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Trial record 1 of 1 for:    NCT02063854
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A Phase II/III, Double-blind, Parallel Group Comparative Study of Oral Administration of NE-58095 Tablets

This study has been completed.
Sponsor:
Collaborator:
EA Pharma Co., Ltd.
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT02063854
First received: February 12, 2014
Last updated: February 7, 2017
Last verified: February 2017
  Purpose
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.

Condition Intervention Phase
Involutional Osteoporosis Drug: NE-58095 IR Drug: NE-58095 IR Placebo Drug: NE-58095 DR Drug: NE-58095 DR Placebo Phase 2 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator, Outcomes Assessor
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • 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 [ Time Frame: Baseline and End of Study (up to Month 12) ]
    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.


Secondary Outcome Measures:
  • Percent Change From Baseline in Mean Lumbar Spine (L2-L4) BMD Measured by DXA at Each Visit [ Time Frame: Baseline and Month 6, Month 12, and End of Study (Last observation carried forward at Month 12) ]
    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.

  • Percent Change From Baseline in Femur (Total Proximal Femur) BMD Measured by DXA at Each Visit [ Time Frame: Baseline and Month 6, Month 12, and End of Study (Last observation carried forward at Month 12) ]
    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.

  • Percent Change From Baseline in Femur (Trochanter) BMD Measured by DXA at Each Visit [ Time Frame: Baseline and Month 6, Month 12, and End of Study (Last observation carried forward at Month 12) ]
    The change in BMD in the femur (trochanter) at each visit relative to baseline. DXA is a means of measuring BMD through x-ray.

  • Percent Change From Baseline in Femur (Femoral Neck) BMD Measured by DXA at Each Visit [ Time Frame: Baseline and Month 6, Month 12, and End of Study (Last observation carried forward at Month 12) ]
    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.

  • Percent Change From Baseline in Bone Turnover Marker Serum Creatinine (CTX) at Each Visit [ Time Frame: Baseline and Months 1, 3, 6, 9 and 12 and End of Study (Last observation carried forward at Month 12) ]
    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.

  • Percent Change From Baseline in Bone Turnover Marker Serum Bone-type Alkaline Phosphatase (BAP) at Each Visit [ Time Frame: Baseline and Months 1, 3, 6, 9 and 12 and End of Study (Last observation carried forward at Month 12) ]
    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.

  • Percent Change From Baseline in Bone Turnover Marker Serum Tartrate-resistant Acid Phosphatase 5b (TRACP-5b) at Each Visit [ Time Frame: Baseline and Months 1, 3, 6, 9 and 12 and End of Study (Last observation carried forward at Month 12) ]
    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.

  • Percent Change From Baseline in Bone Turnover Marker Serum Procollagen 1 N-terminal Peptide (P1NP) at Each Visit [ Time Frame: Baseline and Months 1, 3, 6, 9 and 12 and End of Study (Last observation carried forward at Month 12) ]
    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.

  • Percent Change From Baseline in Bone Turnover Marker Urine Type 1 Collagen Cross-linked N-telopeptide (NTX) at Each Visit [ Time Frame: Baseline and Months 1, 3, 6, 9 and 12 and End of Study (Last observation carried forward at Month 12) ]
    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.

  • Percentage of Participants With New Non-traumatic Vertebral Fractures (Including the Worsening of Pre-existing Fractures) [ Time Frame: Baseline to Month 12 ]
    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.


Enrollment: 871
Study Start Date: February 2014
Study Completion Date: November 2015
Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: NE-58095 IR 2.5 mg Once Daily on Awakening
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
NE-58095 IR tablets
Drug: NE-58095 DR Placebo
NE-58095 DR placebo-matching tablets
Experimental: NE-58095 DR 25 mg Once Monthly on Awakening
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
NE-58095 IR placebo-matching tablets
Drug: NE-58095 DR
NE-58095 DR tablets
Drug: NE-58095 DR Placebo
NE-58095 DR placebo-matching tablets
Experimental: NE-58095 DR 25 mg Once Monthly Following Breakfast
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
NE-58095 IR placebo-matching tablets
Drug: NE-58095 DR
NE-58095 DR tablets
Drug: NE-58095 DR Placebo
NE-58095 DR placebo-matching tablets
Experimental: NE-58095 DR 25 mg Once Monthly 30 Min. After Breakfast
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
NE-58095 IR placebo-matching tablets
Drug: NE-58095 DR
NE-58095 DR tablets
Drug: NE-58095 DR Placebo
NE-58095 DR placebo-matching tablets
Experimental: NE-58095 DR 37.5 mg Once Monthly on Awakening
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
NE-58095 IR placebo-matching tablets
Drug: NE-58095 DR
NE-58095 DR tablets
Drug: NE-58095 DR Placebo
NE-58095 DR placebo-matching tablets
Experimental: NE-58095 DR 37.5 mg Once Monthly Following Breakfast
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
NE-58095 IR placebo-matching tablets
Drug: NE-58095 DR
NE-58095 DR tablets
Drug: NE-58095 DR Placebo
NE-58095 DR placebo-matching tablets
Experimental: NE-58095 DR 37.5 mg Once Monthly 30 Min. After Breakfast
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
NE-58095 IR placebo-matching tablets
Drug: NE-58095 DR
NE-58095 DR tablets
Drug: NE-58095 DR Placebo
NE-58095 DR placebo-matching tablets

Detailed 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.

  Eligibility

Ages Eligible for Study:   50 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02063854

Locations
Japan
Nagoya-shi, Aichi, Japan
Chiba-shi, Chiba, Japan
Narashino-shi, Chiba, Japan
Fukuoka-shi, Fukuoka, Japan
Kitakyushu-shi, Fukuoka, Japan
Onga-gun, Fukuoka, Japan
Ebetsu-shi, Hokkaido, Japan
Sapporo-shi, Hokkaido, Japan
Kako-gun, Hyogo, Japan
Morioka-shi, Iwate, Japan
Atsugi-shi, Kanagawa, Japan
Kawasaki-shi, Kanagawa, Japan
Yokohama-shi, Kanagawa, Japan
Zushi-shi, Kanagawa, Japan
Kumamoto-shi, Kumamoto, Japan
Tamana-shi, Kumamoto, Japan
Sendai-shi, Miyagi, Japan
Tagajo-shi, Miyagi, Japan
Miyazaki-shi, Miyazaki, Japan
Saito-shi, Miyazaki, Japan
Higashi Osaka-shi, Osaka, Japan
Saitama-shi, Saitama, Japan
Daito-ku, Tokyo, Japan
Setagaya-ku, Tokyo, Japan
Wakayama-shi, Wakayama, Japan
Sponsors and Collaborators
Takeda
EA Pharma Co., Ltd.
Investigators
Study Director: Medical Director Clinical Science Takeda
  More Information

Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT02063854     History of Changes
Obsolete Identifiers: NCT02066376
Other Study ID Numbers: CCT-401
JapicCTI-142440 ( Registry Identifier: JapicCTI )
U1111-1153-0440 ( Registry Identifier: WHO )
NE-58095DR/CCT-401 ( Other Identifier: Takeda ID )
Study First Received: February 12, 2014
Results First Received: November 16, 2016
Last Updated: February 7, 2017

Keywords provided by Takeda:
Drug Therapy

Additional relevant MeSH terms:
Osteoporosis
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Polystyrene sulfonic acid
Risedronate Sodium
Etidronic Acid
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Calcium Channel Blockers
Membrane Transport Modulators
Bone Density Conservation Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on June 27, 2017