Trial Outcomes & Findings for Bioequivalence of Pramipexole Extended Release (PPX ER) 1.5mg x 1 Tablet Once Daily (q.d.) vs. PPX ER 0.375mg x 4 Tablets Under Fasted and Fed Conditions in Japanese Healthy Volunteers (NCT NCT01119443)

NCT ID: NCT01119443

Last Updated: 2014-06-09

Results Overview

Area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 28 participants
• Primary outcome timeframe: Serial pharmacokinetic blood samples collected before drug administration, 1, 2, 2.5, 3, 4, 6, 8, 10, 12, and 23.833 hours after drug administration
• Results posted on: 2014-06-09

Participant Flow

Participant milestones

Measure	Treatment Sequence A 1.5 mg x 1 tablet once daily (q.d.) fed -\> 0.375 mg x 4 tablets q.d. fed -\> 1.5 mg x 1 tablet q.d. fasted -\> 0.375 mg x 4 tablets q.d. fasted	Treatment Sequence B 0.375 mg x 4 tablets q.d. fed -\> 1.5 mg x 1 tablet q.d. fed -\> 0.375 mg x 4 tablets q.d. fasted -\> 1.5 mg x 1 tablet q.d. fasted
Up-titration Period (10 Days) STARTED	14	14
Up-titration Period (10 Days) COMPLETED	14	14
Up-titration Period (10 Days) NOT COMPLETED	0	0
Crossover Period 1 (5 Days) STARTED	14	14
Crossover Period 1 (5 Days) COMPLETED	14	13
Crossover Period 1 (5 Days) NOT COMPLETED	0	1
Crossover Period 2 (5 Days) STARTED	14	13
Crossover Period 2 (5 Days) COMPLETED	14	13
Crossover Period 2 (5 Days) NOT COMPLETED	0	0
Crossover Period 3 (5 Days) STARTED	14	13
Crossover Period 3 (5 Days) COMPLETED	14	13
Crossover Period 3 (5 Days) NOT COMPLETED	0	0
Crossover Period 4 (5 Days) STARTED	14	13
Crossover Period 4 (5 Days) COMPLETED	14	13
Crossover Period 4 (5 Days) NOT COMPLETED	0	0
Down-titration Period (1 Day) STARTED	14	13
Down-titration Period (1 Day) COMPLETED	14	13
Down-titration Period (1 Day) NOT COMPLETED	0	0
End of Study (All Patients) STARTED	14	14
End of Study (All Patients) COMPLETED	14	14
End of Study (All Patients) NOT COMPLETED	0	0

Reasons for withdrawal

Measure	Treatment Sequence A 1.5 mg x 1 tablet once daily (q.d.) fed -\> 0.375 mg x 4 tablets q.d. fed -\> 1.5 mg x 1 tablet q.d. fasted -\> 0.375 mg x 4 tablets q.d. fasted	Treatment Sequence B 0.375 mg x 4 tablets q.d. fed -\> 1.5 mg x 1 tablet q.d. fed -\> 0.375 mg x 4 tablets q.d. fasted -\> 1.5 mg x 1 tablet q.d. fasted
Crossover Period 1 (5 Days) Adverse Event	0	1

Baseline Characteristics

Bioequivalence of Pramipexole Extended Release (PPX ER) 1.5mg x 1 Tablet Once Daily (q.d.) vs. PPX ER 0.375mg x 4 Tablets Under Fasted and Fed Conditions in Japanese Healthy Volunteers

Baseline characteristics by cohort

Measure	Treatment Sequence A n=14 Participants 1.5 mg x 1 tablet q.d. fed -\> 0.375 mg x 4 tablets q.d. fed -\> 1.5 mg x 1 tablet q.d. fasted -\> 0.375 mg x 4 tablets q.d. fasted	Treatment Sequence B n=14 Participants 0.375 mg x 4 tablets q.d. fed -\> 1.5 mg x 1 tablet q.d. fed -\> 0.375 mg x 4 tablets q.d. fasted -\> 1.5 mg x 1 tablet q.d. fasted	Total n=28 Participants Total of all reporting groups
Age, Continuous	29.2 years STANDARD_DEVIATION 4.8 • n=5 Participants	29.1 years STANDARD_DEVIATION 5.4 • n=7 Participants	29.1 years STANDARD_DEVIATION 5.0 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	14 Participants n=7 Participants	28 Participants n=5 Participants

PRIMARY outcome

Timeframe: Serial pharmacokinetic blood samples collected before drug administration, 1, 2, 2.5, 3, 4, 6, 8, 10, 12, and 23.833 hours after drug administration

Population: One subject who discontinued the study on Day 1 of Visit 4 (the first day of the first crossover period) was excluded from Pharmacokinetic data set

Area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ

Outcome measures

Measure	Pramipexole ER 1.5 mg x 1 Tablet q.d. in Fed n=27 Participants Pramipexole ER 1.5 mg x 1 tablet once a day (q.d.) under fed conditions	Pramipexole ER 0.375 mg x 4 Tablets q.d. in Fed n=27 Participants Pramipexole ER 0.375 mg x 4 tablets once a day (q.d.) under fed conditions
AUCτ,ss (Fed Conditions)	33.7 ng·h/mL Standard Deviation 5.89	32.3 ng·h/mL Standard Deviation 5.89

PRIMARY outcome

Timeframe: Serial pharmacokinetic blood samples collected before drug administration, 1, 2, 2.5, 3, 4, 6, 8, 10, 12, and 23.833 hours after drug administration

Population: One subject who discontinued the study on Day 1 of Visit 4 (the first day of the first crossover period) was excluded from Pharmacokinetic data set

maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ

Outcome measures

Measure	Pramipexole ER 1.5 mg x 1 Tablet q.d. in Fed n=27 Participants Pramipexole ER 1.5 mg x 1 tablet once a day (q.d.) under fed conditions	Pramipexole ER 0.375 mg x 4 Tablets q.d. in Fed n=27 Participants Pramipexole ER 0.375 mg x 4 tablets once a day (q.d.) under fed conditions
Cmax,ss (Fed Conditions)	2.24 ng/mL Standard Deviation 0.290	2.13 ng/mL Standard Deviation 0.255

PRIMARY outcome

Timeframe: Serial pharmacokinetic blood samples collected before drug administration, 1, 2, 2.5, 3, 4, 6, 8, 10, 12, and 23.833 hours after drug administration

Population: One subject who discontinued the study on Day 1 of Visit 4 (the first day of the first crossover period) was excluded from Pharmacokinetic data set

Area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ

Outcome measures

Measure	Pramipexole ER 1.5 mg x 1 Tablet q.d. in Fed n=27 Participants Pramipexole ER 1.5 mg x 1 tablet once a day (q.d.) under fed conditions	Pramipexole ER 0.375 mg x 4 Tablets q.d. in Fed n=27 Participants Pramipexole ER 0.375 mg x 4 tablets once a day (q.d.) under fed conditions
AUCτ,ss (Fasted Conditions)	31.4 ng/mL Standard Deviation 7.37	33.6 ng/mL Standard Deviation 5.80

PRIMARY outcome

Timeframe: Serial pharmacokinetic blood samples collected before drug administration, 1, 2, 2.5, 3, 4, 6, 8, 10, 12, and 23.833 hours after drug administration

Population: One subject who discontinued the study on Day 1 of Visit 4 (the first day of the first crossover period) was excluded from Pharmacokinetic data set

maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ

Outcome measures

Measure	Pramipexole ER 1.5 mg x 1 Tablet q.d. in Fed n=27 Participants Pramipexole ER 1.5 mg x 1 tablet once a day (q.d.) under fed conditions	Pramipexole ER 0.375 mg x 4 Tablets q.d. in Fed n=27 Participants Pramipexole ER 0.375 mg x 4 tablets once a day (q.d.) under fed conditions
Cmax,ss (Fasted Conditions)	2.13 ng/mL Standard Deviation 0.359	2.12 ng/mL Standard Deviation 0.305

SECONDARY outcome

Timeframe: pharmacokinetic blood samples collected at τ (23.833 hours) after drug administration

Population: One subject who discontinued the study on Day 1 of Visit 4 (the first day of the first crossover period) was excluded from Pharmacokinetic data set

Concentration of the analyte in plasma at time τ at steady state

Outcome measures

Measure	Pramipexole ER 1.5 mg x 1 Tablet q.d. in Fed n=27 Participants Pramipexole ER 1.5 mg x 1 tablet once a day (q.d.) under fed conditions	Pramipexole ER 0.375 mg x 4 Tablets q.d. in Fed n=27 Participants Pramipexole ER 0.375 mg x 4 tablets once a day (q.d.) under fed conditions
Cτ,ss (Fed Conditions)	0.711 ng/mL Standard Error 0.184	0.656 ng/mL Standard Error 0.217

SECONDARY outcome

Timeframe: Serial pharmacokinetic blood samples collected before drug administration, 1, 2, 2.5, 3, 4, 6, 8, 10, 12, and 23.833 hours after drug administration

Population: One subject who discontinued the study on Day 1 of Visit 4 (the first day of the first crossover period) was excluded from Pharmacokinetic data set

Minimum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ

Outcome measures

Measure	Pramipexole ER 1.5 mg x 1 Tablet q.d. in Fed n=27 Participants Pramipexole ER 1.5 mg x 1 tablet once a day (q.d.) under fed conditions	Pramipexole ER 0.375 mg x 4 Tablets q.d. in Fed n=27 Participants Pramipexole ER 0.375 mg x 4 tablets once a day (q.d.) under fed conditions
Cmin,ss (Fed Conditions)	0.676 ng/mL Standard Deviation 0.195	0.633 ng/mL Standard Deviation 0.218

SECONDARY outcome

Timeframe: Serial pharmacokinetic blood samples collected before drug administration, 1, 2, 2.5, 3, 4, 6, 8, 10, 12, and 23.833 hours after drug administration

Population: One subject who discontinued the study on Day 1 of Visit 4 (the first day of the first crossover period) was excluded from Pharmacokinetic data set

Time from dosing to the maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ

Outcome measures

Measure	Pramipexole ER 1.5 mg x 1 Tablet q.d. in Fed n=27 Participants Pramipexole ER 1.5 mg x 1 tablet once a day (q.d.) under fed conditions	Pramipexole ER 0.375 mg x 4 Tablets q.d. in Fed n=27 Participants Pramipexole ER 0.375 mg x 4 tablets once a day (q.d.) under fed conditions
Tmax,ss (Fed Conditions)	5.67 hour Interval 2.0 to 10.0	5.76 hour Interval 2.0 to 10.0

SECONDARY outcome

Timeframe: Serial pharmacokinetic blood samples collected before drug administration, 1, 2, 2.5, 3, 4, 6, 8, 10, 12, and 23.833 hours after drug administration

Population: One subject who discontinued the study on Day 1 of Visit 4 (the first day of the first crossover period) was excluded from Pharmacokinetic data set

Terminal rate constant of the analyte in plasma at steady state

Outcome measures

Measure	Pramipexole ER 1.5 mg x 1 Tablet q.d. in Fed n=27 Participants Pramipexole ER 1.5 mg x 1 tablet once a day (q.d.) under fed conditions	Pramipexole ER 0.375 mg x 4 Tablets q.d. in Fed n=27 Participants Pramipexole ER 0.375 mg x 4 tablets once a day (q.d.) under fed conditions
λz,ss (Fed Conditions)	0.0609 per hour Standard Deviation 0.0170	0.0640 per hour Standard Deviation 0.0169

SECONDARY outcome

Timeframe: Serial pharmacokinetic blood samples collected before drug administration, 1, 2, 2.5, 3, 4, 6, 8, 10, 12, and 23.833 hours after drug administration

Population: One subject who discontinued the study on Day 1 of Visit 4 (the first day of the first crossover period) was excluded from Pharmacokinetic data set

Terminal half-life of the analyte in plasma at steady state

Outcome measures

Measure	Pramipexole ER 1.5 mg x 1 Tablet q.d. in Fed n=27 Participants Pramipexole ER 1.5 mg x 1 tablet once a day (q.d.) under fed conditions	Pramipexole ER 0.375 mg x 4 Tablets q.d. in Fed n=27 Participants Pramipexole ER 0.375 mg x 4 tablets once a day (q.d.) under fed conditions
t1/2,ss (Fed Conditions)	11.4 hour Standard Deviation 5.02	10.8 hour Standard Deviation 6.01

SECONDARY outcome

Timeframe: Serial pharmacokinetic blood samples collected before drug administration, 1, 2, 2.5, 3, 4, 6, 8, 10, 12, and 23.833 hours after drug administration

Population: One subject who discontinued the study on Day 1 of Visit 4 (the first day of the first crossover period) was excluded from Pharmacokinetic data set

Mean residence time of the analyte in the body at steady state after oral administration

Outcome measures

Measure	Pramipexole ER 1.5 mg x 1 Tablet q.d. in Fed n=27 Participants Pramipexole ER 1.5 mg x 1 tablet once a day (q.d.) under fed conditions	Pramipexole ER 0.375 mg x 4 Tablets q.d. in Fed n=27 Participants Pramipexole ER 0.375 mg x 4 tablets once a day (q.d.) under fed conditions
MRTpo,ss (Fed Conditions)	19.1 hour Standard Deviation 6.08	18.4 hour Standard Deviation 7.60

SECONDARY outcome

Timeframe: pharmacokinetic blood samples collected at τ (23.833 hours) after drug administration

Population: One subject who discontinued the study on Day 1 of Visit 4 (the first day of the first crossover period) was excluded from Pharmacokinetic data set

Concentration of the analyte in plasma at time τ at steady state

Outcome measures

Measure	Pramipexole ER 1.5 mg x 1 Tablet q.d. in Fed n=27 Participants Pramipexole ER 1.5 mg x 1 tablet once a day (q.d.) under fed conditions	Pramipexole ER 0.375 mg x 4 Tablets q.d. in Fed n=27 Participants Pramipexole ER 0.375 mg x 4 tablets once a day (q.d.) under fed conditions
Cτ,ss (Fasted Conditions)	0.654 ng/mL Standard Error 0.342	0.757 ng/mL Standard Error 0.283

SECONDARY outcome

Timeframe: Serial pharmacokinetic blood samples collected before drug administration, 1, 2, 2.5, 3, 4, 6, 8, 10, 12, and 23.833 hours after drug administration

Population: One subject who discontinued the study on Day 1 of Visit 4 (the first day of the first crossover period) was excluded from Pharmacokinetic data set

Minimum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ

Outcome measures

Measure	Pramipexole ER 1.5 mg x 1 Tablet q.d. in Fed n=27 Participants Pramipexole ER 1.5 mg x 1 tablet once a day (q.d.) under fed conditions	Pramipexole ER 0.375 mg x 4 Tablets q.d. in Fed n=27 Participants Pramipexole ER 0.375 mg x 4 tablets once a day (q.d.) under fed conditions
Cmin,ss (Fasted Conditions)	0.654 ng/mL Standard Deviation 0.342	0.757 ng/mL Standard Deviation 0.283

SECONDARY outcome

Timeframe: Serial pharmacokinetic blood samples collected before drug administration, 1, 2, 2.5, 3, 4, 6, 8, 10, 12, and 23.833 hours after drug administration

Population: One subject who discontinued the study on Day 1 of Visit 4 (the first day of the first crossover period) was excluded from Pharmacokinetic data set

Time from dosing to the maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ

Outcome measures

Measure	Pramipexole ER 1.5 mg x 1 Tablet q.d. in Fed n=27 Participants Pramipexole ER 1.5 mg x 1 tablet once a day (q.d.) under fed conditions	Pramipexole ER 0.375 mg x 4 Tablets q.d. in Fed n=27 Participants Pramipexole ER 0.375 mg x 4 tablets once a day (q.d.) under fed conditions
Tmax,ss (Fasted Conditions)	4.24 hour Interval 2.0 to 8.0	4.28 hour Interval 2.5 to 8.0

SECONDARY outcome

Timeframe: Serial pharmacokinetic blood samples collected before drug administration, 1, 2, 2.5, 3, 4, 6, 8, 10, 12, and 23.833 hours after drug administration

Population: One subject who discontinued the study on Day 1 of Visit 4 (the first day of the first crossover period) was excluded from Pharmacokinetic data set

Terminal rate constant of the analyte in plasma at steady state

Outcome measures

Measure	Pramipexole ER 1.5 mg x 1 Tablet q.d. in Fed n=27 Participants Pramipexole ER 1.5 mg x 1 tablet once a day (q.d.) under fed conditions	Pramipexole ER 0.375 mg x 4 Tablets q.d. in Fed n=27 Participants Pramipexole ER 0.375 mg x 4 tablets once a day (q.d.) under fed conditions
λz,ss (Fasted Conditions)	0.0520 /hour Standard Deviation 0.0275	0.0474 /hour Standard Deviation 0.0239

SECONDARY outcome

Timeframe: Serial pharmacokinetic blood samples collected before drug administration, 1, 2, 2.5, 3, 4, 6, 8, 10, 12, and 23.833 hours after drug administration

Population: One subject who discontinued the study on Day 1 of Visit 4 (the first day of the first crossover period) was excluded from Pharmacokinetic data set

Terminal half-life of the analyte in plasma at steady state

Outcome measures

Measure	Pramipexole ER 1.5 mg x 1 Tablet q.d. in Fed n=27 Participants Pramipexole ER 1.5 mg x 1 tablet once a day (q.d.) under fed conditions	Pramipexole ER 0.375 mg x 4 Tablets q.d. in Fed n=27 Participants Pramipexole ER 0.375 mg x 4 tablets once a day (q.d.) under fed conditions
t1/2,ss (Fasted Conditions)	13.3 hour Standard Deviation 9.82	14.6 hour Standard Deviation 10.8

SECONDARY outcome

Timeframe: Serial pharmacokinetic blood samples collected before drug administration, 1, 2, 2.5, 3, 4, 6, 8, 10, 12, and 23.833 hours after drug administration

Population: One subject who discontinued the study on Day 1 of Visit 4 (the first day of the first crossover period) was excluded from Pharmacokinetic data set

Mean residence time of the analyte in the body at steady state after oral administration

Outcome measures

Measure	Pramipexole ER 1.5 mg x 1 Tablet q.d. in Fed n=27 Participants Pramipexole ER 1.5 mg x 1 tablet once a day (q.d.) under fed conditions	Pramipexole ER 0.375 mg x 4 Tablets q.d. in Fed n=27 Participants Pramipexole ER 0.375 mg x 4 tablets once a day (q.d.) under fed conditions
MRTpo,ss (Fasted Conditions)	21.2 hour Standard Deviation 13.1	22.9 hour Standard Deviation 13.7

Adverse Events

Up-titration

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

1.5 mg q.d. Fed

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

1.5 mg q.d. Fast

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Up-titration n=28 participants at risk Up-titration to 0.75mg (10 days)	1.5 mg q.d. Fed n=28 participants at risk 1.5 mg x 1 tablet q.d. or 0.375 mg x 4 tablets q.d. in fed condition (10days in crossover)	1.5 mg q.d. Fast n=27 participants at risk 1.5 mg x 1 tablet q.d. or 0.375 mg x 4 tablets q.d. in fast condition (10 days in crossover)
Nervous system disorders Somnolence	14.3% 4/28 • 32 days	7.1% 2/28 • 32 days	0.00% 0/27 • 32 days
Gastrointestinal disorders Epigastric discomfort	3.6% 1/28 • 32 days	7.1% 2/28 • 32 days	0.00% 0/27 • 32 days
Gastrointestinal disorders Nausea	0.00% 0/28 • 32 days	7.1% 2/28 • 32 days	0.00% 0/27 • 32 days

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim Pharmaceuticals

Phone: 1-800-243-0127

Email: clintriage.rdg@boehringer-ingelheim.com

Results disclosure agreements

• Principal investigator is a sponsor employee Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.
• Publication restrictions are in place

Restriction type: OTHER