Safety Tolerability and Pharmacokinetic of BI 409306

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01343706
• Other study ID #: 1289.1
• Secondary ID: 2010-023604-27
• Status: Completed
• Phase: Phase 1
• Start date: April 1, 2011
• Est. completion date: August 5, 2011

Study information

• Verified date: April 2024
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: August 5, 2011
• Est. primary completion date: August 1, 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 21 Years to 50 Years

Eligibility

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)

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Placebo
Solution for oral administration
• Placebo
Immediate release solid oral dosage (film-coated tablet)
• BI 409306
Immediate release solid oral dosage (film-coated tablet)
• BI 409306
solution for oral administration

Locations

Country	Name	City	State
Germany	1289.1.1 Boehringer Ingelheim Investigational Site	Ingelheim

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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
Primary	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
Primary	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	Area Under the Concentration-time Curve of the BI 409306 in Plasma From Time 0 to Time of Last Quantifiable Data Point (AUC0-24)	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.	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.
Secondary	Area Under the Concentration-time Curve of the BI 409306 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-8)	AUC0-8, 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.	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.
Secondary	Maximum Measured Concentration of the BI 409306 in Plasma (Cmax)	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.	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.
Secondary	Amount of BI 409306 Eliminated in Urine From the Time Point t1 to Time Point t2 (Ae0-4)	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.	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.