Bone and Bones, Homeostasis
Conditions
Keywords
Drug Therapy
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.
Interventions
DRUGDexlansoprazole
Dexlansoprazole 60 mg capsules
DRUGEsomeprazole
Esomeprazole 40 mg capsules
DRUGPlacebo
Placebo-matching capsules
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
No minimum to 75 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Total Hip BMD Measured by DXA at Week 26 | Baseline and Week 26 | DXA is a means of measuring BMD through x-ray. |
| Percent Change From Baseline in Lumbar Spine BMD Measured by DXA at Week 26 | Baseline and Week 26 | DXA is a means of measuring BMD through x-ray. |
| Percent Change From Weeks 26 in Total Hip BMD Measured by DXA at Week 52 | Week 26 and Week 52 | DXA is a means of measuring BMD through x-ray. |
| 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 | — |
| Percent Change From Week 26 in Femoral Neck BMD Measured by DXA at Week 52 | Week 26 and Week 52 | DXA is a means of measuring BMD through x-ray. |
| 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 | — |
| Change From Baseline in Parathyroid Hormone (PTH) at Week 26 | Baseline and Week 26 | — |
| Percent Change From Baseline in P1NP at Week 13 | Baseline and Week 13 | Serum samples for P1NP were analyzed using an electrochemiluminescence immunoassay measured in ng/mL. |
| Percent Change From Baseline in CTX at Week 13 | Baseline and Week 13 | Plasma samples were analyzed for bone biomarker CTX using an electrochemiluminescence immunoassay measured in ng/mL. |
| Percent Change From Baseline in Femoral Neck Bone Mineral Density (BMD) Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 26 | Baseline and Week 26 | DXA is a means of measuring BMD through x-ray. |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 10 investigative sites in the United States from 01 November 2010 (first subject signed informed consent form) to 1 February 2015.
Pre-assignment details
Healthy post-menopausal women were enrolled equally in 1 of 3 treatment groups, once a day, placebo, 60 mg dexlansoprazole delayed-release capsules or 40 mg esomeprazole delayed-release capsules.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 41 |
| 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. | 38 |
| Esomeprazole 40 mg 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. | 35 |
| Total | 114 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Calcium Absorption Substudy | Adverse Event | 0 | 2 | 0 |
| Calcium Absorption Substudy | Major Protocol Deviation | 1 | 0 | 0 |
| Calcium Absorption Substudy | Voluntary Withdrawal | 1 | 0 | 0 |
| Main Study | Adverse Event | 1 | 4 | 2 |
| Main Study | Lost to Follow-up | 3 | 1 | 0 |
| Main Study | Major Protocol Deviation | 1 | 0 | 1 |
| Main Study | Other Reason Not Specified | 0 | 1 | 1 |
| Main Study | Randomized, Not Treated | 1 | 0 | 0 |
| Main Study | Voluntary Withdrawal | 2 | 2 | 2 |
Baseline characteristics
| Characteristic | Dexlansoprazole 60 mg | Total | Esomeprazole 40 mg | Placebo |
|---|---|---|---|---|
| Age, Continuous | 62.4 years | 62.2 years | 63.2 years | 61.2 years |
| Alcohol Classification Current drinker | 31 Participants | 88 Participants | 27 Participants | 30 Participants |
| Alcohol Classification Ex-drinker | 1 Participants | 8 Participants | 2 Participants | 5 Participants |
| Alcohol Classification Never drank | 6 Participants | 18 Participants | 6 Participants | 6 Participants |
| Body Mass Index (BMI) | 24.46 kg/m^2 | 25.24 kg/m^2 | 25.65 kg/m^2 | 25.61 kg/m^2 |
| Caffeine Consumption Had caffeine consumption | 34 Participants | 100 Participants | 29 Participants | 37 Participants |
| Caffeine Consumption Not had caffeine consumption | 4 Participants | 14 Participants | 6 Participants | 4 Participants |
| Calcium at Screening Visit | 9.87 mg/dL | 9.92 mg/dL | 9.97 mg/dL | 9.93 mg/dL |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 11 Participants | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 33 Participants | 103 Participants | 32 Participants | 38 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 164.9 cm | 164.6 cm | 164.6 cm | 164.4 cm |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 6 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 34 Participants | 104 Participants | 33 Participants | 37 Participants |
| Region of Enrollment United States | 38 Participants | 114 Participants | 35 Participants | 41 Participants |
| Sex: Female, Male Female | 38 Participants | 114 Participants | 35 Participants | 41 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Smoking Classification Current smoker | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Smoking Classification Ex-smoker | 15 Participants | 34 Participants | 8 Participants | 11 Participants |
| Smoking Classification Never smoked | 23 Participants | 80 Participants | 27 Participants | 30 Participants |
| Vitamin D at Screening Visit | 33.2 ng/mL | 34.1 ng/mL | 33.4 ng/mL | 35.5 ng/mL |
| Weight | 66.54 kg | 68.1 kg | 69.47 kg | 69.25 kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 41 | 0 / 38 | 0 / 35 | 0 / 14 | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 6 / 41 | 8 / 38 | 9 / 35 | 3 / 14 | 4 / 10 | 5 / 10 |
| serious Total, serious adverse events | 0 / 41 | 1 / 38 | 0 / 35 | 0 / 14 | 0 / 10 | 0 / 10 |
Outcome results
Primary
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).
Time frame: Baseline and Week 26
Population: Participants from the Pharmacodynamic Set, all randomized participants who received study drug with evaluable calcium absorption data at Day 1 and Week 26, with data available for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Percent Change From Baseline to Week 26 in Bone Formation Marker Aminoterminal Propeptide of Type 1 Collagen (P1NP) | -0.4 percent change |
| Dexlansoprazole 60 mg | Percent Change From Baseline to Week 26 in Bone Formation Marker Aminoterminal Propeptide of Type 1 Collagen (P1NP) | 19.3 percent change |
| Esomeprazole 40 mg | Percent Change From Baseline to Week 26 in Bone Formation Marker Aminoterminal Propeptide of Type 1 Collagen (P1NP) | 16.9 percent change |
95% CI: [7, 30.2]
95% CI: [6.7, 30.4]
Primary
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.
Time frame: Baseline and Week 26
Population: Participants from the Pharmacodynamic Set, all randomized participants who received study drug with evaluable calcium absorption data at Day 1 and Week 26, with data available for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Percent Change From Baseline to Week 26 in Bone Resorption Marker C-telopeptide of Collagen Cross-links (CTX) | 2.441 percent change |
| Dexlansoprazole 60 mg | Percent Change From Baseline to Week 26 in Bone Resorption Marker C-telopeptide of Collagen Cross-links (CTX) | 29.524 percent change |
| Esomeprazole 40 mg | Percent Change From Baseline to Week 26 in Bone Resorption Marker C-telopeptide of Collagen Cross-links (CTX) | 23.897 percent change |
95% CI: [12.749, 42.957]
95% CI: [8.357, 35.714]
Secondary
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).
Time frame: Baseline and Week 26
Population: Participants from the Pharmacodynamic Set, all randomized participants who received study drug with evaluable calcium absorption data at Day 1 and Week 26, with data available for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Percent Change From Baseline to Week 26 in Bone-specific Alkaline Phosphatase (BsAP) | 0.50 percent change |
| Dexlansoprazole 60 mg | Percent Change From Baseline to Week 26 in Bone-specific Alkaline Phosphatase (BsAP) | 8.68 percent change |
| Esomeprazole 40 mg | Percent Change From Baseline to Week 26 in Bone-specific Alkaline Phosphatase (BsAP) | 6.23 percent change |
95% CI: [0.4, 12.78]
95% CI: [0.59, 12.86]
Secondary
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
Time frame: Baseline and Week 26
Population: Participants from the Pharmacodynamic Set, all randomized participants who received study drug with evaluable calcium absorption data at Day 1 and Week 26, with data available for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Percent Change From Baseline to Week 26 in Urine N-telopeptide of Collagen Cross-links (NTx) Calculated | -6.1 percent change |
| Dexlansoprazole 60 mg | Percent Change From Baseline to Week 26 in Urine N-telopeptide of Collagen Cross-links (NTx) Calculated | 16.9 percent change |
| Esomeprazole 40 mg | Percent Change From Baseline to Week 26 in Urine N-telopeptide of Collagen Cross-links (NTx) Calculated | 6.2 percent change |
95% CI: [4, 34.4]
95% CI: [-2.7, 28.3]
Other Pre-specified
Change From Baseline in 24-hour Urinary Calcium Excretion at Week 26
Time frame: Baseline and Week 26
Population: The pharmacodynamic set included participants from the safety set who had baseline and postbaseline values for any of the primary or secondary endpoints. The pharmacodynamic set where data for baseline and post-baseline assessments was available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in 24-hour Urinary Calcium Excretion at Week 26 | Baseline | 160.3 milligram per day (mg/d) | Standard Deviation 76.16 |
| Placebo | Change From Baseline in 24-hour Urinary Calcium Excretion at Week 26 | Change at Week 26 | -24.4 milligram per day (mg/d) | Standard Deviation 87.16 |
| Dexlansoprazole 60 mg | Change From Baseline in 24-hour Urinary Calcium Excretion at Week 26 | Baseline | 184.8 milligram per day (mg/d) | Standard Deviation 79.52 |
| Dexlansoprazole 60 mg | Change From Baseline in 24-hour Urinary Calcium Excretion at Week 26 | Change at Week 26 | -50.6 milligram per day (mg/d) | Standard Deviation 84.95 |
| Esomeprazole 40 mg | Change From Baseline in 24-hour Urinary Calcium Excretion at Week 26 | Baseline | 153.7 milligram per day (mg/d) | Standard Deviation 90.09 |
| Esomeprazole 40 mg | Change From Baseline in 24-hour Urinary Calcium Excretion at Week 26 | Change at Week 26 | -49.7 milligram per day (mg/d) | Standard Deviation 94.38 |
Other Pre-specified
Change From Baseline in Intestinal Calcium Absorption by True Fractional Calcium Absorption (TFCA) in a Subset of Participants at Week 26
Time frame: Baseline and Week 26
Population: The PD set included participants from the safety set who had baseline and postbaseline values for any of the primary or secondary endpoints. The PD set included participants with evaluable calcium absorption data on Day-1 and Week 26.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Intestinal Calcium Absorption by True Fractional Calcium Absorption (TFCA) in a Subset of Participants at Week 26 | Baseline | 0.18 mg/d | Standard Deviation 0.064 |
| Placebo | Change From Baseline in Intestinal Calcium Absorption by True Fractional Calcium Absorption (TFCA) in a Subset of Participants at Week 26 | Change at week 26 | -0.01 mg/d | Standard Deviation 0.049 |
| Dexlansoprazole 60 mg | Change From Baseline in Intestinal Calcium Absorption by True Fractional Calcium Absorption (TFCA) in a Subset of Participants at Week 26 | Baseline | 0.18 mg/d | Standard Deviation 0.043 |
| Dexlansoprazole 60 mg | Change From Baseline in Intestinal Calcium Absorption by True Fractional Calcium Absorption (TFCA) in a Subset of Participants at Week 26 | Change at week 26 | 0.02 mg/d | Standard Deviation 0.042 |
| Esomeprazole 40 mg | Change From Baseline in Intestinal Calcium Absorption by True Fractional Calcium Absorption (TFCA) in a Subset of Participants at Week 26 | Baseline | 0.17 mg/d | Standard Deviation 0.049 |
| Esomeprazole 40 mg | Change From Baseline in Intestinal Calcium Absorption by True Fractional Calcium Absorption (TFCA) in a Subset of Participants at Week 26 | Change at week 26 | 0.05 mg/d | Standard Deviation 0.05 |
Other Pre-specified
Change From Baseline in Parathyroid Hormone (PTH) at Week 26
Time frame: Baseline and Week 26
Population: The pharmacodynamic set included participants from the safety set who had baseline and postbaseline values for any of the primary or secondary endpoints. The pharmacodynamic set where data for baseline and post-baseline assessments was available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Parathyroid Hormone (PTH) at Week 26 | Baseline | 30.67 picogram per milliliter (pg/mL) | Standard Deviation 10.068 |
| Placebo | Change From Baseline in Parathyroid Hormone (PTH) at Week 26 | Change at Week 26 | 2.16 picogram per milliliter (pg/mL) | Standard Deviation 7.793 |
| Dexlansoprazole 60 mg | Change From Baseline in Parathyroid Hormone (PTH) at Week 26 | Baseline | 30.68 picogram per milliliter (pg/mL) | Standard Deviation 11.917 |
| Dexlansoprazole 60 mg | Change From Baseline in Parathyroid Hormone (PTH) at Week 26 | Change at Week 26 | 2.08 picogram per milliliter (pg/mL) | Standard Deviation 7.765 |
| Esomeprazole 40 mg | Change From Baseline in Parathyroid Hormone (PTH) at Week 26 | Baseline | 31.10 picogram per milliliter (pg/mL) | Standard Deviation 8.254 |
| Esomeprazole 40 mg | Change From Baseline in Parathyroid Hormone (PTH) at Week 26 | Change at Week 26 | 3.37 picogram per milliliter (pg/mL) | Standard Deviation 9.525 |
Other Pre-specified
Change From Baseline in Serum Calcium at Week 26
Time frame: Baseline and Week 26
Population: The pharmacodynamic set included participants from the safety set who had baseline and postbaseline values for any of the primary or secondary endpoints. The pharmacodynamic set where data for baseline and post-baseline assessments was available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Serum Calcium at Week 26 | Change at Week 26 | -0.03 milligram per deciliter (mg/dL) | Standard Deviation 0.44 |
| Placebo | Change From Baseline in Serum Calcium at Week 26 | Baseline | 9.48 milligram per deciliter (mg/dL) | Standard Deviation 0.347 |
| Dexlansoprazole 60 mg | Change From Baseline in Serum Calcium at Week 26 | Change at Week 26 | -0.03 milligram per deciliter (mg/dL) | Standard Deviation 0.333 |
| Dexlansoprazole 60 mg | Change From Baseline in Serum Calcium at Week 26 | Baseline | 9.47 milligram per deciliter (mg/dL) | Standard Deviation 0.291 |
| Esomeprazole 40 mg | Change From Baseline in Serum Calcium at Week 26 | Change at Week 26 | -0.07 milligram per deciliter (mg/dL) | Standard Deviation 0.331 |
| Esomeprazole 40 mg | Change From Baseline in Serum Calcium at Week 26 | Baseline | 9.58 milligram per deciliter (mg/dL) | Standard Deviation 0.308 |
Other Pre-specified
Change From Baseline in Serum Magnesium at Week 26
Time frame: Baseline and Week 26
Population: The pharmacodynamic set included participants from the safety set who had baseline and postbaseline values for any of the primary or secondary endpoints. The pharmacodynamic set where data for baseline and post-baseline assessments was available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Serum Magnesium at Week 26 | Baseline | 1.72 milliequivalent per liter (meq/L) | Standard Deviation 0.124 |
| Placebo | Change From Baseline in Serum Magnesium at Week 26 | Change at Week 26 | -0.01 milliequivalent per liter (meq/L) | Standard Deviation 0.118 |
| Dexlansoprazole 60 mg | Change From Baseline in Serum Magnesium at Week 26 | Baseline | 1.72 milliequivalent per liter (meq/L) | Standard Deviation 0.145 |
| Dexlansoprazole 60 mg | Change From Baseline in Serum Magnesium at Week 26 | Change at Week 26 | -0.02 milliequivalent per liter (meq/L) | Standard Deviation 0.109 |
| Esomeprazole 40 mg | Change From Baseline in Serum Magnesium at Week 26 | Baseline | 1.77 milliequivalent per liter (meq/L) | Standard Deviation 0.127 |
| Esomeprazole 40 mg | Change From Baseline in Serum Magnesium at Week 26 | Change at Week 26 | -0.03 milliequivalent per liter (meq/L) | Standard Deviation 0.096 |
Other Pre-specified
Change From Baseline in Serum Phosphorus at Week 26
Time frame: Baseline and Week 26
Population: The pharmacodynamic set included participants from the safety set who had baseline and postbaseline values for any of the primary or secondary endpoints. The pharmacodynamic set where data for baseline and post-baseline assessments was available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Serum Phosphorus at Week 26 | Baseline | 3.73 mg/dL | Standard Deviation 0.377 |
| Placebo | Change From Baseline in Serum Phosphorus at Week 26 | Change at Week 26 | 0.08 mg/dL | Standard Deviation 0.445 |
| Dexlansoprazole 60 mg | Change From Baseline in Serum Phosphorus at Week 26 | Baseline | 3.92 mg/dL | Standard Deviation 0.422 |
| Dexlansoprazole 60 mg | Change From Baseline in Serum Phosphorus at Week 26 | Change at Week 26 | 0.07 mg/dL | Standard Deviation 0.271 |
| Esomeprazole 40 mg | Change From Baseline in Serum Phosphorus at Week 26 | Baseline | 3.89 mg/dL | Standard Deviation 0.335 |
| Esomeprazole 40 mg | Change From Baseline in Serum Phosphorus at Week 26 | Change at Week 26 | 0.03 mg/dL | Standard Deviation 0.393 |
Other Pre-specified
Change From Baseline in Urine Magnesium at Week 26
Time frame: Baseline and Week 26
Population: The pharmacodynamic set included participants from the safety set who had baseline and postbaseline values for any of the primary or secondary endpoints. The pharmacodynamic set where data for baseline and post-baseline assessments was available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Urine Magnesium at Week 26 | Baseline | 3.8 meq/L | Standard Deviation 2.11 |
| Placebo | Change From Baseline in Urine Magnesium at Week 26 | Change at Week 26 | -0.1 meq/L | Standard Deviation 2.41 |
| Dexlansoprazole 60 mg | Change From Baseline in Urine Magnesium at Week 26 | Baseline | 4.6 meq/L | Standard Deviation 3.46 |
| Dexlansoprazole 60 mg | Change From Baseline in Urine Magnesium at Week 26 | Change at Week 26 | -0.8 meq/L | Standard Deviation 2.83 |
| Esomeprazole 40 mg | Change From Baseline in Urine Magnesium at Week 26 | Baseline | 4.1 meq/L | Standard Deviation 2.85 |
| Esomeprazole 40 mg | Change From Baseline in Urine Magnesium at Week 26 | Change at Week 26 | -0.5 meq/L | Standard Deviation 2.8 |
Other Pre-specified
Change From Baseline to Week 26 in Vitamin D3 (25-OH-D) Level
Time frame: Baseline and Week 26
Population: The pharmacodynamic set included participants from the safety set who had baseline and postbaseline values for any of the primary or secondary endpoints. The pharmacodynamic set where data for baseline and post-baseline assessments was available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Week 26 in Vitamin D3 (25-OH-D) Level | Baseline | 41.3 ng/mL | Standard Deviation 9.96 |
| Placebo | Change From Baseline to Week 26 in Vitamin D3 (25-OH-D) Level | Change at Week 26 | -2.7 ng/mL | Standard Deviation 10.2 |
| Dexlansoprazole 60 mg | Change From Baseline to Week 26 in Vitamin D3 (25-OH-D) Level | Baseline | 39.4 ng/mL | Standard Deviation 11.64 |
| Dexlansoprazole 60 mg | Change From Baseline to Week 26 in Vitamin D3 (25-OH-D) Level | Change at Week 26 | -0.6 ng/mL | Standard Deviation 12.07 |
| Esomeprazole 40 mg | Change From Baseline to Week 26 in Vitamin D3 (25-OH-D) Level | Baseline | 36.4 ng/mL | Standard Deviation 8.48 |
| Esomeprazole 40 mg | Change From Baseline to Week 26 in Vitamin D3 (25-OH-D) Level | Change at Week 26 | 1.1 ng/mL | Standard Deviation 9.75 |
Other Pre-specified
Number of Participants With Fracture Including Vertebral Fracture During Study Treatment
Time frame: Baseline up to Week 26
Population: The pharmacodynamic set included participants from the safety set who had baseline and postbaseline values for any of the primary or secondary endpoints.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Fracture Including Vertebral Fracture During Study Treatment | 0 participants |
| Dexlansoprazole 60 mg | Number of Participants With Fracture Including Vertebral Fracture During Study Treatment | 0 participants |
| Esomeprazole 40 mg | Number of Participants With Fracture Including Vertebral Fracture During Study Treatment | 0 participants |
Other Pre-specified
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.
Time frame: Baseline and Week 13
Population: The pharmacodynamic set included participants from the safety set who had baseline and postbaseline values for any of the primary or secondary endpoints. The pharmacodynamic set where data for baseline and post-baseline assessments was available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in CTX at Week 13 | 7.510 percent change | Standard Deviation 29.9739 |
| Dexlansoprazole 60 mg | Percent Change From Baseline in CTX at Week 13 | 32.069 percent change | Standard Deviation 45.6413 |
| Esomeprazole 40 mg | Percent Change From Baseline in CTX at Week 13 | 23.212 percent change | Standard Deviation 23.89 |
Other Pre-specified
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.
Time frame: Baseline and Week 26
Population: The pharmacodynamic set included participants from the safety set who had baseline and postbaseline values for any of the primary or secondary endpoints. The pharmacodynamic set where data for baseline and post-baseline assessments was available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Femoral Neck Bone Mineral Density (BMD) Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 26 | -0.6632 percent change | Standard Deviation 2.48314 |
| Dexlansoprazole 60 mg | Percent Change From Baseline in Femoral Neck Bone Mineral Density (BMD) Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 26 | -1.6039 percent change | Standard Deviation 2.58207 |
| Esomeprazole 40 mg | Percent Change From Baseline in Femoral Neck Bone Mineral Density (BMD) Measured by Dual Energy X-ray Absorptiometry (DXA) at Week 26 | -1.0596 percent change | Standard Deviation 2.41731 |
Other Pre-specified
Percent Change From Baseline in Lumbar Spine BMD Measured by DXA at Week 26
DXA is a means of measuring BMD through x-ray.
Time frame: Baseline and Week 26
Population: The pharmacodynamic set included participants from the safety set who had baseline and postbaseline values for any of the primary or secondary endpoints. The pharmacodynamic set where data for baseline and post-baseline assessments was available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Lumbar Spine BMD Measured by DXA at Week 26 | -0.2486 percent change | Standard Deviation 3.29581 |
| Dexlansoprazole 60 mg | Percent Change From Baseline in Lumbar Spine BMD Measured by DXA at Week 26 | -1.0753 percent change | Standard Deviation 3.46909 |
| Esomeprazole 40 mg | Percent Change From Baseline in Lumbar Spine BMD Measured by DXA at Week 26 | -1.2873 percent change | Standard Deviation 2.06722 |
Other Pre-specified
Percent Change From Baseline in P1NP at Week 13
Serum samples for P1NP were analyzed using an electrochemiluminescence immunoassay measured in ng/mL.
Time frame: Baseline and Week 13
Population: The pharmacodynamic set included participants from the safety set who had baseline and postbaseline values for any of the primary or secondary endpoints. The pharmacodynamic set where data for baseline and post-baseline assessments was available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in P1NP at Week 13 | 6.7 percent change | Standard Deviation 18.27 |
| Dexlansoprazole 60 mg | Percent Change From Baseline in P1NP at Week 13 | 19.1 percent change | Standard Deviation 25.02 |
| Esomeprazole 40 mg | Percent Change From Baseline in P1NP at Week 13 | 11.6 percent change | Standard Deviation 18.23 |
Other Pre-specified
Percent Change From Baseline in Total Hip BMD Measured by DXA at Week 26
DXA is a means of measuring BMD through x-ray.
Time frame: Baseline and Week 26
Population: The pharmacodynamic set included participants from the safety set who had baseline and postbaseline values for any of the primary or secondary endpoints. The pharmacodynamic set where data for baseline and post-baseline assessments was available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Total Hip BMD Measured by DXA at Week 26 | -0.1928 percent change | Standard Deviation 1.42242 |
| Dexlansoprazole 60 mg | Percent Change From Baseline in Total Hip BMD Measured by DXA at Week 26 | -0.7190 percent change | Standard Deviation 1.78479 |
| Esomeprazole 40 mg | Percent Change From Baseline in Total Hip BMD Measured by DXA at Week 26 | -0.5330 percent change | Standard Deviation 1.50491 |
Other Pre-specified
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.
Time frame: Week 26 and Week 52
Population: The pharmacodynamic set included participants from the safety set who had baseline and postbaseline values for any of the primary or secondary endpoints. The pharmacodynamic set where data for baseline and post-baseline assessments was available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Week 26 in Femoral Neck BMD Measured by DXA at Week 52 | -0.0063 percent change | Standard Deviation 2.57407 |
| Dexlansoprazole 60 mg | Percent Change From Week 26 in Femoral Neck BMD Measured by DXA at Week 52 | -0.3439 percent change | Standard Deviation 2.3968 |
| Esomeprazole 40 mg | Percent Change From Week 26 in Femoral Neck BMD Measured by DXA at Week 52 | 0.2689 percent change | Standard Deviation 2.67283 |
Other Pre-specified
Percent Change From Weeks 26 in Lumbar Spine BMD Measured by DXA at Week 52
Time frame: Week 26 and Week 52
Population: The pharmacodynamic set included participants from the safety set who had baseline and postbaseline values for any of the primary or secondary endpoints. The pharmacodynamic set where data for baseline and post-baseline assessments was available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Weeks 26 in Lumbar Spine BMD Measured by DXA at Week 52 | -0.4913 percent change | Standard Deviation 3.01161 |
| Dexlansoprazole 60 mg | Percent Change From Weeks 26 in Lumbar Spine BMD Measured by DXA at Week 52 | -0.3561 percent change | Standard Deviation 2.42934 |
| Esomeprazole 40 mg | Percent Change From Weeks 26 in Lumbar Spine BMD Measured by DXA at Week 52 | 0.8565 percent change | Standard Deviation 2.4623 |
Other Pre-specified
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.
Time frame: Week 26 and Week 52
Population: The pharmacodynamic set included participants from the safety set who had baseline and postbaseline values for any of the primary or secondary endpoints. The pharmacodynamic set where data for baseline and post-baseline assessments was available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Weeks 26 in Total Hip BMD Measured by DXA at Week 52 | -0.0201 percent change | Standard Deviation 1.28096 |
| Dexlansoprazole 60 mg | Percent Change From Weeks 26 in Total Hip BMD Measured by DXA at Week 52 | -0.3324 percent change | Standard Deviation 1.58091 |
| Esomeprazole 40 mg | Percent Change From Weeks 26 in Total Hip BMD Measured by DXA at Week 52 | -0.0799 percent change | Standard Deviation 1.81755 |