Pramipexole Dihydrochloride 0.25 mg Tablets Under Fasting Conditions

• Sponsor: Teva Pharmaceuticals USA (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01074450
• Collaborator: (none)
• Enrollment: 24
• Location: 1
• Arms: 2
• Duration (Days): 28
• Patients Per Site Per Month: 26.1

Study Details

Study Description

Brief Summary

The object of this study was to compare the relative bioavailability (rate and extent of absorption) of Pramipexole Dihydrochloride Tablets 0.25 mg by Barr Laboratories, Inc. with that of Mirapex® Tablets 0.25 mg distributed by Boehringer Ingelheim Pharmaceuticals, Inc. following a single oral dose in healthy adults under fasting conditions.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Pramipexole Dihydrochloride; Drug: Pramipexole Dihydrochloride	Phase 1

Detailed Description

Criteria for Evaluation: FDA Bioequivalence Criteria

Statistical Methods: FDA Bioequivalence Statistical Methods

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Official Title: A Relative Bioavailability Study of 0.25 mg Pramipexole Dihydrochloride Tablets Under Fasting Conditions
• Study Start Date: Feb 1, 2005
• Actual Primary Completion Date: Mar 1, 2005
• Actual Study Completion Date: Mar 1, 2005

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Pramipexole Dihydrochloride 0.25 mg Tablets	Drug: Pramipexole Dihydrochloride; 0.25 mg Tablet
Active Comparator: 2 Mirapex® 0.25 mg Tablets	Drug: Pramipexole Dihydrochloride; 0.25 mg Tablet; Other Names: Mirapex®

Outcome Measures

Primary Outcome Measures

1. Cmax (Maximum Observed Concentration of Drug Substance in Plasma) [Blood samples collected over a 48 hour period.]

   Bioequivalence based on Cmax.

2. AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) [Blood samples collected over a 48 hour period.]

   Bioequivalence based on AUC0-t.

3. AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) [Blood samples collected over a 48 hour period.]

   Bioequivalence based on AUC0-inf.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• All volunteers selected for this study will be healthy men and women 18 to 45 years of age, inclusive.

• The weight range will not exceed + 20% for height and body frame as per Desirable Weight for Adults - 1983 Metropolitan Height and Weight Table.

• Each volunteer will complete the screening process within 28 days prior to Period I dosing.

• Consent documents for both the screening evaluation and HIV antibody determination will be reviewed, discussed, and signed by each potential participant before full implementation of screening procedures.

• If female: and of child bearing potential, is practicing an acceptable method of birth control for the duration of the study as judged by the investigator(s); is postmenopausal for at least 1 year; or is surgically sterile.

Exclusion Criteria:

• Volunteers with a recent history of drug or alcohol addiction or abuse.

• Volunteers with the presence of a clinically significant disorder involving the cardiovascular, respiratory, renal, gastrointestinal, immunologic, hematologic, endocrine, or neurologic system(s) or psychiatric disease (as determined by the clinical investigator).

• Volunteers whose clinical laboratory test values are outside the accepted reference range and when confirmed on re-examination are deemed to be clinically significant.

• Volunteers demonstrating a reactive screen for hepatitis B surface antigen, hepatitis C antibody or HIV antibody.

• Volunteers demonstrating a positive drug abuse screen when screened for this study.

• Female volunteers demonstrating a positive pregnancy screen.

• Female volunteers who are currently breastfeeding.

• Volunteers with a history of allergic response(s) to pramipexole or related drugs.

• Volunteers with a history of clinically significant allergies including drug allergies.

• Volunteers with a clinically significant illness during the 4 weeks prior to Period I dosing (as determined by the clinical investigator).

• Volunteers who currently use tobacco products

• Volunteers who have taken any drug known to induce or inhibit hepatic drug metabolism in the 28 days prior to Period I dosing.

• Volunteers who report donating greater than 150mL of blood within 28 days prior to Period I dosing. All subjects will be advised not to donate blood for 4 weeks after completing the study.

• Volunteers who have donated plasma (e.g. plasmapheresis) within 14 days prior to Period I dosing. All subjects will be advised not to donate plasma for 4 weeks after completing the study.

• Volunteers who report receiving any investigational drug within 28 days prior to Period 1 dosing.

• Volunteers who report taking any systemic prescription medications in the 14 days prior to Period I dosing. Diltiazem (Cardizem®), triamterene (Dyrenium®), verapamil (Calan®, Covera-HS®), quinidine, and quinine are prohibited throughout the entire study.

• Volunteers using OTC medication 7 days prior to dosing including vitamins, cough and cold preparations. Cimetidine (Tagamet®), ranitidine (Zantac®), probenecid (Pro-Bionate®), any OTC antihistamine products (such as diphenhydramine, chlorpheniramine) are absolutely prohibited throughout the entire study.

• Volunteers who consume food containing poppy seeds in the 48 hours before dosing of each period.

• Volunteers who consume grapefruit or related products 14 days prior to Period I dosing.

• Female volunteers who report the use of oral contraceptives or injectable contraceptives.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	PRACS Institute, Ltd.	Fargo	North Dakota	United States	58104

Sponsors and Collaborators

• Teva Pharmaceuticals USA

Investigators

• Principal Investigator: James D Carlson, Pharm. D, PRACS Institute, Ltd.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT01074450
• Other Study ID Numbers: R04-1202
• First Posted: Feb 24, 2010
• Last Update Posted: Apr 30, 2010
• Last Verified: Apr 1, 2010

• Keywords provided by , ,: Bioequivalence; Healthy Subjects
• Additional relevant MeSH terms: Pramipexole

Study Results

Participant Flow

Arm/Group Title	Test (Pramipexole Dihydrochloride) First	Reference (Mirapex®) First
Arm/Group Description	0.25 mg Pramipexole Dihydrochloride Tablets test product dosed in first period followed by 0.25 mg Mirapex® Tablets reference product dosed in the second period.	0.25 mg Mirapex® Tablets reference product dosed in first period followed by 0.25 mg Pramipexole Dihydrochloride Tablets test product dosed in the second period.
Period Title: First Intervention
STARTED	12	12
COMPLETED	12	10
NOT COMPLETED	0	2
Period Title: First Intervention
STARTED	12	10
COMPLETED	12	10
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	12	10
COMPLETED	11	9
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Test (Pramipexole Dihydrochloride) First	Reference (Mirapex®) First	Total
Arm/Group Description	0.25 mg Pramipexole Dihydrochloride Tablets test product dosed in first period followed by 0.25 mg Mirapex® Tablets reference product dosed in the second period.	0.25 mg Mirapex® Tablets reference product dosed in first period followed by 0.25 mg Pramipexole Dihydrochloride Tablets test product dosed in the second period.	Total of all reporting groups
Overall Participants	12	12	24
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	12 100%	12 100%	24 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	6 50%	7 58.3%	13 54.2%
Male	6 50%	5 41.7%	11 45.8%
Race/Ethnicity, Customized (participants) [Number]
Caucasian	11 91.7%	12 100%	23 95.8%
Native American	1 8.3%	0 0%	1 4.2%
Region of Enrollment (participants) [Number]
United States	12 100%	12 100%	24 100%

Outcome Measures

1. Primary Outcome

Title	Cmax (Maximum Observed Concentration of Drug Substance in Plasma)
Description	Bioequivalence based on Cmax.
Time Frame	Blood samples collected over a 48 hour period.

Outcome Measure Data

Analysis Population Description

All participants that completed the study had their samples analyzed.

Arm/Group Title	Test (Pramipexole Dihydrochloride)	Reference (Mirapex®)
Arm/Group Description	0.25 mg Pramipexole Dihydrochloride Tablets test product dosed in either period.	0.25 mg Mirapex® Tablets reference product dosed in either period.
Measure Participants	20	20
Mean (Standard Deviation) [ng/mL]	0.54 (0.08)	0.55 (0.13)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test (Pramipexole Dihydrochloride), Reference (Mirapex®)
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The ANOVA model was utilized in comparing the effects between the test and reference products. Differences were declared statistically significant at the 5% level (p<0.05).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of the T/R geometric mean x 100
	Estimated Value	100.93
	Confidence Interval	(2-Sided) 90%; 94.23 to 108.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Bioequivalence is established if the 90% confidence interval for the ln-transformed geometric mean between the reference and test product fall within the interval of 80-125%.

2. Primary Outcome

Title	AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)
Description	Bioequivalence based on AUC0-t.
Time Frame	Blood samples collected over a 48 hour period.

Outcome Measure Data

Analysis Population Description

All participants that completed the study had their samples analyzed.

Arm/Group Title	Test (Pramipexole Dihydrochloride)	Reference (Mirapex®)
Arm/Group Description	0.25 mg Pramipexole Dihydrochloride Tablets test product dosed in either period.	0.25 mg Mirapex® Tablets reference product dosed in either period.
Measure Participants	20	20
Mean (Standard Deviation) [ng*h/mL]	6.52 (1.63)	6.26 (1.76)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test (Pramipexole Dihydrochloride), Reference (Mirapex®)
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The ANOVA model was utilized in comparing the effects between the test and reference products. Differences were declared statistically significant at the 5% level (p<0.05).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of the T/R geometric mean x 100
	Estimated Value	104.71
	Confidence Interval	(2-Sided) 90%; 99.74 to 109.92
	Parameter Dispersion	Type: Value:
	Estimation Comments	Bioequivalence is established if the 90% confidence interval for the ln-transformed geometric mean between the reference and test product fall within the interval of 80-125%.

3. Primary Outcome

Title	AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity)
Description	Bioequivalence based on AUC0-inf.
Time Frame	Blood samples collected over a 48 hour period.

Outcome Measure Data

Analysis Population Description

All participants that completed the study had their samples analyzed.

Arm/Group Title	Test (Pramipexole Dihydrochloride)	Reference (Mirapex®)
Arm/Group Description	0.25 mg Pramipexole Dihydrochloride Tablets test product dosed in either period.	0.25 mg Mirapex® Tablets reference product dosed in either period.
Measure Participants	20	20
Mean (Standard Deviation) [ng*h/mL]	7.09 (1.87)	6.82 (1.86)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test (Pramipexole Dihydrochloride), Reference (Mirapex®)
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The ANOVA model was utilized in comparing the effects between the test and reference products. Differences were declared statistically significant at the 5% level (p<0.05).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of the T/R geometric mean x 100
	Estimated Value	104.15
	Confidence Interval	(2-Sided) 90%; 99.05 to 109.52
	Parameter Dispersion	Type: Value:
	Estimation Comments	Bioequivalence is established if the 90% confidence interval for the ln-transformed geometric mean between the reference and test product fall within the interval of 80-125%.

Adverse Events

Time Frame	Adverse event data was collected over the course of the study, which was approximately 2 weeks in duration.
Adverse Event Reporting Description	Volunteers were monitored throughout the study for any adverse experiences. AEs were collected through both solicited and unsolicited methods. The volunteers were encouraged to report signs, symptoms, and any changes in health to the clinic staff.
Arm/Group Title	Test (Pramipexole Dihydrochloride) First		Reference (Mirapex®) First
Arm/Group Description	0.25 mg Pramipexole Dihydrochloride Tablets test product dosed in first period followed by 0.25 mg Mirapex® Tablets reference product dosed in the second period.		0.25 mg Mirapex® Tablets reference product dosed in first period followed by 0.25 mg Pramipexole Dihydrochloride Tablets test product dosed in the second period.
All Cause Mortality
	Test (Pramipexole Dihydrochloride) First		Reference (Mirapex®) First
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Test (Pramipexole Dihydrochloride) First		Reference (Mirapex®) First
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/24 (0%)
Other (Not Including Serious) Adverse Events
	Test (Pramipexole Dihydrochloride) First		Reference (Mirapex®) First
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/24 (25%)		8/24 (33.3%)
General disorders
Dizziness	3/24 (12.5%)	3	4/24 (16.7%)	4
Feeling Hot	0/24 (0%)	0	3/24 (12.5%)	3
Headache	2/24 (8.3%)	2	1/24 (4.2%)	1
Nausea	3/24 (12.5%)	3	4/24 (16.7%)	4
Emesis	0/24 (0%)	0	2/24 (8.3%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Principal Investigator is not permitted to discuss or publish trial results.