Healthy
Conditions
Brief summary
The main objective of this trial is to investigate the relative bioavailability of BI 1015550 intended Commercial Formulation (iCF) compared with Trial Formulation 2 (TF2) and the effect of food on the pharmacokinetics of BI 1015550 iCF following oral administration.
Interventions
DRUGReference (R)
Reference (R): three 6 milligram BI 1015550 film-coated tablets of Trial Formulation 2 (TF2) taken orally following an overnight fast of at least 10 hours.
DRUGTest treatment 1 (T1)
Test treatment 1 (T1): one 18 milligram BI 1015550 film-coated tablet of the intended commercial formulation (iCF) taken orally following an overnight fast of at least 10 hours.
DRUGTest treatment 2 (T2)
Test treatment 2 (T2): one 18 milligram BI 1015550 film-coated tablet of the intended commercial formulation (iCF) taken orally following a high-calorie breakfast.
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male or female 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. * Age of 18 to 55 years (inclusive). * Body mass index (BMI) of 18.5 to 29.9 kg/m2 (inclusive). * Signed and dated written informed consent in accordance with International Council for Harmonisation - Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial. * Either male subject, or female subject who meet any of the following criteria from 30 days before drug administration until 7 days after trial completion: * Use of non-oral hormonal contraception associated with inhibition of ovulation: intravaginal or transdermal combinations of estrogen and progestogen or injectable or implantable progestogen. * Use of intrauterine device (IUD) or intrauterine hormone-releasing system (IUS). * Sexually abstinent, i.e. complete abstinence from male-female sex when this is in line with the preferred and usual lifestyle of the study participant. Periodic abstinence e.g. calendar, ovulation, symptothermal, post-ovulation methods; declaration of abstinence for the duration of exposure to study drug; and withdrawal are not acceptable. * Vasectomised sexual partner with appropriate post-vasectomy documentation of the absence of sperm in the ejaculate, provided that partner is the sole sexual partner of the study participant * Surgically sterilised (including hysterectomy, bilateral salpingectomy, bilateral oophorectomy, bilateral tubal occlusion). * Postmenopausal, defined as no menses for 1 year without an alternative medical cause (in questionable cases a blood sample with levels of follicle stimulating hormone (FSH) above 40 U/L and estradiol below 30 ng/L is confirmatory).
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 millimetre of mercury (mmHg), diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 45 to 90 beats per minute (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 (including but not limited to major depressive disorder or history of suicide attempts). * History of relevant orthostatic hypotension, fainting spells, or blackouts. Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of BI 1015550 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | Within 3 hours before and 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144 hours following drug administration. | Area under the concentration-time curve of BI 1015550 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz). |
| Area Under the Concentration-time Curve of R-BI 1015550 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | Within 3 hours before and 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144 hours following drug administration. | Area under the concentration-time curve of R-BI 1015550 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz). The endpoint was analyzed additionally for the chirally pure (R) form of BI 1015550 (R-BI 1015550, the pharmacologically active form). |
| Maximum Measured Concentration of BI 1015550 in Plasma (Cmax) | Within 3 hours before and 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144 hours following drug administration. | Maximum measured concentration of BI 1015550 in plasma (Cmax). |
| Maximum Measured Concentration of R-BI 1015550 in Plasma (Cmax) | Within 3 hours before and 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144 hours following drug administration. | Maximum measured concentration of R-BI 1015550 in plasma (Cmax). The endpoint was analyzed additionally for the chirally pure (R) form of BI 1015550 (R-BI 1015550, the pharmacologically active form). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of BI 1015550 in Plasma Over the Time Interval From 0 Extrapolated to Infinity, Predicted (AUC0-∞,Pred) | Within 3 hours before and 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144 hours following drug administration. | Area under the concentration-time curve of BI 1015550 in plasma over the time interval from 0 extrapolated to infinity, predicted (AUC0-∞,pred). |
| Area Under the Concentration-time Curve of R-BI 1015550 in Plasma Over the Time Interval From 0 Extrapolated to Infinity, Predicted (AUC0-∞,Pred) | Within 3 hours before and 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144 hours following drug administration. | Area under the concentration-time curve of R-BI 1015550 in plasma over the time interval from 0 extrapolated to infinity, predicted (AUC0-∞,pred). The endpoint was analyzed additionally for the chirally pure (R) form of BI 1015550 (R-BI 1015550, the pharmacologically active form). |
Countries
Germany
Participant flow
Recruitment details
The trial was a randomised, open-label, single-dose, three-way crossover design. The subjects were randomly allocated to 1 of 3 treatment sequences. Each subject participated in 3 treatment periods, receiving a single dose in each, with a washout period of at least 7 days between treatments.
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 |
|---|---|
| R/T1/T2 Three period crossover with treatments in the following order:
Reference (R): three 6 milligram BI 1015550 film-coated tablets of Trial Formulation 2 (TF2) taken orally following an overnight fast of at least 10 hours.
Test treatment 1 (T1): one 18 milligram BI 1015550 film-coated tablet of the intended commercial formulation (iCF) taken orally following an overnight fast of at least 10 hours.
Test treatment 2 (T2): one 18 milligram BI 1015550 film-coated tablet of the intended commercial formulation (iCF) taken orally following a high-calorie breakfast.
Periods were separated by a washout period of at least 7 days between treatments. | 8 |
| T1/T2/R Three period crossover with treatments in the following order:
Test treatment 1 (T1): one 18 milligram BI 1015550 film-coated tablet of the intended commercial formulation (iCF) taken orally following an overnight fast of at least 10 hours.
Test treatment 2 (T2): one 18 milligram BI 1015550 film-coated tablet of the intended commercial formulation (iCF) taken orally following a high-calorie breakfast.
Reference (R): three 6 milligram BI 1015550 film-coated tablets of Trial Formulation 2 (TF2) taken orally following an overnight fast of at least 10 hours.
Periods were separated by a washout period of at least 7 days between treatments. | 8 |
| T2/R/T1 Three period crossover with treatments in the following order:
Test treatment 2 (T2): one 18 milligram BI 1015550 film-coated tablet of the intended commercial formulation (iCF) taken orally following a high-calorie breakfast.
Reference (R): three 6 milligram BI 1015550 film-coated tablets of Trial Formulation 2 (TF2) taken orally following an overnight fast of at least 10 hours.
Test treatment 1 (T1): one 18 milligram BI 1015550 film-coated tablet of the intended commercial formulation (iCF) taken orally following an overnight fast of at least 10 hours.
Periods were separated by a washout period of at least 7 days between treatments | 8 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Period 1 - 2 washout | Adverse Event | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | R/T1/T2 | T1/T2/R | T2/R/T1 | Total |
|---|---|---|---|---|
| Age, Continuous | 38.5 years STANDARD_DEVIATION 11.3 | 40.0 years STANDARD_DEVIATION 11.8 | 39.6 years STANDARD_DEVIATION 14.2 | 39.4 years STANDARD_DEVIATION 11.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 8 Participants | 7 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 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 |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 8 Participants | 8 Participants | 24 Participants |
| Sex: Female, Male Female | 5 Participants | 1 Participants | 3 Participants | 9 Participants |
| Sex: Female, Male Male | 3 Participants | 7 Participants | 5 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 23 | 0 / 23 |
| other Total, other adverse events | 5 / 24 | 3 / 23 | 2 / 23 |
| serious Total, serious adverse events | 0 / 24 | 0 / 23 | 0 / 23 |
Outcome results
Primary
Area Under the Concentration-time Curve of BI 1015550 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
Area under the concentration-time curve of BI 1015550 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, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144 hours following drug administration.
Population: Pharmacokinetic parameter analysis set (PKS): This set included all subjects who were treated with at least one dose of trial drug and who provided at least one Pharmacokinetic (PK) endpoint that was defined as primary or secondary and 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 |
|---|---|---|---|
| Reference treatment (R) - fasted | Area Under the Concentration-time Curve of BI 1015550 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 2290 hours*nanomol/Liter | Geometric Coefficient of Variation 194 |
| Test treatment 1 (T1) - fasted | Area Under the Concentration-time Curve of BI 1015550 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 2740 hours*nanomol/Liter | Geometric Coefficient of Variation 34.7 |
| Test treatment 2 (T2) - fed | Area Under the Concentration-time Curve of BI 1015550 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 3000 hours*nanomol/Liter | Geometric Coefficient of Variation 31.2 |
Comparison: Analysis of Variance (ANOVA) model (logarithmic scale) with the effects: sequence, subjects within sequences, period, and treatment. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.90% CI: [86.14, 170.3]
Comparison: ANOVA model (logarithmic scale) with the effects: sequence, subjects within sequences, period, and treatment. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.90% CI: [76.68, 152.48]
Primary
Area Under the Concentration-time Curve of R-BI 1015550 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
Area under the concentration-time curve of R-BI 1015550 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz). The endpoint was analyzed additionally for the chirally pure (R) form of BI 1015550 (R-BI 1015550, the pharmacologically active form).
Time frame: Within 3 hours before and 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144 hours following drug administration.
Population: Pharmacokinetic parameter analysis set (PKS): This set included all subjects who were treated with at least one dose of trial drug and who provided at least one Pharmacokinetic (PK) endpoint that was defined as primary or secondary and 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 |
|---|---|---|---|
| Reference treatment (R) - fasted | Area Under the Concentration-time Curve of R-BI 1015550 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 1900 hours*nanomol/Liter | Geometric Coefficient of Variation 197 |
| Test treatment 1 (T1) - fasted | Area Under the Concentration-time Curve of R-BI 1015550 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 2310 hours*nanomol/Liter | Geometric Coefficient of Variation 29.6 |
| Test treatment 2 (T2) - fed | Area Under the Concentration-time Curve of R-BI 1015550 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 2500 hours*nanomol/Liter | Geometric Coefficient of Variation 26.9 |
Comparison: Analysis of Variance (ANOVA) model (logarithmic scale) with the effects: sequence, subjects within sequences, period, and treatment (restricted to the two formulation groups (T1 \& R)). The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.90% CI: [79.25, 187.84]
Comparison: ANOVA model (logarithmic scale) with the effects: sequence, subjects within sequences, period, and treatment (restricted to the two treatment groups (T1 \& T2)). The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.90% CI: [104.33, 112.97]
Primary
Maximum Measured Concentration of BI 1015550 in Plasma (Cmax)
Maximum measured concentration of BI 1015550 in plasma (Cmax).
Time frame: Within 3 hours before and 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144 hours following drug administration.
Population: Pharmacokinetic parameter analysis set (PKS): This set included all subjects who were treated with at least one dose of trial drug and who provided at least one Pharmacokinetic (PK) endpoint that was defined as primary or secondary and 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 |
|---|---|---|---|
| Reference treatment (R) - fasted | Maximum Measured Concentration of BI 1015550 in Plasma (Cmax) | 313 nanomol/Liter | Geometric Coefficient of Variation 165 |
| Test treatment 1 (T1) - fasted | Maximum Measured Concentration of BI 1015550 in Plasma (Cmax) | 364 nanomol/Liter | Geometric Coefficient of Variation 36.6 |
| Test treatment 2 (T2) - fed | Maximum Measured Concentration of BI 1015550 in Plasma (Cmax) | 323 nanomol/Liter | Geometric Coefficient of Variation 22.7 |
Comparison: ANOVA model (logarithmic scale) with the effects: sequence, subjects within sequences, period, and treatment. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.90% CI: [85.82, 162.25]
Comparison: ANOVA model (logarithmic scale) with the effects: sequence, subjects within sequences, period, and treatment. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.90% CI: [63.77, 121.28]
Primary
Maximum Measured Concentration of R-BI 1015550 in Plasma (Cmax)
Maximum measured concentration of R-BI 1015550 in plasma (Cmax). The endpoint was analyzed additionally for the chirally pure (R) form of BI 1015550 (R-BI 1015550, the pharmacologically active form).
Time frame: Within 3 hours before and 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144 hours following drug administration.
Population: Pharmacokinetic parameter analysis set (PKS): This set included all subjects who were treated with at least one dose of trial drug and who provided at least one Pharmacokinetic (PK) endpoint that was defined as primary or secondary and 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 |
|---|---|---|---|
| Reference treatment (R) - fasted | Maximum Measured Concentration of R-BI 1015550 in Plasma (Cmax) | 307 nanomol/Liter | Geometric Coefficient of Variation 166 |
| Test treatment 1 (T1) - fasted | Maximum Measured Concentration of R-BI 1015550 in Plasma (Cmax) | 352 nanomol/Liter | Geometric Coefficient of Variation 35.4 |
| Test treatment 2 (T2) - fed | Maximum Measured Concentration of R-BI 1015550 in Plasma (Cmax) | 319 nanomol/Liter | Geometric Coefficient of Variation 23.8 |
Comparison: ANOVA model (logarithmic scale) with the effects: sequence, subjects within sequences, period, and treatment (restricted to the two formulation groups (T1 \& R)). The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.90% CI: [77.64, 172.22]
Comparison: ANOVA model (logarithmic scale) with the effects: sequence, subjects within sequences, period, and treatment (restricted to the two treatment groups (T1 \& T2)). The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.90% CI: [80.82, 101.87]
Secondary
Area Under the Concentration-time Curve of BI 1015550 in Plasma Over the Time Interval From 0 Extrapolated to Infinity, Predicted (AUC0-∞,Pred)
Area under the concentration-time curve of BI 1015550 in plasma over the time interval from 0 extrapolated to infinity, predicted (AUC0-∞,pred).
Time frame: Within 3 hours before and 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144 hours following drug administration.
Population: Pharmacokinetic parameter analysis set (PKS): This set included all subjects who were treated with at least one dose of trial drug and who provided at least one Pharmacokinetic (PK) endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Endpoint only includes subjects where AUC0-∞,pred could be calculated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Reference treatment (R) - fasted | Area Under the Concentration-time Curve of BI 1015550 in Plasma Over the Time Interval From 0 Extrapolated to Infinity, Predicted (AUC0-∞,Pred) | 2970 hours*nanomol/Liter | Geometric Coefficient of Variation 30 |
| Test treatment 1 (T1) - fasted | Area Under the Concentration-time Curve of BI 1015550 in Plasma Over the Time Interval From 0 Extrapolated to Infinity, Predicted (AUC0-∞,Pred) | 2780 hours*nanomol/Liter | Geometric Coefficient of Variation 35.1 |
| Test treatment 2 (T2) - fed | Area Under the Concentration-time Curve of BI 1015550 in Plasma Over the Time Interval From 0 Extrapolated to Infinity, Predicted (AUC0-∞,Pred) | 3050 hours*nanomol/Liter | Geometric Coefficient of Variation 31.7 |
Comparison: ANOVA model (logarithmic scale) with the effects: sequence, subjects within sequences, period, and treatment. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.90% CI: [90.49, 97.21]
Comparison: ANOVA model (logarithmic scale) with the effects: sequence, subjects within sequences, period, and treatment. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.90% CI: [105.72, 113.44]
Secondary
Area Under the Concentration-time Curve of R-BI 1015550 in Plasma Over the Time Interval From 0 Extrapolated to Infinity, Predicted (AUC0-∞,Pred)
Area under the concentration-time curve of R-BI 1015550 in plasma over the time interval from 0 extrapolated to infinity, predicted (AUC0-∞,pred). The endpoint was analyzed additionally for the chirally pure (R) form of BI 1015550 (R-BI 1015550, the pharmacologically active form).
Time frame: Within 3 hours before and 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144 hours following drug administration.
Population: Pharmacokinetic parameter analysis set (PKS): This set included all subjects who were treated with at least one dose of trial drug and who provided at least one Pharmacokinetic (PK) endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Endpoint only includes subjects where AUC0-∞,pred could be calculated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Reference treatment (R) - fasted | Area Under the Concentration-time Curve of R-BI 1015550 in Plasma Over the Time Interval From 0 Extrapolated to Infinity, Predicted (AUC0-∞,Pred) | 2460 hours*nanomol/Liter | Geometric Coefficient of Variation 27 |
| Test treatment 1 (T1) - fasted | Area Under the Concentration-time Curve of R-BI 1015550 in Plasma Over the Time Interval From 0 Extrapolated to Infinity, Predicted (AUC0-∞,Pred) | 2340 hours*nanomol/Liter | Geometric Coefficient of Variation 30 |
| Test treatment 2 (T2) - fed | Area Under the Concentration-time Curve of R-BI 1015550 in Plasma Over the Time Interval From 0 Extrapolated to Infinity, Predicted (AUC0-∞,Pred) | 2530 hours*nanomol/Liter | Geometric Coefficient of Variation 27.2 |
Comparison: ANOVA model (logarithmic scale) with the effects: sequence, subjects within sequences, period, and treatment (restricted to the two formulation groups (T1 \& R)). The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.90% CI: [91.39, 98.77]
Comparison: ANOVA model (logarithmic scale) with the effects: sequence, subjects within sequences, period, and treatment (restricted to the two treatment groups (T1 \& T2)). The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.90% CI: [103.9, 112.89]