnight, participants received a daily dose of one 2 mg tablet BI 706321.
5 mg BI 706321 (Part I)	BI 706321	This trial consisted of two parts: a single-dose part and a multiple-dose part. Single-Dose Part: On Day 1, after fasting for at least 10 hours overnight, participants received a single dose of one 5 mg tablet BI 706321. Multiple-Dose Part: From Day 6 to Day 19, after fasting for at least 10 hours overnight, participants received a daily dose of one 5 mg tablet BI 706321.
8 mg BI 706321 (Part I)	BI 706321	This trial consisted of two parts: a single-dose part and a multiple-dose part. Single-Dose Part: On Day 1, after fasting for at least 10 hours overnight, participants received a single dose of three tablets totaling 8 mg of BI 706321. Multiple-Dose Part: From Day 6 to Day 19, after fasting for at least 10 hours overnight, participants received a daily dose of three tablets totaling 8 mg of BI 706321.
10 mg BI 706321 (Part I)	BI 706321	This trial consisted of two parts: a single-dose part and a multiple-dose part. Single-Dose Part: On Day 1, after fasting for at least 10 hours overnight, participants received a single dose of two tablets totaling 10 mg of BI 706321. Multiple-Dose Part: From Day 6 to Day 19, after fasting for at least 10 hours overnight, participants received a daily dose of two tablets totaling 10 mg of BI 706321.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Drug-related Adverse Events	From 1st drug administration on Day 1 till Day 19 + 16 days Residual Effect Period (REP), up to 35 days.	The percentage of participants treated with investigational drug who experience such an event. Percentage of participants with treatment-emergent adverse events assessed as drug-related by the investigator are reported. Percentages are calculated using total number of participants per treatment as the denominator.

Secondary Outcome Measures

Name	Time	Method
Single-Dose Part: Area Under the Concentration-time Curve of the BI 706321 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUCR0-∞)	Within 3 hours prior to administration and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24 hours, and 1.5, 2, 3, and 4 days after first BI 706321 administration.	The area under the concentration-time curve of the BI 706321 in plasma over the time interval from 0 extrapolated to infinity (AUCR0-∞) after the first dose administration is reported.
Single-Dose Part: Maximum Measured Concentration of BI 706321 in Plasma (Cmax)	Within 3 hours prior to administration and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24 hours, and 1.5, 2, 3, and 4 days after first BI 706321 administration.	The maximum measured concentration of BI 706321 in plasma (Cmax) after the first dose administration is reported.
Single-Dose Part: Time From Dosing to Maximum Measured Concentration of BI 706321 in Plasma	Within 3 hours prior to administration and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24 hours, and 1.5, 2, 3, and 4 days after first BI 706321 administration.	The time from dosing to maximum measured concentration of BI 706321 in plasma after first drug administration is reported.
Area Under the Concentration-time Curve of BI 706321 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss)	Within 3 hours prior to administration and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24 hours, and 1.5, 2, 3, and 4 days, and additional time points up to 26 days after first BI 706321 administration.	Area under the concentration-time curve of BI 706321 in plasma at steady state over a uniform dosing interval τ (AUCτ,ss) after single and multiple dose administration is reported.
Maximum Measured Concentration of BI 706321 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss)	Within 3 hours prior to administration and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24 hours, and 1.5, 2, 3, and 4 days, and additional time points up to 26 days after first BI 706321 administration.	Maximum measured concentration of BI 706321 in plasma at steady state over a uniform dosing interval τ (Cmax,ss) after single and multiple dose administration is reported
Minimum Concentration of BI 706321 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmin,ss)	Within 3 hours prior to administration and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24 hours, and 1.5, 2, 3, and 4 days, and additional time points up to 26 days after first BI 706321 administration.	Minimum concentration of BI 706321 in plasma at steady state over a uniform dosing interval τ (Cmin,ss) after single and multiple dose administration is reported.
Accumulation Ratio Based on Cₘₐₓ (Rᴀ,ᴄₘₐₓ,ₛₛ)	Within 3 hours prior to administration and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24 hours, and 1.5, 2, 3, and 4 days, and additional time points up to 26 days after first BI 706321 administration.	The accumulation ratio based on Cₘₐₓ (Rᴀ,ᴄₘₐₓ,ₛₛ) shows how much the drug concentration increases at steady state compared to the first dose. It is calculated as a ratio of Cₘₐₓ at steady state (Cₘₐₓ,ₛₛ) and Cₘₐₓ after the first dose (Cₘₐₓ). Rᴀ,ᴄₘₐₓ,ₛₛ = Cₘₐₓₛₛ/Cₘₐₓ.
Accumulation Ratio Based on AUC₀-ₜ (Rᴀ,ᴀᴜᴄ₀-ₜ,ₛₛ)	Within 3 hours prior to administration and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24 hours, and 1.5, 2, 3, and 4 days, and additional time points up to 26 days after first BI 706321 administration.	The accumulation ratio based on AUC₀-ₜ (Rᴀ,ᴀᴜᴄ₀-ₜ,ₛₛ) shows how much the total drug exposure over a uniform dosing interval τ increases at steady state compared to the first dose. It is calculated as a ration of AUC₀-ₜ at steady state (AUC₀-ₜₛₛ) and AUC₀-ₜ after the first dose (AUC₀-ₜ). Rᴀ,ᴀᴜᴄ₀-ₜ,ₛₛ = AUC₀-ₜₛₛ/AUC₀-ₜ.