Healthy
Conditions
Brief summary
The main objective of the single-rising dose (SRD) part and the multiple rising dose (MD) part is to investigate safety, tolerability, pharmacokinetics and pharmacodynamics (for MD part only) following single rising doses and multiple oral doses of BI 1323495 in healthy male Japanese subjects genotyped as poor metabolizers (PM) and extensive metabolizers (EM) of UGT2B17. The main objective of the drug-drug interaction (DDI) part is to investigate the relative bioavailability of a single oral dose of BI 1323495 when given alone (treatment R) or in combination with itraconazole (treatment T) in healthy male subjects genotyped as PM of UGT2B17.
Interventions
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
MALE
Age
20 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 medical examination, vital signs (BP, PR), 12- lead 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 20 to 45 years (inclusive) at screening * BMI of 18.5 to 25.0 kg/m2 (inclusive) at screening * Signed and dated written informed consent prior to admission to the trial, in accordance with Good Clinical Practice (GCP) and local legislation * Subjects who agree to minimize the risk of making their partner pregnant by fulfilling any of the following criteria starting from the first administration of trial medication until 90 days after last administration 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 * Subjects genotyped as UGT2B17 poor metabolizers, i.e. carrying allele of UGT2B17 gene (\*2/\*2) (DDI part only)
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 mmHg, diastolic blood pressure outside the range of 40 to 90 mmHg, or pulse rate outside the range of 40 to 99 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 * Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| SRD and MD Part: Number of Participants With Drug-related Adverse Events (AEs) | Up to 7 days (for SRD part), up to 17 days (for MD part). | Number of participants with drug-related adverse events (AEs) is reported for Single rising dose (SRD) and Multiple dose (MD) parts is reported. |
| DDI Part: Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | Within 3 hours (h) before and 20min, 40min, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h, 24h, 34h, 47h, 71h, 95h, 119h, 143h, and 167h after start of BI 1323495 administration on both periods (1 and 2). | The area under the concentration-time curve of BI 1323495 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is reported. The statistical model used for the analysis of this endpoint was an analysis of variance (ANOVA) on the logarithmic scale. That is, the PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. This model included effects accounting for the following sources of variation: subject and treatment. The effect 'subject' was considered as random, whereas the effect 'treatment' was considered as fixed. These quantities were then back-transformed to the original scale. |
| DDI Part: Maximum Measured Concentration of BI 1323495 in Plasma (Cmax) | Within 3 hours (h) before and 20min, 40min, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h, 24h, 34h, 47h, 71h, 95h, 119h, 143h, and 167h after start of BI 1323495 administration on both periods (1 and 2). | Maximum measured concentration of BI 1323495 in plasma is reported. The statistical model used for the analysis of this endpoint was an analysis of variance (ANOVA) on the logarithmic scale. That is, the PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. This model included effects accounting for the following sources of variation: subject and treatment. The effect 'subject' was considered as random, whereas the effect 'treatment' was considered as fixed. These quantities were then back-transformed to the original scale. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| MD Part: Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval of 12 h After Administration of the First Dose (AUC0-12) | Within 3 hours (h) before and 20min, 40min, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h, after start of first dose BI 1323495 administration. | The area under the concentration-time curve of BI 1323495 in plasma over the time interval of 12 h after administration of the first dose (AUC0-12) is reported. |
| MD Part: Maximum Measured Concentration of BI 1323495 in Plasma (Cmax) After First Dose | Within 3 hours (h) before and 20min, 40min, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h, after start of first dose BI 1323495 administration. | Maximum measured concentration of BI 1323495 in plasma (Cmax) after first dose is reported. |
| DDI Part: Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | Within 3 hours (h) before and 20min, 40min, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h, 24h, 34h, 47h, 71h, 95h, 119h, 143h, and 167h after start of BI 1323495 administration on both periods (1 and 2). | The area under the concentration-time curve BI 1323495 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) is reported. The statistical model used for the analysis of this endpoint was an analysis of variance (ANOVA) on the logarithmic scale. That is, the PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. This model included effects accounting for the following sources of variation: subject and treatment. The effect 'subject' was considered as random, whereas the effect 'treatment' was considered as fixed. These quantities were then back-transformed to the original scale. |
| MD Part: Maximum Measured Concentration of BI 1323495 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss) | Within 15 minutes (min) before and 20min, 40min, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h and 24h (only for the 60mg qd administration) after last dose administration. | Maximum measured concentration of BI 1323495 in plasma (Cmax,ss) at steady state over a uniform dosing interval τ is reported. T for 30 mg bid is 12h, for 60 mg qd is 24h. |
| MD Part: Area Under the Concentration-time Curve of BI 1323495 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss) After Last Dose Administration. | Within 15 minutes (min) before and 20min, 40min, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h and 24h (only for the 60mg qd administration) after last dose administration. | Area under the concentration-time curve of BI 1323495 in plasma at steady state over a uniform dosing interval τ (AUCτ,ss) after last dose administration is reported. T for 30 mg bid is 12h, for 60 mg qd is 24h. |
| SRD Part: Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | Within 3 hours (h) before and 20min, 40min, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h, 24h, 34h, 48h, 72h, 96h after start of BI 1323495 administration. Additionally only in the PM group: at 120h, 144h, and 168h. | The area under the concentration-time curve of BI 1323495 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is reported. |
| SRD Part: Maximum Measured Concentration of BI 1323495 in Plasma (Cmax) | Within 3 hours (h) before and 20min, 40min, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h, 24h, 34h, 48h, 72h, 96h after start of BI 1323495 administration. Additionally only in the PM group: at 120h, 144h, and 168h. | Maximum measured concentration of BI 1323495 in plasma (Cmax) is reported. |
Countries
Japan
Participant flow
Recruitment details
This was a two part clinical trial, the first part was single rising dose (SRD) and multiple dose (MD), the second part evaluates drug-drug interaction (DDI) with itraconazole. The study was performed in healthy Japanese men genotyped as poor metabolizers (PM) or as extensive metabolizers (EM) to test how different doses of BI 1323495 are tolerated and how itraconazole influences the amount of BI 1323495 in the blood.
Pre-assignment details
All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated. Administrations of BI 1323495 was separated by a wash-out phase of at least 11 days.
Participants by arm
| Arm | Count |
|---|---|
| SRD Part: PM Subjects, BI1323495 10mg Participants were administered on Day 1 a single oral dose of 10 milligram (mg) of BI 1323495 film-coated tablet together with about 240 milliliter (mL) of water. A standardized meal was served 30 minutes (min) before drug administration. One authorized employee of the trial site was witness of the administration of the trial medication. | 6 |
| SRD Part: PM Subjects, BI1323495 30mg Participants were administered on Day 1 a single oral dose of 30 milligram (mg) of BI 1323495 film-coated tablets together with about 240 milliliter (mL) of water. A standardized meal was served 30 minutes (min) before drug administration.
One authorized employee of the trial site was witness of the administration of the trial medication. | 6 |
| SRD Part: PM Subjects, BI1323495 100mg Participants were administered on Day 1 a single oral dose of 100 milligram (mg) of BI 1323495 film-coated tablets together with about 240 milliliter (mL) of water. A standardized meal was served 30 minutes (min) before drug administration. One authorized employee of the trial site was witness of the administration of the trial medication. | 6 |
| SRD Part: EM Subjects, BI1323495 30mg Participants were administered on Day 1 a single oral dose of 30 milligram (mg) of BI 1323495 film-coated tablets together with about 240 milliliter (mL) of water. A standardized meal was served 30 minutes (min) before drug administration. One authorized employee of the trial site was witness of the administration of the trial medication. | 3 |
| SRD Part: EM Subjects, BI1323495 70mg Participants were administered on Day 1 a single oral dose of 70 milligram (mg) of BI 1323495 film-coated tablets together with about 240 milliliter (mL) of water. A standardized meal was served 30 minutes (min) before drug administration. One authorized employee of the trial site was witness of the administration of the trial medication. | 3 |
| SRD Part: EM Subjects, BI1323495 150mg Participants were administered on Day 1 a single oral dose of 150 milligram (mg) of BI 1323495 film-coated tablets together with about 240 milliliter (mL) of water. A standardized meal was served 30 minutes (min) before drug administration. One authorized employee of the trial site was witness of the administration of the trial medication. | 3 |
| SRD Part: Placebo This arm comprises all placebo treated participants in trial part SRD, regardless of the dose group in which they were treated. Participants were randomized within each dose group in a 3:1 ratio (test treatment to placebo).
Participants were administered on Day 1 a single oral dose of placebo film-coated tablet(s) together with about 240 milliliter (mL) of water. A standardized meal was served 30 minutes (min) before drug administration. One authorized employee of the trial site was witness of the administration of the trial medication. | 9 |
| MD Part: PM Subjects, BI1323495 30mg BID Participants were administered from Day 1 to Day 10 two times per day (bid) an oral dose of 30 milligram (mg) of BI 1323495 film-coated tablets together with about 240 milliliter (mL) of water, At Day 11 participants were administered only a single dose in the morning. Participants took a normal caloric meal 30 minutes (min) before drug administration. Subjects fasted for 4 hours (h) after intake of morning dose. Morning and evening dose were taken with a 12 h time interval approximately at the same time each day during the treatment phase. One authorized employee of the trial site was witness of the administration of the trial medication. | 9 |
| MD Part: PM Subjects, BI1323495 60mg QD Participants were administered from Day 1 to Day 11 one time per day (qd) an oral dose of 60 milligram (mg) of BI 1323495 film-coated tablets together with about 240 milliliter (mL) of water. Participants took a normal caloric meal 30 minutes (min) before drug administration. Subjects fasted for 4 hours (h) after intake of morning dose. One authorized employee of the trial site was witness of the administration of the trial medication. | 9 |
| MD Part: Placebo This arm comprises all placebo treated participants in trial part MD, regardless of the dose group in which they were treated. Participants were randomized within each dose group in a 3:1 ratio (test treatment to placebo). Participants were administered from Day 1 to Day 11 one time per day (qd) an oral dose of placebo film-coated tablets or two times per day (bid) an oral dose of placebo together with about 240 milliliter (mL) of water. Participants took a normal caloric meal 30 minutes (min) before drug administration. Subjects fasted for 4 hours (h) after intake of morning dose. One authorized employee of the trial site was witness of the administration of the trial medication. | 6 |
| DDI Part: PM Subjects, BI1323495 / BI1323495+ Itraconazole * Period 1: Participants were administered the reference treatment (R) which consisted of a single oral dose of 10 milligram (mg) film-coated tablet of BI 1323495 together with about 240 milliliter (mL) of water on Day 1 of Period 1. One authorized employee of the trial site was witness of the administration of the trial medication.
* Period 2: Participants were administered the test treatment (T) which consisted of a single oral dose of 10 milligram (mg) film-coated tablet of BI 1323495 with about 240 milliliter (mL) of water on Day 1 of Period 2, together with multiple oral doses of 200 mg itraconazole from Day -3 to Day 7, in total 10 doses, as oral solution formulation. One authorized employee of the trial site was witness of the administration of the trial medication.
Administration of BI 1323495 in treatment R and T were separated by at least 11 days. | 14 |
| Total | 74 |
Baseline characteristics
| Characteristic | SRD Part: PM Subjects, BI1323495 10mg | SRD Part: PM Subjects, BI1323495 30mg | SRD Part: PM Subjects, BI1323495 100mg | SRD Part: EM Subjects, BI1323495 30mg | SRD Part: EM Subjects, BI1323495 70mg | SRD Part: EM Subjects, BI1323495 150mg | SRD Part: Placebo | MD Part: PM Subjects, BI1323495 30mg BID | MD Part: PM Subjects, BI1323495 60mg QD | MD Part: Placebo | DDI Part: PM Subjects, BI1323495 / BI1323495+ Itraconazole | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 24.3 Years STANDARD_DEVIATION 3.8 | 32.5 Years STANDARD_DEVIATION 10.3 | 33.5 Years STANDARD_DEVIATION 7.6 | 24.7 Years STANDARD_DEVIATION 3.1 | 33.0 Years STANDARD_DEVIATION 4.6 | 29.3 Years STANDARD_DEVIATION 5.5 | 29.3 Years STANDARD_DEVIATION 7 | 32.3 Years STANDARD_DEVIATION 5.6 | 28.6 Years STANDARD_DEVIATION 4.6 | 30.0 Years STANDARD_DEVIATION 6.5 | 30.4 Years STANDARD_DEVIATION 7.2 | 30.0 Years STANDARD_DEVIATION 6.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 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 | 3 Participants | 3 Participants | 3 Participants | 9 Participants | 9 Participants | 9 Participants | 6 Participants | 14 Participants | 74 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 6 Participants | 6 Participants | 3 Participants | 3 Participants | 3 Participants | 9 Participants | 9 Participants | 9 Participants | 6 Participants | 14 Participants | 74 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 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 | 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 | 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 | 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 | 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 6 Participants | 3 Participants | 3 Participants | 3 Participants | 9 Participants | 9 Participants | 9 Participants | 6 Participants | 14 Participants | 74 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 | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 9 | 0 / 9 | 0 / 14 | 0 / 14 | 0 / 14 |
| other Total, other adverse events | 1 / 9 | 1 / 6 | 1 / 6 | 2 / 6 | 4 / 6 | 2 / 3 | 1 / 3 | 0 / 3 | 2 / 9 | 4 / 9 | 4 / 14 | 1 / 14 | 4 / 14 |
| serious Total, serious adverse events | 0 / 9 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 9 | 0 / 9 | 0 / 14 | 0 / 14 | 0 / 14 |
Outcome results
Primary
DDI Part: Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
The area under the concentration-time curve of BI 1323495 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is reported. The statistical model used for the analysis of this endpoint was an analysis of variance (ANOVA) on the logarithmic scale. That is, the PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. This model included effects accounting for the following sources of variation: subject and treatment. The effect 'subject' was considered as random, whereas the effect 'treatment' was considered as fixed. These quantities were then back-transformed to the original scale.
Time frame: Within 3 hours (h) before and 20min, 40min, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h, 24h, 34h, 47h, 71h, 95h, 119h, 143h, and 167h after start of BI 1323495 administration on both periods (1 and 2).
Population: Pharmacokinetic parameter analysis set (PKS): This set includes all subjects in the treated set (TS) who provide at least one primary or secondary PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Only subjects with non-missing values were included.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| SRD Part: PM Subjects, BI1323495 10mg | DDI Part: Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 757.8 hour * nanomol / liter (h*nmol/L) |
| SRD Part: PM Subjects, BI1323495 30mg | DDI Part: Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 2558.3 hour * nanomol / liter (h*nmol/L) |
Comparison: The PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. This model included effects accounting for the following sources of variation: subject and treatment. The effect 'subject' was considered as random, whereas the effect 'treatment' was considered as fixed. These quantities were then back-transformed to the original scale.90% CI: [302.8, 376.4]
Primary
DDI Part: Maximum Measured Concentration of BI 1323495 in Plasma (Cmax)
Maximum measured concentration of BI 1323495 in plasma is reported. The statistical model used for the analysis of this endpoint was an analysis of variance (ANOVA) on the logarithmic scale. That is, the PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. This model included effects accounting for the following sources of variation: subject and treatment. The effect 'subject' was considered as random, whereas the effect 'treatment' was considered as fixed. These quantities were then back-transformed to the original scale.
Time frame: Within 3 hours (h) before and 20min, 40min, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h, 24h, 34h, 47h, 71h, 95h, 119h, 143h, and 167h after start of BI 1323495 administration on both periods (1 and 2).
Population: Pharmacokinetic parameter analysis set (PKS): This set includes all subjects in the treated set (TS) who provide at least one primary or secondary 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_LEAST_SQUARES_MEAN) |
|---|---|---|
| SRD Part: PM Subjects, BI1323495 10mg | DDI Part: Maximum Measured Concentration of BI 1323495 in Plasma (Cmax) | 81.2 nanomol / liter (nmol/L) |
| SRD Part: PM Subjects, BI1323495 30mg | DDI Part: Maximum Measured Concentration of BI 1323495 in Plasma (Cmax) | 149.7 nanomol / liter (nmol/L) |
Comparison: The PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. This model included effects accounting for the following sources of variation: subject and treatment. The effect 'subject' was considered as random, whereas the effect 'treatment' was considered as fixed. These quantities were then back-transformed to the original scale.90% CI: [156, 218]
Primary
SRD and MD Part: Number of Participants With Drug-related Adverse Events (AEs)
Number of participants with drug-related adverse events (AEs) is reported for Single rising dose (SRD) and Multiple dose (MD) parts is reported.
Time frame: Up to 7 days (for SRD part), up to 17 days (for MD part).
Population: Treated set (TS): The treated set includes all subjects who were randomised (SRD and MD part) and treated with at least one dose of trial drug. As pre-specified in the protocol this endpoint only includes the SRD and MD part of the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SRD Part: PM Subjects, BI1323495 10mg | SRD and MD Part: Number of Participants With Drug-related Adverse Events (AEs) | 1 Participants |
| SRD Part: PM Subjects, BI1323495 30mg | SRD and MD Part: Number of Participants With Drug-related Adverse Events (AEs) | 2 Participants |
| SRD Part: PM Subjects, BI1323495 100mg | SRD and MD Part: Number of Participants With Drug-related Adverse Events (AEs) | 1 Participants |
| SRD Part: EM Subjects, BI1323495 30mg | SRD and MD Part: Number of Participants With Drug-related Adverse Events (AEs) | 0 Participants |
| SRD Part: EM Subjects, BI1323495 70mg | SRD and MD Part: Number of Participants With Drug-related Adverse Events (AEs) | 1 Participants |
| SRD Part: EM Subjects, BI1323495 150mg | SRD and MD Part: Number of Participants With Drug-related Adverse Events (AEs) | 0 Participants |
| SRD Part: Placebo | SRD and MD Part: Number of Participants With Drug-related Adverse Events (AEs) | 1 Participants |
| MD Part: PM Subjects, BI1323495 30mg BID | SRD and MD Part: Number of Participants With Drug-related Adverse Events (AEs) | 2 Participants |
| MD Part: PM Subjects, BI1323495 60mg QD | SRD and MD Part: Number of Participants With Drug-related Adverse Events (AEs) | 3 Participants |
| MD Part: Placebo | SRD and MD Part: Number of Participants With Drug-related Adverse Events (AEs) | 1 Participants |
Secondary
DDI Part: Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
The area under the concentration-time curve BI 1323495 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) is reported. The statistical model used for the analysis of this endpoint was an analysis of variance (ANOVA) on the logarithmic scale. That is, the PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. This model included effects accounting for the following sources of variation: subject and treatment. The effect 'subject' was considered as random, whereas the effect 'treatment' was considered as fixed. These quantities were then back-transformed to the original scale.
Time frame: Within 3 hours (h) before and 20min, 40min, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h, 24h, 34h, 47h, 71h, 95h, 119h, 143h, and 167h after start of BI 1323495 administration on both periods (1 and 2).
Population: Pharmacokinetic parameter analysis set (PKS): This set includes all subjects in the treated set (TS) who provide at least one primary or secondary 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_LEAST_SQUARES_MEAN) |
|---|---|---|
| SRD Part: PM Subjects, BI1323495 10mg | DDI Part: Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 704.5 hour * nanomol / liter (h*nmol/L) |
| SRD Part: PM Subjects, BI1323495 30mg | DDI Part: Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 2513.8 hour * nanomol / liter (h*nmol/L) |
Comparison: The PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. This model included effects accounting for the following sources of variation: subject and treatment. The effect 'subject' was considered as random, whereas the effect 'treatment' was considered as fixed. These quantities were then back-transformed to the original scale.90% CI: [315.7, 403.2]
Secondary
MD Part: Area Under the Concentration-time Curve of BI 1323495 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss) After Last Dose Administration.
Area under the concentration-time curve of BI 1323495 in plasma at steady state over a uniform dosing interval τ (AUCτ,ss) after last dose administration is reported. T for 30 mg bid is 12h, for 60 mg qd is 24h.
Time frame: Within 15 minutes (min) before and 20min, 40min, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h and 24h (only for the 60mg qd administration) after last dose administration.
Population: Pharmacokinetic parameter analysis set (PKS): This set includes all subjects in the treated set (TS) who provide at least one primary or secondary 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 |
|---|---|---|---|
| SRD Part: PM Subjects, BI1323495 10mg | MD Part: Area Under the Concentration-time Curve of BI 1323495 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss) After Last Dose Administration. | 2600 hour * nanomol / liter (h*nmol/L) | Geometric Coefficient of Variation 20 |
| SRD Part: PM Subjects, BI1323495 30mg | MD Part: Area Under the Concentration-time Curve of BI 1323495 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss) After Last Dose Administration. | 4770 hour * nanomol / liter (h*nmol/L) | Geometric Coefficient of Variation 17 |
Secondary
MD Part: Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval of 12 h After Administration of the First Dose (AUC0-12)
The area under the concentration-time curve of BI 1323495 in plasma over the time interval of 12 h after administration of the first dose (AUC0-12) is reported.
Time frame: Within 3 hours (h) before and 20min, 40min, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h, after start of first dose BI 1323495 administration.
Population: Pharmacokinetic parameter analysis set (PKS): This set includes all subjects in the treated set (TS) who provide at least one primary or secondary 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 |
|---|---|---|---|
| SRD Part: PM Subjects, BI1323495 10mg | MD Part: Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval of 12 h After Administration of the First Dose (AUC0-12) | 1520 hour * nanomol / liter (h*nmol/L) | Geometric Coefficient of Variation 15.4 |
| SRD Part: PM Subjects, BI1323495 30mg | MD Part: Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval of 12 h After Administration of the First Dose (AUC0-12) | 2350 hour * nanomol / liter (h*nmol/L) | Geometric Coefficient of Variation 15.1 |
Secondary
MD Part: Maximum Measured Concentration of BI 1323495 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss)
Maximum measured concentration of BI 1323495 in plasma (Cmax,ss) at steady state over a uniform dosing interval τ is reported. T for 30 mg bid is 12h, for 60 mg qd is 24h.
Time frame: Within 15 minutes (min) before and 20min, 40min, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h and 24h (only for the 60mg qd administration) after last dose administration.
Population: Pharmacokinetic parameter analysis set (PKS): This set includes all subjects in the treated set (TS) who provide at least one primary or secondary 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 |
|---|---|---|---|
| SRD Part: PM Subjects, BI1323495 10mg | MD Part: Maximum Measured Concentration of BI 1323495 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss) | 417 nanomol / liter (nmol/L) | Geometric Coefficient of Variation 17.1 |
| SRD Part: PM Subjects, BI1323495 30mg | MD Part: Maximum Measured Concentration of BI 1323495 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss) | 570 nanomol / liter (nmol/L) | Geometric Coefficient of Variation 19.7 |
Secondary
MD Part: Maximum Measured Concentration of BI 1323495 in Plasma (Cmax) After First Dose
Maximum measured concentration of BI 1323495 in plasma (Cmax) after first dose is reported.
Time frame: Within 3 hours (h) before and 20min, 40min, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h, after start of first dose BI 1323495 administration.
Population: Pharmacokinetic parameter analysis set (PKS): This set includes all subjects in the treated set (TS) who provide at least one primary or secondary 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 |
|---|---|---|---|
| SRD Part: PM Subjects, BI1323495 10mg | MD Part: Maximum Measured Concentration of BI 1323495 in Plasma (Cmax) After First Dose | 303 nanomol / liter (nmol/L) | Geometric Coefficient of Variation 14 |
| SRD Part: PM Subjects, BI1323495 30mg | MD Part: Maximum Measured Concentration of BI 1323495 in Plasma (Cmax) After First Dose | 431 nanomol / liter (nmol/L) | Geometric Coefficient of Variation 15.2 |
Secondary
SRD Part: Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
The area under the concentration-time curve of BI 1323495 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is reported.
Time frame: Within 3 hours (h) before and 20min, 40min, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h, 24h, 34h, 48h, 72h, 96h after start of BI 1323495 administration. Additionally only in the PM group: at 120h, 144h, and 168h.
Population: Pharmacokinetic parameter analysis set (PKS): This set includes all subjects in the treated set (TS) who provide at least one primary or secondary PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Only subjects with non-missing values were included.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| SRD Part: PM Subjects, BI1323495 10mg | SRD Part: Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 776 hour * nanomol / liter (h*nmol/L) | Geometric Coefficient of Variation 9.14 |
| SRD Part: PM Subjects, BI1323495 30mg | SRD Part: Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 2140 hour * nanomol / liter (h*nmol/L) | Geometric Coefficient of Variation 25.7 |
| SRD Part: PM Subjects, BI1323495 100mg | SRD Part: Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 6700 hour * nanomol / liter (h*nmol/L) | Geometric Coefficient of Variation 13.9 |
| SRD Part: EM Subjects, BI1323495 30mg | SRD Part: Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 715 hour * nanomol / liter (h*nmol/L) | Geometric Coefficient of Variation 55 |
| SRD Part: EM Subjects, BI1323495 70mg | SRD Part: Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 4040 hour * nanomol / liter (h*nmol/L) | Geometric Coefficient of Variation 25.6 |
| SRD Part: EM Subjects, BI1323495 150mg | SRD Part: Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 3550 hour * nanomol / liter (h*nmol/L) | Geometric Coefficient of Variation 42.2 |
Secondary
SRD Part: Maximum Measured Concentration of BI 1323495 in Plasma (Cmax)
Maximum measured concentration of BI 1323495 in plasma (Cmax) is reported.
Time frame: Within 3 hours (h) before and 20min, 40min, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h, 24h, 34h, 48h, 72h, 96h after start of BI 1323495 administration. Additionally only in the PM group: at 120h, 144h, and 168h.
Population: Pharmacokinetic parameter analysis set (PKS): This set includes all subjects in the treated set (TS) who provide at least one primary or secondary 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 |
|---|---|---|---|
| SRD Part: PM Subjects, BI1323495 10mg | SRD Part: Maximum Measured Concentration of BI 1323495 in Plasma (Cmax) | 105 nanomol / liter (nmol/L) | Geometric Coefficient of Variation 18 |
| SRD Part: PM Subjects, BI1323495 30mg | SRD Part: Maximum Measured Concentration of BI 1323495 in Plasma (Cmax) | 276 nanomol / liter (nmol/L) | Geometric Coefficient of Variation 22.1 |
| SRD Part: PM Subjects, BI1323495 100mg | SRD Part: Maximum Measured Concentration of BI 1323495 in Plasma (Cmax) | 643 nanomol / liter (nmol/L) | Geometric Coefficient of Variation 9.15 |
| SRD Part: EM Subjects, BI1323495 30mg | SRD Part: Maximum Measured Concentration of BI 1323495 in Plasma (Cmax) | 86.9 nanomol / liter (nmol/L) | Geometric Coefficient of Variation 37 |
| SRD Part: EM Subjects, BI1323495 70mg | SRD Part: Maximum Measured Concentration of BI 1323495 in Plasma (Cmax) | 196 nanomol / liter (nmol/L) | Geometric Coefficient of Variation 8.72 |
| SRD Part: EM Subjects, BI1323495 150mg | SRD Part: Maximum Measured Concentration of BI 1323495 in Plasma (Cmax) | 230 nanomol / liter (nmol/L) | Geometric Coefficient of Variation 54.9 |