Safety Tolerability and Pharmacokinetic of BI 409306

Phase 1

Completed

Conditions: Healthy

Interventions: Drug: BI 409306
Drug: Placebo

Registration Number: NCT01343706

Lead Sponsor: Boehringer Ingelheim

Brief Summary: The primary objective of the current study is to investigate the safety and tolerability of BI 409306 in healthy male genotyped volunteers following oral administration of single rising doses.

The secondary objectives are: (1) to explore dose proportionality of BI 409306 as immediate release solid oral dosage, (2) to explore the relative bioavailability of BI 409306 when administered as immediate release solid oral dosage compared to oral drinking solution and (3) to compare the safety and pharmacokinetic profiles between two different groups of genotyped subjects.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 80

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
BI 409306 10 mg Tablet [EM]	BI 409306	EM subjects administered 2 immediate release tablets of 5 mg BI 409306 as a single dose (total dosage: 10 mg) orally with 240 mL water after an overnight fast of at least 10 hours.
BI 409306 100 mg Tablet [EM]	BI 409306	EM subjects administered 2 immediate release tablets of 50 mg BI 409306 as single dose (total dosage: 100 mg) orally with 240 mL water after an overnight fast of at least 10 hours.
Placebo matching to BI 409306 film-coated tablet	Placebo	Subjects administered one single dose of placebo matching to the BI 409306 film-coated tablet (5 milligrams (mg), 50 mg, and 150 mg) orally with 240 mL water after an overnight fast of at least 10 hours.
Placebo matching to BI 409306 PiB	Placebo	Subjects administered one single dose of placebo matching to BI 409306 powder in bottle (PiB) after an overnight fast of at least 10 hours.
BI 409306 200 mg Tablet [EM]	BI 409306	EM subjects administered 1 immediate release tablet of 150 mg and 1 immediate release tablet of 50 mg of BI 409306 together as single dose (total dosage: 200 mg) orally with 240 mL water after an overnight fast of at least 10 hours.
BI 409306 350 mg Tablet [EM]	BI 409306	EM subjects administered 2 immediate release tablet of 150 mg and 1 immediate release tablet of 50 mg of BI 409306 together as single dose (total dosage: 350 mg) orally with 240 mL water after an overnight fast of at least 10 hours.
BI 409306 0.5 mg PiB [EM]	BI 409306	Extensive metaboliser \[EM\] subjects administered one single dose of 0.5 milligram (mg) BI 409306 powder in bottle (PiB) reconstituted for oral solution (0.5 mg /milliliter (mL)) in a volume of 80 mL of the solvent containing aqueous 0.5% tartaric acid solution orally with 240 mL water (160 mL containing the respective diluted volume of reconstituted solution and 80 mL drinking water) after an overnight fast of at least 10 hours.
BI 409306 2 mg PiB [EM]	BI 409306	EM subjects administered one single dose of 2 mg BI 409306 PiB reconstituted for oral solution (0.5 mg/mL) in a volume of 80 mL of the solvent containing aqueous 0.5% tartaric acid solution orally with 240 mL water (160 mL containing the respective diluted volume of reconstituted solution and 80 milliliter drinking water) after an overnight fast of at least 10 hours.
BI 409306 5 mg PiB followed by BI 409306 5 mg Tablet [EM]	BI 409306	EM subjects administered one single dose of 5 mg BI 409306 powder in bottle (PiB) reconstituted for oral solution (0.5 mg/ mL) in a volume of 80 mL of the solvent containing aqueous 0.5% tartaric acid solution orally with 240 mL water (160 mL containing the respective diluted volume of reconstituted solution and 80 mL drinking water) after an overnight fast of at least 10 hours in period 1; followed by a washout period of 5 days; followed by one single dose of 5 mg BI 409306 immediate release tablet administered orally with 240 mL water after an overnight fast of at least 10 hours in period 2.
BI 409306 50 mg Tablet followed by BI 409306 50mg PiB [EM]	BI 409306	EM subjects administered one single dose of 50 mg BI 409306 immediate release tablet orally with 240 mL water in period 1; followed by a washout period of 5 days; followed by one single dose of 50 mg BI 409306 powder in bottle (PiB) reconstituted for oral solution (0.5 mg/mL) in a volume of 80 mL of the solvent containing aqueous 0.5% tartaric acid solution administered orally with 240 mL water (160 mL containing the respective diluted volume of reconstituted solution and 80 mL drinking water) after an overnight fast of at least 10 hours in period 2.
BI 409306 10 mg Tablet followed by BI 409306 100mg Tablet [PM]	BI 409306	Poor metaboliser \[PM\] subjects administered 2 immediate release tablets of 5 mg BI 409306 as single dose (total dosage: 10 mg) orally with 240 mL water after an overnight fast of at least 10 hours in period 1; followed by washout period of 5 days; followed by 2 immediate release tablets of 50 mg BI 409306 administered as single dose (total dosage: 100 mg) orally with 240 mL water after an overnight fast of at least 10 hours in period 2.
BI 409306 25 mg Tablet [EM]	BI 409306	EM subjects administered 5 immediate release tablets of 5 mg BI 409306 as a single dose (total dosage: 25 mg) orally with 240 mL water after an overnight fast of at least 10 hours.

Primary Outcome Measures

Name	Time	Method
Percentage of Subjects With Clinical Relevant Abnormalities for Physical Examination, Vital Signs, Clinical Laboratory Tests, Oral Body Temperature and ECG	Day 4	Percentage of subjects with Clinical Relevant abnormalities for Physical examination, Vital Signs blood pressure (BP), pulse rate (PR) respiratory rate (RR), orthostatic test), Clinical laboratory tests (haematology, clinical chemistry and urinalysis), Oral body temperature and ECG were reported.
Percentage of Subjects With Drug-related Adverse Events	From first drug administration until 30 days after last drug administration; up to 31 days.	Percentage of subjects with investigator defined drug-related Adverse Events (AEs)
Percentage of Subjects Per Category for Assessment of Tolerability by Investigator	Day 4	The investigator assessed global clinical assessment and tolerability of BI 409306 were reported in possible categories were 'good', 'satisfactory', 'not satisfactory', and 'bad'.
Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS)	At 24 hours	The B\&L VAS scores were calculated from 16 item with each has a score range from 0 to 10 \[cm\]. The score of each of the 3 categories of effects ("alertness", "calmness", and "contentment") is a weighted average of the scores from the 16 items. The VAS score for alertness/calmness/contentment ranges from 0 to 10 (more alertness/calmness/contentment). The B\&L VAS data was analysed descriptively (change from baseline at 24 hour). The VAS assessment 2 h before drug administration was considered as baseline.

Secondary Outcome Measures

Name	Time	Method
Area Under the Concentration-time Curve of the BI 409306 in Plasma From Time 0 to Time of Last Quantifiable Data Point (AUC0-24)	Pharmacokinetic samples were collected at 2:00 (hour: minute) before 0.167, 0.333, 0.5, 0.75, 1:00, 1.50, 2:00, 2.50, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, and 24:00 hours after the drug administration.	AUC0-24, Area under the concentration-time curve of the BI 409306 in plasma over the time interval from 0 to the time of the last quantifiable data point is presented as geometric mean (gMean) and geometric coefficient of variation (gCV%). Pharmacokinetic samples were also collected at 48:00 and 72:00 hours after the drug administration for dose groups 10 mg onwards.
Area Under the Concentration-time Curve of the BI 409306 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)	Pharmacokinetic samples were collected at 2:00 (hour: minute) before 0.167, 0.333, 0.5, 0.75, 1:00, 1.50, 2:00, 2.50, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, and 24:00 hours after the drug administration.	AUC0-∞, Area under the concentration-time curve of the BI 409306 in plasma over the time interval from 0 extrapolated to infinity. Pharmacokinetic samples were also collected at 48:00 and 72:00 hours after the drug administration for dose groups 10 mg onwards.
Maximum Measured Concentration of the BI 409306 in Plasma (Cmax)	Pharmacokinetic samples were collected at 2:00 (hour: minute) before 0.167, 0.333, 0.5, 0.75, 1:00, 1.50, 2:00, 2.50, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, and 24:00 hours after the drug administration.	Cmax, Maximum measured concentration of the BI 409306 in plasma. Pharmacokinetic samples were also collected at 48:00 and 72:00 hours after the drug administration for dose groups 10 mg onwards.
Amount of BI 409306 Eliminated in Urine From the Time Point t1 to Time Point t2 (Ae0-4)	Urine samples were obtained pre-dose and sampling intervals 0:00 to 4:00, 4:00 to 8:00, 8:00 to 12:00 and 12:00 to 24:00 hours after oral administration.	Ae0-4, Amount of BI 409306 eliminated in urine from the time point t1(0) to time point t2(4). Urine samples were obtained 24:00 to 48:00 and 48:00 to 72:00 hours after oral administration were obtained only from dose group 10 mg onwards.