Clinical trial NCT01216293: Effect of Dexlansoprazole on Bone Homeostasis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Homeostasis
Bone and Bones
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2010-10-07
Enrollment: 115
Sex: FEMALE
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percent Change From Baseline to Week 26 in Bone Formation Marker Aminoterminal Propeptide of Type 1 Collagen (P1NP)
timeFrame: Baseline and Week 26
measure: Percent Change From Baseline to Week 26 in Bone Resorption Marker C-telopeptide of Collagen Cross-links (CTX)
timeFrame: Baseline and Week 26
Secondary outcomes:
measure: Percent Change From Baseline to Week 26 in Urine N-telopeptide of Collagen Cross-links (NTx) Calculated
timeFrame: Baseline and Week 26
measure: Percent Change From Baseline to Week 26 in Bone-specific Alkaline Phosphatase (BsAP)
timeFrame: Baseline and Week 26
Other outcomes:
measure: Percent Change From Baseline in P1NP at Week 13
timeFrame: Baseline and Week 13
measure: Percent Change From Baseline in CTX at Week 13
timeFrame: Baseline and Week 13
measure: Percent Change From Baseline in Femoral Neck Bone Mineral Density (BMD) Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 26
timeFrame: Baseline and Week 26
measure: Percent Change From Baseline in Total Hip BMD Measured by DXA at Week 26
timeFrame: Baseline and Week 26
measure: Percent Change From Baseline in Lumbar Spine BMD Measured by DXA at Week 26
timeFrame: Baseline and Week 26
measure: Percent Change From Week 26 in Femoral Neck BMD Measured by DXA at Week 52
timeFrame: Week 26 and Week 52
measure: Percent Change From Weeks 26 in Total Hip BMD Measured by DXA at Week 52
timeFrame: Week 26 and Week 52
measure: Percent Change From Weeks 26 in Lumbar Spine BMD Measured by DXA at Week 52
timeFrame: Week 26 and Week 52
measure: Number of Participants With Fracture Including Vertebral Fracture During Study Treatment
timeFrame: Baseline up to Week 26
measure: Change From Baseline in 24-hour Urinary Calcium Excretion at Week 26
timeFrame: Baseline and Week 26
measure: Change From Baseline in Parathyroid Hormone (PTH) at Week 26
timeFrame: Baseline and Week 26
measure: Change From Baseline in Serum Calcium at Week 26
timeFrame: Baseline and Week 26
measure: Change From Baseline in Serum Phosphorus at Week 26
timeFrame: Baseline and Week 26
measure: Change From Baseline in Serum Magnesium at Week 26
timeFrame: Baseline and Week 26
measure: Change From Baseline in Urine Magnesium at Week 26
timeFrame: Baseline and Week 26
measure: Change From Baseline to Week 26 in Vitamin D3 (25-OH-D) Level
timeFrame: Baseline and Week 26
measure: Change From Baseline in Intestinal Calcium Absorption by True Fractional Calcium Absorption (TFCA) in a Subset of Participants at Week 26
timeFrame: Baseline and Week 26
Locations:
city: San Diego
country: United States
state: California
city: Walnut Creek
country: United States
state: California
city: Lakewood
country: United States
state: Colorado
city: Hialeah
country: United States
state: Florida
city: Jupiter
country: United States
state: Florida
city: Bethesda
country: United States
state: Maryland
city: Albuquerque
country: United States
state: New Mexico
city: Spartanburg
country: United States
state: South Carolina
city: Austin
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Seattle
country: United States
state: Washington
city: Madison
country: United States
state: Wisconsin
Study officials:
affiliation: Takeda
name: Medical Director Clinical Science
role: STUDY_DIRECTOR
References:
citation: 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.