Effect of Dexlansoprazole on Bone Homeostasis

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

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

Study Overview

• Status: Completed
• Conditions: Bone and Bones; Homeostasis
• Intervention / Treatment: Drug: Placebo; Drug: Dexlansoprazole; Drug: Esomeprazole

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 Type: Interventional
• Enrollment (Actual): 115
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States
    • Walnut Creek, California, United States
  • Colorado
    • Lakewood, Colorado, United States
  • Florida
    • Hialeah, Florida, United States
    • Jupiter, Florida, United States
  • Maryland
    • Bethesda, Maryland, United States
  • New Mexico
    • Albuquerque, New Mexico, United States
  • South Carolina
    • Spartanburg, South Carolina, United States
  • Texas
    • Austin, Texas, United States
    • San Antonio, Texas, United States
  • Washington
    • Seattle, Washington, United States
  • Wisconsin
    • Madison, Wisconsin, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 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.	Drug: Placebo; Placebo-matching capsules
Experimental: Dexlansoprazole 60 mg; 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.	Drug: Dexlansoprazole; Dexlansoprazole 60 mg capsules; Other Names: Kapidex; Dexilant
Active Comparator: Esomeprazole 40mg; 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.	Drug: Esomeprazole; Esomeprazole 40 mg capsules; Other Names: Nexium

What is the study measuring?

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. 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).	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. Plasma samples were analyzed at a central laboratory for bone biomarker CTX using an electrochemiluminescence immunoassay measured in ng/mL.	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) Calculated	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	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. Serum samples were analyzed at a central laboratory for bone biomarker BsAP using an enzyme immunoassay measured in units per liter (U/L).	Baseline and Week 26

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in P1NP at Week 13	Serum samples for P1NP were analyzed using an electrochemiluminescence immunoassay measured in ng/mL.	Baseline and Week 13
Percent Change From Baseline in CTX at Week 13	Plasma samples were analyzed for bone biomarker CTX using an electrochemiluminescence immunoassay measured in ng/mL.	Baseline and Week 13
Percent Change From Baseline in Femoral Neck Bone Mineral Density (BMD) Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 26	DXA is a means of measuring BMD through x-ray.	Baseline and Week 26
Percent Change From Baseline in Total Hip BMD Measured by DXA at Week 26	DXA is a means of measuring BMD through x-ray.	Baseline and Week 26
Percent Change From Baseline in Lumbar Spine BMD Measured by DXA at Week 26	DXA is a means of measuring BMD through x-ray.	Baseline and Week 26
Percent Change From Week 26 in Femoral Neck BMD Measured by DXA at Week 52	DXA is a means of measuring BMD through x-ray.	Week 26 and Week 52
Percent Change From Weeks 26 in Total Hip BMD Measured by DXA at Week 52	DXA is a means of measuring BMD through x-ray.	Week 26 and Week 52
Percent Change From Weeks 26 in Lumbar Spine BMD Measured by DXA at Week 52		Week 26 and Week 52
Number of Participants With Fracture Including Vertebral Fracture During Study Treatment		Baseline up to Week 26
Change From Baseline in 24-hour Urinary Calcium Excretion at Week 26		Baseline and Week 26
Change From Baseline in Parathyroid Hormone (PTH) at Week 26		Baseline and Week 26
Change From Baseline in Serum Calcium at Week 26		Baseline and Week 26
Change From Baseline in Serum Phosphorus at Week 26		Baseline and Week 26
Change From Baseline in Serum Magnesium at Week 26		Baseline and Week 26
Change From Baseline in Urine Magnesium at Week 26		Baseline and Week 26
Change From Baseline to Week 26 in Vitamin D3 (25-OH-D) Level		Baseline and Week 26
Change From Baseline in Intestinal Calcium Absorption by True Fractional Calcium Absorption (TFCA) in a Subset of Participants at Week 26		Baseline and Week 26

Collaborators and Investigators

• Sponsor: Takeda
• Investigators: Study Director: Medical Director Clinical Science, Takeda

Publications and helpful links

General Publications

• Hansen KE, Nieves JW, Nudurupati S, Metz DC, Perez MC. Dexlansoprazole and Esomeprazole Do Not Affect Bone Homeostasis in Healthy Postmenopausal Women. Gastroenterology. 2019 Mar;156(4):926-934.e6. doi: 10.1053/j.gastro.2018.11.023. Epub 2018 Nov 13.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2010
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): February 1, 2015

Study Registration Dates

• First Submitted: October 5, 2010
• First Submitted That Met QC Criteria: October 5, 2010
• First Posted (Estimated): October 7, 2010

Study Record Updates

• Last Update Posted (Actual): March 18, 2024
• Last Update Submitted That Met QC Criteria: September 4, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Drug Therapy
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Dexlansoprazole; Lansoprazole; Esomeprazole
• Other Study ID Numbers: TAK-390MR_104; U1111-1116-1638 (Registry Identifier: WHO)