Safety Tolerability and Pharmacokinetic of BI 409306

NCT01343706 | Completed Phase 1 Results

• 2 other identifiers: 1289.12010-023604-27
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (4)

• Percentage of Subjects With Drug-related Adverse Events

  Percentage of subjects with investigator defined drug-related Adverse Events (AEs)

  From first drug administration until 30 days after last drug administration; up to 31 days.

• Percentage of Subjects With Clinical Relevant Abnormalities for Physical Examination, Vital Signs, Clinical Laboratory Tests, Oral Body Temperature and ECG

  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.

  Day 4

• Percentage of Subjects Per Category for Assessment of Tolerability by Investigator

  The investigator assessed global clinical assessment and tolerability of BI 409306 were reported in possible categories were 'good', 'satisfactory', 'not satisfactory', and 'bad'.

  Day 4

• Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS)

  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.

  At 24 hours

Secondary Outcomes (4)

• 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-∞)

  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.

Study Arms (12)

BI 409306 0.5 mg PiB [EM]

EXPERIMENTAL

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.

Drug: BI 409306

BI 409306 2 mg PiB [EM]

EXPERIMENTAL

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.

Drug: BI 409306

BI 409306 5 mg PiB followed by BI 409306 5 mg Tablet [EM]

EXPERIMENTAL

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.

Drug: BI 409306

BI 409306 10 mg Tablet [EM]

EXPERIMENTAL

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.

Drug: BI 409306

BI 409306 25 mg Tablet [EM]

EXPERIMENTAL

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.

Drug: BI 409306

BI 409306 50 mg Tablet followed by BI 409306 50mg PiB [EM]

EXPERIMENTAL

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.

Drug: BI 409306

BI 409306 100 mg Tablet [EM]

EXPERIMENTAL

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.

Drug: BI 409306

BI 409306 200 mg Tablet [EM]

EXPERIMENTAL

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.

Drug: BI 409306

BI 409306 350 mg Tablet [EM]

EXPERIMENTAL

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.

Drug: BI 409306

BI 409306 10 mg Tablet followed by BI 409306 100mg Tablet [PM]

EXPERIMENTAL

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.

Drug: BI 409306

Placebo matching to BI 409306 PiB

PLACEBO COMPARATOR

Subjects administered one single dose of placebo matching to BI 409306 powder in bottle (PiB) after an overnight fast of at least 10 hours.

Drug: Placebo

Placebo matching to BI 409306 film-coated tablet

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Placebo DRUG

Solution for oral administration

Placebo matching to BI 409306 PiB

BI 409306 DRUG

Immediate release solid oral dosage (film-coated tablet)

BI 409306 10 mg Tablet [EM]; BI 409306 10 mg Tablet followed by BI 409306 100mg Tablet [PM]; BI 409306 100 mg Tablet [EM]; BI 409306 200 mg Tablet [EM]; BI 409306 25 mg Tablet [EM]; BI 409306 350 mg Tablet [EM]; BI 409306 5 mg PiB followed by BI 409306 5 mg Tablet [EM]; BI 409306 50 mg Tablet followed by BI 409306 50mg PiB [EM]

Eligibility Criteria

• Age: 21 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy males according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead electrocardiogram (ECG), clinical laboratory tests
• Age \> 21 and Age \< 50 years
• Body Mass Index (BMI) \> 18.5 and BMI \< 29.9 kg/m2

You may not qualify if:

• Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance
• Any evidence of a clinically relevant concomitant disease
• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
• Surgery of the gastrointestinal tract (except appendectomy)
• Diseases of the central nervous system (including but not limited to any kind of seizures, stroke or psychiatric disorders) within the past 6 month
• History of relevant orthostatic hypotension, fainting spells or blackouts.
• Chronic or relevant acute infections
• History of relevant allergy/hypersensitivity (including allergy to drug or its excipients)
• Use of drugs which might reasonably influence the results of the trial or that prolong the QT/QTc interval based on the knowledge at the time of protocol preparation within 10 days prior to administration or during the trial
• Any laboratory value outside the reference range that is of clinical relevance
• A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval \>450 ms);
• A history of additional risk factors for Torsades de points (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (1)

1289.1.1 Boehringer Ingelheim Investigational Site

Ingelheim, Germany

Location

MeSH Terms

Interventions

BI 409306

Results Point of Contact

• Title: Boehringer Ingelheim, Call Centre
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 6, 2011
• First Posted: April 28, 2011
• Study Start: April 1, 2011
• Primary Completion: August 1, 2011
• Study Completion: August 5, 2011
• Last Updated: April 25, 2024
• Results First Posted: March 12, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)