A Study of Teriparatide in Japanese Osteoporosis Patients

Study Overview
=================
Brief Summary
-----------------
The purpose of this trial is to assess the effects on serum calcium when teriparatide is used with active vitamin D in osteoporosis patients. This study consists of a Screening Period, a 14-day Lead-in Period, a 28-day Treatment Period, and a 7-day Follow-up Period. Patients will take vitamin D and calcium supplementation from the Lead-in Period throughout the study. During the Treatment Period, daily administration of teriparatide will be added.

Official Title
-----------------
A Study to Assess the Effects on Serum Calcium When Teriparatide is Used With Active Vitamin D in Osteoporosis Patients

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

Intervention / Treatment
-----------------
* Drug: Teriparatide
* Drug: Aspara-CA 600 mg
* Drug: Alfarol 1.0 µg


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Ambulatory Japanese males or postmenopausal females with osteoporosis, as determined by the Japanese Society for Bone and Mineral Research (JSBMR) diagnostic criteria Exclusion Criteria: Prior treatment with parathyroid hormone (PTH) or any PTH analog History of metabolic bone disorders other than primary osteoporosis Fractures caused by diseases other than osteoporosis Abnormal thyroid function Hyperparathyroidism or hypoparathyroidism Severe or chronically disabling conditions other than osteoporosis Currently has or has a history of spruce, inflammatory bowel disease, or malabsorption syndrome Currently has, or a has a history of, nephrolithiasis or urolithiasis in the 2 years prior to screening Clinically significant abnormal laboratory values or electrocardiogram Treatment with oral bisphosphonates at any time in the 3 months prior to enrollment, treatment with any bisphosphonate for more than 60 days in the 6 months prior to enrollment, or with intravenous bisphosphonates at any time in the 24 months prior to enrollment; or in case of oral bisphosphonates administered once a week, the equivalent as the above Treatment with injectable calcitonin in the 3 months prior to enrollment Treatment with raloxifene hydrochloride for more than 3 months in the 6 months prior to enrollment Treatment with systemic corticosteroids, except for orally inhaled or nasally inhaled corticosteroids, in doses <= 800 micrograms per day (µg/day) beclomethasone dipropionate or equivalent in the 3 months prior to screening, or for more than 30 days in the 12 months prior to enrollment Treatment with anticonvulsants, except for benzodiazepines, in the 6 months prior to enrollment Prior treatment with strontiumranate or denosumab (anti-RANKL antibody) Prior external beam radiation therapy involving the skeleton Current or a history of malignant neoplasm in the 5 years prior to screening, with the exception of superficial basal cell carcinoma or squamous cell carcinoma of the skin that had been definitively treated

Ages Eligible for Study
-----------------
Minimum Age: 55 Years

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

Accepts Healthy Volunteers
-----------------
No

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

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Teriparatide + Aspara-CA + Alfarol<br>Aspara-CA 600 milligrams (mg) and Alfarol 1.0 microgram (µg) administered orally once daily throughout the study. Teriparatide 20 µg administered subcutaneously once daily for 28 days during the Treatment Period. | Drug: Teriparatide<br>* Administered subcutaneously during the Treatment Period<br>* Other names: Forsteo;Drug: Aspara-CA 600 mg<br>* Administered orally throughout the study<br>Drug: Alfarol 1.0 µg<br>* Administered orally throughout the study<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Serum Calcium Level Over 11.0 Milligrams Per Deciliter (mg/dL) | Total serum calcium concentration adjusted by serum albumin concentration. Corrected calcium (mg/dL) = total serum calcium concentration (mg/dL) + 4.0 - serum albumin concentration (grams per deciliter [g/dL]). Postdose refers to after Teriparatide dose. | Day 28 (16 and 24 hours postdose) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Serum Calcium Level Over 11.0 Milligrams Per Deciliter (mg/dL) and 13.5 mg/dL, Respectively at Any Time Postbaseline | Total serum calcium concentration adjusted by serum albumin concentration. Corrected calcium (mg/dL) = total serum calcium concentration (mg/dL) + 4.0 - serum albumin concentration (grams per deciliter [g/dL]). Serum calcium levels presented are for any time postdose on any day during the 28-day Teriparatide Treatment Period. | Day 1 up to Day 28 (Teriparatide Treatment Period) | 
| Mean Serum Calcium Levels | Daily profiles of corrected mean serum calcium levels were determined for each participant. Corrected calcium (milligram per deciliter [mg/dL]) = total serum calcium concentration (mg/dL) + 4.0 - serum albumin concentration (grams per deciliter [g/dL]). The Least Squares (LS) means were adjusted for Day, Timepoint, Day*Timepoint, and random error. At baseline, participants received only Aspara-CA and Alfarol supplements and the timepoints were based on the times before Aspara-CA and Alfarol administration (predose) and after Aspara-CA and Alfarol administration (postdose). During the 28-day Teriparatide Treatment Period, timepoints were based on before Teriparatide administration (predose) and after Teriparatide administration (postdose). | Baseline (Day -1 of 14-day Lead-in Period) and Day 1 and Day 7 and Day 14 and Day 28 at 0 hours (h), 2 h, 4 h, 6 h, 16 h, and 24 h postdose (28-day Teriparatide Treatment Period) | 
| Change From Baseline in Serum Calcium | Corrected calcium (milligram per deciliter [mg/dL]) = total serum calcium concentration (mg/dL) + 4.0 - serum albumin concentration (grams per deciliter [g/dL]). The Least Squares (LS) means were controlled for Day, Timepoint, Day*Timepoint, and random error. Postdose refers to after Teriparatide dose. | Baseline (Day -1 of the 14-day Lead-in Period), Day 1, Day 7, Day 14, Day 28 at 0 hours (h), 2 h, 4 h, 6 h, 16 h, and 24 h postdose (28-day Teriparatide Treatment Period) | 
| Number of Participants With Daily Urine Calcium Excreted Over 0.3 Grams Per Day (g/Day) at Any Time Postbaseline | Urine calcium levels presented are for any day during the 28-day Teriparatide Treatment Period. | Day 1 up to Day 28 (28-day Teriparatide Treatment Period) | 
| Mean Daily Urine Calcium Excreted |  | Day 1 and Day 7 and Day 14 and Day 28 (28-day Teriparatide Treatment Period) | 
| Change From Baseline in Daily Urine Calcium Excreted |  | Day 1, Day 7, Day 14, Day 28 (28-day Teriparatide Treatment Period) | 
| Concentrations of Serum 25-Hydroxy-Vitamin D |  | Day 1 (Predose, 28-day Teriparatide Treatment Period) and Day 8 and Day 15 and Day 29 (Follow-up Period) and Day 35 (Follow-up Period) | 
| Concentrations of Serum 1,25-Hydroxy-2-Vitamin D3 |  | Day 1 (Predose, 28-day Teriparatide Treatment Period) and Day 8 and Day 15 and Day 29 (Follow-up Period) and Day 35 (Follow-up Period) |