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Clinical Trial Results:
An Open-label, Single-arm Study to Assess the Safety and Tolerability of Cinacalcet HCl in Addition to Standard of Care in Pediatric Subjects Age 28 Days to < 6 years With Chronic Kidney Disease and Secondary Hyperparathyroidism Receiving Dialysis

Summary
EudraCT number	2011-004618-40
Trial protocol	DE NL PL HU CZ IT SK BE Outside EU/EEA
Global end of trial date	03 Jun 2016

Results information
Results version number	v1(current)
This version publication date	18 Dec 2016
First version publication date	18 Dec 2016
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

20110100

ISRCTN number

US NCT number

NCT01439867

WHO universal trial number (UTN)

Sponsor organisation name

Amgen, Inc.

Sponsor organisation address

One Amgen Center Drive, Thousand Oaks, CA, United States, 91320

Public contact

IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.com

Scientific contact

IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

03 Jun 2016

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

03 Jun 2016

Was the trial ended prematurely?

Yes

Main objective of the trial

To characterize corrected serum calcium levels on treatment with cinacalcet in pediatric subjects with secondary hyperparathyroidism.

Protection of trial subjects

This study was conducted in accordance with International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) and applicable Food and Drug Administration (FDA) regulations/guidelines set forth in 21 CFR Parts 11, 50, 54, 56, and 312. The study protocol, amendments, and the informed consent form (ICF) were reviewed by the Institutional Review Boards (IRBs) and Independent Ethics Committees (IECs). No subjects were recruited into the study and no investigational product (IP) was shipped until the IRB/IEC gave written approval of the protocol and ICF and Amgen received copies of these approvals. Before a subject’s participation in the clinical study, the investigator obtained written assent from the subject and/or informed consent from the subject’s legally acceptable representative after adequate explanation of the aims, methods, anticipated benefits, and potential hazards of the study and before any protocol-specific screening procedures or any investigational product was administered.

Background therapy

Evidence for comparator

Actual start date of recruitment

22 Jun 2012

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Czech Republic: 1

Country: Number of subjects enrolled

France: 1

Country: Number of subjects enrolled

Germany: 2

Country: Number of subjects enrolled

Italy: 1

Country: Number of subjects enrolled

Poland: 3

Country: Number of subjects enrolled

Slovakia: 1

Country: Number of subjects enrolled

United States: 9

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

The study was conducted at 14 study centers in Czech Republic (1 site), France (1 site), Germany (1 site), Italy (1 site), Slovakia (1 site), Poland (3 sites), and the US (6 sites). The first subject was enrolled on 22 June 2012, and the last subject completed the study on 03 June 2016.

Screening details

Patients between the ages of 28 days to < 6 years of age, who had chronic kidney disease and secondary hyperparathyroidism and were undergoing either hemodialysis or peritoneal dialysis at the time of screening (subjects 6 months or older should have been receiving dialysis for ≥ 1 month).

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Cohort 1

Arm description

Cohort 1 consists of subjects 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 iPTH, corrected serum calcium levels obtained monthly, and adverse signs and symptoms; the maximum allowed daily dose was 4.2 mg/kg.

Arm type

Experimental

Investigational medicinal product name

Cinacalcet hydrochloride

Investigational medicinal product code

AMG 073

Other name

Sensipar®, Mimpara®

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

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.

Cohort 2

Arm description

Cohort 2 consists of subjects 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.

Arm type

Experimental

Investigational medicinal product name

Cinacalcet hydrochloride

Investigational medicinal product code

AMG 073

Other name

Sensipar®, Mimpara®

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Number of subjects in period 1	Cohort 1	Cohort 2
Started	8	10
Received treatment	7	10
Completed	2	2
Not completed	6	8
Consent withdrawn by subject	1	2
Administrative decision	4	5
Protocol-specified criteria	1	-
Noncompliance	-	1

Baseline characteristics

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Reporting group title

Cohort 1

Reporting group description

Reporting group title

Cohort 2

Reporting group description

Reporting group values	Cohort 1	Cohort 2	Total
Number of subjects	8	10	18
Age Categorical
Units: Subjects
28 days to < 2 years	2	1	3
2 years to < 6 years	6	9	15
Age Continuous
Units: months
arithmetic mean (standard deviation)	37.1 ( 18.9 )	35 ( 15.9 )	-
Gender Categorical
Units: Subjects
Female	3	3	6
Male	5	7	12
Race
Units: Subjects
American Indian or Alaska Native	0	0	0
Asian	0	0	0
Black or African American	1	1	2
Native Hawaiian or Other Pacific Islander	0	0	0
White	6	9	15
Other	1	0	1
Ethnicity
Units: Subjects
Hispanic or Latino	1	2	3
Not Hispanic or Latino	7	8	15
Corrected Serum Calcium
Units: mg/dL
arithmetic mean (standard deviation)	10.56 ( 0.75 )	9.82 ( 0.61 )	-
Intact Parathyroid Hormone
Units: pg/mL
arithmetic mean (standard deviation)	1414.34 ( 699.9 )	1206.92 ( 597.85 )	-

Subject analysis set title

Full Analysis Set

Subject analysis set type

Full analysis

Subject analysis set description

The full analysis set included all enrolled subjects who had at least 1 post-baseline assessment.

Subject analysis set title

Calcium Analysis Set

Subject analysis set type

Sub-group analysis

Subject analysis set description

The calcium analysis set includes all subjects who received at least one dose of study drug and had at least one measured serum calcium value while on study drug.

Subject analysis sets values	Full Analysis Set	Calcium Analysis Set
Number of subjects	17	17
Age Categorical
Units: Subjects
28 days to < 2 years
2 years to < 6 years
Age Continuous
Units: months
arithmetic mean (standard deviation)	( )	( )
Gender Categorical
Units: Subjects
Female
Male
Race
Units: Subjects
American Indian or Alaska Native
Asian
Black or African American
Native Hawaiian or Other Pacific Islander
White
Other
Ethnicity
Units: Subjects
Hispanic or Latino
Not Hispanic or Latino
Corrected Serum Calcium
Units: mg/dL
arithmetic mean (standard deviation)	10.08 ( 0.72 )	( )
Intact Parathyroid Hormone
Units: pg/mL
arithmetic mean (standard deviation)	1298.03 ( 653.68 )	( )

End points

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Reporting group title

Cohort 1

Reporting group description

Reporting group title

Cohort 2

Reporting group description

Subject analysis set title

Full Analysis Set

Subject analysis set type

Full analysis

Subject analysis set description

The full analysis set included all enrolled subjects who had at least 1 post-baseline assessment.

Subject analysis set title

Calcium Analysis Set

Subject analysis set type

Sub-group analysis

Subject analysis set description

The calcium analysis set includes all subjects who received at least one dose of study drug and had at least one measured serum calcium value while on study drug.

Primary: Percentage of participants with Hypocalcemia

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End point title

Percentage of participants with Hypocalcemia ^[1]

End point description

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

End point type

Primary

End point timeframe

26 weeks

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There was no formal statistical testing for this study.

End point values	Cohort 1	Cohort 2	Calcium Analysis Set
Number of subjects analysed	7	10	17
Units: percentage of participants
number (confidence interval 90%)	0 (0 to 34.8)	0 (0 to 25.9)	0 (0 to 16.2)

No statistical analyses for this end point

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

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End point title

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

End point description

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

End point type

Secondary

End point timeframe

26 weeks

End point values	Cohort 1	Cohort 2	Calcium Analysis Set
Number of subjects analysed	7	10	17
Units: percentage of participants
number (confidence interval 90%)	14.3 (0.7 to 52.1)	10 (0.5 to 39.4)	11.8 (2.1 to 32.6)

No statistical analyses for this end point

Secondary: Percent Change From Baseline in Intact Parathyroid Hormone (iPTH)

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End point title

Percent Change From Baseline in Intact Parathyroid Hormone (iPTH)

End point description

The analysis included all enrolled subjects with at least 1 post-baseline assessment. "99999" indicates data that was not calculated due to low number of patients with available data.

End point type

Secondary

End point timeframe

Baseline and weeks 3, 7, 11, 15, 19, 22, and 24

End point values	Cohort 1	Cohort 2	Full Analysis Set
Number of subjects analysed	7	10	17
Units: percent change
arithmetic mean (standard deviation)
Week 3 (N = 7, 9, 16)	-22.96 ( 64.67 )	-3.37 ( 54.82 )	-11.94 ( 58.11 )
Week 7 (n = 4, 9, 13)	3.87 ( 110.94 )	-3.13 ( 52.94 )	-0.98 ( 70.4 )
Week 11 (n = 4, 8, 12)	-51.7 ( 27.18 )	-7.15 ( 75.3 )	-22 ( 65.51 )
Week 15 (n = 2, 7, 9)	-65.31 ( 6.83 )	-51.69 ( 39.91 )	-54.71 ( 35.16 )
Week 19 (n = 1, 3, 4)	-79.02 ( 99999 )	-57.35 ( 32.86 )	-62.76 ( 28.93 )
Week 22 (n = 0, 1 1)	99999 ( 99999 )	-78.04 ( 99999 )	-78.04 ( 99999 )
Week 24 (n = 0, 1, 1)	99999 ( 99999 )	-67.42 ( 99999 )	-67.42 ( 99999 )

No statistical analyses for this end point

Secondary: Percent Change From Baseline in Corrected Serum Calcium

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End point title

Percent Change From Baseline in Corrected Serum Calcium

End point description

The analysis included all enrolled subjects with at least 1 post-baseline assessment. "99999" indicates data that was not calculated due to low number of patients with available data.

End point type

Secondary

End point timeframe

Baseline and weeks 3, 7, 11, 15, 19, 22, and 24

End point values	Cohort 1	Cohort 2	Full Analysis Set
Number of subjects analysed	7	10	17
Units: percent change
arithmetic mean (standard deviation)
Week 3 (n = 7, 10, 17)	-0.5 ( 4.47 )	3.43 ( 6.38 )	1.81 ( 5.86 )
Week 7 (n = 4, 8, 12)	-3.58 ( 12.23 )	3.6 ( 9.31 )	1.21 ( 10.41 )
Week 11 (n = 4, 8, 12)	-3.23 ( 10.51 )	1.46 ( 5.24 )	-0.1 ( 7.28 )
Week 15 (n = 2, 7, 9)	-6.86 ( 12.44 )	2.99 ( 5.09 )	0.8 ( 7.59 )
Week 19 (n = 1, 3, 4)	1.94 ( 99999 )	-0.49 ( 6.62 )	0.12 ( 5.54 )
Week 22 (n = 0, 1, 1)	99999 ( 99999 )	5.88 ( 99999 )	5.88 ( 99999 )
Week 24 (n = 0, 1, 1)	99999 ( 99999 )	2.94 ( 99999 )	2.94 ( 99999 )

No statistical analyses for this end point

Secondary: Percent Change From Baseline in Serum Phosphorous

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End point title

Percent Change From Baseline in Serum Phosphorous

End point description

The analysis included all enrolled subjects with at least 1 post-baseline assessment. "99999" indicates data that was not calculated due to low number of patients with available data.

End point type

Secondary

End point timeframe

Baseline and weeks 3, 7, 11, 15, 19, 22, and 24

End point values	Cohort 1	Cohort 2	Full Analysis Set
Number of subjects analysed	7	10	17
Units: percent change
arithmetic mean (standard deviation)
Week 3 (n = 7, 10, 17)	-10.75 ( 32.49 )	-5.11 ( 39.32 )	-7.43 ( 35.69 )
Week 7 (n = 4, 8, 12)	-8.68 ( 20.88 )	-9.6 ( 29.79 )	-9.29 ( 26.15 )
Week 11 (n = 4, 8, 12)	14.39 ( 22.18 )	4.54 ( 39.08 )	7.82 ( 33.61 )
Week 15 (n = 2, 7, 9)	13.99 ( 26.33 )	-16.07 ( 28.14 )	-9.39 ( 29.26 )
Week 19 (n = 1, 2, 3)	10.87 ( 99999 )	3.45 ( 4.88 )	5.92 ( 5.5 )
Week 22 (n = 0, 1, 1)	99999 ( 99999 )	-1.72 ( 99999 )	-1.72 ( 99999 )
Week 24 (n = 0, 1, 1)	99999 ( 99999 )	8.62 ( 99999 )	8.62 ( 99999 )

No statistical analyses for this end point

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

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End point title

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

End point description

The analysis included all enrolled subjects with at least 1 post-baseline assessment. "99999" indicates data that was not calculated due to low number of patients with available data.

End point type

Secondary

End point timeframe

Baseline and weeks 3, 7, 11, 15, 19, 22, and 24

End point values	Cohort 1	Cohort 2	Full Analysis Set
Number of subjects analysed	7	10	17
Units: percent change
arithmetic mean (standard deviation)
Week 3 (n = 7, 10, 17)	-1.89 ( 39 )	-2.72 ( 38.08 )	-2.37 ( 37.23 )
Week 7 (n = 4, 8, 12)	-11.56 ( 26.35 )	-6.83 ( 29.97 )	-8.4 ( 27.68 )
Week 11 (n = 4, 8, 12)	9.48 ( 17.84 )	5.74 ( 38.78 )	6.99 ( 32.36 )
Week 15 (n = 2, 7, 9)	7.58 ( 38.39 )	-14.24 ( 28.24 )	-9.39 ( 29.58 )
Week 19 (n = 1, 2, 3)	12.34 ( 99999 )	6.41 ( 9.06 )	8.39 ( 7.27 )
Week 22 (n = 0, 1, 1)	99999 ( 99999 )	3.37 ( 99999 )	3.37 ( 99999 )
Week 24 (n = 0, 1, 1)	99999 ( 99999 )	10.96 ( 99999 )	10.96 ( 99999 )

No statistical analyses for this end point

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

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End point title

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

End point description

A subject was considered to have achieved > 30% reduction in iPTH from baseline at any 2 consecutive measurements if percent change of any two consecutive postbaseline iPTH values were < -30% regardless if there was a missing value in between. The analysis included all enrolled subjects with at least 1 post-baseline assessment.

End point type

Secondary

End point timeframe

26 weeks

End point values	Cohort 1	Cohort 2	Full Analysis Set
Number of subjects analysed	7	10	17
Units: percentage of participants
number (confidence interval 90%)	57.1 (22.5 to 87.1)	40 (15 to 69.6)	47.1 (26 to 68.9)

No statistical analyses for this end point

Secondary: Percentage of Participants Who Achieved ≥ 30% Reduction in Intact Parathyroid Hormone From Baseline During the Study

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End point title

Percentage of Participants Who Achieved ≥ 30% Reduction in Intact Parathyroid Hormone From Baseline During the Study

End point description

A subject was considered to have achieved ≥ 30% reduction in iPTH if the percent change of any post-baseline iPTH value was ≤ -30% from baseline. The analysis included all enrolled subjects with at least 1 post-baseline assessment.

End point type

Secondary

End point timeframe

26 weeks

End point values	Cohort 1	Cohort 2	Full Analysis Set
Number of subjects analysed	7	10	17
Units: percentage of participants
number (confidence interval 90%)	100 (65.2 to 100)	50 (22.2 to 77.8)	70.6 (47.8 to 87.6)

No statistical analyses for this end point

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

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End point title

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

End point description

A subject 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.

End point type

Secondary

End point timeframe

26 weeks

End point values	Cohort 1	Cohort 2	Full Analysis Set
Number of subjects analysed	7	10	17
Units: percentage of participants
number (confidence interval 90%)	0 (0 to 34.8)	10 (0.5 to 39.4)	5.9 (0.3 to 25)

No statistical analyses for this end point

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

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End point title

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

End point description

A subject 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. The analysis included all enrolled subjects with at least 1 post-baseline assessment.

End point type

Secondary

End point timeframe

26 weeks

End point values	Cohort 1	Cohort 2	Full Analysis Set
Number of subjects analysed	7	10	17
Units: percentage of participants
number (confidence interval 90%)	57.1 (22.5 to 87.1)	50 (22.2 to 77.8)	52.9 (31.1 to 74)

No statistical analyses for this end point

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

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End point title

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

End point description

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

End point type

Secondary

End point timeframe

Week 12

End point values	Cohort 1	Cohort 2
Number of subjects analysed	3	7
Units: ng/mL/(mgkg)
arithmetic mean (standard deviation)	15.1 ( 16.6 )	17.8 ( 10 )

No statistical analyses for this end point

Secondary: Dose- and Weight-Normalized Area under the Plasma Concentration-time Curve from Time 0 to the Time of Last Quantifiable Concentration (AUClast) for Cinacalcet

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End point title

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

End point description

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

End point type

Secondary

End point timeframe

Week 12

End point values	Cohort 1	Cohort 2
Number of subjects analysed	2	6
Units: hr*ng/mL/(mgkg)
arithmetic mean (standard deviation)	160 ( 195 )	176.8 ( 177 )

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

26 Weeks

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

19.0

Reporting group title

Cohort 1

Reporting group description

Reporting group title

Cohort 2

Reporting group description

Reporting group title

Total

Reporting group description

Participants received cinacalcet administered daily for 24 weeks.

Serious adverse events	Cohort 1	Cohort 2	Total
Total subjects affected by serious adverse events
subjects affected / exposed	4 / 7 (57.14%)	5 / 10 (50.00%)	9 / 17 (52.94%)
number of deaths (all causes)	0	0	0
number of deaths resulting from adverse events
Injury, poisoning and procedural complications
Overdose
subjects affected / exposed	1 / 7 (14.29%)	0 / 10 (0.00%)	1 / 17 (5.88%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Peritoneal dialysis complication
subjects affected / exposed	0 / 7 (0.00%)	1 / 10 (10.00%)	1 / 17 (5.88%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vascular disorders
Hypertension
subjects affected / exposed	1 / 7 (14.29%)	1 / 10 (10.00%)	2 / 17 (11.76%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nervous system disorders
Seizure
subjects affected / exposed	0 / 7 (0.00%)	1 / 10 (10.00%)	1 / 17 (5.88%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Complication associated with device
subjects affected / exposed	1 / 7 (14.29%)	1 / 10 (10.00%)	2 / 17 (11.76%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	0 / 7 (0.00%)	1 / 10 (10.00%)	1 / 17 (5.88%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ileus
subjects affected / exposed	1 / 7 (14.29%)	0 / 10 (0.00%)	1 / 17 (5.88%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
Adenovirus infection
subjects affected / exposed	0 / 7 (0.00%)	1 / 10 (10.00%)	1 / 17 (5.88%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Device related infection
subjects affected / exposed	0 / 7 (0.00%)	1 / 10 (10.00%)	1 / 17 (5.88%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Device related sepsis
subjects affected / exposed	1 / 7 (14.29%)	0 / 10 (0.00%)	1 / 17 (5.88%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Influenza
subjects affected / exposed	1 / 7 (14.29%)	0 / 10 (0.00%)	1 / 17 (5.88%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	0 / 7 (0.00%)	1 / 10 (10.00%)	1 / 17 (5.88%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Product issues
Device malfunction
subjects affected / exposed	0 / 7 (0.00%)	1 / 10 (10.00%)	1 / 17 (5.88%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	0 / 7 (0.00%)	1 / 10 (10.00%)	1 / 17 (5.88%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Failure to thrive
subjects affected / exposed	0 / 7 (0.00%)	1 / 10 (10.00%)	1 / 17 (5.88%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hyperglycaemia
subjects affected / exposed	0 / 7 (0.00%)	1 / 10 (10.00%)	1 / 17 (5.88%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	Cohort 1	Cohort 2	Total
Total subjects affected by non serious adverse events
subjects affected / exposed	5 / 7 (71.43%)	9 / 10 (90.00%)	14 / 17 (82.35%)
Vascular disorders
Hypertension
subjects affected / exposed	1 / 7 (14.29%)	1 / 10 (10.00%)	2 / 17 (11.76%)
occurrences all number	1	1	2
Hypotension
subjects affected / exposed	0 / 7 (0.00%)	1 / 10 (10.00%)	1 / 17 (5.88%)
occurrences all number	0	1	1
Surgical and medical procedures
Catheter removal
subjects affected / exposed	1 / 7 (14.29%)	0 / 10 (0.00%)	1 / 17 (5.88%)
occurrences all number	1	0	1
General disorders and administration site conditions
Asthenia
subjects affected / exposed	0 / 7 (0.00%)	1 / 10 (10.00%)	1 / 17 (5.88%)
occurrences all number	0	1	1
Complication associated with device
subjects affected / exposed	1 / 7 (14.29%)	0 / 10 (0.00%)	1 / 17 (5.88%)
occurrences all number	1	0	1
Pain
subjects affected / exposed	0 / 7 (0.00%)	1 / 10 (10.00%)	1 / 17 (5.88%)
occurrences all number	0	1	1
Pyrexia
subjects affected / exposed	1 / 7 (14.29%)	2 / 10 (20.00%)	3 / 17 (17.65%)
occurrences all number	1	4	5
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	1 / 7 (14.29%)	3 / 10 (30.00%)	4 / 17 (23.53%)
occurrences all number	1	3	4
Nasal congestion
subjects affected / exposed	1 / 7 (14.29%)	0 / 10 (0.00%)	1 / 17 (5.88%)
occurrences all number	1	0	1
Investigations
Platelet count decreased
subjects affected / exposed	1 / 7 (14.29%)	0 / 10 (0.00%)	1 / 17 (5.88%)
occurrences all number	1	0	1
Nervous system disorders
Lethargy
subjects affected / exposed	1 / 7 (14.29%)	0 / 10 (0.00%)	1 / 17 (5.88%)
occurrences all number	1	0	1
Unresponsive to stimuli
subjects affected / exposed	0 / 7 (0.00%)	1 / 10 (10.00%)	1 / 17 (5.88%)
occurrences all number	0	1	1
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 7 (0.00%)	1 / 10 (10.00%)	1 / 17 (5.88%)
occurrences all number	0	4	4
Ear and labyrinth disorders
Ear pain
subjects affected / exposed	1 / 7 (14.29%)	0 / 10 (0.00%)	1 / 17 (5.88%)
occurrences all number	1	0	1
Eye disorders
Eye pain
subjects affected / exposed	1 / 7 (14.29%)	0 / 10 (0.00%)	1 / 17 (5.88%)
occurrences all number	1	0	1
Gastrointestinal disorders
Constipation
subjects affected / exposed	0 / 7 (0.00%)	1 / 10 (10.00%)	1 / 17 (5.88%)
occurrences all number	0	1	1
Diarrhoea
subjects affected / exposed	1 / 7 (14.29%)	1 / 10 (10.00%)	2 / 17 (11.76%)
occurrences all number	3	1	4
Nausea
subjects affected / exposed	1 / 7 (14.29%)	0 / 10 (0.00%)	1 / 17 (5.88%)
occurrences all number	1	0	1
Vomiting
subjects affected / exposed	2 / 7 (28.57%)	2 / 10 (20.00%)	4 / 17 (23.53%)
occurrences all number	3	2	5
Skin and subcutaneous tissue disorders
Dermatitis contact
subjects affected / exposed	0 / 7 (0.00%)	1 / 10 (10.00%)	1 / 17 (5.88%)
occurrences all number	0	1	1
Erythema
subjects affected / exposed	1 / 7 (14.29%)	0 / 10 (0.00%)	1 / 17 (5.88%)
occurrences all number	1	0	1
Pruritus
subjects affected / exposed	1 / 7 (14.29%)	0 / 10 (0.00%)	1 / 17 (5.88%)
occurrences all number	1	0	1
Infections and infestations
Bronchitis
subjects affected / exposed	2 / 7 (28.57%)	0 / 10 (0.00%)	2 / 17 (11.76%)
occurrences all number	2	0	2
Device related sepsis
subjects affected / exposed	1 / 7 (14.29%)	0 / 10 (0.00%)	1 / 17 (5.88%)
occurrences all number	1	0	1
Laryngitis
subjects affected / exposed	0 / 7 (0.00%)	1 / 10 (10.00%)	1 / 17 (5.88%)
occurrences all number	0	1	1
Peritonitis
subjects affected / exposed	0 / 7 (0.00%)	1 / 10 (10.00%)	1 / 17 (5.88%)
occurrences all number	0	1	1
Pharyngitis
subjects affected / exposed	0 / 7 (0.00%)	1 / 10 (10.00%)	1 / 17 (5.88%)
occurrences all number	0	2	2
Upper respiratory tract infection
subjects affected / exposed	1 / 7 (14.29%)	3 / 10 (30.00%)	4 / 17 (23.53%)
occurrences all number	1	3	4
Viral infection
subjects affected / exposed	2 / 7 (28.57%)	0 / 10 (0.00%)	2 / 17 (11.76%)
occurrences all number	2	0	2
Viral upper respiratory tract infection
subjects affected / exposed	1 / 7 (14.29%)	0 / 10 (0.00%)	1 / 17 (5.88%)
occurrences all number	1	0	1
Metabolism and nutrition disorders
Acidosis
subjects affected / exposed	1 / 7 (14.29%)	0 / 10 (0.00%)	1 / 17 (5.88%)
occurrences all number	1	0	1
Hypocalcaemia
subjects affected / exposed	0 / 7 (0.00%)	1 / 10 (10.00%)	1 / 17 (5.88%)
occurrences all number	0	1	1
Hypophosphataemia
subjects affected / exposed	0 / 7 (0.00%)	1 / 10 (10.00%)	1 / 17 (5.88%)
occurrences all number	0	2	2

More information

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Were there any global substantial amendments to the protocol? Yes

10 Mar 2014

•Weekly monitoring of ionized calcium with a point-of-care device was added; required prior to weekly IP dispensing to the patient •Criteria for dose adjustments were added to the protocol based on ionized calcium values •Daily cinacalcet compliance monitoring with an electronic diary by the patient/parent/legal guardian was added. •Cinacalcet treatment period was changed to 24 weeks with a 2-week follow-up period for a total of 26 weeks on study •SAE reporting language was modified. Also the time period for AE/SAE collection was modified to 14 days following the last dose of IP •Updated miscellaneous study conduct procedures

21 Jun 2014

•Aligned the dosing schema being used amongst all studies within the cinacalcet pediatric program. The dosing algorithm in Amendment 2 assigned a dose of cinacalcet across a weight band of several kilograms versus the previous dose assignments based on precise weight increments. The assignment of doses across a weight band in regular increments (eg, 1, 2.5, 5, 7.5, 10 mg, etc) allowed for greater convenience and simplicity for the care-giver administering the drug during the course of the trial. •Changes were made to the study procedures and schedule of clinical laboratory assessments to accommodate the requirements of the revised dosing algorithm.

05 Nov 2014

•Incorporated language regarding adynamic bone disease •Updated language regarding study procedures for consistency within the cinacalcet pediatric program

21 Jul 2015

•Revised the dose adjustments section for clarity. •Clarified the ionized calcium value on Day 1 must be ≥ 1.13 mmol/L for subjects < 2 years of age and ≥ 1.05 mmol/L for subjects ≥ 2 years of age prior to initiation of treatment. •Clarified that, with the exception of the predose PK sample on day 1, PK samples are only collected if the subject has been receiving IP prior to the visit. •Changed “Screening serum calcium” to be “Screening corrected calcium” for eligibility criterion 4.1.4. •Changed number of screening attempts permitted from a maximum of 4 to a maximum of 3. •Clarified that the eDiary will capture the number of capsules or milliliters suspension administered. •Added ionized calcium at week 1 in the Schedule of Assessments. Changed the endpoints to match wording provided in a regulatory response from the US FDA. •Added text to specify that subjects who complete this 26-week study may be eligible to participate in an extension study (Study 20140159). •Clarified that Amgen must be contacted prior to dispensing new bottle(s) of IP in the event unused medication or empty bottles have been permanently misplaced.

Were there any global interruptions to the trial? Yes

Date	Interruption	Restart date
07 Feb 2013	The study and enrollment was placed on partial clinical hold by Amgen and the FDA in February 2013 following the death of a patient in another cinacalcet pediatric study. Following the death, the IRB recommended changes to all of the cinacalcet pediatric studies, which resulted in changes to the protocol; Study 20110100 was restarted in April 2014 following these changes.	23 Apr 2014

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: An Open-label, Single-arm Study to Assess the Safety and Tolerability of Cinacalcet HCl in Addition to Standard of Care in Pediatric Subjects Age 28 Days to < 6 years With Chronic Kidney Disease and Secondary Hyperparathyroidism Receiving Dialysis

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of participants with Hypocalcemia

Primary: Percentage of participants with Hypocalcemia

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

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

Secondary: Percent Change From Baseline in Intact Parathyroid Hormone (iPTH)

Secondary: Percent Change From Baseline in Intact Parathyroid Hormone (iPTH)

Secondary: Percent Change From Baseline in Corrected Serum Calcium

Secondary: Percent Change From Baseline in Corrected Serum Calcium

Secondary: Percent Change From Baseline in Serum Phosphorous

Secondary: Percent Change From Baseline in Serum Phosphorous

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

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

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

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

Secondary: Percentage of Participants Who Achieved ≥ 30% Reduction in Intact Parathyroid Hormone From Baseline During the Study

Secondary: Percentage of Participants Who Achieved ≥ 30% Reduction in Intact Parathyroid Hormone From Baseline During the Study

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

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

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

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

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

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

Secondary: Dose- and Weight-Normalized Area under the Plasma Concentration-time Curve from Time 0 to the Time of Last Quantifiable Concentration (AUClast) for Cinacalcet

Secondary: Dose- and Weight-Normalized Area under the Plasma Concentration-time Curve from Time 0 to the Time of Last Quantifiable Concentration (AUClast) for Cinacalcet

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
An Open-label, Single-arm Study to Assess the Safety and Tolerability of Cinacalcet HCl in Addition to Standard of Care in Pediatric Subjects Age 28 Days to < 6 years With Chronic Kidney Disease and Secondary Hyperparathyroidism Receiving Dialysis