The Relative Bioavailability Study of Two Ropinirole 0.25 mg Tablets Under Fed Conditions

• Sponsor: Teva Pharmaceuticals USA (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00830219
• Collaborator: (none)
• Enrollment: 46
• Location: 1
• Arms: 2

Study Details

Study Description

Brief Summary

The purpose of this study is to compare relative bioavailability of the test formulation of ropinirole hydrochloride 0.25 mg tablets (Manufactured and distributed by TEVA Pharmaceuticals USA) with the already approved formulation REQUIP® (ropinirole hydrochloride) 0.25 mg tablets (GlaxoSmithKline) under fed conditions in healthy, adult subjects.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Ropinirole HCl 0.25 mg Tablets; Drug: Requip® 0.25 mg Tablets	Phase 1

Detailed Description

Criteria for Evaluation: FDA Bioequivalence Criteria

Statistical Methods: FDA bioequivalence statistical methods

Study Design

• Study Type: Interventional
• Actual Enrollment: 46 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Official Title: The Relative Bioavailability Study of Two Ropinirole 0.25 mg Tablets Under Fed Conditions
• Study Start Date: Nov 1, 2004
• Actual Primary Completion Date: Nov 1, 2004
• Actual Study Completion Date: Nov 1, 2004

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: Ropinirole HCl 0.25 mg Tablets; 1 x 0.25 mg, single dose fed
Active Comparator: 2	Drug: Requip® 0.25 mg Tablets; 1 x 0.25 mg, single dose fed

Outcome Measures

Primary Outcome Measures

1. Cmax (Maximum Observed Concentration of Drug Substance in Plasma) [Blood samples collected over a 24 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 24 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 24 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:

• Males and females, 18 to 45 years of age (inclusive), with a body mass index (BMI) of 19-30 kg/m² inclusive and weighing at least 120 lbs.

• Sitting (at least 5 minutes) blood pressure of at least 100/70 and sitting pulse of at least 60 b.p.m.

• Good health as determined by lack of clinically significant abnormalities in health assessments performed at screening.

• Signed and dated informed consent form, which meets all criteria of current FDA regulations.

• If female and of child bearing potential, subjects must be prepared to abstain from sexual intercourse or use a reliable barrier method of contraception (e.g. condom with spermicide, IUD) during the duration of the study. Female subjects who have used oral contraceptives within 14 days or injected or implanted hormonal contraceptives within 180 days of dosing will not be allowed to participate.

Exclusion Criteria:

• If female, pregnant, lactating, or likely to become pregnant during the study.

• History of allergy or sensitivity to ropinirole or other dopamine agonists (e.g. Corolpam®, Dostinex®, Mirapex®, Permax®, Symmetrel®) or history of any drug hypersensitivity or intolerance which, in the opinion of the investigator, would compromise the safety of the subject or the study.

• History of dizziness, lightheadedness or fainting upon standing.

• Significant history or current evidence of chronic infectious disease, system disorders, organ dysfunction, hyper/hypotension, arrhythmia, tachycardia, seizure disorder or glaucoma.

• Presence of gastrointestinal disease or history of malabsorption within the last year.

• History of psychiatric disorders occurring within the last two years that required hospitalization or medication.

• Presence of a medical condition requiring regular treatment with prescription drugs.

• Use of pharmacologic agents known to significantly induce or inhibit drug metabolizing enzymes within 30 days prior to dosing.

• Receipt of any drug as part of a research study within 30 days prior to dosing.

• Drug or alcohol addiction requiring treatment in the past 12 months.

• Donation or significant loss of whole blood (480 ml or more) within 30 days or plasma within 14 days prior to dosing.

• Positive test results for HIC, Hepatitis B surface antigen or Hepatitis C antibody.

• Positive test results for drugs of abuse at screening.

• Positive serum pregnancy test.

• Tobacco user within 90 days of the first study dose.

• Unable, or unwilling to tolerate multiple venipunctures.

• Difficulty fasting or eating the standard meals that will be provided.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novum Pharmaceutical Research Services	Houston	Texas	United States	77042

Sponsors and Collaborators

• Teva Pharmaceuticals USA

Investigators

• Principal Investigator: So Ran Hong, M.D., Novum Pharmaceutical Research Services

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00830219
• Other Study ID Numbers: 10436009
• First Posted: Jan 27, 2009
• Last Update Posted: Sep 15, 2009
• Last Verified: Sep 1, 2009

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

Study Results

Participant Flow

Arm/Group Title	Test (Ropinirole HCl) First	Reference (Requip®) First
Arm/Group Description	0.25 mg Ropinirole HCl Tablets test product dosed in first period followed by 0.25 mg Requip® Tablets reference product dosed in the second period.	0.25 mg Requip® Tablets reference product dosed in first period followed by 0.25 mg Ropinirole HCl Tablets test product dosed in the second period.
Period Title: First Intervention
STARTED	23	23
COMPLETED	23	23
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	23	23
COMPLETED	22	22
NOT COMPLETED	1	1
Period Title: First Intervention
STARTED	22	22
COMPLETED	22	22
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Test (Ropinirole HCl) First	Reference (Requip®) First	Total
Arm/Group Description	0.25 mg Ropinirole HCl Tablets test product dosed in first period followed by 0.25 mg Requip® Tablets reference product dosed in the second period.	0.25 mg Requip® Tablets reference product dosed in first period followed by 0.25 mg Ropinirole HCl Tablets test product dosed in the second period.	Total of all reporting groups
Overall Participants	23	23	46
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	23 100%	23 100%	46 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	10 43.5%	11 47.8%	21 45.7%
Male	13 56.5%	12 52.2%	25 54.3%
Race/Ethnicity, Customized (participants) [Number]
Asian	1 4.3%	0 0%	1 2.2%
Black	13 56.5%	16 69.6%	29 63%
White	4 17.4%	2 8.7%	6 13%
Hispanic	5 21.7%	5 21.7%	10 21.7%
Region of Enrollment (participants) [Number]
United States	23 100%	23 100%	46 100%

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 24 hour period.

Outcome Measure Data

Analysis Population Description

All participants that completed the study had their samples analyzed.

Arm/Group Title	Test (Ropinirole HCl)	Reference (Requip®)
Arm/Group Description	0.25 mg Ropinirole HCl Tablets test product dosed in either period.	0.25 mg Requip® Tablets reference product dosed in either period.
Measure Participants	44	44
Mean (Standard Deviation) [pg/mL]	564.09 (174.53)	543.71 (168.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test (Ropinirole HCl), Reference (Requip®)
	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	103.53
	Confidence Interval	() 90%; 99.16 to 108.09
	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 24 hour period.

Outcome Measure Data

Analysis Population Description

All participants that completed the study had their samples analyzed.

Arm/Group Title	Test (Ropinirole HCl)	Reference (Requip®)
Arm/Group Description	0.25 mg Ropinirole HCl Tablets test product dosed in either period.	0.25 mg Requip® Tablets reference product dosed in either period.
Measure Participants	44	44
Mean (Standard Deviation) [pg*h/mL]	4300.07 (1960.43)	4209.47 (1929.76)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test (Ropinirole HCl), Reference (Requip®)
	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	102.3
	Confidence Interval	() 90%; 97.56 to 107.27
	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 24 hour period.

Outcome Measure Data

Analysis Population Description

All participants that completed the study had their samples analyzed.

Arm/Group Title	Test (Ropinirole HCl)	Reference (Requip®)
Arm/Group Description	0.25 mg Ropinirole HCl Tablets test product dosed in either period.	0.25 mg Requip® Tablets reference product dosed in either period.
Measure Participants	44	44
Mean (Standard Deviation) [pg*h/mL]	4551.89 (2198.95)	4441.31 (2139.77)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test (Ropinirole HCl), Reference (Requip®)
	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	102.54
	Confidence Interval	() 90%; 97.53 to 107.8
	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

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.