Safety, Tolerability and Pharmacokinetics of BI 1026706 in Healthy Chinese and Japanese Male Volunteers

Safety, Tolerability and Pharmacokinetics of Single Rising Oral Doses and Multiple Oral Doses of BI 1026706 in Healthy Chinese and Japanese Male Volunteers (Randomised, Double-blind, Placebo-controlled Trial)

Safety and tolerability of BI 1026706 in healthy Chinese and Japanese male subjects following oral administration of single rising doses (SRD) followed by multiple rising doses (MRD)

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: BI 1026706

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Fukuoka, Japan, 812-0025
    • Souseikai Hakata Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 41 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion criteria:

• Healthy male subjects according to the investigator's assessment, based on a complete medical history including a physical examination, vital signs (BP, PR), 12-lead ECG, and clinical laboratory tests
• Chinese ethnicity or Japanese ethnicity, according to the following criteria:
• Chinese; born in China or ethnic Chinese born outside of China, and a descendent of 4 ethnic Chinese grandparents who were all born in China
• Japanese; 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.) - BMI of 18.5 to 25 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 who agree to minimize the risk of female partners becoming pregnant by fulfilling 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:
• Use of adequate contraception, e.g. any of the following methods plus condom: combined oral contraceptives, intrauterine device
• Vasectomised (vasectomy at least 1 year prior to enrolment)
• Surgically sterilised (including hysterectomy) female partner

Exclusion criteria:

• Any finding in the medical examination (including BP, PR or ECG) is deviating from normal and judged as clinically relevant by the investigator
• 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
• Surgery of the gastrointestinal tract that could interfere with kinetics 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 including HIV, viral hepatitis and (or) tuberculosis or evidence of tuberculosis infection as defined by a positive QuantiFERON TB-Gold (or T-SPOT) test. Subjects with a positive QuantiFERON TB-Gold (or T-SPOT) test may participate in the study if further work up (according to local practice/guidelines) establishes conclusively that the subject has no evidence of active tuberculosis. If presence of latent tuberculosis is established, then treatment must have been initiated and maintained according to local country guidelines.
• History of relevant allergy or hypersensitivity (including allergy to the trial medication or its excipients)
• Intake of biologic agents other than current study medication or drugs considered likely to interfere with the safe conduct of the study
• 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 (including bioequivalence trial) with an investigational drug within 90 days or 5 half-lives (whichever is greater) prior to planned administration of trial medication
• 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 200 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)
• Have received any live bacterial or live viral vaccination in the 12 weeks prior to the date of screening. Subjects must agree not to receive a live bacterial or live viral vaccination during the study and up to 12 months after the last administration of study drug
• Have received Bacille Calmette-Guerin (BCG) vaccination in the 12 months prior to the date of screening. Subjects must agree not to receive BCG vaccination during the study and up to 12 months after the last administration of study drug
• Male patients who do not agree to minimize the risk of female partners becoming pregnant from at least 30 days before the first administration of trial medication and until 30 days after trial completion.
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SRD part (low dose); Chinese, Japanese both	Drug: BI 1026706; oral administration
Experimental: SRD part (medium dose); Chinese, Japanese both	Drug: BI 1026706; oral administration
Experimental: SRD part (high dose); Chinese, Japanese both	Drug: BI 1026706; oral administration
Experimental: MD part (high dose); Chinese, Japanese both	Drug: BI 1026706; oral administration
Experimental: Placebo (SRD part); placebo	Drug: Placebo; placebo
Placebo Comparator: Placebo (MD part); placebo	Drug: Placebo; placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects With Drug-related Adverse Events (AEs)	The percentage of subjects with drug-related AEs indicate the safety and tolerability of BI 1026706 in healthy Chinese and Japanese male subjects following oral administration of single rising doses of 25 mg, 50 mg, and 100 mg, followed by multiple doses of 100 mg bid.	From first drug administration to 4 days after last drug intake, up to 19 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	This outcome measure presents maximum measured concentration of the analyte [BI 1026706] in plasma. TS-SRD part: This subject set included all subjects who were dispensed BI 1026706 and were documented to have taken at least 1 dose of investigational treatment in the SRD part. All subjects in the TS-SRD part who provided at least 1 PK parameter in the SRD part that was not excluded were to be considered for this endpoint.	-1:30 (hours:minutes) before drug administration and 0:15, 0:30, 0:45, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 (hours:minutes) after drug administration.
Tmax	This outcome measure presents time from dosing to maximum measured concentration of the analyte [BI 1026706] in plasma. All subjects in the TS-SRD part who provided at least 1 PK parameter in the SRD part that was not excluded were to be considered for this endpoint.	-1:30 (hours:minutes) before drug administration and 0:15, 0:30, 0:45, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 (hours:minutes) after drug administration.
AUC0-12	This outcome measure presents area under the concentration-time curve of the analyte [BI 1026706] in plasma over the time interval from 0 extrapolated to 12 hours (AUC0-12). All subjects in the TS-SRD part who provided at least 1 PK parameter in the SRD part that was not excluded were to be considered for this endpoint.	-1:30 (hours:minutes) before drug administration and 0:15, 0:30, 0:45, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 (hours:minutes) after drug administration.
AUC0-infinity	This outcome measure presents area under the concentration-time curve of the analyte [BI 1026706] in plasma over the time interval from 0 extrapolated to infinity. All subjects in the TS-SRD part who provided at least 1 PK parameter in the SRD part that was not excluded were to be considered for this endpoint.	-1:30 (hours:minutes) before drug administration and 0:15, 0:30, 0:45, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 (hours:minutes) after drug administration.
t1/2	This outcome measure presents terminal half-life of the analyte [BI 1026706] in plasma. All subjects in the TS-SRD part who provided at least 1 PK parameter in the SRD part that was not excluded were to be considered for this endpoint.	-1:30 (hours:minutes) before drug administration and 0:15, 0:30, 0:45, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 (hours:minutes) after drug administration.
Cmax,ss	This outcome measure presents maximum measured concentration of the analyte [BI 1026706] in plasma at steady state over a uniform dosing interval tau. TS-MD part: This subject set included all subjects from the 100 mg group in the SRD part who were dispensed BI 1026706 and were documented to have taken at least 1 dose of investigational treatment in the MD part. All subjects in the TS-MD part who provide at least 1 PK parameter in the MD part that was not excluded were to be considered for this endpoint.	23:55, 47:55, 71:55, 95:55, 119:55, 167:55, 239:55, 263:55, 264:15, 264:30, 264:45, 265:00, 265:30, 266:00, 266:30, 267:00, 268:00, 270:00, 272:00, 274:00, 276:00, 288:00, 298:00, 312:00 and 336:00 (hours:minutes) after drug administration.
Tmax,ss	This outcome measure presents time from last dosing to maximum concentration of the analyte [BI 1026706] in plasma at steady state (tmax,ss) . All subjects in the TS-MD part who provide at least 1 PK parameter in the MD part that was not excluded were to be considered for this endpoint.	23:55, 47:55, 71:55, 95:55, 119:55, 167:55, 239:55, 263:55, 264:15, 264:30, 264:45, 265:00, 265:30, 266:00, 266:30, 267:00, 268:00, 270:00, 272:00, 274:00, 276:00, 288:00, 298:00, 312:00 and 336:00 (hours:minutes) after drug administration.
AUC Tau,ss	This outcome measure presents area under the concentration-time curve of the analyte [BI 1026706] in plasma at steady state over a uniform dosing interval tau (AUC tau,ss). All subjects in the TS-MD part who provide at least 1 PK parameter in the MD part that was not excluded were to be considered for this endpoint.	23:55, 47:55, 71:55, 95:55, 119:55, 167:55, 239:55, 263:55, 264:15, 264:30, 264:45, 265:00, 265:30, 266:00, 266:30, 267:00, 268:00, 270:00, 272:00, 274:00, 276:00, 288:00, 298:00, 312:00 and 336:00 (hours:minutes) after drug administration.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): September 16, 2016
• Primary Completion (Actual): December 9, 2016
• Study Completion (Actual): December 9, 2016

Study Registration Dates

• First Submitted: January 8, 2016
• First Submitted That Met QC Criteria: January 8, 2016
• First Posted (Estimate): January 11, 2016

Study Record Updates

• Last Update Posted (Actual): July 11, 2019
• Last Update Submitted That Met QC Criteria: April 18, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Other Study ID Numbers: 1320.23