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

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

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

Study Overview

• Status: Completed
• Conditions: Secondary Hyperparathyroidism
• Intervention / Treatment: Drug: Placebo; Drug: ASP7991; Drug: Cinacalcet

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 Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Chubu, Japan
  • Chugoku, Japan
  • Kanto, Japan
  • Kyushu, Japan
  • Shikoku, Japan
  • Tohoku, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ASP7991 group; receiving ASP7991 and Cinacalcet-placebo	Drug: Placebo; oral; Drug: ASP7991; oral
Active Comparator: Cinacalcet group; receiving Cinacalcet and ASP7991-placebo	Drug: Placebo; oral; Drug: Cinacalcet; oral

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc

Publications and helpful links

Helpful Links

• Link to results on the Astellas Clinical Study Results Web site

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2014
• Primary Completion (Actual): November 10, 2014
• Study Completion (Actual): November 10, 2014

Study Registration Dates

• First Submitted: April 29, 2014
• First Submitted That Met QC Criteria: May 6, 2014
• First Posted (Estimate): May 8, 2014

Study Record Updates

• Last Update Posted (Actual): June 14, 2022
• Last Update Submitted That Met QC Criteria: June 13, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Mineral bone disease(MBD); Chronic kidney disease(CKD); secondary hyperparathyroidism(SHPT)
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Endocrine System Diseases; Parathyroid Diseases; Neoplastic Processes; Hyperparathyroidism; Neoplasm Metastasis; Hyperparathyroidism, Secondary; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Calcium-Regulating Hormones and Agents; Calcimimetic Agents; Cinacalcet; ASP7991
• Other Study ID Numbers: 7991-CL-1004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Access to anonymized individual participant level data will not be provided for this trial as it meets one or more of the exceptions described on www.clinicalstudydatarequest.com under "Sponsor Specific Details for Astellas."