Healthy
Conditions
Keywords
Bioequivalence, Healthy Subjects
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.
Detailed description
Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA Bioequivalence Statistical Methods
Interventions
0.25 mg Tablet
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
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax (Maximum Observed Concentration of Drug Substance in Plasma) | Blood samples collected over a 48 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 48 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 48 hour period. | Bioequivalence based on AUC0-inf. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Test (Pramipexole Dihydrochloride) First 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. | 12 |
| Reference (Mirapex®) First 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. | 12 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention | Emesis in Dosing Interval | 0 | 2 |
| Second Intervention | Physician Decision | 0 | 1 |
| Second Intervention | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | Test (Pramipexole Dihydrochloride) First | Reference (Mirapex®) 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 | 12 Participants | 12 Participants | 24 Participants |
| Race/Ethnicity, Customized Caucasian | 11 participants | 12 participants | 23 participants |
| Race/Ethnicity, Customized Native American | 1 participants | 0 participants | 1 participants |
| Region of Enrollment United States | 12 participants | 12 participants | 24 participants |
| Sex: Female, Male Female | 6 Participants | 7 Participants | 13 Participants |
| Sex: Female, Male Male | 6 Participants | 5 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 24 | 8 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 |
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 48 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test (Pramipexole Dihydrochloride) | AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) | 7.09 ng*h/mL | Standard Deviation 1.87 |
| Reference (Mirapex®) | AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) | 6.82 ng*h/mL | Standard Deviation 1.86 |
90% CI: [99.05, 109.52]
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 48 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test (Pramipexole Dihydrochloride) | AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 6.52 ng*h/mL | Standard Deviation 1.63 |
| Reference (Mirapex®) | AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 6.26 ng*h/mL | Standard Deviation 1.76 |
90% CI: [99.74, 109.92]
Primary
Cmax (Maximum Observed Concentration of Drug Substance in Plasma)
Bioequivalence based on Cmax.
Time frame: Blood samples collected over a 48 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test (Pramipexole Dihydrochloride) | Cmax (Maximum Observed Concentration of Drug Substance in Plasma) | 0.54 ng/mL | Standard Deviation 0.08 |
| Reference (Mirapex®) | Cmax (Maximum Observed Concentration of Drug Substance in Plasma) | 0.55 ng/mL | Standard Deviation 0.13 |
90% CI: [94.23, 108.1]