A Study to Evaluate the Effect of ASP7991 in Secondary Hyperparathyroidism Patients Undergoing Hemodialysis

Study Overview
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Brief Summary
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To examine efficacy and safety after 12-week administration of ASP7991 in secondary hyperparathyroidism patients undergoing hemodialysis

Detailed Description
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This study is a multicenter, double-blind, randomized, Cinacalcet hydrochloride-controlled, parallel-group, dose-ascending study. Subjects judged to be eligible will be registered and randomized into either ASP7991 group (receiving ASP7991 and cinacalcet-placebo) or Cinacalcet group (receiving cinacalcet and ASP7991-placebo), and will receive 12-week (84 days) administration of study drug from first dialysis day in a week (treatment period), in a double-blind manner. The dose of the study drugs will be increased every 3 weeks in dose-ascending manner. Follow-up assessment will be performed before starting first dialysis in a week, 1 week (7 days) after the completion of the treatment period.

Official Title
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Phase II Study of ASP7991 -A Double-blind, Cinacalcet Hydrochloride-controlled, Dose-ascending Study in Secondary Hyperparathyroidism Patients Undergoing Hemodialysis -

Conditions
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Secondary Hyperparathyroidism

Intervention / Treatment
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* Drug: ASP7991
* Drug: Cinacalcet
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who are on stable chronic maintenance dialysis who are receiving hemodialysis therapy 3 times/week since before 12-week (84 days) administration and are also scheduled to undergo the regimen of 3 times/week hemodialysis during the study period Patients with secondary hyperparathyroidism Patients whose serum iPTH concentration is >240 pg/mL and corrected serum Ca is ≥ 9.0 mg/dL Patients who have had no changes in the following items ≥4-week (28 days). Dosage and regimen, including new administration, of active vitamin D, calcitonin preparation, phosphate binder, and medication with phosphate absorption (including foods) Ca concentration of the dialysate, membrane area of the dialyzer, and dialysis time of each week Exclusion Criteria: Patients who underwent parathyroid intervention, such as parathyroidectomy (PTx) or percutaneous ethanol injection therapy (PEIT), within 24 weeks (168 days) prior to the administration Patients who have primary hyperparathyroidism Patients who received bisphosphonate, estrogen preparation, parathyroid hormone within 4 weeks (28 days) Patients with uncontrolled hypertension (systolic blood pressure ≥ 180 mmHg and diastolic blood pressure ≥ 120 mmHg are observed at >2/3 of all confirmable measurements Patients who are complicated by severe heart disorder [congestive cardiac failure (NYHA classification III or higher), or wide range of old myocardial infarction], or having a history of hospitalization for cerebro-vascular disease or heart disorder within 12 weeks (84 days) before administration of the study drug Patients with hepatic function abnormal (ALT or AST is >2× ULN, or total bilirubin (T-bil) is > 1.5 × ULN.) Patients with a history of malignant tumor or the patient's condition is complicated by malignant tumor. (However, enrollment is acceptable if the tumor has not relapsed for 5 years or longer.) Patients with a history of serious drug allergy including anaphylactic shock Patients with a history of drug allergy to Cinacalcet hydrochloride Female patients who are potentially child-bearing or lactating, or patients who do not comply with the instructed contraceptive measures Patients who were or are currently involved in trials for other investigational drugs or medical devices, or clinical trial for post-marketing study drugs within 12 weeks (84 days) before the study Patients who have received ASP7991 in the past Patients who were judged ineligible to participate in the study by the investigator / subinvestigator

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 79 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 |
| --- | --- |
| Experimental: ASP7991 group<br>receiving ASP7991 and Cinacalcet-placebo | Drug: ASP7991<br>* oral<br>Drug: Placebo<br>* oral<br>|
| Active Comparator: Cinacalcet group<br>receiving Cinacalcet and ASP7991-placebo | Drug: Cinacalcet<br>* oral<br>Drug: Placebo<br>* oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum iPTH concentration | iPTH: intact parathyroid hormone | Before and at 8, 15, 22, 24, 29, 36, 43, 45, 50, 57, 64, 66, 71, 78, 85 and 92 days after start of the treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Corrected serum Ca, Phosphate(P) concentration | Ca x P will be calculated | Before and at 3, 8, 15, 22, 24, 29, 36, 43, 45, 50, 57, 64, 66, 71, 78, 85 and 92 days after start of the treatment | 
| serum vitamin D concentration |  | Before and at 22, 43, 64, 85 and 92 days after start of the treatment | 
| serum wPTH concentration | wPTH: whole parathyroid hormone | Before and at 22, 43, 64, 85 and 92 days after start of the treatment | 
| Serum concentration of bone metabolism markers | Bone metabolism markers will be BAP (Bone specific alkaline phosphatase) and TRACP5b (Tartrate-resistant acid phosphatase-5b) | Before and at 22, 43, 64, 85 and 92 days after start of the treatment | 
| Serum FGF23 concentration |  | Before and at 22, 43, 64, 85 and 92 days after start of the treatment | 
| Safety assessed by the incidence of adverse events, vital signs, laboratory tests and 12-lead ECGs |  | For 12 weeks after start of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mineral bone disease(MBD), Chronic kidney disease(CKD), secondary hyperparathyroidism(SHPT)