Healthy
Conditions
Brief summary
The main objectives are: * Part I: To investigate safety, tolerability, and pharmacokinetics (PK) of BI 706321 in healthy male subjects following oral administration of single rising doses. * Part II: The relative bioavailability of BI 706321 after administration of tablets and capsules under fasted conditions will be compared with each other and the effect of food on the tablet bioavailability will be investigated.
Interventions
DRUGBI 706321
Capsule or Oral Solution
DRUGPlacebo
Capsule or Oral solution
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
MALE
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 (BP, PR, oral body temperature), 12-lead ECG, and clinical laboratory tests * Age of 18 to 45 years (inclusive) in Part I and of 18 to 55 years (inclusive) in Part II * BMI of 18.5 to 29.9 kg/m2 (inclusive) * Signed and dated written informed consent prior to admission to the study, in accordance with GCP and local legislation
Exclusion criteria
* Any finding in the medical examination (including Blood Pressure (BP), (PR), oral body temperature 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 50 to 90 mmHg, or pulse rate outside the range of 50 to 90 bpm * Any laboratory value outside the reference range that the investigator considers to be of clinical relevance * Any evidence of a concomitant disease 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 * Chronic or relevant acute infections * History of relevant allergy or hypersensitivity (including allergy to the trial medication or its excipients) * Use of drugs within 30 days of planned administration of trial medication that might reasonably influence the results of the trial (including drugs that cause QT/QTc interval prolongation) * Intake of an investigational drug in another clinical trial within 60 days of planned administration of investigational drug in the current trial, or concurrent participation in another clinical trial in which investigational drug is administered * 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 24 g per day) * Drug abuse or positive drug screening * Blood donation of more than 100 mL within 30 days of planned administration of trial medication or intended blood donation during the trial * Intention to perform excessive physical activities within one week prior to the administration of trial medication or during the trial * Inability to comply with the dietary regimen of the 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 Torsade de Pointes (such as heart failure, hypokalaemia, or family history of Long QT Syndrome) * Subject is assessed as unsuitable for inclusion by the investigator, for instance, because the subject is not considered able to understand and comply with study requirements, or has a condition that would not allow safe participation in the study * Male subjects with WOCBP partner who are unwilling to use male contraception (condom or sexual abstinence) from time point of administration of trial medication until 30 days thereafter. Sperm donation is not allowed from the time point of drug administration until 30 days thereafter. * ALT (alanine transaminase), AST (aspartate transaminase), or creatinine exceed upper limit of normal range at screening, confirmed by a repeat test * During COVID-19 pandemic: laboratory test indicative of an ongoing SARS-CoV-2 infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part I: Percentage of Subjects With Drug-related Adverse Events | Between intake of trial medication and the individual subject's end of trial, up to 22 days. | Part I: Percentage of subjects with drug-related adverse events. |
| Part II: Area Under the Concentration-time Curve of BI 706321 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | Within 3 hours before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 34, 48, 72, 168 hours after drug administration. | Part II: Area under the concentration-time curve of BI 706321 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz). |
| Part II: Maximum Measured Concentration of BI 706321 in Plasma (Cmax) | Within 3 hours before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 34, 48, 72, 168 hours after drug administration. | Part II: Maximum measured concentration of BI 706321 in plasma (Cmax). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part I: Area Under the Concentration-time Curve of BI 706321 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | Within 3 hours before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 34, 48, 168 hours after drug administration. | Part I: Area under the concentration-time curve of BI 706321 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞). |
| Part II: Area Under the Concentration-time Curve of BI 706321 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | Within 3 hours before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 34, 48, 72, 168 hours after drug administration. | Part II: Area under the concentration-time curve of BI 706321 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞). |
| Part I: Maximum Measured Concentration of BI 706321 in Plasma (Cmax) | Within 3 hours before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 34, 48, 168 hours after drug administration. | Part I: Maximum measured concentration of BI 706321 in plasma (Cmax). |
| Part I: Time From Dosing to the Maximum Measured Concentration of BI 706321 in Plasma (Tmax) | Within 3 hours before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 34, 48, 168 hours after drug administration. | Part I: Time from dosing to the maximum measured concentration of BI 706321 in plasma (tmax). |
Countries
Germany
Participant flow
Recruitment details
Part I of the trial was designed as randomised, placebo-controlled, and single-blind, within parallel dose groups. Part II of the trial was designed as a randomised, open-label, 3-way crossover to compare the treatments T1 and R (comparison A) and T2 and T1 (comparison B).
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.
Participants by arm
| Arm | Count |
|---|---|
| Part I - Placebo Oral Solution Part I - Placebo oral solution matching BI 706321 as single dose taken orally with 240 milliliter (mL) of water after an overnight fast of at least 10 hours. Placebo subjects were randomised in a 3:1 ratio over the matching BI 706321 arms. | 6 |
| Part I - 0.3 mg BI 706321 Oral Solution Part I - 1.2 mL oral solution of 0.25 mg/mL (0.3 milligram (mg) BI 706321) as single dose taken orally with 240 mL of water after an overnight fast of at least 10 hours. | 6 |
| Part I - 0.6 mg BI 706321 Oral Solution Part I - 2.4 mL oral solution of 0.25 mg/mL (0.6 mg BI 706321) as single dose taken orally with 240 mL of water after an overnight fast of at least 10 hours. | 6 |
| Part I - 1.2 mg BI 706321 Oral Solution Part I - 4.8 mL oral solution of 0.25 mg/mL (1.2 mg BI 706321) as single dose taken orally with 240 mL of water after an overnight fast of at least 10 hours. | 5 |
| Part I - Placebo Capsules Part I - Placebo capsules BI 706321 as single dose taken orally with 240 mL of water after an overnight fast of at least 10 hours. Placebo subjects were randomised in a 3:1 ratio over the matching BI 706321 arms. | 9 |
| Part I - 2 mg BI 706321 Capsules Part I - 2 capsules of 1 mg (2 mg BI 706321) as single dose taken orally with 240 mL of water after an overnight fast of at least 10 hours. | 6 |
| Part I - 4 mg BI 706321 Capsules Part I - 4 capsules of 1 mg (4 mg BI 706321) as single dose taken orally with 240 mL of water after an overnight fast of at least 10 hours. | 6 |
| Part I - 8 mg BI 706321 Capsules Part I - 8 capsules of 1 mg (8 mg BI 706321) as single dose taken orally with 240 mL of water after an overnight fast of at least 10 hours. | 6 |
| Part I - 15 mg BI 706321 Capsules Part I - 3 capsules of 5 mg (15 mg BI 706321) as single dose taken orally with 240 mL of water after an overnight fast of at least 10 hours. | 5 |
| Part I - 25 mg BI 706321 Capsules Part I - 5 capsules of 5 mg (25 mg BI 706321) as single dose taken orally with 240 mL of water after an overnight fast of at least 10 hours. | 6 |
| Part II - R-T1-T2 Part II - R-T1-T2 - Reference (R), fasted: 4 capsules of 1 mg (4 mg BI 706321) as single dose taken orally with 240 mL of water after an overnight fast of at least 10 hours. Test 1 (T1), fasted: 2 tablets of 2 mg (4 mg BI 706321) as single dose taken orally with 240 mL of water after an overnight fast of at least 10 hours. Test 2 (T2), fed: 2 tablets of 2 mg (4 mg BI 706321) as single dose taken orally with 240 mL of water after a high-fat, high-calorie breakfast. Treatments in Part II were separated by a washout period of at least 12 days. | 4 |
| Part II - T1-T2-R Part II - T1-T2-R - Test 1 (T1), fasted: 2 tablets of 2 mg (4 mg BI 706321) as single dose taken orally with 240 mL of water after an overnight fast of at least 10 hours. Test 2 (T2), fed: 2 tablets of 2 mg (4 mg BI 706321) as single dose taken orally with 240 mL of water after a high-fat, high-calorie breakfast. Reference (R), fasted: 4 capsules of 1 mg (4 mg BI 706321) as single dose taken orally with 240 mL of water after an overnight fast of at least 10 hours. Treatments in Part II were separated by a washout period of at least 12 days. | 4 |
| Part II - T2-R-T1 Part II - T2-R-T1 - Test 2 (T2), fed: 2 tablets of 2 mg (4 mg BI 706321) as single dose taken orally with 240 mL of water after a high-fat, high-calorie breakfast. Reference (R), fasted: 4 capsules of 1 mg (4 mg BI 706321) as single dose taken orally with 240 mL of water after an overnight fast of at least 10 hours. Test 1 (T1), fasted: 2 tablets of 2 mg (4 mg BI 706321) as single dose taken orally with 240 mL of water after an overnight fast of at least 10 hours. Treatments in Part II were separated by a washout period of at least 12 days. | 4 |
| Total | 73 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| End of Part I and Part II - Washout | Did not participate in part II of study | 6 | 6 | 6 | 5 | 9 | 6 | 6 | 6 | 5 | 6 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Part I - Placebo Oral Solution | Part I - 0.3 mg BI 706321 Oral Solution | Part I - 0.6 mg BI 706321 Oral Solution | Part I - 1.2 mg BI 706321 Oral Solution | Part I - Placebo Capsules | Part I - 2 mg BI 706321 Capsules | Part I - 4 mg BI 706321 Capsules | Part I - 8 mg BI 706321 Capsules | Part I - 15 mg BI 706321 Capsules | Part I - 25 mg BI 706321 Capsules | Part II - R-T1-T2 | Part II - T1-T2-R | Part II - T2-R-T1 | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 32.8 years STANDARD_DEVIATION 4.7 | 28.8 years STANDARD_DEVIATION 4.8 | 30.3 years STANDARD_DEVIATION 3.9 | 32.8 years STANDARD_DEVIATION 4.4 | 32.3 years STANDARD_DEVIATION 5.9 | 29.2 years STANDARD_DEVIATION 4.9 | 35.3 years STANDARD_DEVIATION 6.8 | 30.2 years STANDARD_DEVIATION 6.2 | 29.6 years STANDARD_DEVIATION 2.9 | 32.2 years STANDARD_DEVIATION 7.8 | 39.8 years STANDARD_DEVIATION 6.4 | 42.0 years STANDARD_DEVIATION 11.5 | 35.0 years STANDARD_DEVIATION 12.5 | 32.6 years STANDARD_DEVIATION 6.9 |
| 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 | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 6 Participants | 6 Participants | 5 Participants | 9 Participants | 6 Participants | 6 Participants | 6 Participants | 5 Participants | 6 Participants | 4 Participants | 4 Participants | 4 Participants | 73 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 | 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 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) 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 | 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 | 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 | 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 6 Participants | 6 Participants | 5 Participants | 9 Participants | 6 Participants | 6 Participants | 6 Participants | 5 Participants | 6 Participants | 4 Participants | 4 Participants | 4 Participants | 73 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 | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 6 Participants | 5 Participants | 9 Participants | 6 Participants | 6 Participants | 6 Participants | 5 Participants | 6 Participants | 4 Participants | 4 Participants | 4 Participants | 73 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 | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 9 | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 6 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 15 | 0 / 46 | 0 / 61 | 0 / 12 | 0 / 58 | 0 / 73 |
| other Total, other adverse events | 3 / 6 | 3 / 9 | 3 / 6 | 2 / 6 | 1 / 5 | 0 / 6 | 3 / 6 | 1 / 6 | 3 / 5 | 2 / 6 | 1 / 12 | 2 / 12 | 2 / 12 | 6 / 15 | 15 / 46 | 21 / 61 | 4 / 12 | 19 / 58 | 25 / 73 |
| serious Total, serious adverse events | 0 / 6 | 0 / 9 | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 6 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 15 | 0 / 46 | 0 / 61 | 0 / 12 | 0 / 58 | 0 / 73 |
Outcome results
Primary
Part II: Area Under the Concentration-time Curve of BI 706321 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
Part II: Area under the concentration-time curve of BI 706321 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz).
Time frame: Within 3 hours before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 34, 48, 72, 168 hours after drug administration.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set included all subjects in the TS who provided at least 1 PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part I - Placebo Oral Solution | Part II: Area Under the Concentration-time Curve of BI 706321 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 150 hour*nanomol/liter | Geometric Coefficient of Variation 27.5 |
| Part I - 0.3 mg BI 706321 Oral Solution | Part II: Area Under the Concentration-time Curve of BI 706321 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 138 hour*nanomol/liter | Geometric Coefficient of Variation 29.9 |
| Part I - 0.6 mg BI 706321 Oral Solution | Part II: Area Under the Concentration-time Curve of BI 706321 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 150 hour*nanomol/liter | Geometric Coefficient of Variation 29.5 |
Comparison: Analysis of variance (ANOVA) on the logarithmic scale including effects for 'sequence', 'subjects nested within sequences', 'period', and 'treatment'. Confidence intervals were calculated based on the residual error from the ANOVA.90% CI: [90.18, 111.48]
Comparison: Analysis of variance (ANOVA) on the logarithmic scale including effects for 'sequence', 'subjects nested within sequences', 'period', and 'treatment'. Confidence intervals were calculated based on the residual error from the ANOVA.90% CI: [85.37, 98.35]
Primary
Part II: Maximum Measured Concentration of BI 706321 in Plasma (Cmax)
Part II: Maximum measured concentration of BI 706321 in plasma (Cmax).
Time frame: Within 3 hours before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 34, 48, 72, 168 hours after drug administration.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set included all subjects in the TS who provided at least 1 PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part I - Placebo Oral Solution | Part II: Maximum Measured Concentration of BI 706321 in Plasma (Cmax) | 5.90 nanomol/liter | Geometric Coefficient of Variation 47.8 |
| Part I - 0.3 mg BI 706321 Oral Solution | Part II: Maximum Measured Concentration of BI 706321 in Plasma (Cmax) | 4.57 nanomol/liter | Geometric Coefficient of Variation 33.6 |
| Part I - 0.6 mg BI 706321 Oral Solution | Part II: Maximum Measured Concentration of BI 706321 in Plasma (Cmax) | 6.02 nanomol/liter | Geometric Coefficient of Variation 41.1 |
Comparison: Analysis of variance (ANOVA) on the logarithmic scale including effects for 'sequence', 'subjects nested within sequences', 'period', and 'treatment'. Confidence intervals were calculated based on the residual error from the ANOVA.90% CI: [84.2, 114.08]
Comparison: Analysis of variance (ANOVA) on the logarithmic scale including effects for 'sequence', 'subjects nested within sequences', 'period', and 'treatment'. Confidence intervals were calculated based on the residual error from the ANOVA.90% CI: [68.11, 88.22]
Primary
Part I: Percentage of Subjects With Drug-related Adverse Events
Part I: Percentage of subjects with drug-related adverse events.
Time frame: Between intake of trial medication and the individual subject's end of trial, up to 22 days.
Population: Treated set (TS): The TS included all subjects who were randomised and treated with at least 1 dose of trial drug. The treatment assignment was determined based on the first treatment the subjects received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part I - Placebo Oral Solution | Part I: Percentage of Subjects With Drug-related Adverse Events | 16.7 Percentage of participants |
| Part I - 0.3 mg BI 706321 Oral Solution | Part I: Percentage of Subjects With Drug-related Adverse Events | 16.7 Percentage of participants |
| Part I - 0.6 mg BI 706321 Oral Solution | Part I: Percentage of Subjects With Drug-related Adverse Events | 0.0 Percentage of participants |
| Part I - 1.2 mg BI 706321 Oral Solution | Part I: Percentage of Subjects With Drug-related Adverse Events | 0.0 Percentage of participants |
| Part I - Placebo Capsules | Part I: Percentage of Subjects With Drug-related Adverse Events | 11.1 Percentage of participants |
| Part I - 2 mg BI 706321 Capsules | Part I: Percentage of Subjects With Drug-related Adverse Events | 0.0 Percentage of participants |
| Part I - 4 mg BI 706321 Capsules | Part I: Percentage of Subjects With Drug-related Adverse Events | 0.0 Percentage of participants |
| Part I - 8 mg BI 706321 Capsules | Part I: Percentage of Subjects With Drug-related Adverse Events | 16.7 Percentage of participants |
| Part I - 15 mg BI 706321 Capsules | Part I: Percentage of Subjects With Drug-related Adverse Events | 20.0 Percentage of participants |
| Part I - 25 mg BI 706321 Capsules | Part I: Percentage of Subjects With Drug-related Adverse Events | 33.3 Percentage of participants |
Secondary
Part I: Area Under the Concentration-time Curve of BI 706321 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
Part I: Area under the concentration-time curve of BI 706321 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞).
Time frame: Within 3 hours before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 34, 48, 168 hours after drug administration.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set included all subjects in the TS who provided at least 1 PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part I - Placebo Oral Solution | Part I: Area Under the Concentration-time Curve of BI 706321 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | NA hour*nanomol/liter | — |
| Part I - 0.3 mg BI 706321 Oral Solution | Part I: Area Under the Concentration-time Curve of BI 706321 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | NA hour*nanomol/liter | — |
| Part I - 0.6 mg BI 706321 Oral Solution | Part I: Area Under the Concentration-time Curve of BI 706321 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | NA hour*nanomol/liter | — |
| Part I - 1.2 mg BI 706321 Oral Solution | Part I: Area Under the Concentration-time Curve of BI 706321 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | NA hour*nanomol/liter | — |
| Part I - Placebo Capsules | Part I: Area Under the Concentration-time Curve of BI 706321 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 151 hour*nanomol/liter | Geometric Coefficient of Variation 33.1 |
| Part I - 2 mg BI 706321 Capsules | Part I: Area Under the Concentration-time Curve of BI 706321 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 314 hour*nanomol/liter | Geometric Coefficient of Variation 25.7 |
| Part I - 4 mg BI 706321 Capsules | Part I: Area Under the Concentration-time Curve of BI 706321 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 618 hour*nanomol/liter | Geometric Coefficient of Variation 36.1 |
| Part I - 8 mg BI 706321 Capsules | Part I: Area Under the Concentration-time Curve of BI 706321 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 1130 hour*nanomol/liter | Geometric Coefficient of Variation 24.2 |
Secondary
Part II: Area Under the Concentration-time Curve of BI 706321 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
Part II: Area under the concentration-time curve of BI 706321 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞).
Time frame: Within 3 hours before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 34, 48, 72, 168 hours after drug administration.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set included all subjects in the TS who provided at least 1 PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part I - Placebo Oral Solution | Part II: Area Under the Concentration-time Curve of BI 706321 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 169 hour*nanomol/liter | Geometric Coefficient of Variation 26.1 |
| Part I - 0.3 mg BI 706321 Oral Solution | Part II: Area Under the Concentration-time Curve of BI 706321 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 154 hour*nanomol/liter | Geometric Coefficient of Variation 28 |
| Part I - 0.6 mg BI 706321 Oral Solution | Part II: Area Under the Concentration-time Curve of BI 706321 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 171 hour*nanomol/liter | Geometric Coefficient of Variation 27.7 |
Comparison: Analysis of variance (ANOVA) on the logarithmic scale including effects for 'sequence', 'subjects nested within sequences', 'period', and 'treatment'. Confidence intervals were calculated based on the residual error from the ANOVA.90% CI: [86.96, 106.9]
Comparison: Analysis of variance (ANOVA) on the logarithmic scale including effects for 'sequence', 'subjects nested within sequences', 'period', and 'treatment'. Confidence intervals were calculated based on the residual error from the ANOVA.90% CI: [85.4, 97.54]
Secondary
Part I: Maximum Measured Concentration of BI 706321 in Plasma (Cmax)
Part I: Maximum measured concentration of BI 706321 in plasma (Cmax).
Time frame: Within 3 hours before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 34, 48, 168 hours after drug administration.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set included all subjects in the TS who provided at least 1 PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part I - Placebo Oral Solution | Part I: Maximum Measured Concentration of BI 706321 in Plasma (Cmax) | 0.388 nanomol/liter | Geometric Coefficient of Variation 32.8 |
| Part I - 0.3 mg BI 706321 Oral Solution | Part I: Maximum Measured Concentration of BI 706321 in Plasma (Cmax) | 0.781 nanomol/liter | Geometric Coefficient of Variation 21.4 |
| Part I - 0.6 mg BI 706321 Oral Solution | Part I: Maximum Measured Concentration of BI 706321 in Plasma (Cmax) | 1.02 nanomol/liter | Geometric Coefficient of Variation 40 |
| Part I - 1.2 mg BI 706321 Oral Solution | Part I: Maximum Measured Concentration of BI 706321 in Plasma (Cmax) | 2.27 nanomol/liter | Geometric Coefficient of Variation 30.1 |
| Part I - Placebo Capsules | Part I: Maximum Measured Concentration of BI 706321 in Plasma (Cmax) | 5.19 nanomol/liter | Geometric Coefficient of Variation 38.6 |
| Part I - 2 mg BI 706321 Capsules | Part I: Maximum Measured Concentration of BI 706321 in Plasma (Cmax) | 11.8 nanomol/liter | Geometric Coefficient of Variation 41.6 |
| Part I - 4 mg BI 706321 Capsules | Part I: Maximum Measured Concentration of BI 706321 in Plasma (Cmax) | 24.6 nanomol/liter | Geometric Coefficient of Variation 43 |
| Part I - 8 mg BI 706321 Capsules | Part I: Maximum Measured Concentration of BI 706321 in Plasma (Cmax) | 41.1 nanomol/liter | Geometric Coefficient of Variation 32.1 |
Secondary
Part I: Time From Dosing to the Maximum Measured Concentration of BI 706321 in Plasma (Tmax)
Part I: Time from dosing to the maximum measured concentration of BI 706321 in plasma (tmax).
Time frame: Within 3 hours before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 34, 48, 168 hours after drug administration.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set included all subjects in the TS who provided at least 1 PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part I - Placebo Oral Solution | Part I: Time From Dosing to the Maximum Measured Concentration of BI 706321 in Plasma (Tmax) | 5.61 hours | Geometric Coefficient of Variation 16.7 |
| Part I - 0.3 mg BI 706321 Oral Solution | Part I: Time From Dosing to the Maximum Measured Concentration of BI 706321 in Plasma (Tmax) | 5.25 hours | Geometric Coefficient of Variation 51.6 |
| Part I - 0.6 mg BI 706321 Oral Solution | Part I: Time From Dosing to the Maximum Measured Concentration of BI 706321 in Plasma (Tmax) | 5.22 hours | Geometric Coefficient of Variation 31.8 |
| Part I - 1.2 mg BI 706321 Oral Solution | Part I: Time From Dosing to the Maximum Measured Concentration of BI 706321 in Plasma (Tmax) | 5.24 hours | Geometric Coefficient of Variation 51.6 |
| Part I - Placebo Capsules | Part I: Time From Dosing to the Maximum Measured Concentration of BI 706321 in Plasma (Tmax) | 4.91 hours | Geometric Coefficient of Variation 22.3 |
| Part I - 2 mg BI 706321 Capsules | Part I: Time From Dosing to the Maximum Measured Concentration of BI 706321 in Plasma (Tmax) | 4.12 hours | Geometric Coefficient of Variation 43.7 |
| Part I - 4 mg BI 706321 Capsules | Part I: Time From Dosing to the Maximum Measured Concentration of BI 706321 in Plasma (Tmax) | 3.37 hours | Geometric Coefficient of Variation 70.7 |
| Part I - 8 mg BI 706321 Capsules | Part I: Time From Dosing to the Maximum Measured Concentration of BI 706321 in Plasma (Tmax) | 3.64 hours | Geometric Coefficient of Variation 62.1 |