Safety Tolerability and Pharmacokinetic of BI 409306

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

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 Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: BI 409306; Drug: BI 409306; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Ingelheim, Germany
    • 1289.1.1 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

12

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: BI 409306; Immediate release solid oral dosage (film-coated tablet); Drug: BI 409306; solution for oral administration
Experimental: 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.	Drug: BI 409306; Immediate release solid oral dosage (film-coated tablet); Drug: BI 409306; solution for oral administration
Experimental: 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.	Drug: BI 409306; Immediate release solid oral dosage (film-coated tablet); Drug: BI 409306; solution for oral administration
Experimental: 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.	Drug: BI 409306; Immediate release solid oral dosage (film-coated tablet); Drug: BI 409306; solution for oral administration
Experimental: 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.	Drug: BI 409306; Immediate release solid oral dosage (film-coated tablet); Drug: BI 409306; solution for oral administration
Experimental: 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.	Drug: BI 409306; Immediate release solid oral dosage (film-coated tablet); Drug: BI 409306; solution for oral administration
Experimental: 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.	Drug: BI 409306; Immediate release solid oral dosage (film-coated tablet); Drug: BI 409306; solution for oral administration
Experimental: 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.	Drug: BI 409306; Immediate release solid oral dosage (film-coated tablet); Drug: BI 409306; solution for oral administration
Experimental: 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.	Drug: BI 409306; Immediate release solid oral dosage (film-coated tablet); Drug: BI 409306; solution for oral administration
Experimental: 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.	Drug: BI 409306; Immediate release solid oral dosage (film-coated tablet); Drug: BI 409306; solution for oral administration
Placebo Comparator: 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.	Drug: Placebo; Solution for oral administration; Drug: Placebo; Immediate release solid oral dosage (film-coated tablet)
Placebo Comparator: 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.	Drug: Placebo; Solution for oral administration; Drug: Placebo; Immediate release solid oral dosage (film-coated tablet)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.
Area Under the Concentration-time Curve of the BI 409306 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)	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.	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)	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.
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.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim
• Investigators: Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2011
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): August 5, 2011

Study Registration Dates

• First Submitted: April 6, 2011
• First Submitted That Met QC Criteria: April 27, 2011
• First Posted (Estimated): April 28, 2011

Study Record Updates

• Last Update Posted (Actual): April 25, 2024
• Last Update Submitted That Met QC Criteria: April 19, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Phosphodiesterase Inhibitors; BI 409306
• Other Study ID Numbers: 1289.1; 2010-023604-27 (EudraCT Number: EudraCT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization).

For more details refer to: https://www.mystudywindow.com/msw/datatransparency