Metabolism and Pharmacokinetics of [14C]-BI 409306 After Administration as Oral Solution in Healthy Male Volunteers

Metabolism and Pharmacokinetics of [14C]-BI 409306 After Administration of 25 mg [14C]-BI 409306 as Oral Solution in Healthy Male Volunteers

The aim of this study is to assess the mass balance recovery from excreta of carbon 14 labelled BI409306 ([14C] BI 409306) in healthy, CYP2C19 genotyped subjects and to provide plasma, urine and faecal samples for metabolite profiling and structural identification.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: 14C-BI 409306

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Nottingham, United Kingdom, NG11 6JS
    • Quotient Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion criteria:

1. Healthy male genotyped as CY2C19 poor metabolizer (PM) or extensive metabolizer (EM) according to the investigator's assessment, based on a complete medical history including a physical examination, vital signs (BP - Blood Pressure, PR - Pulse Rate), 12-lead ECG (Electrogardiogramm), and clinical laboratory tests. PM is defined as carrier of two non-functional alleles *2 and *3 of the CYP2C19 gene (diplotypes *2/*2; *2/*3; *3/*3). EM is defined as carrier of two functional alleles of the CYP2C19 gene (absence of *2, *3, *17; diplotype *1/*1).
2. Age of 30 to 65 years (incl.).
3. BMI (Body Mass Index) of 18.5 to 29.9 kg/m2 (incl.).
4. Signed and dated written informed consent prior to admission to the study in accordance with GCP and local legislation.
5. A history of regular bowel movements (averaging 1 or more bowel movements per day; subjects with regular bowel movements of >3 per day will be excluded).
6. Subjects who are sexually active must use, with their partner, 2 approved methods of highly effective contraception from the time of IMP administration until 90 days after the last dose of IMP.

Exclusion criteria:

1. Any finding in the medical examination (including BP - Blood Pressure, PR - Pulse Rate or ECG - Electrocardiogramm) is deviating from normal and judged as clinically relevant by the investigator
2. Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 45 to 90 bpm
3. Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
4. Any evidence of a concomitant disease judged as clinically relevant by the investigator
5. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders. Any significant history of ocular or eye disease.
6. Surgery of the gastrointestinal tract that could interfere with kinetics of the trial medication (except appendectomy and simple hernia repair)
7. Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 14C-BI 409306 - 25 mg; 14C-BI 409306 oral solution	Drug: 14C-BI 409306; Other Names: 14C-BI 409306 oral solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mass Balance Recovery of Total Radioactivity in Urine and Faeces: Amount Excreted Within the Time Interval From 0 to the Time of the Last Quantifiable Data Point as a Percentage of the Administered Dose (fe0-tz) for Urine and Faeces	Mass balance recovery of total radioactivity in urine and faeces: Amount excreted within the time interval from 0 to the time of the last quantifiable data point as a percentage of the administered dose (fe0-tz) for urine and faeces. Urine collection intervals: -17:00-0:00 hours before drug administration and, 0-4, 4-8, 8-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144, 144-168, 168-192 and 192-216 hours after drug administration. Faeces collection intervals: -17:00-0:00, 0-24, 24-48, 48-72, 72-96, 96- 20, 120-144, 144-168, 168-192 and 192-216 hours after drug administration.	Urine and faeces sample collection: 17 hours before and up to 216 hours after drug administration. The details are mentioned in description section.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Measured Concentration of BI 409306 in Plasma (Cmax)	Maximum measured concentration of BI 409306 in plasma (Cmax).	PK plasma samples were taken at: 2:00 (hour: minute) before drug administration and 0:10, 0:20, 0:30, 0:45, 1, 1:30, 2, 2:30, 3, 4, 6, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120, 144, 168 hours after drug administration.
Maximum Measured Concentration of 14C-BI 409306 Related Radioactivity in Plasma (Cmax)	Maximum measured concentration of 14C-BI 409306 related radioactivity in plasma (Cmax).	PK plasma samples were taken at: 2:00 (hour: minute) before drug administration and 0:10, 0:20, 0:30, 0:45, 1, 1:30, 2, 2:30, 3, 4, 6, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120, 144, 168 hours after drug administration.
Area Under the Concentration-time Curve Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) for BI 409306 in Plasma	Area under the concentration-time curve over the time interval from 0 to the last quantifiable data point (AUC0-tz) for BI 409306 in plasma.	PK plasma samples were taken at: 2:00 (hour: minute) before drug administration and 0:10, 0:20, 0:30, 0:45, 1, 1:30, 2, 2:30, 3, 4, 6, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120, 144, 168 hours after drug administration.
Area Under the Concentration-time Curve Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) for 14C-BI 409306 Related Radioactivity in Plasma	Area under the concentration-time curve over the time interval from 0 to the last quantifiable data point (AUC0-tz) for 14C-BI 409306 related radioactivity in plasma.	PK plasma samples were taken at: 2:00 (hour: minute) before drug administration and 0:10, 0:20, 0:30, 0:45, 1, 1:30, 2, 2:30, 3, 4, 6, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120, 144, 168 hours after drug administration.

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2015
• Primary Completion (Actual): December 11, 2015
• Study Completion (Actual): December 11, 2015

Study Registration Dates

• First Submitted: September 30, 2015
• First Submitted That Met QC Criteria: November 4, 2015
• First Posted (Estimated): November 5, 2015

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: August 10, 2023
• Last Verified: August 1, 2023

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: 1289.26; 2015-001877-42 (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