A Study of Amorphous Calcium Carbonate in Postmenopausal Women

A Study Benchmarking FREEDOM Substudy to Evaluate the Effects of Amorphous Calcium Carbonate in Postmenopausal Women

Using the FREEDOM substudy as a benchmark, evaluate the effects of amorphous calcium carbonate (ACC) on bone mineral density (BMD) in postmenopausal women, both with and without the combination of Denosumab treatment.

This is an open-label study to evaluate the effect of DensityTM, amorphous calcium carbonate (ACC), in postmenopausal women, compared to FREEDOM substudy.

Subjects with a BMD T-score between -4.0 to -2.5 will be invited to enroll into this study. After signed ICF, eligible subject who meet NHI reimbursement criteria for use of denosumab will be assigned to A arm, and subject who does not meet NHI reimbursement criteria for use of denosumab, or who is no willing to receive denosumab treatment during study period, even meet NHI reimbursement criteria will be assigned to B arm. A total of 205 subjects will be enrolled into this study, in which 142 subjects in A arm and 63 subjects in B arm.

In A arm, subject will receive 5 DensityTM tablets (equal to 1000 mg calcium element) daily with injections of 60 mg of ProliaTM (denosumab) every 6 months at study site, while in B arm, eligible subject will receive 5 DensityTM tablets (equal to 1000 mg calcium element) daily only. DensityTM tablets will be administered as follows: 5 tablets will be taken after meal. In addition, all subjects with a baseline 25-hydroxyvitamin D level of 12 to 20 ng/ml will be given 800 IU of vitamin D3 daily, while those with a baseline level above 20 ng/ml received 400 IU of vitamin D3, both administered after meal.

The study will consist of 7 clinical visits. Subjects will come to the clinics at Visit 1 (screening visit, Month -1), Visit 2 (regimen start, Day 0 in Month 0), and Visit 3 to 7 (follow-up visits, Month 1, 6, 12, 18, 24). BMD assessment and blood drawing will be performed before study medication administration and at Month 1, 6, 12, and 24.

Inclusion Criteria:

1. Postmenopausal women who are 60 to 90 years of age.

2. With BMD T-score of lower than -2.5 at the lumbar spine or total hip and -4.0 or higher at both sites. Subject who also meet the following criteria:

   A arm:-Subject who meet National Health Insurance (NHI) reimbursement criteria for use of denosumab.

   B arm:-Subject who does not meet NHI reimbursement criteria for use of denosumab, or who is no willing to receive denosumab treatment during study period, even meet NHI reimbursement criteria.

3. Subject who are naïve to osteoporosis treatment or have received prior bisphosphonate treatment for less than 3 years and not within 12 months prior to screening visit.

4. A minimum of 2 evaluable lumbar vertebrae in the L1-L4 region and 1 evaluable hip (i.e., either the left or right side).

5. Willingness to limit additional Vitamin D3 intake to 400IU or 800IU per day during the study period.

6. Ability to complete the entire procedure and to comply with study instructions.

7. Will provide completed and signed written informed consent.

Exclusion Criteria:

1. Subjects who had conditions that influence bone metabolism (i.e., Paget's disease and osteomalacia).
2. Subject on other osteoporosis therapies, parathyroid hormone or its derivatives, corticosteroids, systemic hormone-replacement therapy, selective estrogen-receptor modulators, tibolone, calcitonin or calcitriol 6 weeks prior to screening visit.
3. Subjects had a serum 25-hydroxyvitamin D level of less than 12 ng/ml.
4. Subjects had a BMD T-score of less than -4.0 at the lumbar spine or total hip.
5. Subjects with any severe or more than two moderate vertebral fractures on spinal x-ray at screening visit.
6. Subject who plan to initiate a new bisphosphonate treatment during study period.
7. Known hypersensitivity to any component of the study drug product.
8. Participation in any other investigational study within 30 days prior to receiving study medication.
9. Any condition that in the opinion of the investigator would jeopardize the evaluation of efficacy or safety.