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| ID | Type | Description | Link |
|---|---|---|---|
| 2008_595 |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sequence 1- alendronate+vitamin D combination then alendronate | Experimental | 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. |
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| Sequence 2 alendronate then alendronate+vitamin D combination | Experimental | 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. |
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| Sequence 3 alendronate+vitamin D combination then vitamin D | Experimental | 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. |
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| Sequence 4- vitamin D then alendronate+vitamin D combination | Experimental | 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| alendronate sodium+vitamin D combination | Drug | A single dose tablet of 70mg alendronate sodium+5600 IU vitamin D combination tablet in one treatment period of each sequence. |
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| 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) |
| 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) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor | Merck Sharp & Dohme LLC | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21148044 | Derived | Denker AE, Lazarus N, Porras A, Ramakrishnan R, Constanzer M, Scott BB, Chavez-Eng C, Woolf E, Maganti L, Larson P, Gottesdiener K, Wagner JA. Bioavailability of alendronate and vitamin D(3) in an alendronate/vitamin D(3) combination tablet. J Clin Pharmacol. 2011 Oct;51(10):1439-48. doi: 10.1177/0091270010382010. Epub 2010 Dec 8. |
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This was a 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). A washout of at least 12 days separated each treatment period within each part of the study. 318 participants were enrolled (251 in Part 1 and 67 in Part 2).
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| ID | Title | Description |
|---|---|---|
| FG000 | Part 1 Alendronate+Vitamin D Combo, Then Alendronate | Participants in Part 1 received a single dose of 70mg alendronate+5600 International Units (IU) vitamin D combination tablet in Period 1 followed by a single dose of 70mg alendronate tablet in Period 2. A washout of at least 12 days separated each treatment period. |
| FG001 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Period 1 |
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| Comparator: alendronate | Drug | A single dose tablet of 70mg alendronate in one treatment period of each sequence. |
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| Comparator: Vitamin D | Dietary Supplement | Two tablets of 2800 IU vitamin D, totaling 5600 IU, in one treatment period of each sequence. |
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| Part 1 Alendronate, Then Alendronate+Vitamin D Combo |
Participants in Part 1 received a single dose of 70mg alendronate tablet in Period 1 followed by a single dose of 70mg alendronate+5600 IU vitamin D combination tablet in Period 2. A washout of at least 12 days separated each treatment period. |
| FG002 | Part 2 Alendronate+Vitamin D Combo, Then Vitamin D | Participants in Part 2 received a single dose of 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. |
| FG003 | Part 2 Vitamin D, Then Alendronate+Vitamin D Combo | 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 single dose of 70mg alendronate+5600 IU vitamin D combination tablet in Period 2. A washout of at least 12 days separated each treatment period. |
| COMPLETED |
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| NOT COMPLETED |
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| Period 2 |
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| ID | Title | Description |
|---|---|---|
| BG000 | Part 1 | Alendronate+vitamin D combo, then alendronate: In Period 1 participants received a single dose of 70mg alendronate+5600 IU vitamin D combination tablet, and in Period 2 a single dose of 70mg alendronate tablet. A washout of at least 12 days separated each treatment period. Alendronate, then alendronate+vitamin D combo: In Period 1 participants received 70mg alendronate tablet, and in Period 2 a single dose of 70mg alendronate+5600 IU vitamin D combination tablet. A washout of at least 12 days separated each treatment period. |
| BG001 | Part 2 | Alendronate+vitamin D combo, then vitamin D: In Period 1 participants received a single dose of 70mg alendronate+5600 IU vitamin D combination tablet, and in Period 2 a single dose of 5600 IU vitamin D, administered as 2 x 2800 IU tablets. A washout of at least 12 days separated each treatment period. Vitamin D, then alendronate+vitamin D combo: In Period 1 participants received a single dose of 5600 IU vitamin D, administered as 2 x 2800 IU tablets, and in Period 2 a single dose of 70mg alendronate+5600 IU vitamin D combination tablet. A washout of at least 12 days separated each treatment period. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
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| Age, Customized | Number | participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | 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. | 220 participants of the 251 enrolled in Part 1 were included in the statistical analysis. 31 participants were excluded: 23 were enrolled but did not complete both study periods and 8 participants had incomplete urine profiles in one or both periods. | Posted | Least Squares Mean | Standard Deviation | μg | Day 1-2 across the 36 hour urinary collection period (Periods 1 and 2) |
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| Primary | 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. | 60 participants of the 67 enrolled in Part 2 were included in the statistical analysis. 7 participants that were enrolled, but did not complete both study periods were excluded. | Posted | Least Squares Mean | Standard Deviation | ng*hr/mL | Day 1 across the 80-hour plasma collection period (Period 1 and 2) |
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| Secondary | 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. | 60 participants of the 67 enrolled in Part 2 were included in the statistical analysis. 7 participants that were enrolled, but did not complete both study periods were excluded. | Posted | Least Squares Mean | Standard Deviation | ng/ml | Day 1 across the 80-hour plasma collection period (Periods 1 and 2) |
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8 weeks
There were 28 missing participants whose discontinuation did not allow for them to receive the treatments assigned in both Periods 1 and 2 (Alendronate= 10, Alendronate+Vitamin D Combo= 16, Vitamin D= 2).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
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| EG000 | Alendronate+Vitamin D Combo | Single dose of 70 mg alendronate+5600 IU vitamin D combination tablet | 0 | 302 | 21 | 302 | ||
| EG001 | Alendronate | Single dose of 70mg alendronate tablet | 0 | 241 | 12 | 241 | ||
| EG002 | Vitamin D | Single dose of 5600 IU vitamin D, administered as 2 x 2800 IU tablets | 0 | 65 | 9 | 65 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA 9.0 | Systematic Assessment |
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The SPONSOR must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the SPONSOR as confidential must be deleted prior to submission. SPONSOR review can be expedited to meet publication timelines.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Vice President, Late Stage Development Group Leader | Merck Sharp & Dohme Corp | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D010024 | Osteoporosis |
| ID | Term |
|---|---|
| D001851 | Bone Diseases, Metabolic |
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| Withdrawal by Subject |
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| Positive Drug Screen or Personal Reasons |
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| Male |
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