Trial Outcomes & Findings for A Study in Healthy People to Compare How 2 Different High Dose Formulations of BI 1015550 Are Taken up in the Body (NCT NCT06393127)

Last Updated: 2025-12-01

Results Overview

Area under the concentration-time curve of nerandomilast (R-BI 1015550) in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) is reported. Geometric least square mean (adjusted geometric mean) and adjusted geometric standard error were calculated using an analysis of variance (ANOVA) model on the logarithmic scale. PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model, which included effects accounting for the following sources of variation: "subjects within sequences" as random effect, "sequence", "period" and "treatment" as fixed effects. These quantities were then back-transformed to the original scale.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

64 participants

Primary outcome timeframe

Within 3 h prior to drug administration, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 34, 48, 58, 72, 96, 120, 144 h after drug administration.

Results posted on

2025-12-01

Participant Flow

This was a open-label, randomised, single-dose, two-way crossover trial in healthy subjects to compare the test treatment (T - nerandomilast \[BI 1015550\] Formulation C2) to the reference treatment (R - nerandomilast Formulation C1, as the phase 3 formulation). Subjects were randomly allocated to the 2 treatment sequences (T-R or R-T), and there was a washout period of at least 10 days between the administration of each treatment.

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. Screening procedures also included physical examination, check of vital signs, electrocardiogram, safety laboratory, demographics, relevant medical history, concomitant therapy. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.

Participant milestones

Participant milestones
Measure	Test treatment (T), then reference treatment (R): T-R Healthy subjects were administered one tablet of nerandomilast (Formulation C2) (Test treatment - T). After a washout period of at least 10 days, subjects were administered one tablet of nerandomilast (Formulation C1 - phase 3 formulation) (Reference treatment - R). Both treatments were administered orally with approximately 240 milliliters (mL) of water after an overnight fast of at least 10 hours (h). After drug administration, subjects additionally fasted for 4 h.	Reference treatment (R), then test treatment (T): R-T Healthy subjects were administered one tablet of nerandomilast (Formulation C1 - phase 3 formulation) (Reference treatment - R). After a washout period of at least 10 days, subjects were administered one tablet of nerandomilast (Formulation C2) (Test treatment - T). Both treatments were administered orally with approximately 240 mL of water after an overnight fast of at least 10 h. After drug administration, subjects additionally fasted for 4 h.
Treatment period 1 STARTED	32	32
Treatment period 1 COMPLETED	32	32
Treatment period 1 NOT COMPLETED	0	0
Washout period STARTED	32	32
Washout period COMPLETED	30	32
Washout period NOT COMPLETED	2	0
Treatment period 2 STARTED	30	32
Treatment period 2 COMPLETED	30	32
Treatment period 2 NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Test treatment (T), then reference treatment (R): T-R Healthy subjects were administered one tablet of nerandomilast (Formulation C2) (Test treatment - T). After a washout period of at least 10 days, subjects were administered one tablet of nerandomilast (Formulation C1 - phase 3 formulation) (Reference treatment - R). Both treatments were administered orally with approximately 240 milliliters (mL) of water after an overnight fast of at least 10 hours (h). After drug administration, subjects additionally fasted for 4 h.	Reference treatment (R), then test treatment (T): R-T Healthy subjects were administered one tablet of nerandomilast (Formulation C1 - phase 3 formulation) (Reference treatment - R). After a washout period of at least 10 days, subjects were administered one tablet of nerandomilast (Formulation C2) (Test treatment - T). Both treatments were administered orally with approximately 240 mL of water after an overnight fast of at least 10 h. After drug administration, subjects additionally fasted for 4 h.
Washout period Withdrawal by Subject	1	0
Washout period Non-compliance from subject with trial procedures	1	0

Baseline Characteristics

A Study in Healthy People to Compare How 2 Different High Dose Formulations of BI 1015550 Are Taken up in the Body

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Test Treatment (T), Then Reference Treatment (R): T-R n=32 Participants Healthy subjects were administered one tablet of nerandomilast (Formulation C2) (Test treatment - T). After a washout period of at least 10 days, subjects were administered one tablet of nerandomilast (Formulation C1 - phase 3 formulation) (Reference treatment - R). Both treatments were administered orally with approximately 240 milliliters (mL) of water after an overnight fast of at least 10 hours (h). After drug administration, subjects additionally fasted for 4 h.	Reference Treatment (R), Then Test Treatment (T): R-T n=32 Participants Healthy subjects were administered one tablet of nerandomilast (Formulation C1 - phase 3 formulation) (Reference treatment - R). After a washout period of at least 10 days, subjects were administered one tablet of nerandomilast (Formulation C2) (Test treatment - T). Both treatments were administered orally with approximately 240 mL of water after an overnight fast of at least 10 h. After drug administration, subjects additionally fasted for 4 h.	Total n=64 Participants Total of all reporting groups
Age, Continuous	36.1 Years STANDARD_DEVIATION 8.4 • n=121 Participants	35.0 Years STANDARD_DEVIATION 8.3 • n=122 Participants	35.5 Years STANDARD_DEVIATION 8.3 • n=243 Participants
Sex: Female, Male Female	17 Participants n=121 Participants	14 Participants n=122 Participants	31 Participants n=243 Participants
Sex: Female, Male Male	15 Participants n=121 Participants	18 Participants n=122 Participants	33 Participants n=243 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=121 Participants	0 Participants n=122 Participants	3 Participants n=243 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	29 Participants n=121 Participants	32 Participants n=122 Participants	61 Participants n=243 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=121 Participants	0 Participants n=122 Participants	0 Participants n=243 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=121 Participants	0 Participants n=122 Participants	1 Participants n=243 Participants
Race (NIH/OMB) Asian	1 Participants n=121 Participants	0 Participants n=122 Participants	1 Participants n=243 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=121 Participants	0 Participants n=122 Participants	0 Participants n=243 Participants
Race (NIH/OMB) Black or African American	1 Participants n=121 Participants	0 Participants n=122 Participants	1 Participants n=243 Participants
Race (NIH/OMB) White	28 Participants n=121 Participants	32 Participants n=122 Participants	60 Participants n=243 Participants
Race (NIH/OMB) More than one race	1 Participants n=121 Participants	0 Participants n=122 Participants	1 Participants n=243 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=121 Participants	0 Participants n=122 Participants	0 Participants n=243 Participants

PRIMARY outcome

Timeframe: Within 3 h prior to drug administration, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 34, 48, 58, 72, 96, 120, 144 h after drug administration.

Population: Pharmacokinetic (PK) parameter analysis set (PKS): includes all subjects in the TS who provided at least 1 PK endpoint that was defined as primary or secondary and 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 they contributed only 1 PK parameter value for 1 period to the statistical assessment. Only participants with available PK data are included in the analysis.

Outcome measures

Outcome measures
Measure	Test treatment (T) n=63 Participants Healthy subjects were administered one tablet of nerandomilast (Formulation C2) orally with approximately 240 mL of water after an overnight fast of at least 10 h. After drug administration, subjects additionally fasted for 4 h.	Reference treatment (R) n=57 Participants Healthy subjects were administered one tablet of nerandomilast (Formulation C1 - phase 3 formulation) orally with approximately 240 mL of water after an overnight fast of at least 10 h. After drug administration, subjects additionally fasted for 4 h.
Area Under the Concentration-time Curve of Nerandomilast in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)	2275.77 hournanomole/Liter (hnmol/L) Standard Error NA Adjusted geometric standard error = 1.04	2166.70 hournanomole/Liter (hnmol/L) Standard Error NA Adjusted geometric standard error = 1.05

PRIMARY outcome

Timeframe: Within 3 h prior to drug administration, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 34, 48, 58, 72, 96, 120, 144 h after drug administration.

Maximum measured concentration of nerandomilast (R-BI 1015550) in plasma (Cmax) is reported. Geometric least square mean (adjusted geometric mean) and adjusted geometric standard error were calculated using an analysis of variance (ANOVA) model on the logarithmic scale. PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model, which included effects accounting for the following sources of variation: "subjects within sequences" as random effect, "sequence", "period" and "treatment" as fixed effects. These quantities were then back-transformed to the original scale.

Outcome measures

Outcome measures
Measure	Test treatment (T) n=63 Participants Healthy subjects were administered one tablet of nerandomilast (Formulation C2) orally with approximately 240 mL of water after an overnight fast of at least 10 h. After drug administration, subjects additionally fasted for 4 h.	Reference treatment (R) n=58 Participants Healthy subjects were administered one tablet of nerandomilast (Formulation C1 - phase 3 formulation) orally with approximately 240 mL of water after an overnight fast of at least 10 h. After drug administration, subjects additionally fasted for 4 h.
Maximum Measured Concentration of Nerandomilast in Plasma (Cmax)	417.47 nanomole/Liter (nmol/L) Standard Error NA Adjusted geometric standard error = 1.05	368.38 nanomole/Liter (nmol/L) Standard Error NA Adjusted geometric standard error = 1.06

SECONDARY outcome

Timeframe: Within 3 h prior to drug administration, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 34, 48, 58, 72, 96, 120, 144 h after drug administration.

Area under the concentration-time curve of nerandomilast (R-BI 1015550) in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is reported. Geometric least square mean (adjusted geometric mean) and adjusted geometric standard error were calculated using an analysis of variance (ANOVA) model on the logarithmic scale. PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model, which included effects accounting for the following sources of variation: "subjects within sequences" as random effect, "sequence", "period" and "treatment" as fixed effects. These quantities were then back-transformed to the original scale.

Outcome measures

Outcome measures
Measure	Test treatment (T) n=63 Participants Healthy subjects were administered one tablet of nerandomilast (Formulation C2) orally with approximately 240 mL of water after an overnight fast of at least 10 h. After drug administration, subjects additionally fasted for 4 h.	Reference treatment (R) n=57 Participants Healthy subjects were administered one tablet of nerandomilast (Formulation C1 - phase 3 formulation) orally with approximately 240 mL of water after an overnight fast of at least 10 h. After drug administration, subjects additionally fasted for 4 h.
Area Under the Concentration-time Curve of Nerandomilast in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)	2298.06 hournanomole/Liter (hnmol/L) Standard Error NA Adjusted geometric standard error = 1.04	2189.77 hournanomole/Liter (hnmol/L) Standard Error NA Adjusted geometric standard error = 1.04

Adverse Events

Reference treatment (R)

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Test treatment (T)

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Reference treatment (R) n=59 participants at risk Healthy subjects were administered one tablet of nerandomilast (Formulation C1 - phase 3 formulation) orally with approximately 240 mL of water after an overnight fast of at least 10 h. After drug administration, subjects additionally fasted for 4 h.	Test treatment (T) n=63 participants at risk Healthy subjects were administered one tablet of nerandomilast (Formulation C2) orally with approximately 240 mL of water after an overnight fast of at least 10 h. After drug administration, subjects additionally fasted for 4 h.
Nervous system disorders Headache	8.5% 5/59 • Adverse events: from drug administration up to 7 days. All-cause mortality: from drug administration until end of study examination, up to 37 days. Treated set (TS): includes all subjects who were treated with at least one dose of trial drug.	3.2% 2/63 • Adverse events: from drug administration up to 7 days. All-cause mortality: from drug administration until end of study examination, up to 37 days. Treated set (TS): includes all subjects who were treated with at least one dose of trial drug.

Additional Information

Boehringer Ingelheim, Call Center

Boehringer Ingelheim

Phone: 1-800-243-0127

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER