Healthy
Conditions
Keywords
Bioequivalence, Healthy Subjects
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.
Detailed description
Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA bioequivalence statistical methods
Interventions
1 x 0.25 mg, single dose fed
1 x 0.25 mg, single dose fed
Sponsors
Teva Pharmaceuticals USA
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax (Maximum Observed Concentration of Drug Substance in Plasma) | Blood samples collected over a 24 hour period. | Bioequivalence based on Cmax. |
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Test (Ropinirole HCl) First 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. | 23 |
| Reference (Requip®) First 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. | 23 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Washout of 7 Days | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Test (Ropinirole HCl) First | Reference (Requip®) First | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 23 Participants | 23 Participants | 46 Participants |
| Race/Ethnicity, Customized Asian | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Black | 13 participants | 16 participants | 29 participants |
| Race/Ethnicity, Customized Hispanic | 5 participants | 5 participants | 10 participants |
| Race/Ethnicity, Customized White | 4 participants | 2 participants | 6 participants |
| Region of Enrollment United States | 23 participants | 23 participants | 46 participants |
| Sex: Female, Male Female | 10 Participants | 11 Participants | 21 Participants |
| Sex: Female, Male Male | 13 Participants | 12 Participants | 25 Participants |
Outcome results
Primary
AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity)
Bioequivalence based on AUC0-inf.
Time frame: Blood samples collected over a 24 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test (Ropinirole HCl) | AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) | 4551.89 pg*h/mL | Standard Deviation 2198.95 |
| Reference (Requip®) | AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) | 4441.31 pg*h/mL | Standard Deviation 2139.77 |
90% CI: [97.53, 107.8]
Primary
AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)
Bioequivalence based on AUC0-t.
Time frame: Blood samples collected over a 24 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test (Ropinirole HCl) | AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 4300.07 pg*h/mL | Standard Deviation 1960.43 |
| Reference (Requip®) | AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 4209.47 pg*h/mL | Standard Deviation 1929.76 |
90% CI: [97.56, 107.27]
Primary
Cmax (Maximum Observed Concentration of Drug Substance in Plasma)
Bioequivalence based on Cmax.
Time frame: Blood samples collected over a 24 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test (Ropinirole HCl) | Cmax (Maximum Observed Concentration of Drug Substance in Plasma) | 564.09 pg/mL | Standard Deviation 174.53 |
| Reference (Requip®) | Cmax (Maximum Observed Concentration of Drug Substance in Plasma) | 543.71 pg/mL | Standard Deviation 168.9 |
90% CI: [99.16, 108.09]