Effect of Dexlansoprazole on Bone Homeostasis

Phase 1

Completed

• Conditions: Homeostasis; Bone and Bones
• Interventions: Drug: Placebo; Drug: Dexlansoprazole; Drug: Esomeprazole

• Registration Number: NCT01216293
• Lead Sponsor: Takeda

Brief Summary

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

Detailed Description

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.

Study Timeline

• Study First Submitted: 2010-10-05
• Study First Submitted QC: 2010-10-05
• Study First Posted: 2010-10-07
• Study Start: 2010-11-01
• Primary Completion: 2014-08-01
• Study Completion: 2015-02-01
• Results First Submitted: 2022-09-26
• Status Verified: 2023-09
• Results First Submitted QC: 2023-09-04
• Last Update Submitted: 2023-09-04
• Results First Posted: 2024-03-18
• Last Update Posted: 2024-03-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 115

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo-matching capsules, orally, once daily for up to 26 weeks. Participants had the option to participate in the calcium absorption sub study to receive calcium isotope 42 calcium (42 Ca) 3 milligram (mg), intravenously and 44 calcium (44 Ca) 8 mg, orally, once on Day-1 and Week 26.
Dexlansoprazole 60 mg	Dexlansoprazole	Dexlansoprazole 60 mg, capsules, orally, once daily for up to 26 weeks. Participants had the option to participate in the calcium absorption sub study to receive calcium isotope 42 Ca 3 mg, intravenously and 44 Ca 8 mg, orally, once on Day-1 and Week 26.
Esomeprazole 40mg	Esomeprazole	Esomeprazole 40 mg, capsules, orally, once daily for up to 26 weeks. Participants had the option to participate in the calcium absorption sub study to receive calcium isotope 42 Ca 3 mg, intravenously and 44 Ca 8 mg, orally, once on Day-1 and Week 26.

Primary Outcome Measures

Name	Time	Method
Percent Change From Baseline to Week 26 in Bone Resorption Marker C-telopeptide of Collagen Cross-links (CTX)	Baseline and Week 26	The percent change in bone resorption marker CTX measured at week 26 from CTX measured at baseline. Plasma samples were analyzed at a central laboratory for bone biomarker CTX using an electrochemiluminescence immunoassay measured in ng/mL.
Percent Change From Baseline to Week 26 in Bone Formation Marker Aminoterminal Propeptide of Type 1 Collagen (P1NP)	Baseline and Week 26	The percent change in bone formation marker P1NP measured at week 26 from P1NP measured at baseline. Serum samples for P1NP were analyzed at a central laboratory for bone biomarker P1NP using an electrochemiluminescence immunoassay measured in nanograms per milliliter (ng/mL).

Secondary Outcome Measures

Name	Time	Method
Percent Change From Baseline to Week 26 in Urine N-telopeptide of Collagen Cross-links (NTx) Calculated	Baseline and Week 26	The percent change in bone resorption marker NTx measured at week 26 from NTx measured at baseline. Urine samples were analyzed at a central laboratory for NTx using an enzyme-linked immunosorbent assay calculated as (nmol BCE/mmol creatinine). BCE=bone collagen equivalent
Percent Change From Baseline to Week 26 in Bone-specific Alkaline Phosphatase (BsAP)	Baseline and Week 26	The percent change in bone formation marker BsAP measured at week 26 from BsAP measured at baseline. Serum samples were analyzed at a central laboratory for bone biomarker BsAP using an enzyme immunoassay measured in units per liter (U/L).