Clinical trial NCT03892616: A Study in Healthy Men to Test if Taking Different Formulations of BI 1358894 With or Without Food Influences the Amount of BI 1358894 in the Blood
Official title: Relative Bioavailability and Food Effect of a Single Dose of Different Solid Formulations of BI 1358894 Compared to a Single Dose of the Reference Tablet Formulation of BI 1358894 Following Oral Administration Under Fed and Fasted Conditions in Healthy Male Subjects (an Open-label, Single-dose, Randomised, Incomplete Blocks Crossover Design Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2019-03-27
Enrollment: 24
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The main objective of this trial is to investigate the relative bioavailability of a single dose of BI 1358894 administered as tablet formulation 2 (TF2a, TF2b) under fasted conditions compared with the tablet formulation 1 (TF1) of BI 1358894 under fed conditions following oral administration and to investigate the effect of food on the exposure with TF2 (TF2a, TF2b).


Eligibility criteria: Inclusion Criteria:

* Healthy male subjects according to the assessment of the investigator, as based on a complete medical history including a physical examination, vital signs (Blood pressure (BP), Pulse rate (PR)), 12-lead Electrocardiogram (ECG), and clinical laboratory tests.
* Age of 18 to 50 years (inclusive)
* Body mass index (BMI) of 18.5 to 29.9 kg/m2 (inclusive)
* Signed and dated written informed consent prior to admission to the study, in accordance with Good Clinical Practice (GCP) and local legislation
* Male subjects who meet any of the following criteria from at least 30 days before the first administration of trial medication until 30 days after trial completion:

  * Use of adequate contraception of the female partner, e.g. any of the following methods plus condom: implants, injectables, combined oral or vaginal contraceptives, intrauterine device (IUD) that started at least 2 months prior to first study drug administration, or barrier method (e.g. diaphragm with spermicide)
  * Sexually abstinent
  * A vasectomy performed at least 1 year prior to screening (with medical assessment of the surgical success)
  * Surgically sterilised female partner (including hysterectomy, bilateral tubal occlusion or bilateral oophorectomy)

Exclusion Criteria:

* Any finding in the medical examination (including Blood pressure (BP), Pulse rate (PR) or Electrocardiogram (ECG)) deviating from normal and assessed 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 50 to 90 bpm
* C-Reactive Protein (CRP) \> upper limit of normal (ULN), erythrocyte sedimentation rate (ESR) ≥15 millimeters/h, liver or kidney parameter above ULN, or any other laboratory value outside the reference range that the investigator considers to be of clinical relevance
* Any evidence of a concomitant disease assessed as clinically relevant by the investigator
* Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
* Cholecystectomy or other 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 of planned administration of trial medication that might reasonably influence the results of the trial (including drugs that cause QT/QTc interval prolongation)
* Intake of an investigational drug in another clinical trial within 60 days of planned administration of investigational drug in the current trial, or concurrent participation in another clinical trial in which investigational drug is administered
* Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day)
* Inability to refrain from smoking on specified trial days
* Alcohol abuse (consumption of more than 30 g per day)
* Drug abuse or positive drug screening
* Blood donation of more than 100 mL within 30 days of planned administration of trial medication or intended blood donation during the trial
* Intention to perform excessive physical activities within one week prior to the administration of trial medication or during the trial
* Inability to comply with the dietary regimen of the trial site
* A marked baseline prolongation of QT/QTc interval (such as QTc intervals that are repeatedly greater than 450 ms) or any other relevant ECG finding at screening
* A history of additional risk factors for Torsade de Pointes (such as heart failure, hypokalaemia, or family history of Long QT Syndrome)
* Subject is assessed as unsuitable for inclusion by the investigator, for instance, because the subject is not considered able to understand and comply with study requirements, or has a condition that would not allow safe participation in the study
* Any lifetime history of suicidal behaviour (i.e. actual attempt, interrupted attempt, aborted attempt, or preparatory acts or behaviour)
* Any suicidal ideation of type 2 to 5 on the Columbia Suicidal Severity Rating scale (C-SSRS) in the past 12 months (i.e. active suicidal thought, active suicidal thought with method, active suicidal thought with intent but without specific plan, or active suicidal thought with plan and intent)

Primary outcomes:
measure: Maximum Measured Concentration of BI 1358894 in Plasma (Cmax)
timeFrame: Within 2 hours (h) before and at 10 minutes (min), 20min, 30min, 1h, 1h30min, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 10h, 12h, 24h, 34h, 48h, 72h, 96h, 144h, 192h, 240h, 312h after drug administration in each treatment period.
measure: Area Under the Concentration-time Curve of BI 1358894 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
timeFrame: Within 2 hours (h) before and at 10 minutes (min), 20min, 30min, 1h, 1h30min, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 10h, 12h, 24h, 34h, 48h, 72h, 96h, 144h, 192h, 240h, 312h after drug administration in each treatment period.
Secondary outcomes:
measure: Area Under the Concentration-time Curve of BI 1358894 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
timeFrame: Within 2 hours (h) before and at 10 minutes (min), 20min, 30min, 1h, 1h30min, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 10h, 12h, 24h, 34h, 48h, 72h, 96h, 144h, 192h, 240h, 312h after drug administration in each treatment period.
measure: Area Under the Concentration-time Curve of BI 1358894 in Plasma Over the Time Interval From 0 to 72 Hours (AUC0-72)
timeFrame: Within 2 hours (h) before and at 10 minutes (min), 20min, 30min, 1h, 1h30min, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration in each treatment period.
Other outcomes:
Locations:
city: Mannheim
country: Germany
facility: CRS Clinical Research Services Mannheim GmbH
Study officials:
References: