Neoplasms

Symptoms and General Pathology

All Conditions

Gland and Hormone Related Diseases

Neoplasm Metastasis

Hyperparathyroidism

Hyperparathyroidism, Secondary

Neoplastic Processes

Parathyroid Diseases

Endocrine System Diseases

All Drugs and Chemicals

Bone Density Conservation Agents

Cinacalcet

Hormones

Calcium

Calcium, Dietary

Hormone Antagonists

KHK7580

Cinacalcet Hydrochloride

The purpose of this study is to evaluate the efficacy and the safety of KHK7580 orally administered once daily for 52 weeks compared to cinacalcet hydrochloride as an active control in subjects with secondary hyperparathyroidism receiving hemodialysis in China, Korea, Hong Kong and Taiwan.

Study of KHK7580 in Subjects With Secondary Hyperparathyroidism in Asia

A Phase 3, Randomized, Double-Blind, Intra-Subject Dose-Adjustment, Parallel-Group Study of KHK7580 and Cinacalcet Hydrochloride in Subjects With Secondary Hyperparathyroidism Receiving Hemodialysis

Kyowa Kirin China Pharmaceutical Co., Ltd.

Kyowa Kirin Korea Co., Ltd.

Kyowa Kirin Co., Ltd.

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Kidney Diseases

Renal Insufficiency, Chronic

Renal Insufficiency

Urologic Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Male Urogenital Diseases

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Micronutrients

Vitamins

Other Dietary Supplements

Vitamin D

Cholecalciferol

Parathyroid Hormone

Vitamin D3

Calciferol

Phytosterol

Prior to the partial clinical hold, the starting dose was 0.25 mg/kg (based on dry weight) and was titrated upwards (maximum allowed daily dose of 4.2 mg/kg) based on plasma intact parathyroid hormone (iPTH), corrected serum calcium levels obtained monthly, and adverse signs and symptoms.

After the partial clinical hold the starting dose was 0.20 mg/kg (based on dry weight) and was titrated upwards (maximum allowed daily dose of 2.5 or 60 mg, whichever was lower) based on plasma iPTH, corrected serum calcium levels obtained monthly, weekly monitoring of ionized calcium levels, and adverse signs and symptoms.

All participants also received standard of care, which may have included vitamin D sterols.

Cinacalcet was provided as 5 mg capsules that were opened, and the contents were either sprinkled on soft food or suspended into a sucrose syrup to create a liquid suspension for administration. All doses were administered with food or shortly after a meal at the same time daily.

Cinacalcet hydrochloride

Standard of care may have included vitamin D sterols (25 OH vitamin D and/or 1-25 OH vitamin D and its analogs) at the discretion of the investigator.

Standard of Care

The primary objective was to characterize corrected serum calcium levels on treatment with cinacalcet in pediatric patients with secondary hyperparathyroidism (HPT).

This is a multicenter, 26-week, single-arm, open-label, safety study. Participants were to remain on study for 26 weeks or until time of kidney transplantation, whichever came first.

The study and enrollment was placed on partial clinical hold in February 2013 which resulted in changes to the protocol. The study was restarted in April 2014 following these changes.

Participants who completed the 26-week study or were on study when the study was closed in June 2016 were eligible to participate in an open-label extension study (Study 20140159; NCT02341417).

Safety & Tolerability of Cinacalcet in Pediatric Patients With Chronic Kidney Disease and Secondary Hyperparathyroidism

An Open-label, Single-arm Study to Assess the Safety & Tolerability of Cinacalcet in Addition to Standard of Care in Pediatric Subjects Age 28 Days to < 6 Yrs With Chronic Kidney Disease & Secondary Hyperparathyroidism Receiving Dialysis

Hypocalcemia was defined as corrected serum calcium levels \< 9.0 mg/dL (2.25 mmol/L) for participants aged 28 days to \< 2 years, and \< 8.4 mg/dL (2.1 mmol/L) for participants aged ≥ 2 years to \< 6 years at any time during the study.

A participant was considered to have achieved \> 30% reduction in iPTH from baseline at any 2 consecutive measurements if percent change of any two consecutive post-baseline iPTH values were \< -30% regardless if there was a missing value in between.

A participant was considered to have achieved ≥ 30% reduction in iPTH if the percent change of any post-baseline iPTH value was ≤ -30% from baseline.

A participant was considered to have achieved iPTH between 200 and 300 pg/mL (21.2 and 31.8 pmol/L) at any 2 consecutive measurements if any two consecutive post-baseline iPTH values were within the range regardless if there was a missing value in between. The analysis included all enrolled subjects with at least 1 post-baseline assessment.

A participant was considered to have achieved iPTH \< 300 pg/mL (31.8 pmol/L) during the study if any post-baseline iPTH value was \< 300 pg/mL.

Amgen

Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

Cohort 1 consists of participants enrolled before the partial clinical hold. Participants received cinacalcet administered daily for 24 weeks. The starting dose was 0.25 mg/kg (based on dry weight) with dose adjustments and withholding based on plasma intact parathyroid hormone (iPTH), corrected serum calcium levels obtained monthly, and adverse signs and symptoms; the maximum allowed daily dose was 4.2 mg/kg.

Cohort 1

Cohort 2 consists of participants enrolled after the partial clinical hold. Participants received cinacalcet administered daily for 24 weeks. The starting dose was 0.20 mg/kg (based on dry weight) with dose adjustments and withholding based on plasma iPTH, corrected serum calcium levels obtained monthly, weekly monitoring of ionized calcium levels, and adverse signs and symptoms; the maximum allowed daily dose was 2.5 mg/kg/day or 60 mg, whichever was lower.

Cohort 2

Participants received cinacalcet administered daily for 24 weeks.

Total

Age, Continuous

28 days to < 2 years

2 years to < 6 years

Age, Customized

Sex: Female, Male

American Indian or Alaska Native

Asian

Black or African American

Native Hawaiian or Other Pacific Islander

White

Other

Race/Ethnicity, Customized

Hispanic or Latino

Not Hispanic or Latino

Corrected Serum Calcium

Intact Parathyroid Hormone

Study Director

The analysis included participants who received at least 1 dose of cinacalcet and had at least 1 measured serum calcium value while on cinacalcet (calcium analysis set).

Percentage of Participants With Hypocalcemia

Percentage of Participants With Corrected Serum Calcium Levels < 8.8 mg/dL (2.2 mmol/L) During the Study

Week 3 (n = 7, 9, 16)

Week 7 (n = 4, 9, 13)

Week 11 (n = 4, 8, 12)

Week 15 (n = 2, 7, 9)

Week 19 (n = 1, 3, 4)

Week 22 (n = 0, 1, 1)

Week 24 (n = 0, 1, 1)

The analysis included all enrolled participants with at least 1 post-baseline assessment (full analysis set) and with available data at each time point.

Percent Change From Baseline in Intact Parathyroid Hormone (iPTH)

Week 3 (n = 7, 10, 17)

Week 7 (n = 4, 8, 12)

Percent Change From Baseline in Corrected Serum Calcium

Week 19 (n = 1, 2, 3)

Percent Change From Baseline in Serum Phosphorous

Percent Change From Baseline in Calcium Phosphorus Product (Ca x P)

The analysis included all enrolled participants with at least 1 post-baseline assessment (full analysis set).

Percentage of Participants Who Achieved > 30% Reduction in iPTH From Baseline at Any Two Consecutive Measurements

Percentage of Participants Who Achieved ≥ 30% Reduction in iPTH From Baseline During the Study

Percentage of Participants Who Achieved iPTH Values Between 200 and 300 pg/mL at Any Two Consecutive Measurements

The analysis included all enrolled subjects with at least 1 post-baseline assessment (full analysis set).

Percentage of Participants Who Achieved iPTH Values < 300 pg/mL During the Study

The Pharmacokinetic/ Pharmacodynamic (PK/PD) analysis set includes all participants who received at least one dose of study drug and had at least one evaluable PK parameter.

Dose- and Weight-Normalized Maximum Plasma Concentration (Cmax) of Cinacalcet

Dose- and Weight-Normalized Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Quantifiable Concentration (AUClast) for Cinacalcet

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of KHK7580 in Subjects With Secondary Hyperparathyroidism in Asia	NCT03822507	Secondary Hyper...	KHK7580 Cinacalcet Hydr...	18 Years -	Kyowa Kirin Co., Ltd.
Safety & Tolerability of Cinacalcet in Pediatric Patients With Chronic Kidney Disease and Secondary Hyperparathyroidism	NCT01439867	Chronic Kidney ... Hyperparathyroi...	Cinacalcet hydr... Standard of Car...	28 Days - 2189 Days	Amgen
Safety & Tolerability of Cinacalcet in Pediatric Patients With Chronic Kidney Disease and Secondary Hyperparathyroidism	NCT01439867	Chronic Kidney ... Hyperparathyroi...	Cinacalcet hydr... Standard of Car...	28 Days - 2189 Days	Amgen

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