Healthy
Conditions
Keywords
Bioequivalence, Healthy Subjects
Brief summary
The objective of this study is to compare the rate and extent of absorption of alendronate sodium 70 mg tablets (test) versus Fosamax® 70 mg tablets (reference) administered as a single dose of 70 mg under fasting conditions. A review of pharmacokinetic data demonstrates Alendronate Sodium Tablets, 70 mg, manufactured and distributed by TEVA Pharmaceuticals USA are bioequivalent to Fosamax® Tablets, 70 mg, manufactured by Merck Sharp & Dohme, USA.
Detailed description
Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA bioequivalence statistical methods
Interventions
DRUGAlendronate Sodium Tablets 70mg
1 x 70mg, single dose fasting
DRUGFosamax® Tablets 70mg
1 x 70 mg, single dose fasting
Sponsors
Teva Pharmaceuticals USA
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Subjects will be males, non-smokers, between 18 and 45 years of age. * Subjects' weight will be within 15% of their ideal body weight based on the Table of Desirable Weight of Adults, Metropolitan Life Insurance Company, 1983 * Subjects should read, sign, and date an Informed Consent Form prior to any study procedures. * Subjects must complete all screening procedures within 28 days prior to the administration of study medication.
Exclusion criteria
* Clinically significant abnormalities found during medical screening. * Any history or presence of significant neurological, hepatic, renal, endocrine, cardiovascular, pulmonary, hematologic, immunologic, psychiatric or metabolic disease. * Any clinically significant history of ongoing gastrointestinal problems or problems known to interfere with the absorption, distribution, metabolism or excretion of drugs (e.g. chronic diarrhea, inflammatory bowel diseases). * Clinically significant illnesses within 4 weeks of the administration of study medication. * Abnormal laboratory tests judged clinically significant. * ECG or vital signs abnormalities (clinically significant). * History of allergic reactions to alendronate or other related drugs (e.g. clodronate, etidronate and pamidronate). * History of allergic reactions to heparin. * Any food allergies, intolerances, restrictions, or special diet which in the opinion of the medical subinvestigator, contraindicates the subject's participation in this study. * Positive urine drug screen at screening or at check-in of period I. * Positive testing for hepatitis B, hepatitis C or HIV at screening. * Use of an investigational drug or participation in an investigational study, within 30 days prior to administration of the study medication. * Recent donation of plasma (500 mL) within 7 days or recent donation or significant loss of whole blood (450 mL) within 56 days prior to administration of the study medication. * History of significant alcohol abuse within six months of the screening visit or any indication of the regular use of more than two units of alcohol per day (1 Unit = 150mL of wine or 360 mL of beer or 45 mL of alcohol 40%). * Recent history of drug abuse or use of illegal drugs: use of soft drugs (such as marijuana, pot) within 3 months of the screening visit or hard drugs (such as cocaine, phencyclidine (PCP), crack) within 1 year of the screening visit. * Subjects who have used tobacco within 90 days of the start of the study. * Subjects who have taken prescription medication 14 days preceding administration of study medication or over-the-counter products 7 days preceding administration of study medication, except for topical products without systemic absorption. * Subjects who have taken any drugs known to induce or inhibit hepatic drug metabolism within 30 days prior to administration of the study medication (examples of inducers: barbiturates, carbamazepine, phenytoin, glucocorticoids, rifampin/rifabutin; examples of inhibitors: antidepressants, cimetidine, diltiazem, erythromycin, ketoconazole, MAO inhibitors, neuroleptics, verapamil, quinidine). * Subjects who have undergone clinically significant surgery 4 weeks prior to the administration of the study medication. * Any reason which, in the opinion of the medical subinvestigator, would prevent the subject from participating in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bioequivalence Based on Rmax | Urine collected over 36 hour period | Rmax = maximum rate of urinary excretion |
| Bioequivalence Based on Ae0-36 | Urine collected over 36 hour period | Ae0-36 = cumulative urine excretion |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Alendronate Sodium First 70 mg Alendronate Sodium Tablets test product dosed in first period followed by 70 mg Fosamax® Tablets reference product dosed in second period | 70 |
| Fosamax® First 70 mg Fosamax® Tablets reference product dosed in first period followed by 70 mg Alendronate Sodium Tablets test product dosed in second period. | 70 |
| Total | 140 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period: First Intervention | Adverse Event | 0 | 1 |
| Period: First Intervention | Withdrawal by Subject | 2 | 0 |
| Period: Washout of 7 Days | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Alendronate Sodium First | Fosamax® 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 | 70 Participants | 70 Participants | 140 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 70 Participants | 69 Participants | 139 Participants |
| Region of Enrollment Canada | 70 participants | 70 participants | 140 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 70 Participants | 70 Participants | 140 Participants |
Outcome results
Primary
Bioequivalence Based on Ae0-36
Ae0-36 = cumulative urine excretion
Time frame: Urine collected over 36 hour period
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Alendronate Sodium | Bioequivalence Based on Ae0-36 | 219.28 ng/mL | Standard Deviation 127.25 |
| Fosamax® | Bioequivalence Based on Ae0-36 | 213.44 ng/mL | Standard Deviation 118.05 |
90% CI: [92.85, 108.48]
Primary
Bioequivalence Based on Rmax
Rmax = maximum rate of urinary excretion
Time frame: Urine collected over 36 hour period
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Alendronate Sodium | Bioequivalence Based on Rmax | 73.96 ng/mL | Standard Deviation 40.48 |
| Fosamax® | Bioequivalence Based on Rmax | 73.99 ng/mL | Standard Deviation 39 |
90% CI: [90.96, 105.45]