Clinical trial NCT02341417: Extension Study of Cinacalcet for Treatment of Secondary Hyperparathyroidism (SHPT) in Pediatric Patients With Chronic Kidney Disease on Dialysis
Official title: A Multicenter Single-arm Extension Study to Characterize the Long-term Safety of Cinacalcet Hydrochloride in the Treatment of Secondary Hyperparathyroidism in Pediatric Subjects With Chronic Kidney Disease on Dialysis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Secondary Hyperparathyroidism, Chronic Kidney Disease
Keywords: Chronic Kidney Disease, Dialysis, Secondary Hyperparathyroidism, Pediatric
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2015-01-19
Enrollment: 28
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective of this study was to characterize the long-term safety and tolerability of cinacalcet in pediatric patients with chronic kidney disease (CKD) receiving dialysis.

Detailed description: This extension study was designed to characterize the long-term safety and tolerability of cinacalcet in pediatric patients from Amgen Studies 20130356 (NCT02138838) and 20110100 (NCT01439867) who either had completed the parent study or were ongoing at the time an administrative decision was made to end the parent study. After enrolling into this study participants were administered cinacalcet for 28 weeks or until the time of renal transplant or parathyroidectomy, whichever occurred first. The treatment period was followed by a 4-week safety follow-up period.

Eligibility criteria: INCLUSION CRITERIA:

All subjects:

* Subject's legally acceptable representative has provided informed consent when the subject is legally too young to provide informed consent and the subject has provided written assent based on local regulations and/or guidelines prior to any Study 20140159 activities/procedures being initiated.
* Dialysate calcium concentration ≥ 2.5 mEq/L at day 1

All subjects with \> 14 days between the last study visit in Study 20130356 or Study 20110100 and screening for Study 20140159:

* Subjects on anti-convulsant medication must be on a stable dose

All subjects from 20130356:

* Completed treatment through week 20 in the 20130356 study or on study at the time of Study 20130356 termination
* Dry weight ≥ 12.5 kg at day 1 of Study 20140159

Subjects Randomized to the 20130356 Standard of Care Arm Only:

* intact parathyroid hormone (iPTH) value ≥ 300 pg/mL (within 7 days of day 1 in Study 20140159)
* Corrected calcium value ≥ 8.8 mg/dL within 7 days of day 1 in Study 20140159

All Subjects from 20110100:

* Completed week 26 End of Study visit in the, 20110100 study or on study at the time of Study 20110100 termination
* Dry weight ≥ 7 kg at day 1 of Study 20140159

EXCLUSION CRITERIA:

General (studies 20130356 and 20110100):

* Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(s), other than Amgen Studies 20130356 or 20110100.
* Other investigational procedures while participating in this study are excluded.
* Malignancy except non-melanoma skin cancers, cervical or breast ductal carcinoma in situ within the last 5 years.
* Subject has known sensitivity to any of the products to be administered during dosing.
* Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (eg, electronic patient diary \[ediary\]) to the best of the subject and investigator's knowledge
* History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.
* Subject previously has entered this study.
* If sexually active, subject is not willing to use acceptable contraception during treatment and for at least 9 days after the end of treatment.
* Subject is pregnant or breast feeding, or planning to become pregnant during the study or within 9 days after the end of treatment
* History of congenital long QT syndrome, second or third degree heart block, ventricular tachyarrythmias, or other conditions associated with prolonged QT interval
* A new onset of seizures or worsening of pre-existing seizure disorder

All Subjects with \> 14 days between the last study visit in Study 20130356 or Study 20110100 and the screening visit in Study 20140159 will have the following exclusion criteria applied during screening and day 1:

* Unstable chronic heart failure defined as worsening pulmonary edema or other signs and symptoms as per investigator assessment during screening
* Received therapy with commercial cinacalcet after the last study visit in Study 20130356 or Study 20110100 before day 1 of Study 20140159
* Scheduled date for kidney transplantation from a known living donor that makes completion of the study unlikely
* Either new or recurrent cardiac ventricular arrhythmias requiring a change in treatment within 10 days prior to screening visit or day 1 of Study 20140159 screening
* Hepatic impairment indicated by elevated levels of hepatic transaminase or bilirubin (aspartate aminotransferase \[AST\] ≥ 1.5 × upper limit of normal \[ULN\] OR alanine aminotransferase \[ALT\] ≥ 1.5 × ULN OR total bilirubin ≥ 1 × ULN per institutional laboratory range) during screening

All Subjects - Day 1 Study Visit:

* Subject has an ongoing adverse event from Studies 20130356 or 20110100 that is considered related to investigational product and is ≥ Common Terminology Criteria for Adverse Events (CTCAE) (v 4.0) grade 3, and/or considered clinically significant in the opinion of the investigator
* Central laboratory values were not obtained/are not available at day 1 in Study 20140159
* Corrected QT Interval (QTc) \> 500 ms, using Bazett's formula
* QTc ≥ 450 to ≤ 500 ms, using Bazett's formula, unless written permission to enroll is provided by the investigator after consultation with a pediatric cardiologist
* Use of grapefruit juice, herbal medications, CYP3A4 inhibitors (eg, erythromycin, clarithromycin, ketoconazole, itraconazole), or CYP2D6 substrates (eg, flecainide, propafenone, metoprolol, desipramine, nortriptyline, clomipramine)
* Use of concomitant medications that may prolong the QTc interval (eg, ondansetron, albuterol)

Primary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: From first dose of study drug in the extension study up to 4 weeks after the last dose; 32 weeks.
Secondary outcomes:
measure: Percentage of Participants Achieving ≥ 30% Reduction in iPTH From Baseline to Mean Value During Weeks 11 and 15
timeFrame: Baseline (defined as the mean values of samples collected during the screening period and day 1 pre-dose in the extension study) and weeks 11 and 15
measure: Percentage of Participants Achieving ≥ 30% Reduction in iPTH From Baseline to Mean Value During Weeks 23 and 28
timeFrame: Extension study baseline and weeks 23 and 28
measure: Percent Change From Baseline in iPTH to the Mean Value During Weeks 23 and 28
timeFrame: Extension study baseline and weeks 23 and 28
measure: Percentage of Participants Who Achieved Mean iPTH ≤ 300 pg/mL During Weeks 23 and 28
timeFrame: Weeks 23 and 28
measure: Change From Baseline in Corrected Serum Calcium to the Mean Value During Weeks 23 to 28
timeFrame: Extension study baseline and weeks 23 and 28
measure: Change From Baseline in Serum Phosphorus to the Mean Value During Weeks 23 to 28
timeFrame: Extension study baseline and weeks 23 and 28
measure: Serum Corrected Calcium at Baseline, Week 11, and Week 28
timeFrame: Extension study baseline, week 11 and week 28
measure: Serum Phosphorus at Baseline, Week 11, and Week 28
timeFrame: Extension study baseline, week 11 and week 28
measure: Percentage of Participants Achieving ≥ 30% Reduction in iPTH From Day 1 of Cinacalcet Treatment to Mean Value During Weeks 11 and 15
timeFrame: Baseline and weeks 11 and 15, relative to day 1 of cinacalcet treatment.
measure: Percentage of Participants Achieving ≥ 30% Reduction in iPTH From Day 1 of Cinacalcet Treatment to Mean Value During Weeks 23 and 28
timeFrame: Baseline and weeks 23 and 28, relative to day 1 of cinacalcet treatment.
measure: Percent Change From Day 1 of Cinacalcet Treatment in iPTH Over Time
timeFrame: Baseline and weeks 3, 7, 11, 15, 17, 18, 19, 20, 23, 27, 31, 35, 39, 43, 48, 52, relative to day 1 of cinacalcet treatment, and at the end of treatment visit and end of study visit (4 weeks after the end of treatment visit).
measure: Change From Day 1 of Cinacalcet Treatment in Serum Corrected Calcium Over Time
timeFrame: Baseline and weeks 3, 7, 11, 15, 17, 18, 19, 20, 23, 27, 31, 35, 39, 43, 48, 52, relative to day 1 of cinacalcet treatment, and at the end of treatment visit and end of study visit (4 weeks after the end of treatment visit).
measure: Change From Day 1 of Cinacalcet Treatment in Serum Phosphorus Over Time
timeFrame: Baseline and weeks 3, 7, 11, 15, 17, 18, 19, 20, 23, 27, 31, 35, 39, 43, 48, 52, relative to day 1 of cinacalcet treatment, and at the end of treatment visit and end of study visit (4 weeks after the end of treatment visit).
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Tucker
country: United States
facility: Research Site
state: Georgia
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Minneapolis
country: United States
facility: Research Site
state: Minnesota
city: Jackson
country: United States
facility: Research Site
state: Mississippi
city: Kansas City
country: United States
facility: Research Site
state: Missouri
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: West Orange
country: United States
facility: Research Site
state: New Jersey
city: New York
country: United States
facility: Research Site
state: New York
city: Greenville
country: United States
facility: Research Site
state: North Carolina
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Columbus
country: United States
facility: Research Site
state: Ohio
city: Oklahoma City
country: United States
facility: Research Site
state: Oklahoma
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Salt Lake City
country: United States
facility: Research Site
state: Utah
city: Bruxelles
country: Belgium
facility: Research Site
city: Praha 5
country: Czechia
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Hannover
country: Germany
facility: Research Site
city: Heidelberg
country: Germany
facility: Research Site
city: Marburg
country: Germany
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Szeged
country: Hungary
facility: Research Site
city: Genova
country: Italy
facility: Research Site
city: Krakow
country: Poland
facility: Research Site
city: Lodz
country: Poland
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Samara
country: Russian Federation
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Warady BA, Ng E, Bloss L, Mo M, Schaefer F, Bacchetta J. Cinacalcet studies in pediatric subjects with secondary hyperparathyroidism receiving dialysis. Pediatr Nephrol. 2020 Sep;35(9):1679-1697. doi: 10.1007/s00467-020-04516-4. Epub 2020 May 4.