Healthy
Conditions
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.
Interventions
DRUGBI 706321
BI 706321, tablet, oral use
DRUGPlacebo
Placebo, tablet, oral use
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
20 Years to 45 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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 |
Countries
Japan
Participant flow
Recruitment details
This was a randomized, placebo-controlled, double-blind trial conducted in two parts. Part I involved 48 healthy Japanese males who received BI 706321 as single and multiple rising doses. Part II was planned to involve healthy Chinese males receiving a single dose of BI 706321, but the trial was prematurely discontinued before starting Part II, and no participants were enrolled in Part II.
Pre-assignment details
48 Japanese male participants who met all inclusion criteria and no exclusion criteria were enrolled in Part I of the trial. All received the trial medication and placebo as planned and completed the trial per protocol. Participants were free to withdraw at any time and were closely monitored. The trial was prematurely discontinued per protocol before Part II began.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matching BI 706321 (Part I) 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. | 12 |
| 2 mg BI 706321 (Part I) 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. | 9 |
| 5 mg BI 706321 (Part I) 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. | 9 |
| 8 mg BI 706321 (Part I) 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. | 9 |
| 10 mg BI 706321 (Part I) 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. | 9 |
| Total | 48 |
Baseline characteristics
| Characteristic | Placebo Matching BI 706321 (Part I) | 2 mg BI 706321 (Part I) | 5 mg BI 706321 (Part I) | 8 mg BI 706321 (Part I) | 10 mg BI 706321 (Part I) | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 32.8 Years STANDARD_DEVIATION 7.9 | 31.9 Years STANDARD_DEVIATION 8.2 | 29.4 Years STANDARD_DEVIATION 7.6 | 31.9 Years STANDARD_DEVIATION 7.5 | 32.3 Years STANDARD_DEVIATION 6.5 | 31.7 Years STANDARD_DEVIATION 7.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 9 Participants | 9 Participants | 9 Participants | 9 Participants | 48 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 12 Participants | 9 Participants | 9 Participants | 9 Participants | 9 Participants | 48 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 12 Participants | 9 Participants | 9 Participants | 9 Participants | 9 Participants | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 9 | 0 / 9 | 0 / 9 | 0 / 9 |
| other Total, other adverse events | 5 / 12 | 2 / 9 | 5 / 9 | 6 / 9 | 8 / 9 |
| serious Total, serious adverse events | 0 / 12 | 0 / 9 | 0 / 9 | 0 / 9 | 0 / 9 |
Outcome results
Primary
Percentage of Participants With Drug-related Adverse Events
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.
Time frame: From 1st drug administration on Day 1 till Day 19 + 16 days Residual Effect Period (REP), up to 35 days.
Population: Treated set: all participants who were randomized and treated with at least one dose of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Matching BI 706321 (Part I) | Percentage of Participants With Drug-related Adverse Events | 8.3 Percentage (%) of participants |
| 2 mg BI 706321 (Part I) | Percentage of Participants With Drug-related Adverse Events | 11.1 Percentage (%) of participants |
| 5 mg BI 706321 (Part I) | Percentage of Participants With Drug-related Adverse Events | 44.4 Percentage (%) of participants |
| 8 mg BI 706321 (Part I) | Percentage of Participants With Drug-related Adverse Events | 66.7 Percentage (%) of participants |
| 10 mg BI 706321 (Part I) | Percentage of Participants With Drug-related Adverse Events | 88.9 Percentage (%) of participants |
Secondary
Accumulation Ratio Based on AUC₀-ₜ (Rᴀ,ᴀᴜᴄ₀-ₜ,ₛₛ)
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.
Time frame: 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.
Population: Pharmacokinetic parameter analysis set (PKS): This set includes all participants in the treated set (TS) who provide at least one PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matching BI 706321 (Part I) | Accumulation Ratio Based on AUC₀-ₜ (Rᴀ,ᴀᴜᴄ₀-ₜ,ₛₛ) | 3.03 Ratio - no unit | Geometric Coefficient of Variation 29.1 |
| 2 mg BI 706321 (Part I) | Accumulation Ratio Based on AUC₀-ₜ (Rᴀ,ᴀᴜᴄ₀-ₜ,ₛₛ) | 3.00 Ratio - no unit | Geometric Coefficient of Variation 23.2 |
| 5 mg BI 706321 (Part I) | Accumulation Ratio Based on AUC₀-ₜ (Rᴀ,ᴀᴜᴄ₀-ₜ,ₛₛ) | 3.52 Ratio - no unit | Geometric Coefficient of Variation 31 |
| 8 mg BI 706321 (Part I) | Accumulation Ratio Based on AUC₀-ₜ (Rᴀ,ᴀᴜᴄ₀-ₜ,ₛₛ) | 3.12 Ratio - no unit | Geometric Coefficient of Variation 18.9 |
Secondary
Accumulation Ratio Based on Cₘₐₓ (Rᴀ,ᴄₘₐₓ,ₛₛ)
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.
Time frame: 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.
Population: Pharmacokinetic parameter analysis set (PKS): This set includes all participants in the treated set (TS) who provide at least one PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matching BI 706321 (Part I) | Accumulation Ratio Based on Cₘₐₓ (Rᴀ,ᴄₘₐₓ,ₛₛ) | 2.43 Ratio - no unit | Geometric Coefficient of Variation 34.5 |
| 2 mg BI 706321 (Part I) | Accumulation Ratio Based on Cₘₐₓ (Rᴀ,ᴄₘₐₓ,ₛₛ) | 2.44 Ratio - no unit | Geometric Coefficient of Variation 25.2 |
| 5 mg BI 706321 (Part I) | Accumulation Ratio Based on Cₘₐₓ (Rᴀ,ᴄₘₐₓ,ₛₛ) | 2.85 Ratio - no unit | Geometric Coefficient of Variation 36.2 |
| 8 mg BI 706321 (Part I) | Accumulation Ratio Based on Cₘₐₓ (Rᴀ,ᴄₘₐₓ,ₛₛ) | 2.44 Ratio - no unit | Geometric Coefficient of Variation 23.1 |
Secondary
Area Under the Concentration-time Curve of BI 706321 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss)
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.
Time frame: 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.
Population: Pharmacokinetic parameter analysis set (PKS): This set includes all participants in the treated set (TS) who provide at least one PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matching BI 706321 (Part I) | Area Under the Concentration-time Curve of BI 706321 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss) | 144 Hours*(nanomoles/L) | Geometric Coefficient of Variation 44.8 |
| 2 mg BI 706321 (Part I) | Area Under the Concentration-time Curve of BI 706321 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss) | 297 Hours*(nanomoles/L) | Geometric Coefficient of Variation 21.9 |
| 5 mg BI 706321 (Part I) | Area Under the Concentration-time Curve of BI 706321 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss) | 764 Hours*(nanomoles/L) | Geometric Coefficient of Variation 19.3 |
| 8 mg BI 706321 (Part I) | Area Under the Concentration-time Curve of BI 706321 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss) | 641 Hours*(nanomoles/L) | Geometric Coefficient of Variation 23 |
Secondary
Maximum Measured Concentration of BI 706321 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss)
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
Time frame: 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.
Population: Pharmacokinetic parameter analysis set (PKS): This set includes all participants in the treated set (TS) who provide at least one PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matching BI 706321 (Part I) | Maximum Measured Concentration of BI 706321 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss) | 7.30 Nanomoles per Liters | Geometric Coefficient of Variation 55.4 |
| 2 mg BI 706321 (Part I) | Maximum Measured Concentration of BI 706321 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss) | 20.0 Nanomoles per Liters | Geometric Coefficient of Variation 25.7 |
| 5 mg BI 706321 (Part I) | Maximum Measured Concentration of BI 706321 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss) | 52.4 Nanomoles per Liters | Geometric Coefficient of Variation 11.1 |
| 8 mg BI 706321 (Part I) | Maximum Measured Concentration of BI 706321 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss) | 43.3 Nanomoles per Liters | Geometric Coefficient of Variation 24.5 |
Secondary
Minimum Concentration of BI 706321 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmin,ss)
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.
Time frame: 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.
Population: Pharmacokinetic parameter analysis set (PKS): This set includes all participants in the treated set (TS) who provide at least one PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matching BI 706321 (Part I) | Minimum Concentration of BI 706321 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmin,ss) | 3.47 Nanomoles per Liters | Geometric Coefficient of Variation 39 |
| 2 mg BI 706321 (Part I) | Minimum Concentration of BI 706321 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmin,ss) | 7.88 Nanomoles per Liters | Geometric Coefficient of Variation 31.9 |
| 5 mg BI 706321 (Part I) | Minimum Concentration of BI 706321 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmin,ss) | 20.8 Nanomoles per Liters | Geometric Coefficient of Variation 27 |
| 8 mg BI 706321 (Part I) | Minimum Concentration of BI 706321 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmin,ss) | 17.4 Nanomoles per Liters | Geometric Coefficient of Variation 25.1 |
Secondary
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-∞)
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.
Time frame: 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.
Population: Pharmacokinetic parameter analysis set (PKS): This set includes all participants in the treated set (TS) who provide at least one PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matching BI 706321 (Part I) | 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-∞) | 78.0 Hours*(nanomoles/L) | Geometric Coefficient of Variation 31.8 |
| 2 mg BI 706321 (Part I) | 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-∞) | 196 Hours*(nanomoles/L) | Geometric Coefficient of Variation 28.7 |
| 5 mg BI 706321 (Part I) | 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-∞) | 447 Hours*(nanomoles/L) | Geometric Coefficient of Variation 32.9 |
| 8 mg BI 706321 (Part I) | 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-∞) | 393 Hours*(nanomoles/L) | Geometric Coefficient of Variation 25.7 |
Secondary
Single-Dose Part: Maximum Measured Concentration of BI 706321 in Plasma (Cmax)
The maximum measured concentration of BI 706321 in plasma (Cmax) after the first dose administration is reported.
Time frame: 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.
Population: Pharmacokinetic parameter analysis set (PKS): This set includes all participants in the treated set (TS) who provide at least one PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matching BI 706321 (Part I) | Single-Dose Part: Maximum Measured Concentration of BI 706321 in Plasma (Cmax) | 3.00 Nanomoles per Liters | Geometric Coefficient of Variation 30.6 |
| 2 mg BI 706321 (Part I) | Single-Dose Part: Maximum Measured Concentration of BI 706321 in Plasma (Cmax) | 8.20 Nanomoles per Liters | Geometric Coefficient of Variation 47.9 |
| 5 mg BI 706321 (Part I) | Single-Dose Part: Maximum Measured Concentration of BI 706321 in Plasma (Cmax) | 18.4 Nanomoles per Liters | Geometric Coefficient of Variation 35.4 |
| 8 mg BI 706321 (Part I) | Single-Dose Part: Maximum Measured Concentration of BI 706321 in Plasma (Cmax) | 17.7 Nanomoles per Liters | Geometric Coefficient of Variation 36.4 |
Secondary
Single-Dose Part: Time From Dosing to Maximum Measured Concentration of BI 706321 in Plasma
The time from dosing to maximum measured concentration of BI 706321 in plasma after first drug administration is reported.
Time frame: 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.
Population: Pharmacokinetic parameter analysis set (PKS): This set includes all participants in the treated set (TS) who provide at least one PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo Matching BI 706321 (Part I) | Single-Dose Part: Time From Dosing to Maximum Measured Concentration of BI 706321 in Plasma | 5.00 Hours |
| 2 mg BI 706321 (Part I) | Single-Dose Part: Time From Dosing to Maximum Measured Concentration of BI 706321 in Plasma | 5.00 Hours |
| 5 mg BI 706321 (Part I) | Single-Dose Part: Time From Dosing to Maximum Measured Concentration of BI 706321 in Plasma | 5.00 Hours |
| 8 mg BI 706321 (Part I) | Single-Dose Part: Time From Dosing to Maximum Measured Concentration of BI 706321 in Plasma | 5.00 Hours |