Osteoporosis
Conditions
Keywords
Osteoporosis, 2-methylene-19-nor-(20S)-1a, 25-dihydroxyvitamin D3, Vitamin D, Bone Density Conservation Agents, Bone Regeneration
Brief summary
This study will evaluate the effect of a 1-year administration of the vitamin D analog 2-methylene-19-nor-(20S)-1alpha, 25-dihydroxyvitamin D3 (DP001) on bone mineral density (BMD), safety, and tolerability.
Detailed description
DP001 is a vitamin D analog that has been shown to stimulate bone formation in pre-clinical studies. In a Phase 1B study of postmenopausal women, an increase in the bone formation marker, osteocalcin, was evident without an increase in serum calcium. The aim of this study is to determine if 1-year administration of DP001 to postmenopausal women with osteopenia results in a significant increase in BMD at doses that are safe and well tolerated.
Interventions
DRUGPlacebo
oral, once daily
DRUGDP001
oral, once daily
Sponsors
Deltanoid Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
55 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Postmenopausal female subjects, defined as amenorrheic for at least 5 years * Body Mass Index of 18 to 35 * Osteopenic * Generally healthy * Informed consent
Exclusion criteria
* History or evidence of acute or unstable chronic hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, psychiatric, or neurologic diseases * Current or recent treatment with any medications or products affecting vitamin D metabolism, calcium balance, bone turnover, or an investigational drug therapy * 12-lead electrocardiogram demonstrating QTc (QT interval corrected for heart rate) \>450 milliseconds at screening * Abnormal creatinine clearance * Elevated urinary calcium levels * Vitamin D deficiency * Excessive dietary calcium or vitamin D intake * Current use of any illicit drug and/or history of alcohol abuse
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Week 52 | Baseline and Week 52 | Percent change in lumbar spine BMD (relative to baseline) at Week 52 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Femoral Neck Bone Mineral Density (BMD) at Week 52 | Baseline and Week 52 | Percent change in femoral neck BMD (relative to baseline) at Week 52 |
| Percent Change From Baseline in Trochanter Bone Mineral Density (BMD) at Week 52 | Baseline and Week 52 | Percent change in trochanter BMD (relative to baseline) at Week 52 |
| Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 52 | Baseline and Week 52 | The percent change in hip BMD (relative to baseline) at Week 52 |
| Percent Change From Baseline in Serum Bone Markers at Week 26 | Baseline and Week 26 | Percent change from baseline at Week 26 |
| Number of Subjects With at Least 1 Treatment-emergent Adverse Event | 1 year | To assess safety and tolerability, the number of subjects in each treatment group who had one or more adverse events recorded after the beginning of study drug administration were determined. |
| Change From Baseline in Serum Calcium Levels at Week 52 | Baseline and Week 52 | Change in serum calcium value (relative to baseline) at Week 52 |
Countries
United States
Participant flow
Recruitment details
Subjects were enrolled from 5 March 2007 to 19 December 2007 at 9 centers within the United States.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo soft gel capsules, oral, once daily | 49 |
| 220 ng DP001 220 ng DP001 soft gel capsules, oral, once daily | 54 |
| 440 ng DP001 440 ng DP001 soft gel capsules, oral, once daily | 53 |
| Total | 156 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 5 | 21 |
| Overall Study | Did Not Meet Entry Criteria | 0 | 0 | 1 |
| Overall Study | Elevated Blood Glucose | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 2 | 1 |
| Overall Study | Terminated by Sponsor | 1 | 0 | 0 |
| Overall Study | Use of Exclusionary Medication | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 3 | 8 |
Baseline characteristics
| Characteristic | Placebo | 220 ng DP001 | 440 ng DP001 | Total |
|---|---|---|---|---|
| Age Continuous | 61.1 years STANDARD_DEVIATION 6.5 | 61.6 years STANDARD_DEVIATION 5.5 | 61.9 years STANDARD_DEVIATION 5.3 | 61.5 years STANDARD_DEVIATION 5.8 |
| Sex: Female, Male Female | 49 Participants | 54 Participants | 53 Participants | 156 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 38 / 49 | 37 / 54 | 44 / 53 |
| serious Total, serious adverse events | 1 / 49 | 1 / 54 | 3 / 53 |
Outcome results
Primary
Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Week 52
Percent change in lumbar spine BMD (relative to baseline) at Week 52
Time frame: Baseline and Week 52
Population: This analysis was performed on the Full Analysis Set, which included all subjects who received at least one dose of study drug. Multiple imputation was used for missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Week 52 | -0.537 Percent change | Standard Deviation 2.545 |
| 220 ng DP001 | Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Week 52 | -0.174 Percent change | Standard Deviation 2.82 |
| 440 ng DP001 | Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Week 52 | 0.309 Percent change | Standard Deviation 3.904 |
Comparison: A sample size of 49 per treatment group was calculated to have at least 90% power to detect a 2% or greater increase over placebo assuming the following: (1) a standard deviation of the percent change of 2.75% (2) a dropout rate of 30%, and (3) one-sided 0.05 level of significancep-value: 0.641ANOVA
Comparison: A sample size of 49 per treatment group was calculated to have at least 90% power to detect a 2% or greater increase over placebo assuming the following: (1) a standard deviation of the percent change of 2.75% (2) a dropout rate of 30%, and (3) one-sided 0.05 level of significancep-value: 0.243ANOVA
Secondary
Change From Baseline in Serum Calcium Levels at Week 52
Change in serum calcium value (relative to baseline) at Week 52
Time frame: Baseline and Week 52
Population: This analysis was done for all subjects for whom both baseline and Week 52 data was available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Serum Calcium Levels at Week 52 | -0.06 mg/dL | Standard Deviation 0.268 |
| 220 ng DP001 | Change From Baseline in Serum Calcium Levels at Week 52 | 0.11 mg/dL | Standard Deviation 0.286 |
| 440 ng DP001 | Change From Baseline in Serum Calcium Levels at Week 52 | 0.29 mg/dL | Standard Deviation 0.243 |
90% CI: [0.164, 0.181]
90% CI: [0.573, 0.591]
Secondary
Number of Subjects With at Least 1 Treatment-emergent Adverse Event
To assess safety and tolerability, the number of subjects in each treatment group who had one or more adverse events recorded after the beginning of study drug administration were determined.
Time frame: 1 year
Population: The participants for this analysis included all randomized subjects who received a dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Subjects With at Least 1 Treatment-emergent Adverse Event | 41 Participants |
| 220 ng DP001 | Number of Subjects With at Least 1 Treatment-emergent Adverse Event | 45 Participants |
| 440 ng DP001 | Number of Subjects With at Least 1 Treatment-emergent Adverse Event | 46 Participants |
Secondary
Percent Change From Baseline in Femoral Neck Bone Mineral Density (BMD) at Week 52
Percent change in femoral neck BMD (relative to baseline) at Week 52
Time frame: Baseline and Week 52
Population: This analysis was performed on the Full Analysis Set, which included all subjects who received at least one dose of study drug. Multiple imputation was used for missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Femoral Neck Bone Mineral Density (BMD) at Week 52 | -0.428 Percent change | Standard Deviation 2.511 |
| 220 ng DP001 | Percent Change From Baseline in Femoral Neck Bone Mineral Density (BMD) at Week 52 | -1.085 Percent change | Standard Deviation 3.15 |
| 440 ng DP001 | Percent Change From Baseline in Femoral Neck Bone Mineral Density (BMD) at Week 52 | -0.680 Percent change | Standard Deviation 2.507 |
p-value: 0.395ANOVA
p-value: 0.523ANOVA
Secondary
Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 52
The percent change in hip BMD (relative to baseline) at Week 52
Time frame: Baseline and Week 52
Population: This analysis was conducted on the Full Analysis Set, which included all randomized subjects who received at least one dose of study drug. Multiple imputation was used for missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 52 | -0.315 Percent Change | Standard Deviation 1.894 |
| 220 ng DP001 | Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 52 | -0.540 Percent Change | Standard Deviation 1.782 |
| 440 ng DP001 | Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 52 | -0.887 Percent Change | Standard Deviation 1.833 |
p-value: 0.778ANOVA
p-value: 0.173ANOVA
Secondary
Percent Change From Baseline in Serum Bone Markers at Week 26
Percent change from baseline at Week 26
Time frame: Baseline and Week 26
Population: Analyses were performed using subjects for whom both Baseline and Week 26 samples were available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline in Serum Bone Markers at Week 26 | Osteocalcin | 3.8 Percent change | Standard Deviation 19.4 |
| Placebo | Percent Change From Baseline in Serum Bone Markers at Week 26 | Serum C-telopeptide cross-links of type 1 collagen | 4.5 Percent change | Standard Deviation 25.4 |
| Placebo | Percent Change From Baseline in Serum Bone Markers at Week 26 | Procollagen type 1 N-propeptide | 1.0 Percent change | Standard Deviation 29.5 |
| 220 ng DP001 | Percent Change From Baseline in Serum Bone Markers at Week 26 | Osteocalcin | 22.4 Percent change | Standard Deviation 38 |
| 220 ng DP001 | Percent Change From Baseline in Serum Bone Markers at Week 26 | Serum C-telopeptide cross-links of type 1 collagen | 13.8 Percent change | Standard Deviation 32.4 |
| 220 ng DP001 | Percent Change From Baseline in Serum Bone Markers at Week 26 | Procollagen type 1 N-propeptide | 11.8 Percent change | Standard Deviation 40.7 |
| 440 ng DP001 | Percent Change From Baseline in Serum Bone Markers at Week 26 | Serum C-telopeptide cross-links of type 1 collagen | 54.5 Percent change | Standard Deviation 54.2 |
| 440 ng DP001 | Percent Change From Baseline in Serum Bone Markers at Week 26 | Procollagen type 1 N-propeptide | 9.2 Percent change | Standard Deviation 33.4 |
| 440 ng DP001 | Percent Change From Baseline in Serum Bone Markers at Week 26 | Osteocalcin | 80.3 Percent change | Standard Deviation 73.3 |
Secondary
Percent Change From Baseline in Trochanter Bone Mineral Density (BMD) at Week 52
Percent change in trochanter BMD (relative to baseline) at Week 52
Time frame: Baseline and Week 52
Population: This analysis was performed on the Full Analysis Set, which included all subjects who received at least one dose of study drug. Multiple imputation was used for missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Trochanter Bone Mineral Density (BMD) at Week 52 | -0.375 Percent change | Standard Deviation 2.604 |
| 220 ng DP001 | Percent Change From Baseline in Trochanter Bone Mineral Density (BMD) at Week 52 | -0.341 Percent change | Standard Deviation 2.565 |
| 440 ng DP001 | Percent Change From Baseline in Trochanter Bone Mineral Density (BMD) at Week 52 | -0.941 Percent change | Standard Deviation 2.554 |
p-value: 0.928ANOVA
p-value: 0.124ANOVA