Clinical trial NCT04241458: A Study to Test How Well Healthy Men and Women Tolerate Different Doses of BI 706321
Official title: Safety, Tolerability, and Pharmacokinetics of Multiple Rising Oral Doses of BI 706321 in Healthy Male and Female Subjects (Doubleblind, Randomised, Placebo-controlled, Parallel Group Design)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2020-01-27
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main objectives of this trial are to investigate safety, tolerability and pharmacokinetics (PK) of BI 706321 in healthy male and female subjects following oral administration of multiple rising doses for 14 days.


Eligibility criteria: Inclusion Criteria:

* Healthy male or female subjects according to the assessment of the investigator, as based on a complete medical history including a physical examination, vital signs (BP, PR, temperature), 12-lead ECG, and clinical laboratory tests
* Age of 18 to 55 years (inclusive, at screening)
* BMI of 18.5 to 29.9 kg/m2 (inclusive, at screening)
* Signed and dated written informed consent prior to admission to the study, in accordance with GCP and local legislation

Exclusion Criteria:

* Any finding in the medical examination (including BP, PR, temperature or 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 45 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 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 or 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 30 days (or 5 half-lives (whichever longer)) of planned administration of investigational drug in the current trial, or concurrent participation in another clinical trial in which investigational drug is administered
* Smoker of more than 10 cigarettes or 3 cigars or 3 pipes per day
* Inability to refrain from smoking while in-house stay
* Alcohol abuse (consumption of more than 20 g per day for females and 30 g per day for males), and unwillingness/inability to refrain from intake of alcoholic beverages from 48 hours prior to the trial medication administration and until Day 7 post trial medication administration.
* 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 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 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
* ALT (alanine transaminase), AST (aspartate transaminase), or creatinine exceed upper limit of normal range at screening, confirmed by a repeat test
* Hb, platelets and neutrophils below lower limit of normal range at screening, confirmed by a repeat test
* Positive result for HIV, HBV, and HCV infection at screening.
* History of TB or positive finding in IGRA.

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

* Not surgically sterilised⃰or not postmenopausal, defined as at least 1 year of spontaneous amenorrhea without an alternative medical cause (in questionable cases a blood sample with simultaneous levels of FSH above 30 U/L and estradiol below 20 ng/L is confirmatory)
* Positive pregnancy test
* Lactation

Male subjects will not be allowed to participate, if any of the following apply:

- Male subjects with WOCBP partner who are unwilling to use male contraception (condom or sexual abstinence) from time point of administration of trial medication until 30 days thereafter. Sperm donation is not allowed from the time point of drug administration until 30 days thereafter.

Primary outcomes:
measure: Number [N (%)] of subjects with drug-related adverse events
timeFrame: up to day 27
Secondary outcomes:
measure: AUCτ,ss (area under the concentration-time curve of BI 706321 in plasma at steady state over a uniform dosing interval τ)
timeFrame: up to day 27
measure: Cmax,ss (maximum measured concentration of BI 706321 in plasma at steady state over a uniform dosing interval τ)
timeFrame: up to day 27
measure: Cmin,ss (minimum concentration of BI 706321 in plasma at steady state over a uniform dosing interval τ)
timeFrame: up to day 27
measure: RA,Cmax (accumulation ratio based on Cmax,ss)
timeFrame: up to day 27
measure: RA,AUC (accumulation ratio based on AUC0-τ)
timeFrame: up to day 27
Other outcomes:
Locations:
city: Antwerpen
country: Belgium
facility: SGS Life Science Services - Clinical Research
Study officials:
References: