Clinical trial NCT03123094: Single Rising Dose Trial of Spesolimab (BI 655130) for Healthy Japanese Male Subjects
Official title: Safety, Tolerability and Pharmacokinetics of Single Rising Intravenous Dose and Single Subcutaneous Dose of BI 655130 in Healthy Japanese Male Volunteers (Double-blind, Randomised, Placebo-controlled Design).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2017-04-21
Enrollment: 32
Sex: MALE
Minimum age (years): 20
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 spesolimab following administration of single rising intravenous doses and single subcutaneous dose in healthy Japanese male volunteers.

Secondary objective is the exploration of the pharmacokinetics including dose proportionality of spesolimab in healthy Japanese male volunteers.


Eligibility criteria: Inclusion Criteria:

* Healthy male 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 tests.
* Japanese ethnicity, according to the following criteria:

  -- born in Japan, have lived outside of Japan \<10 years, and have parents and grandparents who were all born in Japan
* Age of 20 to 45 years (incl.)
* Body Mass Index \[BMI\] of 18.5 to 25.0 kg/m2 (incl.)
* Signed and dated written informed consent prior to admission to the study in accordance with GCP and local legislation
* Male subjects who agree to minimize the risk of female partners being pregnant by fulfilling any of the following criteria starting from the first administration of trial medication and until 30 days after trial completion:

  * Use of adequate contraception, e.g. any of the following methods plus condom:

combined oral contraceptives, intrauterine device

* A vasectomised sexual partner (vasectomy at least 1 year prior to enrolment)
* Surgically sterilised (including hysterectomy) female partner

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 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
* 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 including active tuberculosis, HIV or viral hepatitis; QuantiFERON TB test will be performed at screening.
* 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 5 half-lives prior to planned administration of trial medication, or current participation in another trial involving administration of investigational drug.
* Administered live vaccine within 6 weeks prior to randomisation or Have plans for administration of live vaccines during the study period.
* 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 in males) or any other relevant Electrocardiogram \[ECG\] 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
* Further exclusion criteria apply

Primary outcomes:
measure: Number of Subjects With Drug-related Adverse Events (AEs)
timeFrame: From first drug administration until the end of trial examination, up to 151 days.
Secondary outcomes:
measure: Area Under the Concentration-time Curve of Spesolimab in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
timeFrame: Up to 3528 hours after administration of spesolimab.
measure: Maximum Measured Concentration of Spesolimab in Plasma (Cmax)
timeFrame: Up to 3528 hours after administration of spesolimab.
measure: Total Clearance of Spesolimab in Plasma After Intravenous Administration (CL)
timeFrame: Pharmacokinetic samples were collected within 2 hours (h) pre-dose and at 1.5, 2, 3, 4, 8, 12, 24, 48, 72, 96, 168, 336, 504, 672, 840, 1008, 1344, 1680, 2184, 2856 and 3528 h after dosing of dose groups with intravenous administration of spesolimab.
measure: Volume of Distribution at Steady State After Intravenous Administration of Spesolimab (Vss)
timeFrame: Pharmacokinetic samples were collected within 2 hours (h) pre-dose and at 1.5, 2, 3, 4, 8, 12, 24, 48, 72, 96, 168, 336, 504, 672, 840, 1008, 1344, 1680, 2184, 2856 and 3528 h after dosing of dose groups with intravenous administration of spesolimab.
Other outcomes:
Locations:
city: Busan
country: Korea, Republic of
facility: Inje University Busan Paik Hospital
Study officials:
References: