Effect of Dexlansoprazole on Bone Homeostasis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effect of dexlansoprazole modified release (MR), once daily (QD), on bone homeostasis.

Detailed Description
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Research on drugs that affect bone homeostasis have shown changes in levels of bone formation and resorption biomarkers. This study will evaluate the effect of dexlansoprazole on bone homeostasis by assessing changes in biochemical markers of bone formation and bone resorption. This study will also assess changes in bone mineral density by dual-energy x-ray absorptiometry scan and other markers of bone homeostasis. The study will consist of a 12-week screening period, a 26-week treatment period with a total of 5 visits during the treatment period and a follow-up visit at Week 52 for bone mineral density assessment.

Official Title
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Phase 1, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Effect of Dexlansoprazole 60 mg Delayed Release Capsules and Esomeprazole 40 mg Delayed Release Capsules on Bone Homeostasis in Healthy Postmenopausal Female Subjects

Conditions
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Homeostasis, Bone and Bones

Intervention / Treatment
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* Drug: Dexlansoprazole
* Drug: Esomeprazole
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is postmenopausal female in general good health with a body mass index of ≥18 and ≤30 kg/m2. Must have biochemical markers of bone formation, procollagen type 1 N-terminal propeptide and bone-specific alkaline phosphatase, and bone resorption, crosslinked β-C-terminal telopeptide of type 1 collagen and urine N-telopeptide within normal postmenopausal female ranges. Has not taken proton pump inhibitor medications within 6 months prior to screening and agrees to refrain from taking them through the last dose of study drug, except study-supplied dexlansoprazole or esomeprazole. Exclusion Criteria: Has parathyroid hormone or thyroid stimulating hormone levels outside of the reference range at Week -12 and has 25-OH-D level <32 ng/mL at Week -2. Has baseline bone mineral density by dual-energy x-ray absorptiometry defined as a T-score lower than -2.0 at the total hip, spine, or femoral neck based on Caucasian reference values. Has a disorder strongly associated with osteoporosis Has a history of lumbar laminectomy, vertebroplasty, vertebral deformity or severe lumbar scoliosis that interferes with measurement or performance of the dual x-ray absorptiometry . Has a history or clinical manifestations of uncontrolled or significant metabolic, hematologic, pulmonary, cardiovascular, gastrointestinal, neurologic, hepatic, renal, urologic, immunologic, or psychiatric disorder as determined by the investigator which may affect the ability of the subject to participate or potentially confound the trial results. Has family history of genetic bone disorders.

Ages Eligible for Study
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Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dexlansoprazole 60 mg QD<br> | Drug: Dexlansoprazole<br>* Dexlansoprazole 60 mg, capsules, orally, once daily for up to 26 weeks.<br>* Other names: Kapidex;|
| Active Comparator: Esomeprazole 40mg QD<br> | Drug: Esomeprazole<br>* Esomeprazole 40 mg, capsules, orally, once daily for up to 26 weeks.<br>* Other names: Nexium;|
| Placebo Comparator: Placebo QD<br> | Drug: Placebo<br>* Placebo-matching capsules, orally, once daily for up to 26 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change from Baseline to Week 26 in Bone Formation Marker Aminoterminal Propeptide of Type 1 Collagen (P1NP). | The percent change in bone formation marker P1NP measured at week 26 from P1NP measured at baseline. | Baseline and Week 26. | 
| Percent Change from Baseline to Week 26 in Bone Resorption Marker C-telopeptide of Collagen Cross-links (CTX). | The percent change in bone resorption marker CTX measured at week 26 from CTX measured at baseline. | Baseline and Week 26. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change from Baseline to Week 26 in Urine N-telopeptide of Collagen Cross-links (NTx). | The percent change in bone resorption marker NTx measured at week 26 from NTx measured at baseline. | Baseline and Week 26. | 
| Percent Change from Baseline to Week 26 in Bone-specific Alkaline Phosphatase (BsAP). | The percent change in bone formation marker BsAP measured at week 26 from BsAP measured at baseline. | Baseline and Week 26. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug Therapy