A Study in Healthy People to Test How BI 1015550 is Taken up in the Body When Given With or Without Food

• BI 1015550 (Drug), also known as Nerandomilast, JASCAYD®: Participants received a single 18 mg Nerandomilast Formulation C2 film-coated tablet either after an overnight fast of at least 10 hours or following a high-fat, high-calorie meal.

Primary outcomes

• Area Under the Concentration-time Curve of Nerandomilast in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point) (AUC0-tz) [Within 3 hours before Nerandomilast administration and at 0:15, 0:30, 0:45, 1:00, 1:15, 1:30, 1:45, 2:00, 2:30, 3:00, 3:30, 4:00, 6:00, 8:00, 11:00, 12:00, 24:00, 34:00, 48:00, 58:00, 72:00, 96:00, 120:00, and 144:00 hours after administration.]: Area under the concentration-time curve of Nerandomilast in plasma over the time interval from 0 to the last quantifiable data point is presented. Geometric least square mean (adjusted geometric mean) and geometric standard error were calculated using an analysis of variance (ANOVA) model on the logarithmic scale. The pharmacokinetic (PK) endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. These quantities will then be back-transformed to the original scale to provide the point estimate and 90% confidence intervals (CIs) for each endpoint. This model will include effects accounting for the following sources of variation: sequence, subjects within sequences, period and treatment.
• Maximum Measured Concentration of Nerandomilast in Plasma (Cmax) [Within 3 hours before Nerandomilast administration and at 0:15, 0:30, 0:45, 1:00, 1:15, 1:30, 1:45, 2:00, 2:30, 3:00, 3:30, 4:00, 6:00, 8:00, 11:00, 12:00, 24:00, 34:00, 48:00, 58:00, 72:00, 96:00, 120:00, and 144:00 hours after administration.]: Maximum measured concentration of Nerandomilast in plasma (Cmax) is presented. Geometric least square mean (adjusted geometric mean) and geometric standard error were calculated using an analysis of variance (ANOVA) model on the logarithmic scale. The pharmacokinetic (PK) endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. These quantities will then be back-transformed to the original scale to provide the point estimate and 90% confidence intervals (CIs) for each endpoint. This model will include effects accounting for the following sources of variation: sequence, subjects within sequences, period and treatment.

Secondary outcomes

• Area Under the Concentration-time Curve of Nerandomilast in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) [Within 3 hours before Nerandomilast administration and at 0:15, 0:30, 0:45, 1:00, 1:15, 1:30, 1:45, 2:00, 2:30, 3:00, 3:30, 4:00, 6:00, 8:00, 11:00, 12:00, 24:00, 34:00, 48:00, 58:00, 72:00, 96:00, 120:00, and 144:00 hours after administration.]: Area under the concentration-time curve of Nerandomilast in plasma over the time interval from 0 extrapolated to infinity is presented. Geometric least square mean (adjusted geometric mean) and geometric standard error were calculated using an analysis of variance (ANOVA) model on the logarithmic scale. The pharmacokinetic (PK) endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. These quantities will then be back-transformed to the original scale to provide the point estimate and 90% confidence intervals (CIs) for each endpoint. This model will include effects accounting for the following sources of variation: sequence, subjects within sequences, period and treatment.

Sex: All, ages: 18 Years to 50 Years, accepts healthy volunteers

Inclusion Criteria :

* Healthy male or female 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)), 12-lead electrocardiogram (ECG), and clinical laboratory tests
* Age of 18 to 50 years (inclusive)
* Body mass index (BMI) of 18.5 to 29.9 kg/m\^2 (inclusive)
* Signed and dated written informed consent in accordance with International Conference of Harmonization-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial
* Female subject who meets the criteria defined in the protocol for a highly effective contraception from at least 30 days before the first administration of trial medication until 7 days after last administration

Exclusion Criteria :

* Any finding in the medical examination (including BP, PR 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 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 50 to 90 betas per minute (bpm) at screening
* Any laboratory value outside the reference range that the investigator considers to be of clinical relevance, in particular, hepatic parameters (Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), total bilirubin) or renal parameters (creatinine) exceeding the upper limit of normal (ULN) at screening
* Any evidence of a concomitant disease assessed as clinically relevant by the investigator
* Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders assessed as clinically relevant by the investigator
* 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 including but not limited to depression and suicidal behavior
* History of relevant orthostatic hypotension, fainting spells, or blackouts Further exclusion criteria apply.

Participant flow

Outcome results

• Area Under the Concentration-time Curve of Nerandomilast in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point) (AUC0-tz) (Primary), Geometric least squares mean, hour*nanomol/Liter (h*nmol/L): Nerandomilast fasted state (Reference (R)) 2225.20 +/- NA; Nerandomilast fed state (Test (T)) 2563.65 +/- NA
• Maximum Measured Concentration of Nerandomilast in Plasma (Cmax) (Primary), Geometric least squares mean, nanomol/Liter (nmol/L): Nerandomilast fasted state (Reference (R)) 412.88 +/- NA; Nerandomilast fed state (Test (T)) 354.35 +/- NA
• Area Under the Concentration-time Curve of Nerandomilast in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (Secondary), Geometric least squares mean, hour*nanomol/Liter (h*nmol/L): Nerandomilast fasted state (Reference (R)) 2240.58 +/- NA; Nerandomilast fed state (Test (T)) 2578.16 +/- NA

Adverse events

Time frame: Adverse event collection period: up to 7 days from first Nerandomilast administration. All-cause mortality: up to 28 days from first Nerandomilast administration.

Other adverse events by term

• Study Protocol (PDF, 2024-05-16)
• Statistical Analysis Plan (PDF, 2024-08-06)

NIH grants: 2023