Healthy
Conditions
Brief summary
The main objectives of this trial are to investigate safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of BI 3006337 in healthy male subjects following s.c. administration of single rising doses and multiple doses over 6 weeks.
Interventions
DRUGBI 3006337
BI 3006337
DRUGPlacebo
Placebo
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
The trial is designed single-blind. The treatments administered (BI 3006337 or placebo) will be blinded to subjects but will be known to the investigators (outcome assessors).
Intervention model description
Trial consists of a single-rising dose (SRD) and multiple dose (MD) part. In SRD part, the groups will be dosed consecutively in ascending order. The decision proceeding to MD part will be based upon safety and tolerability of all the preceding dose groups in SRD part. Within each dose group, patients will be randomized to either BI 3006337 or placebo.
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male subjects according to the assessment of the investigator, as 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 are Japanese * Age of 18 to 45 years (inclusive) * Body mass index (BMI) of 18.5 to 25.0 kg/m2 (inclusive) * Signed and dated written informed consent in accordance with International Conference of Harmonization - Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial * Subjects who agree to minimise the risk of making their partner pregnant by fulfilling any of the following criteria starting from the start of injection of trial medication until 30 days after end of injection of trial medication: * Use of adequate contraception, any of the following methods plus condom: intrauterine device, combined oral contraceptives that started at least 2 months prior to the first drug administration * Vasectomized (vasectomy at least 1 year prior to enrolment) * Surgical sterilization (including bilateral tubal occlusion, hysterectomy or bilateral oophorectomy) of the subject's female partner * Female partner is postmenopausal, defined as no menses for 1 year without an alternative medical cause
Exclusion criteria
* Any finding in the medical examination (including BP, PR 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 millimeter of mercury (mmHg), diastolic blood pressure outside the range of 50 to 90 mmHg, or PR outside the range of 50 to 90 bpm at screening visit * 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 * Clinically relevant 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 Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAE) | SRD part: From BI 3006337 administration until end of residual effect period (REP), 3 weeks. MD part: From first until last BI 3006337 administration + REP, up to 9 weeks. | Number of participants with treatment-emergent adverse events (TEAE) is presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of BI 3006337 in Serum Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | Within 3 hours (hrs) before BI 3006337 administration and at 1.5, 3, 7, 11, 15, 23, 27, 31, 35, 39, 47, 58, 72, 96, 120, 168, 240, 336, 504, and 672 hrs, and at end of trial examination, up to Day 40 after BI 3006337 administration. | Area under the concentration-time curve of BI 3006337 in serum over the time interval from 0 extrapolated to infinity (AUC0-inf) is presented. |
| Maximum Measured Concentration of BI 3006337 in Serum (Cmax) | Within 3 hours (hrs) before BI 3006337 administration and at 1.5, 3, 7, 11, 15, 23, 27, 31, 35, 39, 47, 58, 72, 96, 120, 168, 240, 336, 504, and 672 hrs, and at end of trial examination, up to Day 40 after BI 3006337 administration. | Maximum measured concentration of BI 3006337 in serum (Cmax) is presented. |
| Area Under the Concentration-time Curve of BI 3006337 in Serum Over the Dosing Interval Tau at Steady State (AUCtau, ss) After the Last Dose in Week 6 | Within 3 hours (hrs) before last BI 3006337 administration and at 3, 7, 11, 15, 23, 27, 31, 35, 39, 47, 72, and 168 hrs after last BI 3006337 administration. | Area under the concentration-time curve of BI 3006337 in serum over the dosing interval tau at steady state (AUCtau, ss) after the last dose in Week 6 is presented. |
| Maximum Measured Concentration of BI 3006337 in Serum at Steady State (Cmax, ss) After the Last Dose in Week 6 | Within 3 hours (hrs) before last BI 3006337 administration and at 3, 7, 11, 15, 23, 27, 31, 35, 39, 47, 72, and 168 hrs after last BI 3006337 administration. | Maximum measured concentration of BI 3006337 in serum at steady state (Cmax, ss) after the last dose in Week 6 is presented. |
Countries
Japan
Participant flow
Recruitment details
The purpose of this study was to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single rising subcutaneous doses and multiple subcutaneous doses over 6 weeks of BI 3006337 in healthy male Japanese subjects (single-blind, randomised within dose groups, placebo controlled, parallel group design).
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 medication was allowed for all patients as required.
Participants by arm
| Arm | Count |
|---|---|
| Placebo (SRD) Participants received one single dose of Placebo matching BI 3006337, as subcutaneous injection on Day 1 of the single-rising dose part. | 6 |
| Single-rising Dose Part (SRD): BI 3006337 50 mg Dose Participants received one single 50 milligrams (mg) dose of BI 3006337 as subcutaneous injection on Day 1 of the single-rising dose part. | 6 |
| SRD Part: BI 3006337 100 mg Dose Participants received one single 100 mg dose of BI 3006337 as subcutaneous injection on Day 1 of the single-rising dose part. | 6 |
| SRD Part: BI 3006337 150 mg Dose Participants received one single 150 mg dose of BI 3006337 as subcutaneous injection on Day 1 of the single-rising dose part. | 6 |
| Placebo (MD) Participants received one dose of Placebo matching BI 3006337, as subcutaneous injection once per week for 6 weeks (multiple dose part (MD)). | 3 |
| Multiple Dose Part (MD): BI 3006337 150 mg Dose Participants received one 150 mg dose of BI 3006337 as subcutaneous injection once per week for 6 weeks (multiple dose part (MD)). | 9 |
| Total | 36 |
Baseline characteristics
| Characteristic | Placebo (SRD) | Single-rising Dose Part (SRD): BI 3006337 50 mg Dose | SRD Part: BI 3006337 100 mg Dose | SRD Part: BI 3006337 150 mg Dose | Placebo (MD) | Multiple Dose Part (MD): BI 3006337 150 mg Dose | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 31.7 Years STANDARD_DEVIATION 6.7 | 34.5 Years STANDARD_DEVIATION 10.9 | 28.2 Years STANDARD_DEVIATION 9.1 | 27.7 Years STANDARD_DEVIATION 8.1 | 31.3 Years STANDARD_DEVIATION 10.1 | 31.4 Years STANDARD_DEVIATION 8.8 | 30.8 Years STANDARD_DEVIATION 8.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 3 Participants | 9 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 3 Participants | 9 Participants | 36 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 3 Participants | 9 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 3 | 0 / 9 |
| other Total, other adverse events | 4 / 6 | 4 / 6 | 2 / 6 | 2 / 6 | 0 / 3 | 8 / 9 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 3 | 0 / 9 |
Outcome results
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAE)
Number of participants with treatment-emergent adverse events (TEAE) is presented.
Time frame: SRD part: From BI 3006337 administration until end of residual effect period (REP), 3 weeks. MD part: From first until last BI 3006337 administration + REP, up to 9 weeks.
Population: Treated set (TS): The treated set included all participants who were treated with at least one dose of trial drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (SRD) | Number of Participants With Treatment-emergent Adverse Events (TEAE) | 4 Participants |
| Single-rising Dose Part (SRD): BI 3006337 50 mg Dose | Number of Participants With Treatment-emergent Adverse Events (TEAE) | 4 Participants |
| SRD Part: BI 3006337 100 mg Dose | Number of Participants With Treatment-emergent Adverse Events (TEAE) | 2 Participants |
| SRD Part: BI 3006337 150 mg Dose | Number of Participants With Treatment-emergent Adverse Events (TEAE) | 2 Participants |
| Placebo (MD) | Number of Participants With Treatment-emergent Adverse Events (TEAE) | 0 Participants |
| Multiple Dose Part (MD): BI 3006337 150 mg Dose | Number of Participants With Treatment-emergent Adverse Events (TEAE) | 8 Participants |
Secondary
Area Under the Concentration-time Curve of BI 3006337 in Serum Over the Dosing Interval Tau at Steady State (AUCtau, ss) After the Last Dose in Week 6
Area under the concentration-time curve of BI 3006337 in serum over the dosing interval tau at steady state (AUCtau, ss) after the last dose in Week 6 is presented.
Time frame: Within 3 hours (hrs) before last BI 3006337 administration and at 3, 7, 11, 15, 23, 27, 31, 35, 39, 47, 72, and 168 hrs after last BI 3006337 administration.
Population: Pharmacokinetic parameter analysis set (PKS): This set included all participants in the TS who provided at least one pharmacokinetic (PK) endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (SRD) | Area Under the Concentration-time Curve of BI 3006337 in Serum Over the Dosing Interval Tau at Steady State (AUCtau, ss) After the Last Dose in Week 6 | 91600 hours*nanograms/milliliters (h*ng/ml) | Geometric Coefficient of Variation 41.5 |
Secondary
Area Under the Concentration-time Curve of BI 3006337 in Serum Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf)
Area under the concentration-time curve of BI 3006337 in serum over the time interval from 0 extrapolated to infinity (AUC0-inf) is presented.
Time frame: Within 3 hours (hrs) before BI 3006337 administration and at 1.5, 3, 7, 11, 15, 23, 27, 31, 35, 39, 47, 58, 72, 96, 120, 168, 240, 336, 504, and 672 hrs, and at end of trial examination, up to Day 40 after BI 3006337 administration.
Population: Pharmacokinetic parameter analysis set (PKS): This set included all participants in the TS who provided at least one pharmacokinetic (PK) endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (SRD) | Area Under the Concentration-time Curve of BI 3006337 in Serum Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 41400 hours*nanograms/milliliters (h*ng/ml) | Geometric Coefficient of Variation 35.7 |
| Single-rising Dose Part (SRD): BI 3006337 50 mg Dose | Area Under the Concentration-time Curve of BI 3006337 in Serum Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 61400 hours*nanograms/milliliters (h*ng/ml) | Geometric Coefficient of Variation 23.1 |
| SRD Part: BI 3006337 100 mg Dose | Area Under the Concentration-time Curve of BI 3006337 in Serum Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 109000 hours*nanograms/milliliters (h*ng/ml) | Geometric Coefficient of Variation 34.6 |
Secondary
Maximum Measured Concentration of BI 3006337 in Serum at Steady State (Cmax, ss) After the Last Dose in Week 6
Maximum measured concentration of BI 3006337 in serum at steady state (Cmax, ss) after the last dose in Week 6 is presented.
Time frame: Within 3 hours (hrs) before last BI 3006337 administration and at 3, 7, 11, 15, 23, 27, 31, 35, 39, 47, 72, and 168 hrs after last BI 3006337 administration.
Population: Pharmacokinetic parameter analysis set (PKS): This set included all participants in the TS who provided at least one pharmacokinetic (PK) endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (SRD) | Maximum Measured Concentration of BI 3006337 in Serum at Steady State (Cmax, ss) After the Last Dose in Week 6 | 1720 nanograms/milliliters (ng/ml) | Geometric Coefficient of Variation 76 |
Secondary
Maximum Measured Concentration of BI 3006337 in Serum (Cmax)
Maximum measured concentration of BI 3006337 in serum (Cmax) is presented.
Time frame: Within 3 hours (hrs) before BI 3006337 administration and at 1.5, 3, 7, 11, 15, 23, 27, 31, 35, 39, 47, 58, 72, 96, 120, 168, 240, 336, 504, and 672 hrs, and at end of trial examination, up to Day 40 after BI 3006337 administration.
Population: Pharmacokinetic parameter analysis set (PKS): This set included all participants in the TS who provided at least one pharmacokinetic (PK) endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (SRD) | Maximum Measured Concentration of BI 3006337 in Serum (Cmax) | 665 nanograms/milliliters (ng/ml) | Geometric Coefficient of Variation 43.7 |
| Single-rising Dose Part (SRD): BI 3006337 50 mg Dose | Maximum Measured Concentration of BI 3006337 in Serum (Cmax) | 1050 nanograms/milliliters (ng/ml) | Geometric Coefficient of Variation 78.9 |
| SRD Part: BI 3006337 100 mg Dose | Maximum Measured Concentration of BI 3006337 in Serum (Cmax) | 1730 nanograms/milliliters (ng/ml) | Geometric Coefficient of Variation 46.4 |