Trial Outcomes & Findings for Relative Bioavailability of BI 1467335 Tablet and Oral Solution, and Food Effect on Tablet in Healthy Male Subjects (NCT NCT02999191)

Last Updated: 2021-06-07

Results Overview

This outcome measure presents AUC0-tz \[area under the concentration-time curve of BI 1467335 in plasma over the time interval from 0 to the last quantifiable data point\].

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

18 participants

Primary outcome timeframe

At -1:00h [hours (h): minutes (min)] before drug administration and at 0:15, 0:30, 0:45, 1:00, 1:15, 1:30, 1:45, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00 and 24:00 h:min after drug administration.

Results posted on

2021-06-07

Participant Flow

The study was randomised, open-label, single-dose, three-way crossover trial. 18 subjects entered in the study. 18 subjects were treated in Treatment A: BI 1467335 10 mg tablets, fasted. 18 subjects were treated in Treatment B: BI 1467335 10 mg oral solution, fasted and 17 subjects were treated in Treatment C: BI 1467335 10 mg tablets, fed.

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.

Participant milestones

Participant milestones
Measure	BI 1467335: Tablets, Fasted/Solution, Fasted/Tablets, Fed The subjects were administered BI 1467335 10 mg \[2\5 mg\] film-coated tablets orally in the fasted state \[Treatment A\] in period 1, followed by BI 1467335 10 mg oral solution in the fasted state orally with 240 mL of water after an overnight fast of at least 10 hours \[h\] \[Treatment B\] in period 2, then followed by BI 1467335 10 mg \[2\5 mg\] film-coated tablets orally in the fed state \[Treatment C\] in period 3. The treatment duration was one day for each treatment \[3 single doses\], separated by washout phases of at least 21 days.	BI 1467335: Solution, Fasted/Tablets, Fed/Tablets, Fasted The subjects were administered BI 1467335 10 mg oral solution in the fasted state orally with 240 mL of water after an overnight fast at least 10h \[Treatment B\] in period 1, followed by BI 1467335 10 mg \[2\5 mg\] film-coated tablets orally in the fed state \[Treatment C\] in period 2, then followed by BI 1467335 10 mg \[2\5 mg\] film-coated tablets in the fasted state \[Treatment A\] orally with 240 mL of water after an overnight fast of at least 10h in period 3. The treatment duration was one day for each treatment \[3 single doses\], separated by washout phases of at least 21 days.	BI 1467335: Tablets, Fed/Tablets, Fasted/Solution, Fasted The subjects were administered BI 1467335 10 mg \[2\5 mg\] film-coated tablets orally in the fed state \[Treatment C\] in period 1, followed by BI 1467335 10 mg \[2\5 mg\] film-coated tablets orally in the fasted state \[Treatment A\] in period 2, then followed by BI 1467335 10 mg oral solution in the fasted state orally with 240 mL of water after an overnight fast of at least 10h \[Treatment B\] in period 3. The treatment duration was one day for each treatment \[3 single doses\], separated by washout phases of at least 21 days.
Treatment Period 1 [1 Day] STARTED	6	6	6
Treatment Period 1 [1 Day] COMPLETED	6	6	6
Treatment Period 1 [1 Day] NOT COMPLETED	0	0	0
Wash-out Period 1 [21 Days] STARTED	6	6	6
Wash-out Period 1 [21 Days] COMPLETED	6	5	6
Wash-out Period 1 [21 Days] NOT COMPLETED	0	1	0
Treatment Period 2 [1 Day] STARTED	6	5	6
Treatment Period 2 [1 Day] COMPLETED	6	5	6
Treatment Period 2 [1 Day] NOT COMPLETED	0	0	0
Wash-out Period 2 [21 Days] STARTED	6	5	6
Wash-out Period 2 [21 Days] COMPLETED	6	5	6
Wash-out Period 2 [21 Days] NOT COMPLETED	0	0	0
Treatment Period 3 [1 Day] STARTED	6	6	6
Treatment Period 3 [1 Day] COMPLETED	6	6	6
Treatment Period 3 [1 Day] NOT COMPLETED	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	BI 1467335: Tablets, Fasted/Solution, Fasted/Tablets, Fed The subjects were administered BI 1467335 10 mg \[2\5 mg\] film-coated tablets orally in the fasted state \[Treatment A\] in period 1, followed by BI 1467335 10 mg oral solution in the fasted state orally with 240 mL of water after an overnight fast of at least 10 hours \[h\] \[Treatment B\] in period 2, then followed by BI 1467335 10 mg \[2\5 mg\] film-coated tablets orally in the fed state \[Treatment C\] in period 3. The treatment duration was one day for each treatment \[3 single doses\], separated by washout phases of at least 21 days.	BI 1467335: Solution, Fasted/Tablets, Fed/Tablets, Fasted The subjects were administered BI 1467335 10 mg oral solution in the fasted state orally with 240 mL of water after an overnight fast at least 10h \[Treatment B\] in period 1, followed by BI 1467335 10 mg \[2\5 mg\] film-coated tablets orally in the fed state \[Treatment C\] in period 2, then followed by BI 1467335 10 mg \[2\5 mg\] film-coated tablets in the fasted state \[Treatment A\] orally with 240 mL of water after an overnight fast of at least 10h in period 3. The treatment duration was one day for each treatment \[3 single doses\], separated by washout phases of at least 21 days.	BI 1467335: Tablets, Fed/Tablets, Fasted/Solution, Fasted The subjects were administered BI 1467335 10 mg \[2\5 mg\] film-coated tablets orally in the fed state \[Treatment C\] in period 1, followed by BI 1467335 10 mg \[2\5 mg\] film-coated tablets orally in the fasted state \[Treatment A\] in period 2, then followed by BI 1467335 10 mg oral solution in the fasted state orally with 240 mL of water after an overnight fast of at least 10h \[Treatment B\] in period 3. The treatment duration was one day for each treatment \[3 single doses\], separated by washout phases of at least 21 days.
Wash-out Period 1 [21 Days] Adverse Event	0	1	0

Baseline Characteristics

Relative Bioavailability of BI 1467335 Tablet and Oral Solution, and Food Effect on Tablet in Healthy Male Subjects

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	BI 1467335: Tablets, Fasted/Solution, Fasted/Tablets, Fed n=6 Participants The subjects were administered BI 1467335 10 mg \[2\5 mg\] film-coated tablets orally in the fasted state \[Treatment A\] in period 1, followed by BI 1467335 10 mg oral solution in the fasted state orally with 240 mL of water after an overnight fast of at least 10 hours \[h\] \[Treatment B\] in period 2, then followed by BI 1467335 10 mg \[2\5 mg\] film-coated tablets orally in the fed state \[Treatment C\] in period 3. The treatment duration was one day for each treatment \[3 single doses\], separated by washout phases of at least 21 days.	BI 1467335: Solution, Fasted/Tablets, Fed/Tablets, Fasted n=6 Participants The subjects were administered BI 1467335 10 mg oral solution in the fasted state orally with 240 mL of water after an overnight fast at least 10h \[Treatment B\] in period 1, followed by BI 1467335 10 mg \[2\5 mg\] film-coated tablets orally in the fed state \[Treatment C\] in period 2, then followed by BI 1467335 10 mg \[2\5 mg\] film-coated tablets in the fasted state \[Treatment A\] orally with 240 mL of water after an overnight fast of at least 10h in period 3. The treatment duration was one day for each treatment \[3 single doses\], separated by washout phases of at least 21 days.	BI 1467335: Tablets, Fed/Tablets, Fasted/Solution, Fasted n=6 Participants The subjects were administered BI 1467335 10 mg \[2\5 mg\] film-coated tablets orally in the fed state \[Treatment C\] in period 1, followed by BI 1467335 10 mg \[2\5 mg\] film-coated tablets orally in the fasted state \[Treatment A\] in period 2, then followed by BI 1467335 10 mg oral solution in the fasted state orally with 240 mL of water after an overnight fast of at least 10h \[Treatment B\] in period 3. The treatment duration was one day for each treatment \[3 single doses\], separated by washout phases of at least 21 days.	Total n=18 Participants Total of all reporting groups
Age, Continuous	42.2 Years STANDARD_DEVIATION 12.2 • n=5 Participants	45.7 Years STANDARD_DEVIATION 9.8 • n=7 Participants	45.7 Years STANDARD_DEVIATION 6.3 • n=5 Participants	44.5 Years STANDARD_DEVIATION 9.3 • n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	18 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	17 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	18 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: At -1:00h [hours (h): minutes (min)] before drug administration and at 0:15, 0:30, 0:45, 1:00, 1:15, 1:30, 1:45, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00 and 24:00 h:min after drug administration.

Population: PharmacoKinetic Set \[PKS\]: This subject set included all subjects in the Treated Set \[All subjects who received at least one dose of study medication\] who provided at least one primary PK parameter that was not excluded due to a relevant protocol violation \[PV\] or non-evaluable plasma concentrations. One subject did not receive the dose in period 2 \[Tablets, fed\].

This outcome measure presents AUC0-tz \[area under the concentration-time curve of BI 1467335 in plasma over the time interval from 0 to the last quantifiable data point\].

Outcome measures

Outcome measures
Measure	BI 1467335: Tablets, Fed n=17 Participants The subjects were administered BI 1467335 10 mg \[2\*5 mg\] film-coated tablets orally in the fed state. The treatment duration was one day.	BI 1467335: Tablets, Fasted n=18 Participants The subjects were administered BI 1467335 10 mg \[2\*5 mg\] film-coated tablets in the fasted state orally with 240 mL of water after an overnight fast of at least 10h. The treatment duration was one day.	BI 1467335: Solution, Fasted n=18 Participants The subjects were administered BI 1467335 10 mg oral solution in the fasted state orally with 240 mL of water after an overnight fast of at least 10h. The treatment duration was one day.
AUC0-tz of BI 1467335	3.90 nanomolehour/Liter (nmolh/L) Geometric Coefficient of Variation 90.5	2.24 nanomolehour/Liter (nmolh/L) Geometric Coefficient of Variation 101	2.49 nanomolehour/Liter (nmolh/L) Geometric Coefficient of Variation 121

PRIMARY outcome

This outcome measure presents the maximum measured concentration of BI 1467335 in plasma (Cmax of BI 1467335).

Outcome measures

Outcome measures
Measure	BI 1467335: Tablets, Fed n=17 Participants The subjects were administered BI 1467335 10 mg \[2\*5 mg\] film-coated tablets orally in the fed state. The treatment duration was one day.	BI 1467335: Tablets, Fasted n=18 Participants The subjects were administered BI 1467335 10 mg \[2\*5 mg\] film-coated tablets in the fasted state orally with 240 mL of water after an overnight fast of at least 10h. The treatment duration was one day.	BI 1467335: Solution, Fasted n=18 Participants The subjects were administered BI 1467335 10 mg oral solution in the fasted state orally with 240 mL of water after an overnight fast of at least 10h. The treatment duration was one day.
Cmax of BI 1467335	2.55 nanomole/Liter (nmol/L) Geometric Coefficient of Variation 120	1.85 nanomole/Liter (nmol/L) Geometric Coefficient of Variation 107	2.20 nanomole/Liter (nmol/L) Geometric Coefficient of Variation 126

Adverse Events

BI 1467335: Tablets, Fasted

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

BI 1467335: Solution, Fasted

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

BI 1467335: Tablets, Fed

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	BI 1467335: Tablets, Fasted n=18 participants at risk The subjects were administered BI 1467335 10 mg \[2\*5 mg\] film-coated tablets in the fasted state orally with 240 mL of water after an overnight fast of at least 10h. The treatment duration was one day.	BI 1467335: Solution, Fasted n=18 participants at risk The subjects were administered BI 1467335 10 mg oral solution in the fasted state orally with 240 mL of water after an overnight fast of at least 10h. The treatment duration was one day	BI 1467335: Tablets, Fed n=17 participants at risk The subjects were administered BI 1467335 10 mg \[2\*5 mg\] film-coated tablets orally in the fed state. The treatment duration was one day.
Infections and infestations Bronchitis	0.00% 0/18 • From the first day of study drug administration until 21 days after the first drug administration, up to 22 days. Treated set \[TS\]: All subjects who received at least one dose of study medication.	0.00% 0/18 • From the first day of study drug administration until 21 days after the first drug administration, up to 22 days. Treated set \[TS\]: All subjects who received at least one dose of study medication.	5.9% 1/17 • From the first day of study drug administration until 21 days after the first drug administration, up to 22 days. Treated set \[TS\]: All subjects who received at least one dose of study medication.
Infections and infestations Epididymitis	0.00% 0/18 • From the first day of study drug administration until 21 days after the first drug administration, up to 22 days. Treated set \[TS\]: All subjects who received at least one dose of study medication.	5.6% 1/18 • From the first day of study drug administration until 21 days after the first drug administration, up to 22 days. Treated set \[TS\]: All subjects who received at least one dose of study medication.	0.00% 0/17 • From the first day of study drug administration until 21 days after the first drug administration, up to 22 days. Treated set \[TS\]: All subjects who received at least one dose of study medication.
Infections and infestations Viral upper respiratory tract infection	5.6% 1/18 • From the first day of study drug administration until 21 days after the first drug administration, up to 22 days. Treated set \[TS\]: All subjects who received at least one dose of study medication.	5.6% 1/18 • From the first day of study drug administration until 21 days after the first drug administration, up to 22 days. Treated set \[TS\]: All subjects who received at least one dose of study medication.	5.9% 1/17 • From the first day of study drug administration until 21 days after the first drug administration, up to 22 days. Treated set \[TS\]: All subjects who received at least one dose of study medication.
Injury, poisoning and procedural complications Joint injury	0.00% 0/18 • From the first day of study drug administration until 21 days after the first drug administration, up to 22 days. Treated set \[TS\]: All subjects who received at least one dose of study medication.	0.00% 0/18 • From the first day of study drug administration until 21 days after the first drug administration, up to 22 days. Treated set \[TS\]: All subjects who received at least one dose of study medication.	5.9% 1/17 • From the first day of study drug administration until 21 days after the first drug administration, up to 22 days. Treated set \[TS\]: All subjects who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/18 • From the first day of study drug administration until 21 days after the first drug administration, up to 22 days. Treated set \[TS\]: All subjects who received at least one dose of study medication.	5.6% 1/18 • From the first day of study drug administration until 21 days after the first drug administration, up to 22 days. Treated set \[TS\]: All subjects who received at least one dose of study medication.	0.00% 0/17 • From the first day of study drug administration until 21 days after the first drug administration, up to 22 days. Treated set \[TS\]: All subjects who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	0.00% 0/18 • From the first day of study drug administration until 21 days after the first drug administration, up to 22 days. Treated set \[TS\]: All subjects who received at least one dose of study medication.	5.6% 1/18 • From the first day of study drug administration until 21 days after the first drug administration, up to 22 days. Treated set \[TS\]: All subjects who received at least one dose of study medication.	0.00% 0/17 • From the first day of study drug administration until 21 days after the first drug administration, up to 22 days. Treated set \[TS\]: All subjects who received at least one dose of study medication.
Nervous system disorders Headache	0.00% 0/18 • From the first day of study drug administration until 21 days after the first drug administration, up to 22 days. Treated set \[TS\]: All subjects who received at least one dose of study medication.	5.6% 1/18 • From the first day of study drug administration until 21 days after the first drug administration, up to 22 days. Treated set \[TS\]: All subjects who received at least one dose of study medication.	5.9% 1/17 • From the first day of study drug administration until 21 days after the first drug administration, up to 22 days. Treated set \[TS\]: All subjects who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Cough	5.6% 1/18 • From the first day of study drug administration until 21 days after the first drug administration, up to 22 days. Treated set \[TS\]: All subjects who received at least one dose of study medication.	0.00% 0/18 • From the first day of study drug administration until 21 days after the first drug administration, up to 22 days. Treated set \[TS\]: All subjects who received at least one dose of study medication.	0.00% 0/17 • From the first day of study drug administration until 21 days after the first drug administration, up to 22 days. Treated set \[TS\]: All subjects who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	0.00% 0/18 • From the first day of study drug administration until 21 days after the first drug administration, up to 22 days. Treated set \[TS\]: All subjects who received at least one dose of study medication.	5.6% 1/18 • From the first day of study drug administration until 21 days after the first drug administration, up to 22 days. Treated set \[TS\]: All subjects who received at least one dose of study medication.	0.00% 0/17 • From the first day of study drug administration until 21 days after the first drug administration, up to 22 days. Treated set \[TS\]: All subjects who received at least one dose of study medication.

Additional Information

Boehringer Ingelheim, Call Center

Boehringer Ingelheim

Phone: 1800-243-0127

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place