Trial Outcomes & Findings for A Study of the Bioequivalence of 70-mg Alendronate and 70-mg Alendronate in Combination With 5600 IU Vitamin D (MK0217A-253) (NCT NCT00803790)
NCT ID: NCT00803790
Last Updated: 2022-02-03
Results Overview
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.
COMPLETED
PHASE1
318 participants
Day 1-2 across the 36 hour urinary collection period (Periods 1 and 2)
2022-02-03
Participant Flow
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).
Participant milestones
| Measure |
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.
|
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.
|
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.
|
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.
|
|---|---|---|---|---|
|
Period 1
STARTED
|
125
|
126
|
32
|
35
|
|
Period 1
COMPLETED
|
116
|
114
|
31
|
31
|
|
Period 1
NOT COMPLETED
|
9
|
12
|
1
|
4
|
|
Period 2
STARTED
|
116
|
114
|
31
|
31
|
|
Period 2
COMPLETED
|
114
|
114
|
30
|
30
|
|
Period 2
NOT COMPLETED
|
2
|
0
|
1
|
1
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
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.
|
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.
|
|---|---|---|---|---|
|
Period 1
Adverse Event
|
0
|
1
|
0
|
0
|
|
Period 1
Lost to Follow-up
|
1
|
2
|
0
|
0
|
|
Period 1
Withdrawal by Subject
|
8
|
6
|
0
|
0
|
|
Period 1
positive drug screen or personal reasons
|
0
|
3
|
0
|
4
|
|
Period 1
Protocol Violation
|
0
|
0
|
1
|
0
|
|
Period 2
Adverse Event
|
0
|
0
|
1
|
1
|
|
Period 2
Withdrawal by Subject
|
1
|
0
|
0
|
0
|
|
Period 2
Positive Drug Screen or Personal Reasons
|
1
|
0
|
0
|
0
|
Baseline Characteristics
A Study of the Bioequivalence of 70-mg Alendronate and 70-mg Alendronate in Combination With 5600 IU Vitamin D (MK0217A-253)
Baseline characteristics by cohort
| Measure |
Part 1
n=251 Participants
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.
|
Part 2
n=67 Participants
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.
|
Total
n=318 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
Between 18 and 78 years
|
251 participants
n=5 Participants
|
67 participants
n=7 Participants
|
318 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
132 Participants
n=5 Participants
|
29 Participants
n=7 Participants
|
161 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
119 Participants
n=5 Participants
|
38 Participants
n=7 Participants
|
157 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 1-2 across the 36 hour urinary collection period (Periods 1 and 2)Population: 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.
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.
Outcome measures
| Measure |
Alendronate+Vitamin D Combo
n=220 Participants
Single dose of 70mg alendronate+5600 IU vitamin D combination tablet
|
Alendronate
n=220 Participants
Single dose of 70mg alendronate tablet
|
|---|---|---|
|
Part 1: Urinary Excretion of Alendronate
|
133.6 μg
Standard Deviation 189.2
|
132.2 μg
Standard Deviation 273.4
|
PRIMARY outcome
Timeframe: Day 1 across the 80-hour plasma collection period (Period 1 and 2)Population: 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.
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.
Outcome measures
| Measure |
Alendronate+Vitamin D Combo
n=60 Participants
Single dose of 70mg alendronate+5600 IU vitamin D combination tablet
|
Alendronate
n=60 Participants
Single dose of 70mg alendronate tablet
|
|---|---|---|
|
Part II: AUC (Area Under the Plasma Concentration-time Curve) of Vitamin D
|
490.2 ng*hr/mL
Standard Deviation 259.6
|
518.7 ng*hr/mL
Standard Deviation 269.8
|
SECONDARY outcome
Timeframe: Day 1 across the 80-hour plasma collection period (Periods 1 and 2)Population: 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.
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.
Outcome measures
| Measure |
Alendronate+Vitamin D Combo
n=60 Participants
Single dose of 70mg alendronate+5600 IU vitamin D combination tablet
|
Alendronate
n=60 Participants
Single dose of 70mg alendronate tablet
|
|---|---|---|
|
Part II : Maximum Concentration (Cmax) of Vitamin D
|
12.2 ng/ml
Standard Deviation 5.6
|
13.0 ng/ml
Standard Deviation 5.9
|
Adverse Events
Alendronate+Vitamin D Combo
Alendronate
Vitamin D
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Alendronate+Vitamin D Combo
n=302 participants at risk
Single dose of 70 mg alendronate+5600 IU vitamin D combination tablet
|
Alendronate
n=241 participants at risk
Single dose of 70mg alendronate tablet
|
Vitamin D
n=65 participants at risk
Single dose of 5600 IU vitamin D, administered as 2 x 2800 IU tablets
|
|---|---|---|---|
|
Nervous system disorders
Headache
|
7.0%
21/302 • 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).
|
5.0%
12/241 • 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).
|
13.8%
9/65 • 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).
|
Additional Information
Vice President, Late Stage Development Group Leader
Merck Sharp & Dohme Corp
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER