A Phase II/III, Double-blind, Parallel Group Comparative Study of Oral Administration of NE-58095 Tablets

Study Overview
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Brief Summary
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The present phase II/III, multicenter, randomized, double-blind, parallel group comparative study is designed to evaluate the efficacy and safety of once-monthly oral administration of NE-58095 delayed release (DR) tablets for 12 months in participants with involutional osteoporosis. For this study, participants receiving oral NE-58095 immediate release (IR) 2.5 mg tablets once daily for 12 months are set as the control group.

Detailed Description
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The primary objective of the present study is to verify the non-inferiority of once-monthly oral administration of NE-58095 DR tablets for 12 months to once-daily oral administration of NE-58095 IR 2.5 mg tablets for 12 months, in terms of efficacy in participants with involutional osteoporosis. Secondary objectives of the present study are as follows: to compare the safety of once-monthly oral administration of NE-58095 DR tablets for 12 months with the safety of once-daily oral administration of NE-58095 IR tablets (at 2.5 mg) for 12 months in participants with involutional osteoporosis at time of wakening.

Official Title
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A Phase 2/3, Multicenter, Randomized, Double-blind, Parallel Group Comparative Study to Evaluate the Efficacy and Safety of Once-monthly Oral Administration of NE-58095DR Tablet (25 mg or 37.5 mg) Versus Once-daily Oral Administration of NE-58095IR Tablet (2.5 mg) for the Treatment of Involutional Osteoporosis

Conditions
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Involutional Osteoporosis

Intervention / Treatment
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* Drug: NE-58095 IR
* Drug: NE-58095 IR Placebo
* Drug: NE-58095 DR
* Drug: NE-58095 DR Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a diagnosis of involutional osteoporosis Male or female outpatients (including patients admitted to the hospital for tests) aged ≥ 50 years at the time of consent Women for whom at least 2 years have passed since the last natural menstruation Exclusion Criteria: Patients with secondary osteoporosis Patients with diseases (other than secondary osteoporosis) that present with decreased bone mass Patients with findings that affects the measurement of mean bone mineral density of the lumbar spine by dual-energy X-ray absorptiometry (DXA) Patients with a history of radiotherapy to the lumbar spine or the pelvis Patients who are planning to receive surgical dental procedures such as tooth extraction (including dental implant treatment) during the treatment period Patients with a history of treatment with any anti-receptor activator of nuclear factor-κB ligand (RANKL) monoclonal antibodies or parathyroid hormone products within 1 year before the start of the treatment period Patients with a history of treatment with any bisphosphonate products within 24 weeks before the start of the treatment period Patients who have received any drugs that affect bone metabolism within 8 weeks before the start of the treatment period Patients with disorders such as esophagitis, peptic ulcer (e.g., esophageal ulcer, gastric ulcer, and duodenal ulcer), or gastrointestinal bleeding Patients with disorders that delay esophageal emptying (e.g., dysphagia, esophagostenosis, or achalasia of the esophagus) Patients with hypocalcemia Patients with hypercalcemia Patients with a diagnosis of renal calculus Patients with serious renal, hepatic, or cardiac disease Patients who have received surgical dental procedures, such as a tooth extraction (including dental implant treatment), but whose dental problems remain unresolved at the start of the treatment period.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: NE-58095 IR 2.5 mg Once Daily on Awakening<br>NE-58095 immediate release (IR) 2.5 mg tablet, orally, once, daily, at time of wakening + NE-58095 delayed release (DR) placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication. | Drug: NE-58095 IR<br>* NE-58095 IR tablets<br>Drug: NE-58095 DR Placebo<br>* NE-58095 DR placebo-matching tablets<br>|
| Experimental: NE-58095 DR 25 mg Once Monthly on Awakening<br>NE-58095 DR 25 mg tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication. | Drug: NE-58095 IR Placebo<br>* NE-58095 IR placebo-matching tablets<br>Drug: NE-58095 DR<br>* NE-58095 DR tablets<br>Drug: NE-58095 DR Placebo<br>* NE-58095 DR placebo-matching tablets<br>|
| Experimental: NE-58095 DR 25 mg Once Monthly Following Breakfast<br>NE-58095 DR 25 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication. | Drug: NE-58095 IR Placebo<br>* NE-58095 IR placebo-matching tablets<br>Drug: NE-58095 DR<br>* NE-58095 DR tablets<br>Drug: NE-58095 DR Placebo<br>* NE-58095 DR placebo-matching tablets<br>|
| Experimental: NE-58095 DR 25 mg Once Monthly 30 Min. After Breakfast<br>NE-58095 DR 25 mg tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication. | Drug: NE-58095 IR Placebo<br>* NE-58095 IR placebo-matching tablets<br>Drug: NE-58095 DR<br>* NE-58095 DR tablets<br>Drug: NE-58095 DR Placebo<br>* NE-58095 DR placebo-matching tablets<br>|
| Experimental: NE-58095 DR 37.5 mg Once Monthly on Awakening<br>NE-58095 DR 37.5 mg tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication. | Drug: NE-58095 IR Placebo<br>* NE-58095 IR placebo-matching tablets<br>Drug: NE-58095 DR<br>* NE-58095 DR tablets<br>Drug: NE-58095 DR Placebo<br>* NE-58095 DR placebo-matching tablets<br>|
| Experimental: NE-58095 DR 37.5 mg Once Monthly Following Breakfast<br>NE-58095 DR 37.5 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication. | Drug: NE-58095 IR Placebo<br>* NE-58095 IR placebo-matching tablets<br>Drug: NE-58095 DR<br>* NE-58095 DR tablets<br>Drug: NE-58095 DR Placebo<br>* NE-58095 DR placebo-matching tablets<br>|
| Experimental: NE-58095 DR 37.5 mg Once Monthly 30 Min. After Breakfast<br>NE-58095 DR 37.5 mg tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication. | Drug: NE-58095 IR Placebo<br>* NE-58095 IR placebo-matching tablets<br>Drug: NE-58095 DR<br>* NE-58095 DR tablets<br>Drug: NE-58095 DR Placebo<br>* NE-58095 DR placebo-matching tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Mean Lumbar Spine (L2-L4) Bone Mineral Density (BMD) Measured by Dual Energy X-Ray Absorptiometry (DXA) at End of Study | The change in BMD in the second to the fourth lumbar vertebrae, L2 to L4, and the averages of L2 to L4 at end of study relative to baseline. DXA is a means of measuring BMD through x-ray. | Baseline and End of Study (up to Month 12) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Mean Lumbar Spine (L2-L4) BMD Measured by DXA at Each Visit | The change in BMD in each vertebra, L2 to L4, and the averages of L2 to L4 at each visit relative to baseline. DXA is a means of measuring BMD through x-ray. | Baseline and Month 6, Month 12, and End of Study (Last observation carried forward at Month 12) | 
| Percent Change From Baseline in Femur (Total Proximal Femur) BMD Measured by DXA at Each Visit | The change in BMD in the total proximal femur (whole bone, trochanteric region, and neck region) at each visit relative to baseline. DXA is a means of measuring BMD through x-ray. | Baseline and Month 6, Month 12, and End of Study (Last observation carried forward at Month 12) | 
| Percent Change From Baseline in Femur (Trochanter) BMD Measured by DXA at Each Visit | The change in BMD in the femur (trochanter) at each visit relative to baseline. DXA is a means of measuring BMD through x-ray. | Baseline and Month 6, Month 12, and End of Study (Last observation carried forward at Month 12) | 
| Percent Change From Baseline in Femur (Femoral Neck) BMD Measured by DXA at Each Visit | The change in BMD in the femur (femoral neck) at each visit relative to baseline. DXA is a means of measuring BMD through x-ray. | Baseline and Month 6, Month 12, and End of Study (Last observation carried forward at Month 12) | 
| Percent Change From Baseline in Bone Turnover Marker Serum Creatinine (CTX) at Each Visit | Blood samples for serum bone turnover markers were collected at specified visits according to the study schedule. Blood samples were to be collected at about the same time of the day, as far as possible, throughout the study. | Baseline and Months 1, 3, 6, 9 and 12 and End of Study (Last observation carried forward at Month 12) | 
| Percent Change From Baseline in Bone Turnover Marker Serum Bone-type Alkaline Phosphatase (BAP) at Each Visit | Blood samples for serum bone turnover markers were collected at specified visits according to the study schedule. Blood samples were to be collected at about the same time of the day, as far as possible, throughout the study. | Baseline and Months 1, 3, 6, 9 and 12 and End of Study (Last observation carried forward at Month 12) | 
| Percent Change From Baseline in Bone Turnover Marker Serum Tartrate-resistant Acid Phosphatase 5b (TRACP-5b) at Each Visit | Blood samples for serum bone turnover markers were collected at specified visits according to the study schedule. Blood samples were to be collected at about the same time of the day, as far as possible, throughout the study. | Baseline and Months 1, 3, 6, 9 and 12 and End of Study (Last observation carried forward at Month 12) | 
| Percent Change From Baseline in Bone Turnover Marker Serum Procollagen 1 N-terminal Peptide (P1NP) at Each Visit | Blood samples for serum bone turnover markers were collected at specified visits according to the study schedule. Blood samples were to be collected at about the same time of the day, as far as possible, throughout the study. | Baseline and Months 1, 3, 6, 9 and 12 and End of Study (Last observation carried forward at Month 12) | 
| Percent Change From Baseline in Bone Turnover Marker Urine Type 1 Collagen Cross-linked N-telopeptide (NTX) at Each Visit | Urine samples for urine bone turnover markers were collected at specified visits according to the study schedule. Urine samples were to be collected at about the same time of the day, as far as possible, throughout the study. Urine NTX was corrected by creatinine value. | Baseline and Months 1, 3, 6, 9 and 12 and End of Study (Last observation carried forward at Month 12) | 
| Percentage of Participants With New Non-traumatic Vertebral Fractures (Including the Worsening of Pre-existing Fractures) | New non-traumatic vertebral fractures were identified by interpretable X-ray images of 13 vertebrae from the fourth thoracic to the fourth lumbar vertebra. A Central Review Committee member for X-ray determined the presence or absence of new vertebral fractures, the number of new fractures, the presence or absence of worsening pre-existing vertebral fractures, and the number of worsened fractures. The assessment of new vertebral fractures and the worsening of pre-existing vertebral fractures was semiquantitative. The X-ray images were visually inspected and classified into normal (Grade 0), mild deformation (Grade 1), moderate deformation (Grade 2), or severe deformation (Grade 3). If the assessment of any vertebra became worse by at least 1 grade after starting the treatment, its height was measured. A new vertebral fracture or a worsening pre-existing vertebral fracture was concluded if the vertebra's height was reduced from the baseline by at least 20% and by at least 4 mm. | Baseline to Month 12 | 

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