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

Phase 2

Completed

• Conditions: Secondary Hyperparathyroidism
• Interventions: Drug: Cinacalcet; Drug: ASP7991; Drug: Placebo

• Registration Number: NCT02133404
• Lead Sponsor: Astellas Pharma Inc

Brief Summary

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

Detailed Description

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.

Study Timeline

• Study Start: 2014-03-14
• Study First Submitted: 2014-04-29
• Study First Submitted QC: 2014-05-06
• Study First Posted: 2014-05-08
• Primary Completion: 2014-11-10
• Study Completion: 2014-11-10
• Status Verified: 2024-10
• Last Update Submitted: 2024-11-05
• Last Update Posted: 2024-11-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 62

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ASP7991 group	Placebo	receiving ASP7991 and Cinacalcet-placebo
Cinacalcet group	Cinacalcet	receiving Cinacalcet and ASP7991-placebo
Cinacalcet group	Placebo	receiving Cinacalcet and ASP7991-placebo
ASP7991 group	ASP7991	receiving ASP7991 and Cinacalcet-placebo

Primary Outcome Measures

Name	Time	Method
Serum iPTH concentration	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	iPTH: intact parathyroid hormone

Secondary Outcome Measures

Name	Time	Method
Corrected serum Ca, Phosphate(P) concentration	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	Ca x P will be calculated
Safety assessed by the incidence of adverse events, vital signs, laboratory tests and 12-lead ECGs	For 12 weeks after start of treatment
serum vitamin D concentration	Before and at 22, 43, 64, 85 and 92 days after start of the treatment
serum wPTH concentration	Before and at 22, 43, 64, 85 and 92 days after start of the treatment	wPTH: whole parathyroid hormone
Serum concentration of bone metabolism markers	Before and at 22, 43, 64, 85 and 92 days after start of the treatment	Bone metabolism markers will be BAP (Bone specific alkaline phosphatase) and TRACP5b (Tartrate-resistant acid phosphatase-5b)
Serum FGF23 concentration	Before and at 22, 43, 64, 85 and 92 days after start of the treatment