Healthy
Conditions
Brief summary
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)
Interventions
DRUGBI 1026706
oral administration
DRUGPlacebo
placebo
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
20 Years to 45 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Drug-related Adverse Events (AEs) | From first drug administration to 4 days after last drug intake, up to 19 days. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tmax | -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. | 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. |
| AUC0-12 | -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. | 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. |
| AUC0-infinity | -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. | 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. |
| Cmax | -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. | 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. |
| Tmax,ss | 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. | 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. |
| Cmax,ss | 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. | 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. |
| AUC Tau,ss | 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. | 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. |
| t1/2 | -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. | 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. |
Countries
Japan
Participant flow
Recruitment details
This was a randomised, double-blind, placebo-controlled, single-centre trial investigating single rising dose (SRD) groups (25 milligram (mg), 50 mg and 100 mg) and a multiple dose (MD) (100 mg) in healthy Chinese and Japanese male subjects. This trial had an SRD plus MD nested design. All subjects from SRD 100 mg also participated in the MD part.
Pre-assignment details
Only subjects that met all the study inclusion and none of the exclusion criteria were to be entered in the study. All subjects were free to withdraw from the clinical trial at any time for any reason given. Close monitoring of all subjects was adhered to throughout the trial conduct. Rescue therapies was allowed for all subjects as required.
Participants by arm
| Arm | Count |
|---|---|
| Placebo The subjects were administered film-coated tablets matching placebo orally with 240 milliliter (mL) water after an overnight fast of at least 10 hours (h). | 18 |
| BI 1026706 25 mg The subjects were administered 25 mg film-coated tablet single dose orally with 240 mL water after an overnight fast of at least 10h. | 18 |
| BI 1026706 50 mg The subjects were administered 50 mg \[25 mg\*2\] film-coated tablets single dose orally with 240 mL water after an overnight fast of at least 10h. | 18 |
| BI 1026706 100 mg The subjects were administered 100 mg film-coated tablet \[SRD\] as single dose followed with 100 mg film-coated tablets \[MD\] twice daily for 11 days with a final single dose in the morning of Day 12 orally with 240 mL water after an overnight fast of at least 10h. | 18 |
| Total | 72 |
Baseline characteristics
| Characteristic | Placebo | BI 1026706 25 mg | BI 1026706 50 mg | BI 1026706 100 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 30.4 Years STANDARD_DEVIATION 7.74 | 28.6 Years STANDARD_DEVIATION 7.83 | 26.4 Years STANDARD_DEVIATION 5.72 | 28.1 Years STANDARD_DEVIATION 5.4 | 28.4 Years STANDARD_DEVIATION 6.78 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 18 Participants | 18 Participants | 18 Participants | 18 Participants | 72 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 18 | 0 / 18 | 0 / 18 | 2 / 18 |
| serious Total, serious adverse events | 0 / 18 | 0 / 18 | 0 / 18 | 0 / 18 |
Outcome results
Primary
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.
Time frame: From first drug administration to 4 days after last drug intake, up to 19 days.
Population: Treated set (TS) : This subject set included all subjects who were dispensed study medication and were documented to have taken at least 1 dose of investigational treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Subjects With Drug-related Adverse Events (AEs) | 0.0 Percentage of participants |
| BI 1026706 25 mg | Percentage of Subjects With Drug-related Adverse Events (AEs) | 0.0 Percentage of participants |
| BI 1026706 50 mg | Percentage of Subjects With Drug-related Adverse Events (AEs) | 0.0 Percentage of participants |
| BI 1026706 100 mg | Percentage of Subjects With Drug-related Adverse Events (AEs) | 5.6 Percentage of participants |
Secondary
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.
Time frame: -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.
Population: PKS-SRD part.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | AUC0-12 | Chinese | 1340 nmol*h/L | Geometric Coefficient of Variation 51 |
| Placebo | AUC0-12 | Japanese | 1650 nmol*h/L | Geometric Coefficient of Variation 43.5 |
| BI 1026706 25 mg | AUC0-12 | Chinese | 3260 nmol*h/L | Geometric Coefficient of Variation 62.1 |
| BI 1026706 25 mg | AUC0-12 | Japanese | 3270 nmol*h/L | Geometric Coefficient of Variation 31.5 |
| BI 1026706 50 mg | AUC0-12 | Chinese | 5340 nmol*h/L | Geometric Coefficient of Variation 42.4 |
| BI 1026706 50 mg | AUC0-12 | Japanese | 4620 nmol*h/L | Geometric Coefficient of Variation 45.4 |
Secondary
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.
Time frame: -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.
Population: PKS-SRD part.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | AUC0-infinity | Chinese | 1830 nmol*h/L | Geometric Coefficient of Variation 45.9 |
| Placebo | AUC0-infinity | Japanese | 2290 nmol*h/L | Geometric Coefficient of Variation 40.4 |
| BI 1026706 25 mg | AUC0-infinity | Chinese | 4170 nmol*h/L | Geometric Coefficient of Variation 59.1 |
| BI 1026706 25 mg | AUC0-infinity | Japanese | 4240 nmol*h/L | Geometric Coefficient of Variation 29.7 |
| BI 1026706 50 mg | AUC0-infinity | Chinese | 7350 nmol*h/L | Geometric Coefficient of Variation 37.1 |
| BI 1026706 50 mg | AUC0-infinity | Japanese | 6500 nmol*h/L | Geometric Coefficient of Variation 37.7 |
Secondary
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.
Time frame: 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.
Population: PKS-MD part.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | AUC Tau,ss | Chinese | 9390 nmol*h/L | Geometric Coefficient of Variation 35.2 |
| Placebo | AUC Tau,ss | Japanese | 8550 nmol*h/L | Geometric Coefficient of Variation 26.4 |
Secondary
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.
Time frame: -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.
Population: PharmacoKinetic Set (PKS)-SRD part: This set included all evaluable subjects of the TS-SRD part who were administered BI 1026706, and provided at least 1 observation for at least 1 pharmacokinetic (PK) secondary endpoint without important protocol violations relevant for the evaluation of PK secondary endpoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Cmax | Chinese | 298 nanomole (nmol)/Liter (L) | Geometric Coefficient of Variation 42.8 |
| Placebo | Cmax | Japanese | 338 nanomole (nmol)/Liter (L) | Geometric Coefficient of Variation 45.5 |
| BI 1026706 25 mg | Cmax | Chinese | 677 nanomole (nmol)/Liter (L) | Geometric Coefficient of Variation 54.6 |
| BI 1026706 25 mg | Cmax | Japanese | 595 nanomole (nmol)/Liter (L) | Geometric Coefficient of Variation 30.3 |
| BI 1026706 50 mg | Cmax | Chinese | 1120 nanomole (nmol)/Liter (L) | Geometric Coefficient of Variation 45.7 |
| BI 1026706 50 mg | Cmax | Japanese | 900 nanomole (nmol)/Liter (L) | Geometric Coefficient of Variation 51.2 |
Secondary
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.
Time frame: 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.
Population: PKS-MD part: This set included all evaluable subjects of the TS-MD part who were administered BI 1026706, and provided at least 1 observation for at least 1 PK secondary endpoint without important protocol violations relevant for the evaluation of PK secondary endpoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Cmax,ss | Chinese | 1570 nmol/L | Geometric Coefficient of Variation 36.5 |
| Placebo | Cmax,ss | Japanese | 1540 nmol/L | Geometric Coefficient of Variation 25.7 |
Secondary
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.
Time frame: -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.
Population: PKS-SRD part.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | t1/2 | Chinese | 11.5 h | Geometric Coefficient of Variation 70.3 |
| Placebo | t1/2 | Japanese | 14.3 h | Geometric Coefficient of Variation 65.4 |
| BI 1026706 25 mg | t1/2 | Chinese | 9.44 h | Geometric Coefficient of Variation 37.3 |
| BI 1026706 25 mg | t1/2 | Japanese | 8.86 h | Geometric Coefficient of Variation 56.4 |
| BI 1026706 50 mg | t1/2 | Chinese | 13.6 h | Geometric Coefficient of Variation 64.6 |
| BI 1026706 50 mg | t1/2 | Japanese | 12.3 h | Geometric Coefficient of Variation 45.6 |
Secondary
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.
Time frame: -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.
Population: PKS-SRD part.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Tmax | Chinese | 2.50 h |
| Placebo | Tmax | Japanese | 3.00 h |
| BI 1026706 25 mg | Tmax | Chinese | 1.50 h |
| BI 1026706 25 mg | Tmax | Japanese | 4.00 h |
| BI 1026706 50 mg | Tmax | Chinese | 2.00 h |
| BI 1026706 50 mg | Tmax | Japanese | 3.00 h |
Secondary
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.
Time frame: 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.
Population: PKS-MD part.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Tmax,ss | Chinese | 2.50 h |
| Placebo | Tmax,ss | Japanese | 2.00 h |