A Study of the Bioequivalence of 70-mg Alendronate and 70-mg Alendronate in Combination With 5600 IU Vitamin D (MK0217A-253)

Study Overview
=================
Brief Summary
-----------------
This study will evaluate the bioequivalence of alendronate in combination with vitamin D compared to alendronate alone and the bioequivalence of vitamin D in combination with alendronate compared to vitamin D alone. This was an open-label, randomized, 2-part, crossover study. Each participant participated in one part of the study only (i.e., each participant participated only in Part I or only in Part II). Participants entered the study sequentially within each part of the study. A washout of at least 12 days separated each treatment period within each part of the study.

Official Title
-----------------
A 2-Part, Open-Label, Randomized, Crossover Study to Evaluate the Bioequivalence of the 70-mg Alendronate/5600 IU Vitamin D3 Final Market Combination Tablet to a 70-mg Alendronate Marketed Tablet, and the Relative Bioavailability of Vitamin D3

Conditions
-----------------
Osteoporosis

Intervention / Treatment
-----------------
* Drug: alendronate sodium+vitamin D combination
* Drug: Comparator: alendronate
* Dietary Supplement: Comparator: Vitamin D


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or nonpregnant female age 18 to 85 years female of childbearing potential on appropriate method of contraception and not nursing Body Mass Index (BMI) less than or equal to 30 kg/m2 subject is in good health Exclusion Criteria: mental or legal incapacitation received bisphosphonate treatment within 3 months of enrollment. unable to sit or stand upright for at least 2 hours unwilling to refrain from consumption of alcohol or caffeinated products from 24 hours prior and 36 hours after study drug administration unwilling to limit alcohol consumption to no more than 2 drinks per day unwilling to limit caffeinated products to the equivalent of 4 cups of coffee per day or equivalent. unwilling to refrain from smoking during the study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

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- alendronate+vitamin D combination then alendronate<br>Participants in Part 1 received 70mg alendronate+5600 International Units (IU) vitamin D combination tablet in Period 1 followed by 70mg alendronate tablet in Period 2. A washout of at least 12 days separated each treatment period. | Drug: alendronate sodium+vitamin D combination<br>* A single dose tablet of 70mg alendronate sodium+5600 IU vitamin D combination tablet in one treatment period of each sequence.<br>Drug: Comparator: alendronate<br>* A single dose tablet of 70mg alendronate in one treatment period of each sequence.<br>|
| Experimental: Sequence 2 alendronate then alendronate+vitamin D combination<br>Participants in Part 1 received 70mg alendronate tablet in Period 1 followed by 70mg alendronate+5600 IU vitamin D combination tablet in Period 2. A washout of at least 12 days separated each treatment period. | Drug: alendronate sodium+vitamin D combination<br>* A single dose tablet of 70mg alendronate sodium+5600 IU vitamin D combination tablet in one treatment period of each sequence.<br>Drug: Comparator: alendronate<br>* A single dose tablet of 70mg alendronate in one treatment period of each sequence.<br>|
| Experimental: Sequence 3 alendronate+vitamin D combination then vitamin D<br>Participants in Part 2 received 70mg alendronate+5600 IU vitamin D combination tablet in Period 1 followed by a single dose of 5600 IU vitamin D, administered as two 2800 IU tablets in Period 2. A washout of at least 12 days separated each treatment period. | Drug: alendronate sodium+vitamin D combination<br>* A single dose tablet of 70mg alendronate sodium+5600 IU vitamin D combination tablet in one treatment period of each sequence.<br>Dietary Supplement: Comparator: Vitamin D<br>* Two tablets of 2800 IU vitamin D, totaling 5600 IU, in one treatment period of each sequence.<br>|
| Experimental: Sequence 4- vitamin D then alendronate+vitamin D combination<br>Participants in Part 2 received a single dose of 5600 IU vitamin D, administered as two 2800 IU tablets in Period 1 followed by a 70mg alendronate+5600 IU vitamin D combination tablet in Period 2. A washout of at least 12 days separated each treatment period. | Drug: alendronate sodium+vitamin D combination<br>* A single dose tablet of 70mg alendronate sodium+5600 IU vitamin D combination tablet in one treatment period of each sequence.<br>Dietary Supplement: Comparator: Vitamin D<br>* Two tablets of 2800 IU vitamin D, totaling 5600 IU, in one treatment period of each sequence.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Urinary Excretion of Alendronate | Bioequivalence was demonstrated by measuring the total urinary excretion of alendronate which was determined over a 36-hour period following single dose administration of 70-mg alendronate+5600 International Units (IU) vitamin D combination tablet and 70mg alendronate tablet alone. 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 Days 1 and 2. | Day 1-2 across the 36 hour urinary collection period (Periods 1 and 2) | 
| Part II: AUC (Area Under the Plasma Concentration-time Curve) of Vitamin D | The serum vitamin D pharmacokinetic parameter was calculated following the treatment of 70mg alendronate+5600 IU vitamin D combination tablet and 5600 IU vitamin D tablet on Day 1: area under the plasma concentration-time curve (AUC0-80hr). Serum samples for determination of vitamin D concentrations were obtained at -2 and 0 hrs predose on Day 1 and at 2, 3, 5, 7, 9, 12, 16, 24, 36, 48, 72 and 80 hours post dose for each treatment period. | Day 1 across the 80-hour plasma collection period (Period 1 and 2) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part II : Maximum Concentration (Cmax) of Vitamin D | Serum vitamin D pharmacokinetic parameter was calculated for the following: maximum concentration of drug observed in serum (Cmax). Serum samples for determination of vitamin D concentrations were obtained at -2 and 0 hrs predose on Day 1 and at 2, 3, 5, 7, 9, 12, 16, 24, 36, 48, 72 and 80 hours post dose for each treatment period. | Day 1 across the 80-hour plasma collection period (Periods 1 and 2) |