A Study of the Bioequivalence of 70 mg Alendronate and 70 mg Alendronate in Combination With 2800 IU Vitamin D

Study Overview
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Brief Summary
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This study will evaluate the bioequivalence of alendronate in combination with vitamin D (cholecalciferol) compared to alendronate alone and the bioequivalence of vitamin D in combination with alendronate compared to vitamin D alone.

Official Title
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A 2-Part, Open-Label, Randomized, Crossover Study to Evaluate the Bioequivalence of the 70 mg Alendronate/2800 IU Vitamin D3 Final Market Combination Tablet to a 70 mg Alendronate Marketed Tablet, and the Relative Bioavailability of Vitamin D3

Conditions
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Osteoporosis

Intervention / Treatment
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* Drug: alendronate sodium (+) cholecalciferol
* Drug: Comparator: alendronate
* Dietary Supplement: Comparator: cholecalciferol (Vitamin D)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or nonpregnant female age 18 to 65 years Female of childbearing potential on appropriate method of contraception and not nursing BMI (body mass index) less than or equal to 30 kg/m2 Subject is in good health Willing to limit direct sunlight and apply sunscreen if in the sun more than 1 hour Exclusion Criteria: mental or legal incapacitation received bisphosphonate treatment within 3 months of screening unable to sit or stand upright for at least 2 hours

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence 1<br>alendronate/vitamin D combination then alendronate | Drug: alendronate sodium (+) cholecalciferol<br>* A single dose tablet of 70 mg alendronate/2800 IU (international unit) vitamin D in one treatment period of each sequence. There will be a 12 day interval between each treatment period.<br>Drug: Comparator: alendronate<br>* A single dose table of 70 mg alendronate in one treatment period of each sequence. There will be a 12 day interval between each treatment period.<br>|
| Experimental: Sequence 2<br>alendronate then alendronate/vitamin D combination | Drug: alendronate sodium (+) cholecalciferol<br>* A single dose tablet of 70 mg alendronate/2800 IU (international unit) vitamin D in one treatment period of each sequence. There will be a 12 day interval between each treatment period.<br>Drug: Comparator: alendronate<br>* A single dose table of 70 mg alendronate in one treatment period of each sequence. There will be a 12 day interval between each treatment period.<br>|
| Experimental: Sequence 3<br>alendronate/vitamin D combination then vitamin D | Drug: alendronate sodium (+) cholecalciferol<br>* A single dose tablet of 70 mg alendronate/2800 IU (international unit) vitamin D in one treatment period of each sequence. There will be a 12 day interval between each treatment period.<br>Dietary Supplement: Comparator: cholecalciferol (Vitamin D)<br>* A single dose tablet of 2800 IU vitamin D in one treatment period of each sequence. There will be a 12 day interval between each treatment period.<br>|
| Experimental: Sequence 4<br>vitamin D then alendronate/vitamin D combination | Drug: alendronate sodium (+) cholecalciferol<br>* A single dose tablet of 70 mg alendronate/2800 IU (international unit) vitamin D in one treatment period of each sequence. There will be a 12 day interval between each treatment period.<br>Dietary Supplement: Comparator: cholecalciferol (Vitamin D)<br>* A single dose tablet of 2800 IU vitamin D in one treatment period of each sequence. There will be a 12 day interval between each treatment period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: The Total Urinary Excretion of Alendronate With Alendronate/Vitamin D Combination Tablet Relative to Alendronate Tablet | Urinary excretion of alendronate was determined over a 36-hour period following single-dose administration of a 70 mg alendronate/2800-IU vitamin D3 combination tablet or 70 mg alendronate alone tablet. Urine for each treatment period was collected at -2 to 0 hours predose, 0 to 8, 8 to 24, and 24 to 36 hours postdose. | On Day 1 across the 36-hour urinary collection period (Periods 1 and 2). | 
| Part II : The Pharmacokinetic Parameters AUC0-120 hr of Vitamin D in Combination Tablet Relative to Vitamin D Tablet | Serum vitamin D3 pharmacokinetic parameter AUC0-120 hr (area under the serum concentration-time curve) after treatment on Day 1was calculated following single-dose administration of a 70 mg alendronate/2800-IU vitamin D3 combination tablet or 2800-IU vitamin D3 tablet. Serum for each treatment period was collected at -24, -18, -12, -6, and 0 hours predose, and 2, 3, 5, 7, 9, 12, 16, 24, 36, 48, 72, 96, and 120 hours postdose. | On Day 1 across the 120-hour plasma collection period (Periods 1 and 2). | 
| Part II : The Pharmacokinetic Parameters Cmax of Vitamin D in Combination Tablet Relative to Vitamin D Tablet | Serum vitamin D3 pharmacokinetic parameter Cmax (maximum concentration observed in serum) after treatmen on Day 1was calculated following single-dose administration of a 70 mg alendronate/2800-IU vitamin D3 combination tablet or 2800-IU vitamin D3 tablet. Serum for each treatment period was collected at -24, -18, -12, -6, and 0 hours predose, and 2, 3, 5, 7, 9, 12, 16, 24, 36, 48, 72, 96, and 120 hours postdose. | On Day 1 across the 120-hour plasma collection period (Periods 1 and 2). |