Healthy
Conditions
Brief summary
To establish bioequivalence at steady state of: 1)0.375 mg pramipexole extended release tablet q.d. in fasted status versus 0.125 mg pramipexole Immediate release tablet t.i.d. in fasted status 2)1.5 mg pramipexole extended release tablet q.d. in fasted status versus 0.5 mg pramipexole Immediate release tablet t.i.d. in fasted status To investigate dose proportionality of pharmacokinetics parameters for: 1)pramipexole extended release dosage of 0.375 to 1.5 mg q.d.
Interventions
0.375mg once per day for 5 days (cross-over), 0.75mg once per day for 5 days (up-titration), 1.5mg once per day for 5 days (cross-over)
0.125mg three times a day for 5 days (crossover), 0.5mg three times a day for 5 days (cross over)
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy males according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs (blood pressure, pulse rate), 12-lead electrocardiogram, clinical laboratory tests 2. Age older than or equal 18 and Age younger than or equal 40 years 3. Body Mass Index larger than or equal 19 and Body Mass Index less than or equal 24kg/m2 4. Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice and the local legislation.
Exclusion criteria
1. Any finding of the medical examination (including Pulse Rate and electrocardiogram) deviating from normal and of clinical relevance 2. Any evidence of a clinically relevant concomitant disease 3. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders 4. Surgery of the gastrointestinal tract (except appendectomy) 5. Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders 6. History of relevant orthostatic hypotension, fainting spells or blackouts. 7. Chronic or relevant acute infections 8. History of relevant allergy/hypersensitivity (including allergy to drug or its excipients) 9. Intake of drugs with a long half-life (longer than 24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial 10. Use of drugs which might reasonably influence the results of the trial up to 7 days before the start of drug administration in the study or during the study period 11. Participation in another trial with an investigational drug within one months prior to administration or during the trial 12. Smoker (more than 10 cigarettes or more than 3 cigars or more than 3 pipes/day) 13. Inability to refrain from smoking on trial days 14. Alcohol abuse (more than 40 g/day) 15. Drug abuse 16. Blood donation (more than 100 mL within four weeks prior to administration or during the trial) 17. Excessive physical activities (within one week prior to administration or during the trial) 18. Any laboratory value outside the reference range that is of clinical relevance 19. Any positive results in hepatitis B surface antigen (HBsAg), anti hepatitis B core (HBc) antibodies, anti hepatitis C virus (HCV) antibodies and human immunodeficiency virus (HIV) test
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of Pramipexole in Plasma at Steady State Over 24 Hours (AUC0-24,ss); in Case of ER up to the Time Point of Next Dosing (AUCtau,ss) for Pharmacokinetic (PK) Population (All Subjects) | 27 days | AUC0-24,ss = area under the plasma concentration-time curve between 0 and 24 hours at steady state. AUCtau,ss = area under the plasma concentration-time curve over a dosing interval at steady state |
| Area Under the Concentration-time Curve of Pramipexole in Plasma at Steady State Over 24 Hours (AUC0-24,ss); in Case of ER up to the Time Point of Next Dosing (AUCtau,ss) for PK Population (Excluding Subjects Due to Emesis) | 27 days | AUC0-24,ss = area under the plasma concentration-time curve between 0 and 24 hours at steady state. AUCtau,ss = area under the plasma concentration-time curve over a dosing interval at steady state |
| Maximum Steady State Concentration (Cmax,ss) for PK Population (All Subjects) | 27 days | Cmax = maximum observed concentration of the analyte in plasma at steady state |
| Maximum Steady State Concentration (Cmax,ss) for PK Population (Excluding Subjects Due to Emesis) | 27 days | Cmax,ss = maximum observed concentration of the analyte in plasma at steady state |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Predose Steady State Concentration of the Analyte Immediately Before Administration of the Next Drug Administration (Cpre,ss) for PK Population (All Subjects) | 27 days | Cpre,ss = pre-dose concentration of the analyte in plasma at steady state immediately before administration of the next dose |
| Predose Steady State Concentration of the Analyte Immediately Before Administration of the Next Drug Administration (Cpre,ss) for PK Population (Excluding Subjects Due to Emesis) | 27 days | Cpre,ss = pre-dose concentration of the analyte in plasma at steady state immediately before administration of the next dose |
| Average Concentration in Plasma Under Steady-state Conditions (Cavg) for PK Population (All Subjects) | 27 days | Cavg = Average concentration of the analyte in plasma at steady state |
| Average Concentration in Plasma Under Steady-state Conditions (Cavg) for PK Population (Excluding Subjects Due to Emesis) | 27 days | Cavg = Average concentration of the analyte in plasma at steady state |
| Terminal Half-life of the Analyte in Plasma at Steady State (t1/2,ss) for PK Population (All Subjects) | 27 days | t1/2,ss - Apparent plasma terminal elimination half-life at steady state |
| Terminal Half-life of the Analyte in Plasma at Steady State (t1/2,ss) for PK Population (Excluding Subjects Due to Emesis) | 27 days | t1/2,ss - Apparent plasma terminal elimination half-life at steady state |
| Time From Dosing to the Maximum Measured Concentration of the Analyte in Plasma (Tmax) for PK Population (All Subjects) | 27 days | tmax = time of maximum observed plasma concentration |
| Minimum Steady State Concentration (Cmin,ss) for PK Population (Excluding Subjects Due to Emesis) | 27 days | Cmin,ss = Minimum observed concentration of the analyte in plasma at steady state |
| The Apparent Clearance of the Analyte in Plasma at Steady State Following Oral Administration (CL/F,ss) for PK Population (All Subjects) | 27 days | CL/F,ss = Apparent clearance of the analyte in the plasma at steady state following oral administration |
| The Apparent Clearance of the Analyte in Plasma at Steady State Following Oral Administration (CL/F,ss) for PK Population (Excluding Subjects Due to Emesis) | 27 days | CL/F,ss = Apparent clearance of the analyte in the plasma at steady state following oral administration |
| Apparent Volume of Distribution During the Terminal Phase at Steady State Following Oral Administration (Vz/F,ss) for PK Population (All Subjects) | 27 days | Vz/F,ss = Apparent volume of distribution during the terminal phase λz at steady state following oral administration |
| Apparent Volume of Distribution During the Terminal Phase at Steady State Following Oral Administration (Vz/F,ss) for PK Population (Excluding Subjects Due to Emesis) | 27 days | Vz/F,ss = Apparent volume of distribution during the terminal phase λz at steady state following oral administration |
| Minimum Steady State Concentration (Cmin,ss) for PK Population (All Subjects) | 27 days | Cmin,ss = Minimum observed concentration of the analyte in plasma at steady state |
| Time From Dosing to the Maximum Measured Concentration of the Analyte in Plasma (Tmax) for PK Population (Excluding Subjects Due to Emesis) | 27 days | tmax = time of maximum observed plasma concentration |
| Peak-to-trough Fluctuation (PTF) for PK Population (All Subjects) | 27 days | PTF = Peak-to-trough fluctuation is measured as a percent |
| Peak-to-trough Fluctuation (PTF) for PK Population (Excluding Subjects Due to Emesis) | 27 days | PTF = Peak-to-trough fluctuation is measured as a percent |
Countries
China
Participant flow
Pre-assignment details
24 subjects were equally randomised to one of two groups / sequences, and in general terms, ABCD or BADC. Hence, 12 subjects were in group ABCD and 12 in BADC. All 24 subjects received all treatments, A, B, C, D. The numbers presented in the milestone are by overall treatment, A, B, C or D.
Participants by arm
| Arm | Count |
|---|---|
| All Subjects 24 subjects were equally randomised to one of two groups / sequences, and in general terms, ABCD or BADC. Hence, 12 subjects were in group ABCD and 12 in BADC. All 24 subjects received all treatments, A, B, C, D. The numbers presented are by overall treatment. | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | All Subjects |
|---|---|
| Age, Continuous | 31 years STANDARD_DEVIATION 2.2 |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 24 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 |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 14 / 24 | 9 / 24 | 12 / 24 | 6 / 24 | 0 / 24 | 8 / 24 | 14 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 |
Outcome results
Primary
Area Under the Concentration-time Curve of Pramipexole in Plasma at Steady State Over 24 Hours (AUC0-24,ss); in Case of ER up to the Time Point of Next Dosing (AUCtau,ss) for Pharmacokinetic (PK) Population (All Subjects)
AUC0-24,ss = area under the plasma concentration-time curve between 0 and 24 hours at steady state. AUCtau,ss = area under the plasma concentration-time curve over a dosing interval at steady state
Time frame: 27 days
Population: PK population - Subjects with values for AUC0-24,ss for IR and values for AUCtau,ss for ER
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.375 mg q.d.ER | Area Under the Concentration-time Curve of Pramipexole in Plasma at Steady State Over 24 Hours (AUC0-24,ss); in Case of ER up to the Time Point of Next Dosing (AUCtau,ss) for Pharmacokinetic (PK) Population (All Subjects) | 6.20 ng*h/mL | Geometric Coefficient of Variation 29.7 |
| 0.125 mg t.i.d. IR | Area Under the Concentration-time Curve of Pramipexole in Plasma at Steady State Over 24 Hours (AUC0-24,ss); in Case of ER up to the Time Point of Next Dosing (AUCtau,ss) for Pharmacokinetic (PK) Population (All Subjects) | 7.50 ng*h/mL | Geometric Coefficient of Variation 21.5 |
| 1.5 mg q.d. ER | Area Under the Concentration-time Curve of Pramipexole in Plasma at Steady State Over 24 Hours (AUC0-24,ss); in Case of ER up to the Time Point of Next Dosing (AUCtau,ss) for Pharmacokinetic (PK) Population (All Subjects) | 19.1 ng*h/mL | Geometric Coefficient of Variation 113 |
| 0.5 mg t.i.d. IR | Area Under the Concentration-time Curve of Pramipexole in Plasma at Steady State Over 24 Hours (AUC0-24,ss); in Case of ER up to the Time Point of Next Dosing (AUCtau,ss) for Pharmacokinetic (PK) Population (All Subjects) | 20.4 ng*h/mL | Geometric Coefficient of Variation 104 |
Comparison: 0.125 mg t.i.d. IR is the reference treatment, 0.375 mg q.d. ER is the test treatment90% CI: [74.45, 91.69]ANOVA
Comparison: 0.5 mg t.i.d. IR is the reference treatment, 1.5 mg q.d. ER is the test treatment90% CI: [69.33, 133.42]ANOVA
Primary
Area Under the Concentration-time Curve of Pramipexole in Plasma at Steady State Over 24 Hours (AUC0-24,ss); in Case of ER up to the Time Point of Next Dosing (AUCtau,ss) for PK Population (Excluding Subjects Due to Emesis)
AUC0-24,ss = area under the plasma concentration-time curve between 0 and 24 hours at steady state. AUCtau,ss = area under the plasma concentration-time curve over a dosing interval at steady state
Time frame: 27 days
Population: PK population excluding subjects with reported emesis - Subjects with values for AUC0-24,ss for IR and values for AUCtau,ss for ER, excluding subjects with reported emesis
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.375 mg q.d.ER | Area Under the Concentration-time Curve of Pramipexole in Plasma at Steady State Over 24 Hours (AUC0-24,ss); in Case of ER up to the Time Point of Next Dosing (AUCtau,ss) for PK Population (Excluding Subjects Due to Emesis) | 6.64 ng*h/mL | Geometric Coefficient of Variation 19.6 |
| 0.125 mg t.i.d. IR | Area Under the Concentration-time Curve of Pramipexole in Plasma at Steady State Over 24 Hours (AUC0-24,ss); in Case of ER up to the Time Point of Next Dosing (AUCtau,ss) for PK Population (Excluding Subjects Due to Emesis) | 7.44 ng*h/mL | Geometric Coefficient of Variation 22.6 |
| 1.5 mg q.d. ER | Area Under the Concentration-time Curve of Pramipexole in Plasma at Steady State Over 24 Hours (AUC0-24,ss); in Case of ER up to the Time Point of Next Dosing (AUCtau,ss) for PK Population (Excluding Subjects Due to Emesis) | 24.8 ng*h/mL | Geometric Coefficient of Variation 34.6 |
| 0.5 mg t.i.d. IR | Area Under the Concentration-time Curve of Pramipexole in Plasma at Steady State Over 24 Hours (AUC0-24,ss); in Case of ER up to the Time Point of Next Dosing (AUCtau,ss) for PK Population (Excluding Subjects Due to Emesis) | 27.4 ng*h/mL | Geometric Coefficient of Variation 40.4 |
Comparison: 0.125 mg t.i.d. IR vs. 0.375 mg q.d. ER 0.125 mg t.i.d. IR is the reference treatment, 0.375 mg q.d. ER is the test treatment90% CI: [80.76, 95.92]ANOVA
Comparison: 0.5 mg t.i.d. IR vs. 1.5 mg q.d. ER 0.5 mg t.i.d. IR is the reference treatment, 1.5 mg q.d. ER is the test treatment90% CI: [81.16, 98.42]ANOVA
Primary
Maximum Steady State Concentration (Cmax,ss) for PK Population (All Subjects)
Cmax = maximum observed concentration of the analyte in plasma at steady state
Time frame: 27 days
Population: PK population - Subjects with values for Cmax,ss
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.375 mg q.d.ER | Maximum Steady State Concentration (Cmax,ss) for PK Population (All Subjects) | 0.416 ng/mL | Geometric Coefficient of Variation 25.3 |
| 0.125 mg t.i.d. IR | Maximum Steady State Concentration (Cmax,ss) for PK Population (All Subjects) | 0.469 ng/mL | Geometric Coefficient of Variation 22.1 |
| 1.5 mg q.d. ER | Maximum Steady State Concentration (Cmax,ss) for PK Population (All Subjects) | 1.10 ng/mL | Geometric Coefficient of Variation 130 |
| 0.5 mg t.i.d. IR | Maximum Steady State Concentration (Cmax,ss) for PK Population (All Subjects) | 1.20 ng/mL | Geometric Coefficient of Variation 112 |
Comparison: 0.125 mg t.i.d. IR vs. 0.375 mg q.d. ER 0.125 mg t.i.d. IR is the reference treatment, 0.375 mg q.d. ER is the test treatment90% CI: [79.89, 98.76]ANOVA
Comparison: 0.5 mg t.i.d. IR vs. 1.5 mg q.d. ER 0.5 mg t.i.d. IR is the reference treatment, 1.5 mg q.d. ER is the test treatment90% CI: [60.07, 140.25]ANOVA
Primary
Maximum Steady State Concentration (Cmax,ss) for PK Population (Excluding Subjects Due to Emesis)
Cmax,ss = maximum observed concentration of the analyte in plasma at steady state
Time frame: 27 days
Population: PK population excluding subjects with reported emesis - Subjects with values for Cmax,ss excluding subjects with reported emesis
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.375 mg q.d.ER | Maximum Steady State Concentration (Cmax,ss) for PK Population (Excluding Subjects Due to Emesis) | 0.436 ng/mL | Geometric Coefficient of Variation 20.6 |
| 0.125 mg t.i.d. IR | Maximum Steady State Concentration (Cmax,ss) for PK Population (Excluding Subjects Due to Emesis) | 0.463 ng/mL | Geometric Coefficient of Variation 22.8 |
| 1.5 mg q.d. ER | Maximum Steady State Concentration (Cmax,ss) for PK Population (Excluding Subjects Due to Emesis) | 1.56 ng/mL | Geometric Coefficient of Variation 26.5 |
| 0.5 mg t.i.d. IR | Maximum Steady State Concentration (Cmax,ss) for PK Population (Excluding Subjects Due to Emesis) | 1.61 ng/mL | Geometric Coefficient of Variation 42.6 |
Comparison: 0.125 mg t.i.d. IR is the reference treatment, 0.375 mg q.d. ER is the test treatment90% CI: [83.8, 102.86]ANOVA
Comparison: 0.5 mg t.i.d. IR is the reference treatment, 1.5 mg q.d. ER is the test treatment90% CI: [84.88, 106.43]ANOVA
Secondary
Apparent Volume of Distribution During the Terminal Phase at Steady State Following Oral Administration (Vz/F,ss) for PK Population (All Subjects)
Vz/F,ss = Apparent volume of distribution during the terminal phase λz at steady state following oral administration
Time frame: 27 days
Population: PK Population - Subjects with values for Vz/F,ss
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.375 mg q.d.ER | Apparent Volume of Distribution During the Terminal Phase at Steady State Following Oral Administration (Vz/F,ss) for PK Population (All Subjects) | 1167 L | Geometric Coefficient of Variation 50.3 |
| 0.125 mg t.i.d. IR | Apparent Volume of Distribution During the Terminal Phase at Steady State Following Oral Administration (Vz/F,ss) for PK Population (All Subjects) | 545 L | Geometric Coefficient of Variation 40.6 |
| 1.5 mg q.d. ER | Apparent Volume of Distribution During the Terminal Phase at Steady State Following Oral Administration (Vz/F,ss) for PK Population (All Subjects) | 1671 L | Geometric Coefficient of Variation 135 |
| 0.5 mg t.i.d. IR | Apparent Volume of Distribution During the Terminal Phase at Steady State Following Oral Administration (Vz/F,ss) for PK Population (All Subjects) | 897 L | Geometric Coefficient of Variation 138 |
Secondary
Apparent Volume of Distribution During the Terminal Phase at Steady State Following Oral Administration (Vz/F,ss) for PK Population (Excluding Subjects Due to Emesis)
Vz/F,ss = Apparent volume of distribution during the terminal phase λz at steady state following oral administration
Time frame: 27 days
Population: PK Population excluding subjects with reported emesis - Subjects with values for Vz/F,ss excluding subjects with reported emesis
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.375 mg q.d.ER | Apparent Volume of Distribution During the Terminal Phase at Steady State Following Oral Administration (Vz/F,ss) for PK Population (Excluding Subjects Due to Emesis) | 1092 L | Geometric Coefficient of Variation 47 |
| 0.125 mg t.i.d. IR | Apparent Volume of Distribution During the Terminal Phase at Steady State Following Oral Administration (Vz/F,ss) for PK Population (Excluding Subjects Due to Emesis) | 547 L | Geometric Coefficient of Variation 43.2 |
| 1.5 mg q.d. ER | Apparent Volume of Distribution During the Terminal Phase at Steady State Following Oral Administration (Vz/F,ss) for PK Population (Excluding Subjects Due to Emesis) | 1211 L | Geometric Coefficient of Variation 37.8 |
| 0.5 mg t.i.d. IR | Apparent Volume of Distribution During the Terminal Phase at Steady State Following Oral Administration (Vz/F,ss) for PK Population (Excluding Subjects Due to Emesis) | 625 L | Geometric Coefficient of Variation 45.8 |
Secondary
Average Concentration in Plasma Under Steady-state Conditions (Cavg) for PK Population (All Subjects)
Cavg = Average concentration of the analyte in plasma at steady state
Time frame: 27 days
Population: PK Population - Subjects with values for Cavg
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.375 mg q.d.ER | Average Concentration in Plasma Under Steady-state Conditions (Cavg) for PK Population (All Subjects) | 0.259 ng/mL | Geometric Coefficient of Variation 29.7 |
| 0.125 mg t.i.d. IR | Average Concentration in Plasma Under Steady-state Conditions (Cavg) for PK Population (All Subjects) | 0.312 ng/mL | Geometric Coefficient of Variation 21.5 |
| 1.5 mg q.d. ER | Average Concentration in Plasma Under Steady-state Conditions (Cavg) for PK Population (All Subjects) | 0.796 ng/mL | Geometric Coefficient of Variation 113 |
| 0.5 mg t.i.d. IR | Average Concentration in Plasma Under Steady-state Conditions (Cavg) for PK Population (All Subjects) | 0.848 ng/mL | Geometric Coefficient of Variation 104 |
Secondary
Average Concentration in Plasma Under Steady-state Conditions (Cavg) for PK Population (Excluding Subjects Due to Emesis)
Cavg = Average concentration of the analyte in plasma at steady state
Time frame: 27 days
Population: PK Population excluding subjects with reported emesis - Subjects with values for Cavg excluding subjects with reported emesis
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.375 mg q.d.ER | Average Concentration in Plasma Under Steady-state Conditions (Cavg) for PK Population (Excluding Subjects Due to Emesis) | 0.277 ng/mL | Geometric Coefficient of Variation 19.6 |
| 0.125 mg t.i.d. IR | Average Concentration in Plasma Under Steady-state Conditions (Cavg) for PK Population (Excluding Subjects Due to Emesis) | 0.310 ng/mL | Geometric Coefficient of Variation 22.6 |
| 1.5 mg q.d. ER | Average Concentration in Plasma Under Steady-state Conditions (Cavg) for PK Population (Excluding Subjects Due to Emesis) | 1.04 ng/mL | Geometric Coefficient of Variation 34.6 |
| 0.5 mg t.i.d. IR | Average Concentration in Plasma Under Steady-state Conditions (Cavg) for PK Population (Excluding Subjects Due to Emesis) | 1.14 ng/mL | Geometric Coefficient of Variation 40.4 |
Secondary
Minimum Steady State Concentration (Cmin,ss) for PK Population (All Subjects)
Cmin,ss = Minimum observed concentration of the analyte in plasma at steady state
Time frame: 27 days
Population: PK Population - Subjects with values for Cmin,ss
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.375 mg q.d.ER | Minimum Steady State Concentration (Cmin,ss) for PK Population (All Subjects) | NA ng/mL | — |
| 0.125 mg t.i.d. IR | Minimum Steady State Concentration (Cmin,ss) for PK Population (All Subjects) | NA ng/mL | — |
| 1.5 mg q.d. ER | Minimum Steady State Concentration (Cmin,ss) for PK Population (All Subjects) | NA ng/mL | — |
| 0.5 mg t.i.d. IR | Minimum Steady State Concentration (Cmin,ss) for PK Population (All Subjects) | 0.478 ng/mL | Geometric Coefficient of Variation 95.3 |
Secondary
Minimum Steady State Concentration (Cmin,ss) for PK Population (Excluding Subjects Due to Emesis)
Cmin,ss = Minimum observed concentration of the analyte in plasma at steady state
Time frame: 27 days
Population: PK Population excluding subjects with reported emesis - Subjects with values for Cmin,ss excluding subjects with reported emesis
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.375 mg q.d.ER | Minimum Steady State Concentration (Cmin,ss) for PK Population (Excluding Subjects Due to Emesis) | NA ng/mL | — |
| 0.125 mg t.i.d. IR | Minimum Steady State Concentration (Cmin,ss) for PK Population (Excluding Subjects Due to Emesis) | NA ng/mL | — |
| 1.5 mg q.d. ER | Minimum Steady State Concentration (Cmin,ss) for PK Population (Excluding Subjects Due to Emesis) | 0.403 ng/mL | Geometric Coefficient of Variation 102 |
| 0.5 mg t.i.d. IR | Minimum Steady State Concentration (Cmin,ss) for PK Population (Excluding Subjects Due to Emesis) | 0.609 ng/mL | Geometric Coefficient of Variation 57.2 |
Secondary
Peak-to-trough Fluctuation (PTF) for PK Population (All Subjects)
PTF = Peak-to-trough fluctuation is measured as a percent
Time frame: 27 days
Population: PK population - Subjects with values for PTF
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.375 mg q.d.ER | Peak-to-trough Fluctuation (PTF) for PK Population (All Subjects) | 112 percent | Geometric Coefficient of Variation 29.4 |
| 0.125 mg t.i.d. IR | Peak-to-trough Fluctuation (PTF) for PK Population (All Subjects) | 86.6 percent | Geometric Coefficient of Variation 27.5 |
| 1.5 mg q.d. ER | Peak-to-trough Fluctuation (PTF) for PK Population (All Subjects) | 101 percent | Geometric Coefficient of Variation 33.8 |
| 0.5 mg t.i.d. IR | Peak-to-trough Fluctuation (PTF) for PK Population (All Subjects) | 78.2 percent | Geometric Coefficient of Variation 34.5 |
Secondary
Peak-to-trough Fluctuation (PTF) for PK Population (Excluding Subjects Due to Emesis)
PTF = Peak-to-trough fluctuation is measured as a percent
Time frame: 27 days
Population: PK population excluding subjects with reported emesis - Subjects with values for PTF excluding subjects with reported emesis
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.375 mg q.d.ER | Peak-to-trough Fluctuation (PTF) for PK Population (Excluding Subjects Due to Emesis) | 109 percent | Geometric Coefficient of Variation 28.9 |
| 0.125 mg t.i.d. IR | Peak-to-trough Fluctuation (PTF) for PK Population (Excluding Subjects Due to Emesis) | 86.2 percent | Geometric Coefficient of Variation 29.1 |
| 1.5 mg q.d. ER | Peak-to-trough Fluctuation (PTF) for PK Population (Excluding Subjects Due to Emesis) | 103 percent | Geometric Coefficient of Variation 28.3 |
| 0.5 mg t.i.d. IR | Peak-to-trough Fluctuation (PTF) for PK Population (Excluding Subjects Due to Emesis) | 82.5 percent | Geometric Coefficient of Variation 24.8 |
Secondary
Predose Steady State Concentration of the Analyte Immediately Before Administration of the Next Drug Administration (Cpre,ss) for PK Population (All Subjects)
Cpre,ss = pre-dose concentration of the analyte in plasma at steady state immediately before administration of the next dose
Time frame: 27 days
Population: PK population - Subjects with values for Cpre,ss
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.375 mg q.d.ER | Predose Steady State Concentration of the Analyte Immediately Before Administration of the Next Drug Administration (Cpre,ss) for PK Population (All Subjects) | NA ng/mL | — |
| 0.125 mg t.i.d. IR | Predose Steady State Concentration of the Analyte Immediately Before Administration of the Next Drug Administration (Cpre,ss) for PK Population (All Subjects) | NA ng/mL | — |
| 1.5 mg q.d. ER | Predose Steady State Concentration of the Analyte Immediately Before Administration of the Next Drug Administration (Cpre,ss) for PK Population (All Subjects) | NA ng/mL | — |
| 0.5 mg t.i.d. IR | Predose Steady State Concentration of the Analyte Immediately Before Administration of the Next Drug Administration (Cpre,ss) for PK Population (All Subjects) | 0.507 ng/mL | Geometric Coefficient of Variation 90.4 |
Secondary
Predose Steady State Concentration of the Analyte Immediately Before Administration of the Next Drug Administration (Cpre,ss) for PK Population (Excluding Subjects Due to Emesis)
Cpre,ss = pre-dose concentration of the analyte in plasma at steady state immediately before administration of the next dose
Time frame: 27 days
Population: PK population excluding subjects with reported emesis - Subjects with values for Cpre,ss excluding subjects with reported emesis
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.375 mg q.d.ER | Predose Steady State Concentration of the Analyte Immediately Before Administration of the Next Drug Administration (Cpre,ss) for PK Population (Excluding Subjects Due to Emesis) | NA ng/mL | — |
| 0.125 mg t.i.d. IR | Predose Steady State Concentration of the Analyte Immediately Before Administration of the Next Drug Administration (Cpre,ss) for PK Population (Excluding Subjects Due to Emesis) | NA ng/mL | — |
| 1.5 mg q.d. ER | Predose Steady State Concentration of the Analyte Immediately Before Administration of the Next Drug Administration (Cpre,ss) for PK Population (Excluding Subjects Due to Emesis) | 0.487 ng/mL | Geometric Coefficient of Variation 105 |
| 0.5 mg t.i.d. IR | Predose Steady State Concentration of the Analyte Immediately Before Administration of the Next Drug Administration (Cpre,ss) for PK Population (Excluding Subjects Due to Emesis) | 0.616 ng/mL | Geometric Coefficient of Variation 57.2 |
Secondary
Terminal Half-life of the Analyte in Plasma at Steady State (t1/2,ss) for PK Population (All Subjects)
t1/2,ss - Apparent plasma terminal elimination half-life at steady state
Time frame: 27 days
Population: PK Population - Subjects with values for t1/2,ss
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.375 mg q.d.ER | Terminal Half-life of the Analyte in Plasma at Steady State (t1/2,ss) for PK Population (All Subjects) | 13.3 h | Geometric Coefficient of Variation 40.7 |
| 0.125 mg t.i.d. IR | Terminal Half-life of the Analyte in Plasma at Steady State (t1/2,ss) for PK Population (All Subjects) | 7.69 h | Geometric Coefficient of Variation 28.6 |
| 1.5 mg q.d. ER | Terminal Half-life of the Analyte in Plasma at Steady State (t1/2,ss) for PK Population (All Subjects) | 14.4 h | Geometric Coefficient of Variation 42.8 |
| 0.5 mg t.i.d. IR | Terminal Half-life of the Analyte in Plasma at Steady State (t1/2,ss) for PK Population (All Subjects) | 8.43 h | Geometric Coefficient of Variation 25.3 |
Secondary
Terminal Half-life of the Analyte in Plasma at Steady State (t1/2,ss) for PK Population (Excluding Subjects Due to Emesis)
t1/2,ss - Apparent plasma terminal elimination half-life at steady state
Time frame: 27 days
Population: PK Population excluding subjects with reported emesis - Subjects with values for t1/2,ss excluding subjects with reported emesis
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.375 mg q.d.ER | Terminal Half-life of the Analyte in Plasma at Steady State (t1/2,ss) for PK Population (Excluding Subjects Due to Emesis) | 13.4 h | Geometric Coefficient of Variation 42.6 |
| 0.125 mg t.i.d. IR | Terminal Half-life of the Analyte in Plasma at Steady State (t1/2,ss) for PK Population (Excluding Subjects Due to Emesis) | 7.68 h | Geometric Coefficient of Variation 30.5 |
| 1.5 mg q.d. ER | Terminal Half-life of the Analyte in Plasma at Steady State (t1/2,ss) for PK Population (Excluding Subjects Due to Emesis) | 14.5 h | Geometric Coefficient of Variation 46.9 |
| 0.5 mg t.i.d. IR | Terminal Half-life of the Analyte in Plasma at Steady State (t1/2,ss) for PK Population (Excluding Subjects Due to Emesis) | 7.92 h | Geometric Coefficient of Variation 16.6 |
Secondary
The Apparent Clearance of the Analyte in Plasma at Steady State Following Oral Administration (CL/F,ss) for PK Population (All Subjects)
CL/F,ss = Apparent clearance of the analyte in the plasma at steady state following oral administration
Time frame: 27 days
Population: PK Population - Subjects with values for CL/F,ss
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.375 mg q.d.ER | The Apparent Clearance of the Analyte in Plasma at Steady State Following Oral Administration (CL/F,ss) for PK Population (All Subjects) | 1007 mL/min | Geometric Coefficient of Variation 29.7 |
| 0.125 mg t.i.d. IR | The Apparent Clearance of the Analyte in Plasma at Steady State Following Oral Administration (CL/F,ss) for PK Population (All Subjects) | 833 mL/min | Geometric Coefficient of Variation 21.5 |
| 1.5 mg q.d. ER | The Apparent Clearance of the Analyte in Plasma at Steady State Following Oral Administration (CL/F,ss) for PK Population (All Subjects) | 1310 mL/min | Geometric Coefficient of Variation 113 |
| 0.5 mg t.i.d. IR | The Apparent Clearance of the Analyte in Plasma at Steady State Following Oral Administration (CL/F,ss) for PK Population (All Subjects) | 1228 mL/min | Geometric Coefficient of Variation 104 |
Secondary
The Apparent Clearance of the Analyte in Plasma at Steady State Following Oral Administration (CL/F,ss) for PK Population (Excluding Subjects Due to Emesis)
CL/F,ss = Apparent clearance of the analyte in the plasma at steady state following oral administration
Time frame: 27 days
Population: PK Population excluding subjects with reported emesis - Subjects with values for CL/F,ss excluding subjects with reported emesis
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.375 mg q.d.ER | The Apparent Clearance of the Analyte in Plasma at Steady State Following Oral Administration (CL/F,ss) for PK Population (Excluding Subjects Due to Emesis) | 942 mL/min | Geometric Coefficient of Variation 19.6 |
| 0.125 mg t.i.d. IR | The Apparent Clearance of the Analyte in Plasma at Steady State Following Oral Administration (CL/F,ss) for PK Population (Excluding Subjects Due to Emesis) | 839 mL/min | Geometric Coefficient of Variation 22.6 |
| 1.5 mg q.d. ER | The Apparent Clearance of the Analyte in Plasma at Steady State Following Oral Administration (CL/F,ss) for PK Population (Excluding Subjects Due to Emesis) | 1008 mL/min | Geometric Coefficient of Variation 34.6 |
| 0.5 mg t.i.d. IR | The Apparent Clearance of the Analyte in Plasma at Steady State Following Oral Administration (CL/F,ss) for PK Population (Excluding Subjects Due to Emesis) | 911 mL/min | Geometric Coefficient of Variation 40.4 |
Secondary
Time From Dosing to the Maximum Measured Concentration of the Analyte in Plasma (Tmax) for PK Population (All Subjects)
tmax = time of maximum observed plasma concentration
Time frame: 27 days
Population: PK population - Subjects with values for tmax
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 0.375 mg q.d.ER | Time From Dosing to the Maximum Measured Concentration of the Analyte in Plasma (Tmax) for PK Population (All Subjects) | 4.00 hours |
| 0.125 mg t.i.d. IR | Time From Dosing to the Maximum Measured Concentration of the Analyte in Plasma (Tmax) for PK Population (All Subjects) | 1.00 hours |
| 1.5 mg q.d. ER | Time From Dosing to the Maximum Measured Concentration of the Analyte in Plasma (Tmax) for PK Population (All Subjects) | 4.00 hours |
| 0.5 mg t.i.d. IR | Time From Dosing to the Maximum Measured Concentration of the Analyte in Plasma (Tmax) for PK Population (All Subjects) | 1.00 hours |
Secondary
Time From Dosing to the Maximum Measured Concentration of the Analyte in Plasma (Tmax) for PK Population (Excluding Subjects Due to Emesis)
tmax = time of maximum observed plasma concentration
Time frame: 27 days
Population: PK population excluding subjects with reported emesis - Subjects with values for t\_max excluding subjects with reported emesis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 0.375 mg q.d.ER | Time From Dosing to the Maximum Measured Concentration of the Analyte in Plasma (Tmax) for PK Population (Excluding Subjects Due to Emesis) | 4.00 hours |
| 0.125 mg t.i.d. IR | Time From Dosing to the Maximum Measured Concentration of the Analyte in Plasma (Tmax) for PK Population (Excluding Subjects Due to Emesis) | 1.00 hours |
| 1.5 mg q.d. ER | Time From Dosing to the Maximum Measured Concentration of the Analyte in Plasma (Tmax) for PK Population (Excluding Subjects Due to Emesis) | 4.00 hours |
| 0.5 mg t.i.d. IR | Time From Dosing to the Maximum Measured Concentration of the Analyte in Plasma (Tmax) for PK Population (Excluding Subjects Due to Emesis) | 1.00 hours |