A Randomized, Double-blind, Placebo-controlled (Within Dose Groups) Phase I Study to Assess Safety, Tolerability and Pharmacokinetics of Single Rising Doses 0.5 mg to 500 mg of BI 409306 Administered Orally in Healthy Male Volunteers
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Boehringer Ingelheim
- Enrollment
- 80
- Locations
- 1
- Primary Endpoint
- Percentage of Subjects With Clinical Relevant Abnormalities for Physical Examination, Vital Signs, Clinical Laboratory Tests, Oral Body Temperature and ECG
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double
Eligibility Criteria
- Ages
- 21 Years to 50 Years (Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
BI 409306 0.5 mg PiB [EM]
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.
Intervention: BI 409306 (Drug)
BI 409306 2 mg PiB [EM]
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.
Intervention: BI 409306 (Drug)
BI 409306 5 mg PiB followed by BI 409306 5 mg Tablet [EM]
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.
Intervention: BI 409306 (Drug)
BI 409306 10 mg Tablet [EM]
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.
Intervention: BI 409306 (Drug)
BI 409306 25 mg Tablet [EM]
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.
Intervention: BI 409306 (Drug)
BI 409306 50 mg Tablet followed by BI 409306 50mg PiB [EM]
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.
Intervention: BI 409306 (Drug)
BI 409306 100 mg Tablet [EM]
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.
Intervention: BI 409306 (Drug)
BI 409306 200 mg Tablet [EM]
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.
Intervention: BI 409306 (Drug)
BI 409306 350 mg Tablet [EM]
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.
Intervention: BI 409306 (Drug)
BI 409306 10 mg Tablet followed by BI 409306 100mg Tablet [PM]
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.
Intervention: BI 409306 (Drug)
Placebo matching to BI 409306 PiB
Subjects administered one single dose of placebo matching to BI 409306 powder in bottle (PiB) after an overnight fast of at least 10 hours.
Intervention: Placebo (Drug)
Placebo matching to BI 409306 film-coated tablet
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.
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Percentage of Subjects With Clinical Relevant Abnormalities for Physical Examination, Vital Signs, Clinical Laboratory Tests, Oral Body Temperature and ECG
Time Frame: 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
Time Frame: 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
Time Frame: 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)
Time Frame: 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 Outcomes
- 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.)
- Area Under the Concentration-time Curve of the BI 409306 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-β)(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.)
- 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.)
- 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.)