Clinical trial NCT03505151: This Study in Healthy Men and Women Tests How the Body Takes up BI 409306
Official title: Absolute Bioavailability and Pharmacokinetics of BI 409306 Using a Single Oral Dose of BI 409306 Co-administered With an Intravenous Stable Labeled Isotope BI 409306 (C-13/N-15) in Healthy Male and Female Subjects (Non-Randomised, Open-label, Single Arm, Single Period Design)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2018-04-23
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective of this trial is to investigate the absolute bioavailability of BI 409306. The secondary objective is the evaluation and comparison of several pharmacokinetic parameters for the different treatments.


Eligibility criteria: Inclusion Criteria:

* Healthy male or female subjects according to the assessment of the investigator, based on a complete medical history including a physical examination, vital signs (BP, PR), 12-lead ECG, and clinical laboratory tests
* Age of 18 to 55 years (incl.)
* BMI of 18.5 to 29.9 kg/m2 (incl.)
* Signed and dated written informed consent prior to admission to the study in accordance with GCP and local legislation
* Known CYP 2C19 metabolizer status
* Male subjects, or female subjects who meet any of the following criteria starting from at least 30 days before the first administration of trial medication and until 30 days after trial completion:

  * Use of adequate contraception, e.g. non-hormonal intrauterine device plus condom.
  * Sexually abstinent
  * A vasectomised sexual partner (vasectomy at least 1 year prior to enrolment)
  * Surgically sterilised (including hysterectomy)
  * Postmenopausal, defined as at least 1 year of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous levels of FSH (follicle stimulating hormone) above 40 U/L and estradiol below 30 ng/L is confirmatory)

Exclusion Criteria:

* Any finding in the medical examination (including BP, PR or ECG) is deviating from normal and judged as clinically relevant by the investigator
* 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
* Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
* Any evidence of a concomitant disease judged as clinically relevant by the investigator
* Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
* Cholecystectomy and/or surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy and simple hernia repair)
* Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders
* History of relevant orthostatic hypotension, fainting spells, or blackouts
* Chronic or relevant acute infections
* History of relevant allergy or hypersensitivity (including allergy to the trial medication or its excipients)
* Use of drugs within 30 days prior to administration of trial medication if that might reasonably influence the results of the trial (incl. QT/QTc interval prolongation)
* Participation in another trial where an investigational drug has been administered within 60 days prior to planned administration of trial medication, or current participation in another trial involving administration of investigational drug
* Current smoker or ex-smoker who quit smoking less than 30 days prior to screening
* Alcohol abuse (consumption of more than 20 g per day for females and 30 g per day for males)
* Drug abuse or positive drug screening
* Blood donation of more than 100 mL within 30 days prior to administration of trial medication or intended donation during the trial
* Intention to perform excessive physical activities within one week prior to administration of trial medication or during the trial
* Inability to comply with dietary regimen of trial site
* A marked baseline prolongation of QT/QTc interval (such as QTc intervals that are repeatedly greater than 450 msec in males or repeatedly greater than 470 msec in females) or any other relevant ECG finding at screening
* A history of additional risk factors for Torsades de Pointes (such as heart failure, hypokalemia, or family history of Long QT Syndrome)
* Subject is assessed as unsuitable for inclusion by the investigator, for instance, because considered not able to understand and comply with study requirements, or has a condition that would not allow safe participation in the study

Female subjects will not be allowed to participate if any of the following applies:

* Positive pregnancy test, pregnancy or plans to become pregnant within 30 days after study completion
* Lactation period
* Concomitant use of hormonal replacement therapy or hormonal contraceptives

Primary outcomes:
measure: Area Under the Concentration-time Curve of BI 409306 and Stable Labelled Isotope BI 409306 (C-13/N-15) Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
timeFrame: T and R:Within 3 hours (h) before dosing, 0.75h, 0.97h, 1.333h, 1.75h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h and 24h after dosing. Only T: 0.17h, 0.333h, 0.47h. Only R:0.58h, 0.83h, 1.17h, 1.5h.
measure: Maximum Measured Concentration of BI 409306 and Stable Labelled Isotope BI 409306 (C-13/N-15), (Cmax)
timeFrame: T and R:Within 3 hours (h) before dosing, 0.75h, 0.97h, 1.333h, 1.75h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h and 24h after dosing. Only T: 0.17h, 0.333h, 0.47h. Only R:0.58h, 0.83h, 1.17h, 1.5h.
Secondary outcomes:
measure: Terminal Half-life of BI 409306 and Stable Labelled Isotope BI 409306 (C-13/N-15) in Plasma (t1/2)
timeFrame: T and R:Within 3 hours (h) before dosing, 0.75h, 0.97h, 1.333h, 1.75h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h and 24h after dosing. Only T: 0.17h, 0.333h, 0.47h. Only R:0.58h, 0.83h, 1.17h, 1.5h.
measure: Time From Dosing to Maximum Measured Concentration of BI 409306 and Stable Labelled Isotope BI 409306 (C-13/N-15) in Plasma (Tmax)
timeFrame: T and R:Within 3 hours (h) before dosing, 0.75h, 0.97h, 1.333h, 1.75h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h and 24h after dosing. Only T: 0.17h, 0.333h, 0.47h. Only R:0.58h, 0.83h, 1.17h, 1.5h.
measure: For: BI 409306 (C-13/N-15): Total Clearance (CL) of BI 409306 (C-13/N-15)
timeFrame: Within 3 hours (h) before drug administration, 0.58h, 0.75h, 0.83h, 0.97h, 1.17h, 1.333h, 1.5h, 1.75h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h and 24h after dosing.
measure: For BI 409306 (C-13/N-15): Apparent Volume of Distribution During the Terminal Phase After Intravascular Administration (Vz) of BI 409306 (C-13/N-15)
timeFrame: Within 3 hours (h) before drug administration, 0.58h, 0.75h, 0.83h, 0.97h, 1.17h, 1.333h, 1.5h, 1.75h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h and 24h after dosing.
measure: Absolute Bioavailability of BI 409306 (Fabs)
timeFrame: T and R:Within 3 hours (h) before dosing, 0.75h, 0.97h, 1.333h, 1.75h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h and 24h after dosing. Only T: 0.17h, 0.333h, 0.47h. Only R:0.58h, 0.83h, 1.17h, 1.5h.
Other outcomes:
Locations:
city: Biberach
country: Germany
facility: Humanpharmakologisches Zentrum Biberach
Study officials:
References: