Clinical trial NCT02733627: To Investigate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BI 1467335 Following Multiple Dose Administration Over 28 Days
Official title: Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Oral Doses of BI 1467335 in Healthy Male and Female Subjects (Double-blind, Randomised, Placebo-controlled Within Dose Groups)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2016-04-11
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this trial is to investigate the safety and tolerability of BI 1467335 in healthy male and female subjects following oral administration of multiple rising doses over 28 days.

Secondary objectives are the exploration of the pharmacokinetics (PK) and target engagement biomarkers of BI 1467335 after multiple dosing.


Eligibility criteria: Inclusion criteria:

* Healthy male or female subjects according to the investigator's assessment, 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
* Age of 18 to 50 years (incl.)
* Body mass index (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 Good Clinical Practice (GCP) and local legislation
* 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:
* Surgically sterilised (including hysterectomy)
* Postmenopausal, defined as at least 1 year of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous levels of Follicle Stimulating Hormone (FSH) above 40 U/L and estradiol below 30 ng/L is confirmatory)

Exclusion criteria:

* Any finding in the medical examination (including Blood pressure(BP),Pulse rate (PR) or Electrocardiogram (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 50 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)
* Intake of drugs with a long half-life (more than 24 h) within 30 days or less than 10 half-lives of the respective drug prior to administration of trial medication
* Within 10 days prior to administration of trial medication, use of drugs that might reasonably influence the results of the trial or that might prolong the QT/QTc interval
* Participation in another trial where an investigational drug has been administered within 60 days prior to planned administration of trial medication
* Used nicotine-containing products (e.g., cigarettes, cigars, chewing tobacco, snuff) within 6 weeks before screening and unable to abstain from using these products until study completion
* 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/corrected QT (QTc) interval (such as QTc intervals that are repeatedly greater than 450 ms in males or repeatedly greater than 470 ms 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
* Detection of cataract in slit lamp examination
* GFR according to CKD-EPI-Formula \< 90 mL/min at screening
* Further exclusion criteria apply

Primary outcomes:
measure: Number of Subjects With Investigator Defined Drug-related Adverse Events
timeFrame: From first day of study drug administration until 20 days after last dose of study drug administration, up to 48 days.
Secondary outcomes:
measure: Cmax
timeFrame: 0:00 hour (h) (within 30 minutes prior to dosing) and 0:15 h, 0:30 h, 0:45 h, 1:00 h, 1:30 h, 2:00 h, 3:00 h, 4:00 h, 6:00 h, 8:00 h, 10:00 h, 12:00 h and 24:00 h after drug administration on Day 1.
measure: AUC0-24
timeFrame: 0:00 hour (h) (within 30 minutes prior to dosing) and 0:15 h, 0:30 h, 0:45 h, 1:00 h, 1:30 h, 2:00 h, 3:00 h, 4:00 h, 6:00 h, 8:00 h, 10:00 h, 12:00 h and 24:00 h after drug administration on Day 1.
measure: Cmax,28
timeFrame: 648:00 hours (h) (within 30 minutes prior to dosing) and 648:15 h, 648:30 h, 648:45 h, 649:00h, 649:30 h, 650:00 h, 651:00 h, 652:00 h, 654:00 h, 656:00 h, 658:00 h, 660:00 h, 672:00 h after first drug administration on Day 1.
measure: AUC0-24,28
timeFrame: 648:00 hours (h) (within 30 minutes prior to dosing) and 648:15 h, 648:30 h, 648:45 h, 649:00 h, 649:30 h, 650:00 h, 651:00 h, 652:00 h, 654:00 h, 656:00 h, 658:00 h, 660:00 h and 672:00 h after first drug administration on Day 1.
Other outcomes:
Locations:
city: Mannheim
country: Germany
facility: CRS Clinical Research Services Mannheim GmbH
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: