Trial Outcomes & Findings for Safety, Tolerability and Pharmacokinetics of Multiple Rising Oral Doses of BI 1015550 Powder for Oral Solution (NCT NCT01835899)

Results Overview

Percentage of subjects with drug related Adverse events, as assessed by the investigator.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

24 participants

Primary outcome timeframe

From first drug administration until last drug administration, upto 18 days.

Results posted on

2016-01-22

Participant Flow

This study of multiple doses over 14 days was randomised, double-blind, and placebo-controlled within dose groups.

Participant milestones

Participant milestones
Measure	Placebo to BI 1015550 Subjects were orally administered twice daily with matching Placebo to BI 1015550 Powder for oral solution (PFOS), to have Volume identical to the active drug of the respective dose group.	1 mg BI 1015550 Subjects were orally administered twice daily with BI 1015550 1 mg PfOS (to have 4 mL volume of oral solution in total).	6 mg BI 1015550 Subjects were orally administered twice daily with BI 1015550 6 mg PfOS (to have 24 mL volume of oral solution in total).
Overall Study STARTED	6	9	9
Overall Study COMPLETED	6	8	8
Overall Study NOT COMPLETED	0	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo to BI 1015550 Subjects were orally administered twice daily with matching Placebo to BI 1015550 Powder for oral solution (PFOS), to have Volume identical to the active drug of the respective dose group.	1 mg BI 1015550 Subjects were orally administered twice daily with BI 1015550 1 mg PfOS (to have 4 mL volume of oral solution in total).	6 mg BI 1015550 Subjects were orally administered twice daily with BI 1015550 6 mg PfOS (to have 24 mL volume of oral solution in total).
Overall Study Adverse Event	0	0	1
Overall Study Other than stated above	0	1	0

Baseline Characteristics

Safety, Tolerability and Pharmacokinetics of Multiple Rising Oral Doses of BI 1015550 Powder for Oral Solution

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo to BI 1015550 n=6 Participants Subjects were orally administered twice daily with matching Placebo to BI 1015550 Powder for oral solution (PFOS), to have Volume identical to the active drug of the respective dose group.	1 mg BI 1015550 n=9 Participants Subjects were orally administered twice daily with BI 1015550 1 mg PfOS (to have 4 mL volume of oral solution in total).	6 mg BI 1015550 n=9 Participants Subjects were orally administered twice daily with BI 1015550 6 mg PfOS (to have 24 mL volume of oral solution in total).	Total n=24 Participants Total of all reporting groups
Age, Continuous	43.5 Years STANDARD_DEVIATION 9.9 • n=99 Participants	38.7 Years STANDARD_DEVIATION 8.5 • n=107 Participants	44.3 Years STANDARD_DEVIATION 8.3 • n=206 Participants	42.0 Years STANDARD_DEVIATION 8.8 • n=7 Participants
Sex: Female, Male Female	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Sex: Female, Male Male	6 Participants n=99 Participants	9 Participants n=107 Participants	9 Participants n=206 Participants	24 Participants n=7 Participants

PRIMARY outcome

Timeframe: From first drug administration until last drug administration, upto 18 days.

Population: The treated set (TS) included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.

Percentage of subjects with drug related Adverse events, as assessed by the investigator.

Outcome measures

Outcome measures
Measure	Placebo to BI 1015550 n=6 Participants Subjects were orally administered twice daily with matching Placebo to BI 1015550 Powder for oral solution (PFOS), to have Volume identical to the active drug of the respective dose group.	1 mg BI 1015550 n=9 Participants Subjects were orally administered twice daily with BI 1015550 1 mg PfOS (to have 4 mL volume of oral solution in total).	6 mg BI 1015550 n=9 Participants Subjects were orally administered twice daily with BI 1015550 6 mg PfOS (to have 24 mL volume of oral solution in total).
Percentage of Subjects With Drug-related Adverse Events	16.7 Percentage of participants	44.4 Percentage of participants	11.1 Percentage of participants

SECONDARY outcome

Timeframe: 0:15h(hours); 0:30h; 0:45h; 1h;1:15h;1:30h; 2h;3h; 4h; 6h; 8h;10h; 12h; 24h; 34h and 47:55h after first drug administration.

Population: The PK analysis set (PKS) included all subjects of the TS who provided at least 1 observation for at least 1 secondary PK endpoint and who did not have a protocol violation relevant to the evaluation of PK.

Maximum measured concentration of BI 1015550 in plasma.

Outcome measures

Outcome measures
Measure	Placebo to BI 1015550 n=9 Participants Subjects were orally administered twice daily with matching Placebo to BI 1015550 Powder for oral solution (PFOS), to have Volume identical to the active drug of the respective dose group.	1 mg BI 1015550 n=9 Participants Subjects were orally administered twice daily with BI 1015550 1 mg PfOS (to have 4 mL volume of oral solution in total).	6 mg BI 1015550 Subjects were orally administered twice daily with BI 1015550 6 mg PfOS (to have 24 mL volume of oral solution in total).
Cmax	24.0 nmol/L Geometric Coefficient of Variation 25.1	133.0 nmol/L Geometric Coefficient of Variation 14.9	—

SECONDARY outcome

Timeframe: 0:15h(hours); 0:30h; 0:45h; 1h;1:15h;1:30h; 2h;3h; 4h; 6h; 8h;10h and 12h after first drug administration

Population: PK set

Area under the concentration-time curve of BI 1015550 in plasma over a uniform dosing interval t after administration of the first dose

Outcome measures

Outcome measures
Measure	Placebo to BI 1015550 n=9 Participants Subjects were orally administered twice daily with matching Placebo to BI 1015550 Powder for oral solution (PFOS), to have Volume identical to the active drug of the respective dose group.	1 mg BI 1015550 n=9 Participants Subjects were orally administered twice daily with BI 1015550 1 mg PfOS (to have 4 mL volume of oral solution in total).	6 mg BI 1015550 Subjects were orally administered twice daily with BI 1015550 6 mg PfOS (to have 24 mL volume of oral solution in total).
AUCt,1	94.9 nmol*h/L Geometric Coefficient of Variation 10.3	622 nmol*h/L Geometric Coefficient of Variation 20.7	—

SECONDARY outcome

Timeframe: 0:15h(hours); 0:30h; 0:45h; 1h;1:15h;1:30h; 2h;3h; 4h; 6h; 8h;10h; 12h; 24h; 34h and 47:55h after first drug administration.

Population: PK set

Area under the concentration-time curve of BI 1015550 in plasma over the time interval from 0 extrapolated to infinity.

Outcome measures

Outcome measures
Measure	Placebo to BI 1015550 n=9 Participants Subjects were orally administered twice daily with matching Placebo to BI 1015550 Powder for oral solution (PFOS), to have Volume identical to the active drug of the respective dose group.	1 mg BI 1015550 n=9 Participants Subjects were orally administered twice daily with BI 1015550 1 mg PfOS (to have 4 mL volume of oral solution in total).	6 mg BI 1015550 Subjects were orally administered twice daily with BI 1015550 6 mg PfOS (to have 24 mL volume of oral solution in total).
AUC0-infinity	131 nmol*h/L Geometric Coefficient of Variation 18.6	958 nmol*h/L Geometric Coefficient of Variation 20.9	—

SECONDARY outcome

Timeframe: 311:55h (hours); 312:15h; 312:30h; 312:45; 313h; 313:15h; 313:30h; 314h; 315h; 316h; 318h; 320h; 322h; 324h; 336h; 346h; 360h; 384h & 408h after first drug administration; last drug administration was at 312 h.

Population: PK set

Maximum measured concentration of BI 1015550 in plasma at steady state over a uniform dosing interval t.

Outcome measures

Outcome measures
Measure	Placebo to BI 1015550 n=8 Participants Subjects were orally administered twice daily with matching Placebo to BI 1015550 Powder for oral solution (PFOS), to have Volume identical to the active drug of the respective dose group.	1 mg BI 1015550 n=8 Participants Subjects were orally administered twice daily with BI 1015550 1 mg PfOS (to have 4 mL volume of oral solution in total).	6 mg BI 1015550 Subjects were orally administered twice daily with BI 1015550 6 mg PfOS (to have 24 mL volume of oral solution in total).
Cmax,ss	28.6 nmol/L Geometric Coefficient of Variation 15.3	199 nmol/L Geometric Coefficient of Variation 14.5	—

SECONDARY outcome

Timeframe: 311:55h; 312:15h; 312:30h; 312:45; 313h; 313:15h; 313:30h; 314h; 315h; 316h; 318h; 320h; 322h and 324h after first drug administration; last drug administration was at 312 h.

Population: PK set

Area under the concentration-time curve of BI 1015550 in plasma at steady state over a uniform dosing interval t.

Outcome measures

Outcome measures
Measure	Placebo to BI 1015550 n=8 Participants Subjects were orally administered twice daily with matching Placebo to BI 1015550 Powder for oral solution (PFOS), to have Volume identical to the active drug of the respective dose group.	1 mg BI 1015550 n=8 Participants Subjects were orally administered twice daily with BI 1015550 1 mg PfOS (to have 4 mL volume of oral solution in total).	6 mg BI 1015550 Subjects were orally administered twice daily with BI 1015550 6 mg PfOS (to have 24 mL volume of oral solution in total).
AUCt,ss	148 nmol*h/L Geometric Coefficient of Variation 10.7	1090 nmol*h/L Geometric Coefficient of Variation 19.6	—

Adverse Events

Placebo to BI 1015550

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

1 mg BI 1015550

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

6 mg BI 1015550

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Placebo to BI 1015550 n=6 participants at risk Subjects were orally administered twice daily with matching Placebo to BI 1015550 Powder for oral solution (PFOS), to have Volume identical to the active drug of the respective dose group.	1 mg BI 1015550 n=9 participants at risk Subjects were orally administered twice daily with BI 1015550 1 mg PfOS (to have 4 mL volume of oral solution in total).	6 mg BI 1015550 n=9 participants at risk Subjects were orally administered twice daily with BI 1015550 6 mg PfOS (to have 24 mL volume of oral solution in total).
Gastrointestinal disorders Abdominal pain	0.00% 0/6 • From first drug administration until last drug administration, upto 18 days.	11.1% 1/9 • From first drug administration until last drug administration, upto 18 days.	11.1% 1/9 • From first drug administration until last drug administration, upto 18 days.
Gastrointestinal disorders Abdominal pain lower	0.00% 0/6 • From first drug administration until last drug administration, upto 18 days.	0.00% 0/9 • From first drug administration until last drug administration, upto 18 days.	11.1% 1/9 • From first drug administration until last drug administration, upto 18 days.
Gastrointestinal disorders Aphthous stomatitis	0.00% 0/6 • From first drug administration until last drug administration, upto 18 days.	11.1% 1/9 • From first drug administration until last drug administration, upto 18 days.	0.00% 0/9 • From first drug administration until last drug administration, upto 18 days.
Gastrointestinal disorders Constipation	0.00% 0/6 • From first drug administration until last drug administration, upto 18 days.	0.00% 0/9 • From first drug administration until last drug administration, upto 18 days.	11.1% 1/9 • From first drug administration until last drug administration, upto 18 days.
Gastrointestinal disorders Diarrhoea	0.00% 0/6 • From first drug administration until last drug administration, upto 18 days.	11.1% 1/9 • From first drug administration until last drug administration, upto 18 days.	0.00% 0/9 • From first drug administration until last drug administration, upto 18 days.
Infections and infestations Oral herpes	0.00% 0/6 • From first drug administration until last drug administration, upto 18 days.	11.1% 1/9 • From first drug administration until last drug administration, upto 18 days.	0.00% 0/9 • From first drug administration until last drug administration, upto 18 days.
Injury, poisoning and procedural complications Contusion	0.00% 0/6 • From first drug administration until last drug administration, upto 18 days.	0.00% 0/9 • From first drug administration until last drug administration, upto 18 days.	11.1% 1/9 • From first drug administration until last drug administration, upto 18 days.
Injury, poisoning and procedural complications Traumatic haematoma	0.00% 0/6 • From first drug administration until last drug administration, upto 18 days.	0.00% 0/9 • From first drug administration until last drug administration, upto 18 days.	11.1% 1/9 • From first drug administration until last drug administration, upto 18 days.
Investigations C-reactive protein increased	0.00% 0/6 • From first drug administration until last drug administration, upto 18 days.	0.00% 0/9 • From first drug administration until last drug administration, upto 18 days.	11.1% 1/9 • From first drug administration until last drug administration, upto 18 days.
Nervous system disorders Headache	16.7% 1/6 • From first drug administration until last drug administration, upto 18 days.	11.1% 1/9 • From first drug administration until last drug administration, upto 18 days.	0.00% 0/9 • From first drug administration until last drug administration, upto 18 days.

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
Publication restrictions are in place

Restriction type: OTHER