Healthy
Conditions
Brief summary
The main objectives of this trial are to investigate pharmacokinetics (PK) of R-BI 1015550 in Japanese healthy male subjects following oral administration of two different single BI 1015550 doses.
Interventions
DRUGNerandomilast
Participants were administered a single film-coated tablet of nerandomilast (Formulation C1), orally with 240 milliliters (mL) of water after an overnight fast of at least 10 hours (h).
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
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), Respiratory rate (RR)), 12-lead Electrocardiogram (ECG), and clinical laboratory tests * Age of 18 to 45 years (inclusive) * Body mass index (BMI) of 18.5 to 25 kg/m2 (inclusive) * Signed and dated written informed consent in accordance with International Council for Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial
Exclusion criteria
* Any finding in the medical examination (including BP, PR, RR or ECG) deviating from normal and assessed as clinically relevant by the investigator * Repeated measurement of systolic blood pressure outside the range of 90 to 140 millimetre(s) of mercury (mmHg), diastolic blood pressure outside the range of 40 to 90 mmHg, or PR outside the range of 40 to 99 beats per minute (bpm) * Any laboratory value outside the reference range that the investigator considers to be of clinical relevance * 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 * History of relevant orthostatic hypotension, fainting spells, or blackouts Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of Nerandomilast in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | Within 3 hours (hrs) before drug intake and at 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 and 144 hrs after drug intake. | Area under the concentration-time curve of nerandomilast in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf) is reported. |
| Maximum Measured Concentration (Cmax) of Nerandomilast in Plasma | Within 3 hours (hrs) before drug intake and at 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 and 144 hrs after drug intake. | Maximum measured concentration (Cmax) of nerandomilast in plasma is reported. |
Countries
Japan
Participant flow
Recruitment details
This was an open-label, non-randomized, and parallel group design study aimed to investigate pharmacokinetics of R-BI 1015550 (nerandomilast) in healthy Japanese male subjects following oral administrations of a single nerandomilast dose of 9 milligrams (mg) or 18 mg.
Pre-assignment details
All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.
Participants by arm
| Arm | Count |
|---|---|
| Nerandomilast 9 mg Participants were administered a single film-coated tablet of 9 mg of nerandomilast (Formulation C1), orally with 240 milliliters (mL) of water after an overnight fast of at least 10 hours (h). | 6 |
| Nerandomilast 18 mg Participants were administered a single film-coated tablet of 18 mg of nerandomilast (Formulation C1), orally with 240 milliliters (mL) of water after an overnight fast of at least 10 hours (h). | 6 |
| Total | 12 |
Baseline characteristics
| Characteristic | Nerandomilast 9 mg | Total | Nerandomilast 18 mg |
|---|---|---|---|
| Age, Continuous | 31.8 Years STANDARD_DEVIATION 10.1 | 29.0 Years STANDARD_DEVIATION 9.9 | 26.2 Years STANDARD_DEVIATION 9.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 12 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 12 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 12 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 1 / 6 | 0 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 |
Outcome results
Primary
Area Under the Concentration-time Curve of Nerandomilast in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf)
Area under the concentration-time curve of nerandomilast in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf) is reported.
Time frame: Within 3 hours (hrs) before drug intake and at 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 and 144 hrs after drug intake.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): The PKS set included all subjects in the treated set (TS) who provided 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. Thus, a subject was included in the PKS, even if he contributed only one PK parameter value for one period to the statistical assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Nerandomilast 9 mg | Area Under the Concentration-time Curve of Nerandomilast in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 2070 hours*nanomoles/Liter (h*nmol/L) | Geometric Coefficient of Variation 13.8 |
| Nerandomilast 18 mg | Area Under the Concentration-time Curve of Nerandomilast in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 3740 hours*nanomoles/Liter (h*nmol/L) | Geometric Coefficient of Variation 52.8 |
Primary
Maximum Measured Concentration (Cmax) of Nerandomilast in Plasma
Maximum measured concentration (Cmax) of nerandomilast in plasma is reported.
Time frame: Within 3 hours (hrs) before drug intake and at 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 and 144 hrs after drug intake.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): The PKS set included all subjects in the treated set (TS) who provided 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. Thus, a subject was included in the PKS, even if he contributed only one PK parameter value for one period to the statistical assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Nerandomilast 9 mg | Maximum Measured Concentration (Cmax) of Nerandomilast in Plasma | 455 nanomoles/Liter (nmol/L) | Geometric Coefficient of Variation 10.6 |
| Nerandomilast 18 mg | Maximum Measured Concentration (Cmax) of Nerandomilast in Plasma | 628 nanomoles/Liter (nmol/L) | Geometric Coefficient of Variation 138 |