Clinical trial NCT03588390: This Study in Healthy Men Tests How Different Doses of BI 1323495 Are Taken up in the Body and How Well They Are Tolerated.
Official title: Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Rising Oral Doses of BI 1323495 in Healthy Male Subjects (Single-blind, Partially Randomised, Placebo-controlled Parallel Group Design)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2018-07-17
Enrollment: 63
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
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 1323495 in healthy male subjects following oral administration of single rising doses.

Secondary objectives are the exploration of the pharmacokinetics (PK) including dose proportionality and pharmacodynamics (PD) of BI 1323495 after single dosing and the assessment of the PK/PD relationship.


Eligibility criteria: Inclusion Criteria:

* Healthy male subjects according to the assessment of the investigator, 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 45 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

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)
* 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
* 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 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 ms 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

In addition, the following trial-specific exclusion criteria apply:

* Male subjects with female partner of childbearing potential who are unwilling to use male contraception (condom or sexual abstinence) from the first administration of trial medication until 30 days after last administration of trial medication
* Current or history of relevant kidney, urinary tract diseases or abnormalities (e.g. nephrolithiasis, hydronephrosis, acute or chronic nephritis, renal injury, renal failure)
* Estimated glomerular filtration rate according to CKD-EPI formula \< 90 mL/min at screening
* Within 10 days prior to administration of trial medication, use of any drug that could reasonably inhibit platelet aggregation or coagulation (e.g., acetylsalicylic acid)
* Further exclusion criteria apply

Primary outcomes:
measure: Percentage of Participants With Drug-related Adverse Events
timeFrame: From drug administration until end of trial, up to 15 days.
Secondary outcomes:
measure: Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
timeFrame: 1 hour (h) before drug administration and 1, 2, 3, 4, 6, 7, 8, 9, 10, 12, 24, 34, 48, 72 and 96 h and additionally 4.75, 5.5, 6.5, 7.5 h for dose group 1/2/3 and 0.333, 0.667, 1.5, 5 h for dose group 4/5/6/7/8 after drug administration.
measure: Maximum Measured Concentration of BI 1323495 in Plasma (Cmax)
timeFrame: 1 hour (h) before drug administration and 1, 2, 3, 4, 6, 7, 8, 9, 10, 12, 24, 34, 48, 72 and 96 h and additionally 4.75, 5.5, 6.5, 7.5 h for dose group 1/2/3 and 0.333, 0.667, 1.5, 5 h for dose group 4/5/6/7/8 after drug administration.
Other outcomes:
Locations:
city: Biberach
country: Germany
facility: Humanpharmakologisches Zentrum Biberach
Study officials:
References: