Trial Outcomes & Findings for Efficacy and Safety of Cinacalcet in Pediatric Patients With Secondary Hyperparathyroidism (SHPT) and Chronic Kidney Disease (CKD) on Dialysis (NCT NCT02138838)

Last Updated: 2020-06-29

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

55 participants

Primary outcome timeframe

Baseline and weeks 11 to 15

Results posted on

2020-06-29

Participant Flow

This study was conducted at 32 centers in Belgium, Czech Republic, France, Germany, Greece, Hungary, Lithuania, Poland, Portugal, Russia Federation, Slovakia, Spain, Ukraine, and the United States.

Eligible participants were randomized to 1 of 2 treatment groups in a 1:1 ratio: cinacalcet daily in addition to standard of care (SOC) therapy or SOC therapy alone. Randomization was stratified by age group (6 to \< 12 and 12 to \< 18 years). Participants remained on treatment for 20 weeks or until the time of renal transplant or parathyroidectomy.

Participant milestones

Participant milestones
Measure	Standard of Care Standard of care therapy included the use of vitamin D sterols, calcium supplementation, and phosphate binders.	Cinacalcet 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.
Overall Study STARTED	28	27
Overall Study Received Study Drug	28	25
Overall Study COMPLETED	20	16
Overall Study NOT COMPLETED	8	11

Reasons for withdrawal

Reasons for withdrawal
Measure	Standard of Care Standard of care therapy included the use of vitamin D sterols, calcium supplementation, and phosphate binders.	Cinacalcet 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.
Overall Study Study Closure	7	6
Overall Study Withdrawal by Subject	1	5

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Standard of Care n=28 Participants Standard of care therapy included the use of vitamin D sterols, calcium supplementation, and phosphate binders.	Cinacalcet n=27 Participants 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.	Total n=55 Participants Total of all reporting groups
Age, Customized 12 to < 18 years	19 participants n=5 Participants	18 participants n=7 Participants	37 participants n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants	12 Participants n=7 Participants	27 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	15 Participants n=7 Participants	28 Participants n=5 Participants
Race/Ethnicity, Customized Black (or African American)	4 participants n=5 Participants	5 participants n=7 Participants	9 participants n=5 Participants
Race/Ethnicity, Customized White	23 participants n=5 Participants	19 participants n=7 Participants	42 participants n=5 Participants
Race/Ethnicity, Customized Mixed Race	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Other	1 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants
Race/Ethnicity, Customized Hispanic/Latino	4 participants n=5 Participants	0 participants n=7 Participants	4 participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic/Latino	24 participants n=5 Participants	27 participants n=7 Participants	51 participants n=5 Participants
Intact Parathyroid Hormone Level	1228.43 pg/mL STANDARD_DEVIATION 732.08 • n=5 Participants	945.72 pg/mL STANDARD_DEVIATION 635.35 • n=7 Participants	1092.31 pg/mL STANDARD_DEVIATION 695.53 • n=5 Participants
Age, Customized 6 to < 12 years	9 participants n=5 Participants	9 participants n=7 Participants	18 participants n=5 Participants
Age, Continuous	12.4 years STANDARD_DEVIATION 3.5 • n=5 Participants	12.8 years STANDARD_DEVIATION 3.9 • n=7 Participants	12.6 years STANDARD_DEVIATION 3.6 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and weeks 11 to 15

Population: 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).

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.

Outcome measures

Outcome measures
Measure	Standard of Care n=28 Participants Standard of care therapy included the use of vitamin D sterols, calcium supplementation, and phosphate binders.	Cinacalcet n=27 Participants 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.
Percentage of Participants Who Achieved a ≥ 30% Reduction From Baseline In Mean Plasma iPTH During Weeks 11 to 15	17.9 percentage of participants	25.9 percentage of participants

PRIMARY outcome

Timeframe: Baseline and the efficacy assessment period (EAP), weeks 17 to 20

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Standard of Care n=28 Participants Standard of care therapy included the use of vitamin D sterols, calcium supplementation, and phosphate binders.	Cinacalcet n=27 Participants 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.
Percentage of Participants Who Achieved a ≥ 30% Reduction From Baseline in Mean Plasma Intact Parathyroid Hormone During the Efficacy Assessment Period	32.1 percentage of participants	22.2 percentage of participants

SECONDARY outcome

Timeframe: Efficacy assessment period, weeks 17 to 20

Population: 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.

Outcome measures

Outcome measures
Measure	Standard of Care n=28 Participants Standard of care therapy included the use of vitamin D sterols, calcium supplementation, and phosphate binders.	Cinacalcet n=27 Participants 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.
Percentage of Participants Who Achieved a Mean iPTH ≤ 300 pg/mL (31.8 Pmol/L) During Weeks 17 to 20	17.9 percentage of participants	7.4 percentage of participants

SECONDARY outcome

Timeframe: Baseline and weeks 17 to 20

Population: 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.

Outcome measures

Outcome measures
Measure	Standard of Care n=27 Participants Standard of care therapy included the use of vitamin D sterols, calcium supplementation, and phosphate binders.	Cinacalcet n=24 Participants 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.
Percent Change in iPTH From Baseline to the Mean Value During Weeks 17 to 20	-11.3 percent change Standard Error 11.10	7.7 percent change Standard Error 11.73

SECONDARY outcome

Timeframe: Baseline and weeks 17 to 20

Population: 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.

Outcome measures

Outcome measures
Measure	Standard of Care n=28 Participants Standard of care therapy included the use of vitamin D sterols, calcium supplementation, and phosphate binders.	Cinacalcet n=24 Participants 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.
Change in Corrected Serum Calcium From Baseline to the Mean Value During Weeks 17 to 20	0.06 mg/dL Standard Error 0.126	-0.28 mg/dL Standard Error 0.135

SECONDARY outcome

Timeframe: Baseline and weeks 17 to 20

Population: 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.

Outcome measures

Outcome measures
Measure	Standard of Care n=26 Participants Standard of care therapy included the use of vitamin D sterols, calcium supplementation, and phosphate binders.	Cinacalcet n=24 Participants 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.
Change in Serum Phosphorus From Baseline to the Mean Value During Weeks 17 to 20	-0.09 mg/dL Standard Error 0.258	0.67 mg/dL Standard Error 0.266

Adverse Events

Standard of Care

Serious events: 2 serious events

Other events: 17 other events

Deaths: 0 deaths

Cinacalcet

Serious events: 4 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Standard of Care n=30 participants at risk Standard of care therapy included the use of vitamin D sterols, calcium supplementation, and phosphate binders.	Cinacalcet n=25 participants at risk 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.
Gastrointestinal disorders Ileus	0.00% 0/30 • 24 Weeks 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.	4.0% 1/25 • 24 Weeks 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.
Infections and infestations Bacterial infection	3.3% 1/30 • 24 Weeks 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.	0.00% 0/25 • 24 Weeks 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.
Infections and infestations Device related infection	0.00% 0/30 • 24 Weeks 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.	4.0% 1/25 • 24 Weeks 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.
Infections and infestations Peritonitis	0.00% 0/30 • 24 Weeks 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.	4.0% 1/25 • 24 Weeks 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.
Infections and infestations Postoperative wound infection	0.00% 0/30 • 24 Weeks 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.	4.0% 1/25 • 24 Weeks 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.
Infections and infestations Soft tissue infection	0.00% 0/30 • 24 Weeks 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.	4.0% 1/25 • 24 Weeks 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.
Injury, poisoning and procedural complications Arteriovenous fistula site haemorrhage	0.00% 0/30 • 24 Weeks 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.	4.0% 1/25 • 24 Weeks 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.
Metabolism and nutrition disorders Fluid overload	0.00% 0/30 • 24 Weeks 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.	4.0% 1/25 • 24 Weeks 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.
Product Issues Device dislocation	0.00% 0/30 • 24 Weeks 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.	4.0% 1/25 • 24 Weeks 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.
Respiratory, thoracic and mediastinal disorders Asthma	3.3% 1/30 • 24 Weeks 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.	0.00% 0/25 • 24 Weeks 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.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/30 • 24 Weeks 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.	4.0% 1/25 • 24 Weeks 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.
Vascular disorders Renovascular hypertension	0.00% 0/30 • 24 Weeks 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.	4.0% 1/25 • 24 Weeks 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.

Other adverse events

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Results disclosure agreements

Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Publication restrictions are in place

Restriction type: OTHER