Safety Tolerability and Pharmacokinetic of BI 409306

Boehringer Ingelheim

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: BI 409306; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01343706

1289.1

2010-023604-27 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 80 patients

Sex: Male

Ages: 21 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. 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
2. Age > 21 and Age < 50 years
3. Body Mass Index (BMI) > 18.5 and BMI < 29.9 kg/m2

Exclusion criteria

1. Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance
2. Any evidence of a clinically relevant concomitant disease
3. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
4. Surgery of the gastrointestinal tract (except appendectomy)
5. Diseases of the central nervous system (including but not limited to any kind of seizures, stroke or psychiatric disorders) within the past 6 month
6. History of relevant orthostatic hypotension, fainting spells or blackouts.
7. Chronic or relevant acute infections
8. History of relevant allergy/hypersensitivity (including allergy to drug or its excipients)
9. 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
10. Any laboratory value outside the reference range that is of clinical relevance
11. A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 ms);
12. A history of additional risk factors for Torsades de points (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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80 participants in 12 patient groups, including a placebo group

BI 409306 0.5 mg PiB [EM]

Experimental group

Description:

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.

Treatment:

Drug: BI 409306

Drug: BI 409306

BI 409306 2 mg PiB [EM]

Experimental group

Description:

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.

Treatment:

Drug: BI 409306

Drug: BI 409306

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

Experimental group

Description:

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.

Treatment:

Drug: BI 409306

Drug: BI 409306

BI 409306 10 mg Tablet [EM]

Experimental group

Description:

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.

Treatment:

Drug: BI 409306

Drug: BI 409306

BI 409306 25 mg Tablet [EM]

Experimental group

Description:

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.

Treatment:

Drug: BI 409306

Drug: BI 409306

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

Experimental group

Description:

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.

Treatment:

Drug: BI 409306

Drug: BI 409306

BI 409306 100 mg Tablet [EM]

Experimental group

Description:

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.

Treatment:

Drug: BI 409306

Drug: BI 409306

BI 409306 200 mg Tablet [EM]

Experimental group

Description:

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.

Treatment:

Drug: BI 409306

Drug: BI 409306

BI 409306 350 mg Tablet [EM]

Experimental group

Description:

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.

Treatment:

Drug: BI 409306

Drug: BI 409306

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

Experimental group

Description:

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.

Treatment:

Drug: BI 409306

Drug: BI 409306

Placebo matching to BI 409306 PiB

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

Drug: Placebo

Placebo matching to BI 409306 film-coated tablet

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

Drug: Placebo