Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Neoplasms

Symptoms and General Pathology

Gland and Hormone Related Diseases

Rare Diseases

Kidney Diseases

Neoplasm Metastasis

Hyperparathyroidism

Hyperparathyroidism, Secondary

Neoplastic Processes

Parathyroid Diseases

Endocrine System Diseases

Chronic Graft Versus Host Disease

All Drugs and Chemicals

Bone Density Conservation Agents

Micronutrients

Vitamins

Cinacalcet

Vitamin D

Cholecalciferol

1 alpha-hydroxyergocalciferol

Trace Elements

Hormones

Calcium

Calcium, Dietary

Hormone Antagonists

Vitamin D3

Calciferol

Sensipar®

The purpose of this study is to compare the proportion of chronic kidney disease (CKD) subjects on dialysis receiving Sensipar® and low dose vitamin D or escalating doses of vitamin D alone who are able to achieve the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI) secondary hyperparathyroidism (HPT) treatment targets for both biointact parathyroid hormone (biPTH) and calcium-phosphorus (Ca x P) product.

ACHIEVE: Optimizing the Treatment of Secondary Hyperparathyroidism

ACHIEVE: Optimizing the Treatment of Secondary Hyperparathyroidism: A Comparison of Sensipar® and Low Dose Vitamin D vs. Escalating Doses of Vitamin D Alone

Proportion of subjects in each treatment group simultaneously achieving the National Kidney Foundation - Kidney Disease Outcome Quality Initiative (NKF-K/DOQI) targets for both biPTH (80-160 pg/mL, equivalent to iPTH 150-300 pg/mL) and Ca x P (\< 55 mg\^2/dL\^2) during the assessment phase (last 11 weeks of study following a 16-week titration phase)

Absolute change from baseline for serum phosphorus (P) during the assessment phase

Proportion of participants with ≥ 30% reduction from baseline in mean intact parathyroid hormone (iPTH) during the assessment phase.

Percent Change from Baseline for Calcium (Ca) During the Assessment Phase

Percent change from baseline for Phosphorus (P) during the assessment phase

Percent change from baseline for calcium x phosphorus (Ca x P) during the assessment phase

Percent change from baseline for intact parathyroid hormone (iPTH) during the assessment phase

Proportion of participants who attained the K/DOQI target range for calcium x phosphorus (Ca x P) during the assessment phase.

Proportion of participants who attained the K/DOQI target range for calcium (Ca) during the assessment phase.

Proportion of participants who attained the K/DOQI target range for intact parathyroid hormone (iPTH) during the assessment phase.

Proportion of participants who attained the K/DOQI target range for phosphorus (P) during the assessment phase.

Absolute change from baseline for intact parathyroid hormone (iPTH) during the assessment phase.

Absolute change from baseline for calcium (Ca) during the assessment phase

Absolute change from baseline for calcium x phosphorus (Ca x P) during the assessment phase.

Amgen

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

Other Dietary Supplements

Phytosterol

Standard of care therapy included the use of vitamin D sterols, calcium supplementation, and phosphate binders.

In addition to standard of care participants received cinacalcet at a starting dose (based on dry body weight) of 0.20 mg/kg administered once a day by mouth. Dose adjustments and withholding were based on ionized calcium levels, plasma iPTH, and corrected calcium levels.

Capsules were opened and either sprinkled onto soft food (≥ 5 mg dose) or suspended into a sucrose syrup (≥ 2.5 mg dose) to create a liquid suspension for administration. Tablets were used for doses of 30 mg and higher in participants who could swallow tablets.

Cinacalcet HCl

Standard of Care

The primary objective was to evaluate the efficacy of cinacalcet for reducing the plasma intact parathyroid hormone (iPTH) level by ≥ 30%.

This was a 24-week, randomized, multicenter, open-label, controlled study. Participants were randomized into one of two treatment arms; oral administration of cinacalcet daily in addition to standard of care treatment, or standard of care alone. Randomization was stratified by age group (6 to \< 12 and 12 to \< 18 years of age). All participants received standard of care which could include therapy with Vitamin D sterols, calcium supplementation, and phosphate binders.

Participants in both treatment groups who completed the 20-week treatment period and those who ended the study due to study closure were eligible to enroll in an open-label extension study (20140159; NCT02341417) for further safety follow-up.

Efficacy and Safety of Cinacalcet in Pediatric Patients With Secondary Hyperparathyroidism (SHPT) and Chronic Kidney Disease (CKD) on Dialysis

A Randomized, Open-label, Controlled Study to Assess the Efficacy and Safety of Cinacalcet HCl in Pediatric Subjects With Secondary Hyperparathyroidism and Chronic Kidney Disease Receiving Dialysis

Intact parathyroid hormone (iPTH) levels were measured at weeks 11 and 15; the mean value from these 2 measurements was calculated.

This endpoint was the primary endpoint in the US only.

Intact parathyroid hormone (iPTH) levels were measured at weeks 17, 18, 19 and 20; the mean value from these measurements was calculated.

This endpoint was specified as the the primary endpoint in all countries except the United States (US). In the US this endpoint was specified as a secondary efficacy endpoint.

Two participants who were randomized to the cinacalcet group but did not receive cinacalcet were included in the Standard of Care group for safety analysis.

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

Total

Age, Continuous

6 to < 12 years

12 to < 18 years

Age, Customized

Sex: Female, Male

Black (or African American)

White

Mixed Race

Other

Race/Ethnicity, Customized

Hispanic/Latino

Not Hispanic/Latino

Intact Parathyroid Hormone Level

Study Director

The analysis was conducted using the full analysis set; participants who had no week 11 or 15 iPTH values were considered non-responders (non-responder imputation).

Percentage of Participants Who Achieved a ≥ 30% Reduction From Baseline In Mean Plasma iPTH During Weeks 11 to 15

A hierarchical testing procedure was used to test the primary and biochemical secondary endpoints. The primary endpoint was tested at a 2-sided significance level of 0.05. The secondary endpoints were tested using Holm's method at 0.05 (2-sided) should the primary endpoint achieve a significant result.

The full analysis set (all randomized participants) was used for this analysis. For participants with no iPTH values in the EAP, the mean of the last 2 available postbaseline values was used. If only 1 postbaseline value was available, this value was used. If no postbaseline value was available, the participant was considered a non-responder.

Percentage of Participants Who Achieved a ≥ 30% Reduction From Baseline in Mean Plasma Intact Parathyroid Hormone During the Efficacy Assessment Period

This analysis was conducted using the full analysis set. For participants with no iPTH values in the EAP, the mean of the last 2 available postbaseline values was used. If only 1 postbaseline value was available, this value was used. If no postbaseline value was available, the participant was considered a non-responder.

Percentage of Participants Who Achieved a Mean iPTH ≤ 300 pg/mL (31.8 Pmol/L) During Weeks 17 to 20

This analysis was conducted using the full analysis set using last value carried forward imputation. Participants with no post-baseline values available were excluded from the analysis.

Percent Change in iPTH From Baseline to the Mean Value During Weeks 17 to 20

Change in Corrected Serum Calcium From Baseline to the Mean Value During Weeks 17 to 20

Change in Serum Phosphorus From Baseline to the Mean Value During Weeks 17 to 20

Overall Study

Pharmaceutical Solutions

Subjects who meet all inclusion/exclusion criteria at baseline will be given cinacalcet 30mg film-coated tablet, for oral use added to phosphate binders and vitamin D analogue.

For subjects receiving a cinacalcet dose \<30mg, commercially available cinacalcet 30mg tab will be ground and diluted with a 5% dextrose solution. Then, an aliquot of this solution corresponding to the individually prescribed dose will be administered as indicated.

Initial dosing of cinacalcet will be 0.5-0.75mg/kg or 30 mg po once daily (OD) each evening with food.

During the cinacalcet dose-titration 6-month period for efficacy assessment, the dose will be increased on monthly basis by 0.5 mg/kg or by 30mg OD to achieve the target iPTH value \<180 pg/mL, as tolerated by the subject, up to maximum of 180mg OD in absence of signs of hypocalcemia, according to the current summary of product characteristics.

The 6-month pre-treatment period will be followed by a run-in period with a baseline evaluation prior to the drug administration, followed by a 6-month cinacalcet dose titration period, during which the dose will be increased on monthly basis by 0.5 mg/kg or by 30 mg OD up to the achievement of target iPTH value \<180 pg/mL as tolerated by the patient

Enrico E. Verrina, MD

Ornella Della Casa Alberighi, MD PhD

Enrico E Verrina, MD

Twelve-month, multicenter, intra-subject controlled (retrospective-prospective), open-label, active-treatment study to evaluate the dose-response and pharmacokinetics (PK) of cinacalcet HCl for the treatment of Secondary Hyperparathyroidism (SHPT) in paediatric subjects with chronic kidney disease (CKD) on dialysis, followed by 12-month study extension.

This multicenter, intra-subject controlled, open-label, active-treatment study will assess in children affected by Secondary Hyperparathyroidism, aged 2-18 years on chronic dialysis not responsive to standard of care (SoC) therapy, the response after 6-month cinacalcet compared intra-subject to SoC alone at screening visit 6 months prior to cinacalcet start. Secondary objectives are to evaluate effects on growth over 18 months and PK profile. At baseline children have PTH levels\>300 pg/mL, plasma P\<6 mg/dL, and Ca 8.4-10.5 mg/dL, or Ca x P product\>60 not responsive to SoC. Initial dosing of cinacalcet will be 0.5-0.75 mg/Kg per os OD to be adjusted up to a max of 180mg OD for target PTH values\<180 pg/mL in absence of hypocalcemia. Thirty children will be enrolled at 12 centres participating in a national paediatric dialysis registry, corresponding to an α=0.05 and a power of 80% using the McNemar test, with an expected % of responders to cinacalcet or SoC of 40% or 5% respectively, with a drop-out rate of 15. Primary study endpoint (EP) will be the % of children who will have a reduction from baseline \>25% in mean PTH levels during the 6-mo efficacy-assessment period. Among secondary EPs over 18 mos will be the % of patients with mean PTH levels\<300 pg/mL; the % change in PTH, Ca, P values, and the Ca x P product; PK profile (or population profile by age) and its correlation with PTH and testosterone levels; auxological indices and growth velocity; % of children with treatment-emergent adverse events and lab abnormalities; retention on treatment and reasons of treatment withdrawal. The study will evaluate whether cinacalcet represents a safe and effective therapeutic option for SHPT children.

Cinacalcet in Paediatric Secondary Hyperparathyroidism (SHPT) Due to Chronic Kidney Disease (CKD)

Twelve-month, Multicenter, Intra-subject Controlled (Retrospective-prospective), Open-label, Active-treatment Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics (PK) of Cinacalcet Hydrochloride for the Treatment of Secondary Hyperparathyroidism (SHPT) in Paediatric Subjects With Chronic Kidney Disease (CKD) on Dialysis, Followed by 12-month Study Extension.

This composite EP will address the needed information on the appropriate dose of cinacalcet to be adopted in paediatric patients, and especially in younger children, as well as on the impact of treatment with calcimimetics on serum Ca and P levels, and on SHPT control over the long term

ENRICO VERRINA

Director of Dialysis Unit

Nutritional and Metabolic Diseases

Carcinoma

Hyperparathyroidism, Primary

Hypercalcemia

Parathyroid Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Metabolic Diseases

Calcium Metabolism Disorders

Water-Electrolyte Imbalance

Endocrine Gland Neoplasms

Head and Neck Neoplasms

Primary Hyperparathyroidism

Parathyroid Carcinoma

Parathyroid Hormone

This is an intra-individual titration study of KRN1493 to evaluate the safety and efficacy of KRN1493 for the treatment of hypercalcemia in patients with parathyroid carcinoma or intractable primary hyperparathyroidism (PHPT).

An Intra-individual Titration Study of KRN1493 for the Treatment of Hypercalcemia in Patients With Parathyroid Carcinoma or Intractable Primary Hyperparathyroidism

Kyowa Kirin Co., Ltd.

Maria Coco, MD, MS

Secondary hyperparathyroidism can persist following successful renal transplantation and can cause high blood calcium, kidney dysfunction or failure and excessive bone loss among other problems. If the condition does not resolve, surgery is frequently required to remove the parathyroid glands, with all the inherent risks of surgery. Cinacalcet, a medicine used to treat secondary hyperparathyroidism in patients with kidney disease, may be effective in treating this condition in the renal transplant recipient. We will study the effect of cinacalcet on calcium, bone and renal function in a 6 month treatment protocol.

Secondary Hyperparathyroidism in the renal transplant recipient can cause abnormal bone and mineral metabolism, resulting in hypercalcemia that is detrimental to renal function, causing renal dysfunction and calcinosis. These patients often require parathyroidectomy to correct the hypercalcemia. Surgery is not without significant risk to the patient. Risks include vocal cord paralysis, protracted hypocalcemia, cardiac arrhythmias, muscle cramps. In addition, parathyroidectomy has been associated with subsequent renal impairment.

Cinacalcet is a calcimimetic agent that is very effective in the treatment of secondary hyperparathyroidism in patients with renal failure as well as in hypercalcemia of parathyroid cancer. There have been reports of short term Cinacalcet use in renal transplant recipients. Serum calcium was improved in these patients.

However, little is known about the effect of cinacalcet on bone activity and turnover. It is not known whether Cinacalcet causes low turnover bone activity with adynamic bone disease. It is known that low turnover bone disease in renal patients can by itself cause hypercalcemia as the bone becomes static and unable to respond to everyday calcium loads.

We have shown that adynamic bone can develop in renal transplant recipients under a variety of conditions. It is not known what effect, if any, cinacalcet has on the bone activity of renal transplant recipients with persistent secondary hyperparathyroidism.

The purpose of the study is to determine the effect of Cinacalcet on serum calcium, renal function and bone histology in renal transplant recipients.

This is a prospective, open-label study. Stable adult renal transplant recipients who are at least 3 months post renal transplant, are hypercalcemic and have persistent hyperparathyroidism with inappropriately elevated Parathyroid hormone will be eligible.

Protocol procedures will include baseline and 6 month measurements of bone mineral density, bone biochemical parameters, glomerular filtration rate, anterior iliac crest bone biopsy. Subjects will start cinacalcet after the first biopsy. The medication will be titrated to normalize serum calcium. Medication will be supplied by the study. Serum electrolytes will be monitored as indicated.

Cinacalcet to Treat Hypercalcemia in Renal Transplant Recipients

Cinacalcet for Treatment of Persistent Secondary Hyperparathyroidism in Renal Transplant Recipients: Effect on Renal Function, Serum Calcium and Bone Histomorphometry

Montefiore Medical Center

Musculoskeletal Diseases

Chronic Kidney Disease-Mineral and Bone Disorder

Administer Cinacalcet HCL to subjects whose iPTH\>900 pg/ml from 1st to 32nd week.

Administer Cinacalcet HCL to subjects whose 600≤iPTH\<900 pg/ml from 1st to 32nd week.

Administer Cinacalcet HCL to subjects whose 300≤iPTH\<600 pg/ml from 1st to 32nd week.

Administer Cinacalcet HCL to all subjects from 1st to 32nd week. Subjects choose to buy and take Cinacalcet HCL in real-world period from 33rd to 52nd week.

Zhihong Liu

Zhaohui Ni

Zhangsuo Liu

Jiazhuang Lou

Guanqing Xiao

Li Hao

Ping Fu

Yisheng Ling

Xuemei Li

Shixiang Wang

Aihua Zhang

Xiaonong Chen

Jing Chen

Li Zuo

Aili Jiang

Guohua Ding

Jianying Niu

Yonghui Mao

Qiang He

Chaosheng Chen

Hong Liu

Junwei Yang

Jianming Ye

1. To evaluate achievement ratio of iPTH,Calcium and phosphorus after taking Cinacalcet HCL in hemodialysis subjects with mild, moderate and severe SHPT;
2. To explore the impact of Cinacalcet HCL using on the combined use of drugs;
3. To explore the difference of patients who continued or discontinued Cinacalcet HCL in real-world period from 33rd to 52nd week.

Efficacy and Safety of Cinacalcet in Ca, P and iPTH Levels in Patients With Mild, Moderate and Severe SHPT

A Multi-center Study Evaluating Efficacy and Safety of Cinacalcet Hydrochloride(HCL) in Calcium, Phosphorus and Intact Parathyroid Hormone(iPTH) Serum Levels in Chinese Chronic Kidney Disease(CKD) Hemodialysis(HD) Patients With Mild, Moderate and Severe Secondary Hyperparathyroidism(SHPT)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
ACHIEVE: Optimizing the Treatment of Secondary Hyperparathyroidism	NCT00135304	Secondary Hyper...	Sensipar® Vitamin D	18 Years -	Amgen
Efficacy and Safety of Cinacalcet in Pediatric Patients With Secondary Hyperparathyroidism (SHPT) and Chronic Kidney Disease (CKD) on Dialysis	NCT02138838	Chronic Kidney ...	Cinacalcet HCl Standard of Car...	6 Years - 17 Years	Amgen
ACHIEVE: Optimizing the Treatment of Secondary Hyperparathyroidism	NCT00135304	Secondary Hyper...	Sensipar® Vitamin D	18 Years -	Amgen
Cinacalcet in Paediatric Secondary Hyperparathyroidism (SHPT) Due to Chronic Kidney Disease (CKD)	NCT01479088	Secondary Hyper...	Cinacalcet HCl	2 Years - 18 Years	Istituto Giannina Gaslini
An Intra-individual Titration Study of KRN1493 for the Treatment of Hypercalcemia in Patients With Parathyroid Carcinoma or Intractable Primary Hyperparathyroidism	NCT01460030	Parathyroid Car... Hypercalcemia Primary Hyperpa...	Cinacalcet HCl	20 Years -	Kyowa Kirin Co., Ltd.
An Intra-individual Titration Study of KRN1493 for the Treatment of Hypercalcemia in Patients With Parathyroid Carcinoma or Intractable Primary Hyperparathyroidism	NCT01460030	Parathyroid Car... Hypercalcemia Primary Hyperpa...	Cinacalcet HCl	20 Years -	Kyowa Kirin Co., Ltd.
Cinacalcet to Treat Hypercalcemia in Renal Transplant Recipients	NCT00415584	Secondary Hyper... Hypercalcemia	Cinacalcet HCl	18 Years -	Montefiore Medical Center
Efficacy and Safety of Cinacalcet in Ca, P and iPTH Levels in Patients With Mild, Moderate and Severe SHPT	NCT03123406	Hyperparathyroi...	Cinacalcet HCl	18 Years - 75 Years	Kyowa Kirin Co., Ltd.
Efficacy and Safety of Cinacalcet in Pediatric Patients With Secondary Hyperparathyroidism (SHPT) and Chronic Kidney Disease (CKD) on Dialysis	NCT02138838	Chronic Kidney ...	Cinacalcet HCl Standard of Car...	6 Years - 17 Years	Amgen

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