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

Takeda

Status and phase: Completed; Phase 3; Phase 2

Conditions: Involutional Osteoporosis

Treatments: Drug: NE-58095 DR Placebo; Drug: NE-58095 IR; Drug: NE-58095 IR Placebo; Drug: NE-58095 DR

Study type: Interventional

Funder types: Industry

Identifiers

NCT02063854

U1111-1153-0440 (Registry Identifier)

NE-58095DR/CCT-401 (Other Identifier)

JapicCTI-142440 (Registry Identifier)

CCT-401

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 871 patients

Sex: All

Ages: 50+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patients with a diagnosis of involutional osteoporosis
2. Male or female outpatients (including patients admitted to the hospital for tests) aged ≥ 50 years at the time of consent
3. Women for whom at least 2 years have passed since the last natural menstruation

Exclusion criteria

1. Patients with secondary osteoporosis
2. Patients with diseases (other than secondary osteoporosis) that present with decreased bone mass
3. Patients with findings that affects the measurement of mean bone mineral density of the lumbar spine by dual-energy X-ray absorptiometry (DXA)
4. Patients with a history of radiotherapy to the lumbar spine or the pelvis
5. Patients who are planning to receive surgical dental procedures such as tooth extraction (including dental implant treatment) during the treatment period
6. 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
7. Patients with a history of treatment with any bisphosphonate products within 24 weeks before the start of the treatment period
8. Patients who have received any drugs that affect bone metabolism within 8 weeks before the start of the treatment period
9. Patients with disorders such as esophagitis, peptic ulcer (e.g., esophageal ulcer, gastric ulcer, and duodenal ulcer), or gastrointestinal bleeding
10. Patients with disorders that delay esophageal emptying (e.g., dysphagia, esophagostenosis, or achalasia of the esophagus)
11. Patients with hypocalcemia
12. Patients with hypercalcemia
13. Patients with a diagnosis of renal calculus
14. Patients with serious renal, hepatic, or cardiac disease
15. 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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871 participants in 7 patient groups

NE-58095 IR 2.5 mg Once Daily on Awakening

Active Comparator group

Description:

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.

Treatment:

Drug: NE-58095 DR Placebo

Drug: NE-58095 IR

NE-58095 DR 25 mg Once Monthly on Awakening

Experimental group

Description:

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.

Treatment:

Drug: NE-58095 DR Placebo

Drug: NE-58095 IR Placebo

Drug: NE-58095 DR

NE-58095 DR 25 mg Once Monthly Following Breakfast

Experimental group

Description:

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.

Treatment:

Drug: NE-58095 DR Placebo

Drug: NE-58095 IR Placebo

Drug: NE-58095 DR

NE-58095 DR 25 mg Once Monthly 30 Min. After Breakfast

Experimental group

Description:

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.

Treatment:

Drug: NE-58095 DR Placebo

Drug: NE-58095 IR Placebo

Drug: NE-58095 DR

NE-58095 DR 37.5 mg Once Monthly on Awakening

Experimental group

Description:

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.

Treatment:

Drug: NE-58095 DR Placebo

Drug: NE-58095 IR Placebo

Drug: NE-58095 DR

NE-58095 DR 37.5 mg Once Monthly Following Breakfast

Experimental group

Description:

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.

Treatment:

Drug: NE-58095 DR Placebo

Drug: NE-58095 IR Placebo

Drug: NE-58095 DR

NE-58095 DR 37.5 mg Once Monthly 30 Min. After Breakfast

Experimental group

Description:

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.

Treatment:

Drug: NE-58095 DR Placebo

Drug: NE-58095 IR Placebo

Drug: NE-58095 DR