Trial Outcomes & Findings for Safety & Tolerability of Cinacalcet in Pediatric Patients With Chronic Kidney Disease and Secondary Hyperparathyroidism (NCT NCT01439867)

Last Updated: 2020-06-17

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

18 participants

Primary outcome timeframe

26 weeks

Results posted on

2020-06-17

Participant Flow

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 United States (6 sites). The first participant was enrolled on 22 June 2012, and the last participant completed the study on 03 June 2016.

Because of changes to the study design that were implemented after the partial clinical hold, data are presented overall and for 2 cohorts: participants enrolled before the partial clinical hold (Cohort 1) and participants enrolled after the partial clinical hold (Cohort 2).

Participant milestones

Participant milestones
Measure	Cohort 1 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 2 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.
Overall Study STARTED	8	10
Overall Study Received Treatment	7	10
Overall Study COMPLETED	2	2
Overall Study NOT COMPLETED	6	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1 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 2 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.
Overall Study Non-compliance	0	1
Overall Study Withdrawal by Subject	1	2
Overall Study Administrative Decision	4	5
Overall Study Protocol-specified Criteria	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1 n=8 Participants 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 2 n=10 Participants 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.	Total n=18 Participants Total of all reporting groups
Sex: Female, Male Female	3 Participants n=99 Participants	3 Participants n=107 Participants	6 Participants n=206 Participants
Sex: Female, Male Male	5 Participants n=99 Participants	7 Participants n=107 Participants	12 Participants n=206 Participants
Age, Continuous	37.1 months STANDARD_DEVIATION 18.9 • n=99 Participants	35.0 months STANDARD_DEVIATION 15.9 • n=107 Participants	35.9 months STANDARD_DEVIATION 16.8 • n=206 Participants
Age, Customized 28 days to < 2 years	2 participants n=99 Participants	1 participants n=107 Participants	3 participants n=206 Participants
Age, Customized 2 years to < 6 years	6 participants n=99 Participants	9 participants n=107 Participants	15 participants n=206 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants n=99 Participants	0 participants n=107 Participants	0 participants n=206 Participants
Race/Ethnicity, Customized Asian	0 participants n=99 Participants	0 participants n=107 Participants	0 participants n=206 Participants
Race/Ethnicity, Customized Black or African American	1 participants n=99 Participants	1 participants n=107 Participants	2 participants n=206 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 participants n=99 Participants	0 participants n=107 Participants	0 participants n=206 Participants
Race/Ethnicity, Customized White	6 participants n=99 Participants	9 participants n=107 Participants	15 participants n=206 Participants
Race/Ethnicity, Customized Other	1 participants n=99 Participants	0 participants n=107 Participants	1 participants n=206 Participants
Race/Ethnicity, Customized Hispanic or Latino	1 participants n=99 Participants	2 participants n=107 Participants	3 participants n=206 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	7 participants n=99 Participants	8 participants n=107 Participants	15 participants n=206 Participants
Corrected Serum Calcium	10.56 mg/dL STANDARD_DEVIATION 0.75 • n=99 Participants	9.82 mg/dL STANDARD_DEVIATION 0.61 • n=107 Participants	10.15 mg/dL STANDARD_DEVIATION 0.76 • n=206 Participants
Intact Parathyroid Hormone	1414.34 pg/mL STANDARD_DEVIATION 699.90 • n=99 Participants	1206.92 pg/mL STANDARD_DEVIATION 597.85 • n=107 Participants	1299.11 pg/mL STANDARD_DEVIATION 634.18 • n=206 Participants

PRIMARY outcome

Timeframe: 26 weeks

Population: 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).

Outcome measures

Outcome measures
Measure	Cohort 1 n=7 Participants 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 2 n=10 Participants 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.	Total n=17 Participants Participants received cinacalcet administered daily for 24 weeks.
Percentage of Participants With Hypocalcemia	0.0 percentage of participants Interval 0.0 to 34.8	0.0 percentage of participants Interval 0.0 to 25.9	0.0 percentage of participants Interval 0.0 to 16.2

SECONDARY outcome

Timeframe: 26 weeks

Population: 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).

Outcome measures

Outcome measures
Measure	Cohort 1 n=7 Participants 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 2 n=10 Participants 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.	Total n=17 Participants Participants received cinacalcet administered daily for 24 weeks.
Percentage of Participants With Corrected Serum Calcium Levels < 8.8 mg/dL (2.2 mmol/L) During the Study	14.3 percentage of participants Interval 0.7 to 52.1	10.0 percentage of participants Interval 0.5 to 39.4	11.8 percentage of participants Interval 2.1 to 32.6

SECONDARY outcome

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

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

Outcome measures

Outcome measures
Measure	Cohort 1 n=7 Participants 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 2 n=10 Participants 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.	Total n=17 Participants Participants received cinacalcet administered daily for 24 weeks.
Percent Change From Baseline in Intact Parathyroid Hormone (iPTH) Week 15 (n = 2, 7, 9)	-65.31 percent change Standard Deviation 6.83	-51.69 percent change Standard Deviation 39.91	-54.71 percent change Standard Deviation 35.16
Percent Change From Baseline in Intact Parathyroid Hormone (iPTH) Week 19 (n = 1, 3, 4)	-79.02 percent change Standard Deviation NA Could not be calculated for a sample size = 1	-57.35 percent change Standard Deviation 32.86	-62.76 percent change Standard Deviation 28.93
Percent Change From Baseline in Intact Parathyroid Hormone (iPTH) Week 3 (n = 7, 9, 16)	-22.96 percent change Standard Deviation 64.67	-3.37 percent change Standard Deviation 54.82	-11.94 percent change Standard Deviation 58.11
Percent Change From Baseline in Intact Parathyroid Hormone (iPTH) Week 7 (n = 4, 9, 13)	3.87 percent change Standard Deviation 110.94	-3.13 percent change Standard Deviation 52.94	-0.98 percent change Standard Deviation 70.40
Percent Change From Baseline in Intact Parathyroid Hormone (iPTH) Week 11 (n = 4, 8, 12)	-51.70 percent change Standard Deviation 27.18	-7.15 percent change Standard Deviation 75.30	-22.00 percent change Standard Deviation 65.51
Percent Change From Baseline in Intact Parathyroid Hormone (iPTH) Week 22 (n = 0, 1, 1)	NA percent change Standard Deviation NA No participants with available data	-78.04 percent change Standard Deviation NA Could not be calculated for a sample size = 1	-78.04 percent change Standard Deviation NA Could not be calculated for a sample size = 1
Percent Change From Baseline in Intact Parathyroid Hormone (iPTH) Week 24 (n = 0, 1, 1)	NA percent change Standard Deviation NA No participants with available data	-67.42 percent change Standard Deviation NA Could not be calculated for a sample size = 1	-67.42 percent change Standard Deviation NA Could not be calculated for a sample size = 1

SECONDARY outcome

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

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

Outcome measures

Outcome measures
Measure	Cohort 1 n=7 Participants 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 2 n=10 Participants 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.	Total n=17 Participants Participants received cinacalcet administered daily for 24 weeks.
Percent Change From Baseline in Corrected Serum Calcium Week 7 (n = 4, 8, 12)	-3.58 percent change Standard Deviation 12.23	3.60 percent change Standard Deviation 9.31	1.21 percent change Standard Deviation 10.41
Percent Change From Baseline in Corrected Serum Calcium Week 11 (n = 4, 8, 12)	-3.23 percent change Standard Deviation 10.51	1.46 percent change Standard Deviation 5.24	-0.10 percent change Standard Deviation 7.28
Percent Change From Baseline in Corrected Serum Calcium Week 3 (n = 7, 10, 17)	-0.50 percent change Standard Deviation 4.47	3.43 percent change Standard Deviation 6.38	1.81 percent change Standard Deviation 5.86
Percent Change From Baseline in Corrected Serum Calcium Week 15 (n = 2, 7, 9)	-6.86 percent change Standard Deviation 12.44	2.99 percent change Standard Deviation 5.09	0.80 percent change Standard Deviation 7.59
Percent Change From Baseline in Corrected Serum Calcium Week 19 (n = 1, 3, 4)	1.94 percent change Standard Deviation NA Could not be calculated for a sample size of 1	-0.49 percent change Standard Deviation 6.62	0.12 percent change Standard Deviation 5.54
Percent Change From Baseline in Corrected Serum Calcium Week 22 (n = 0, 1, 1)	NA percent change Standard Deviation NA No participants with available data	5.88 percent change Standard Deviation NA Could not be calculated for a sample size of 1	5.88 percent change Standard Deviation NA Could not be calculated for a sample size of 1
Percent Change From Baseline in Corrected Serum Calcium Week 24 (n = 0, 1, 1)	NA percent change Standard Deviation NA No participants with available data	2.94 percent change Standard Deviation NA Could not be calculated for a sample size of 1	2.94 percent change Standard Deviation NA Could not be calculated for a sample size of 1

SECONDARY outcome

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

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

Outcome measures

Outcome measures
Measure	Cohort 1 n=7 Participants 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 2 n=10 Participants 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.	Total n=17 Participants Participants received cinacalcet administered daily for 24 weeks.
Percent Change From Baseline in Serum Phosphorous Week 22 (n = 0, 1, 1)	NA percent change Standard Deviation NA No participants with available data	-1.72 percent change Standard Deviation NA Could not be calculated for a sample size of 1	-1.72 percent change Standard Deviation NA Could not be calculated for a sample size of 1
Percent Change From Baseline in Serum Phosphorous Week 3 (n = 7, 10, 17)	-10.75 percent change Standard Deviation 32.49	-5.11 percent change Standard Deviation 39.32	-7.43 percent change Standard Deviation 35.69
Percent Change From Baseline in Serum Phosphorous Week 7 (n = 4, 8, 12)	-8.68 percent change Standard Deviation 20.88	-9.60 percent change Standard Deviation 29.79	-9.29 percent change Standard Deviation 26.15
Percent Change From Baseline in Serum Phosphorous Week 11 (n = 4, 8, 12)	14.39 percent change Standard Deviation 22.18	4.54 percent change Standard Deviation 39.08	7.82 percent change Standard Deviation 33.61
Percent Change From Baseline in Serum Phosphorous Week 15 (n = 2, 7, 9)	13.99 percent change Standard Deviation 26.33	-16.07 percent change Standard Deviation 28.14	-9.39 percent change Standard Deviation 29.26
Percent Change From Baseline in Serum Phosphorous Week 19 (n = 1, 2, 3)	10.87 percent change Standard Deviation NA Could not be calculated for sample size of 1	3.45 percent change Standard Deviation 4.88	5.92 percent change Standard Deviation 5.50
Percent Change From Baseline in Serum Phosphorous Week 24 (n = 0, 1, 1)	NA percent change Standard Deviation NA No participants with available data	8.62 percent change Standard Deviation NA Could not be calculated for a sample size of 1	8.62 percent change Standard Deviation NA Could not be calculated for a sample size of 1

SECONDARY outcome

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

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

Outcome measures

Outcome measures
Measure	Cohort 1 n=7 Participants 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 2 n=10 Participants 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.	Total n=17 Participants Participants received cinacalcet administered daily for 24 weeks.
Percent Change From Baseline in Calcium Phosphorus Product (Ca x P) Week 24 (n = 0, 1, 1)	NA percent change Standard Deviation NA No participants with available data	10.96 percent change Standard Deviation NA Could not be calculated for a sample size of 1	10.96 percent change Standard Deviation NA Could not be calculated for a sample size of 1
Percent Change From Baseline in Calcium Phosphorus Product (Ca x P) Week 3 (n = 7, 10, 17)	-1.89 percent change Standard Deviation 39.00	-2.72 percent change Standard Deviation 38.08	-2.37 percent change Standard Deviation 37.23
Percent Change From Baseline in Calcium Phosphorus Product (Ca x P) Week 7 (n = 4, 8, 12)	-11.56 percent change Standard Deviation 26.35	-6.83 percent change Standard Deviation 29.97	-8.40 percent change Standard Deviation 27.68
Percent Change From Baseline in Calcium Phosphorus Product (Ca x P) Week 11 (n = 4, 8, 12)	9.48 percent change Standard Deviation 17.84	5.74 percent change Standard Deviation 38.78	6.99 percent change Standard Deviation 32.36
Percent Change From Baseline in Calcium Phosphorus Product (Ca x P) Week 15 (n = 2, 7, 9)	7.58 percent change Standard Deviation 38.39	-14.24 percent change Standard Deviation 28.24	-9.39 percent change Standard Deviation 29.58
Percent Change From Baseline in Calcium Phosphorus Product (Ca x P) Week 19 (n = 1, 2, 3)	12.34 percent change Standard Deviation NA Could not be calculated for a sample size of 1	6.41 percent change Standard Deviation 9.06	8.39 percent change Standard Deviation 7.27
Percent Change From Baseline in Calcium Phosphorus Product (Ca x P) Week 22 (n = 0, 1, 1)	NA percent change Standard Deviation NA No participants with available data	3.37 percent change Standard Deviation NA Could not be calculated for a sample size of 1	3.37 percent change Standard Deviation NA Could not be calculated for a sample size of 1

SECONDARY outcome

Timeframe: 26 weeks

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

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.

Outcome measures

Outcome measures
Measure	Cohort 1 n=7 Participants 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 2 n=10 Participants 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.	Total n=17 Participants Participants received cinacalcet administered daily for 24 weeks.
Percentage of Participants Who Achieved > 30% Reduction in iPTH From Baseline at Any Two Consecutive Measurements	57.1 percentage of participants Interval 22.5 to 87.1	40.0 percentage of participants Interval 15.0 to 69.6	47.1 percentage of participants Interval 26.0 to 68.9

SECONDARY outcome

Timeframe: 26 weeks

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

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.

Outcome measures

Outcome measures
Measure	Cohort 1 n=7 Participants 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 2 n=10 Participants 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.	Total n=17 Participants Participants received cinacalcet administered daily for 24 weeks.
Percentage of Participants Who Achieved ≥ 30% Reduction in iPTH From Baseline During the Study	100.0 percentage of participants Interval 65.2 to 100.0	50.0 percentage of participants Interval 22.2 to 77.8	70.6 percentage of participants Interval 47.8 to 87.6

SECONDARY outcome

Timeframe: 26 weeks

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

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.

Outcome measures

Outcome measures
Measure	Cohort 1 n=7 Participants 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 2 n=10 Participants 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.	Total n=17 Participants Participants received cinacalcet administered daily for 24 weeks.
Percentage of Participants Who Achieved iPTH Values Between 200 and 300 pg/mL at Any Two Consecutive Measurements	0.0 percentage of participants Interval 0.0 to 34.8	10.0 percentage of participants Interval 0.5 to 39.4	5.9 percentage of participants Interval 0.3 to 25.0

SECONDARY outcome

Timeframe: 26 weeks

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

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.

Outcome measures

Outcome measures
Measure	Cohort 1 n=7 Participants 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 2 n=10 Participants 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.	Total n=17 Participants Participants received cinacalcet administered daily for 24 weeks.
Percentage of Participants Who Achieved iPTH Values < 300 pg/mL During the Study	57.1 percentage of participants Interval 22.5 to 87.1	50.0 percentage of participants Interval 22.2 to 77.8	52.9 percentage of participants Interval 31.1 to 74.0

SECONDARY outcome

Timeframe: Week 12

Population: 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.

Outcome measures

Outcome measures
Measure	Cohort 1 n=3 Participants 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 2 n=7 Participants 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.	Total Participants received cinacalcet administered daily for 24 weeks.
Dose- and Weight-Normalized Maximum Plasma Concentration (Cmax) of Cinacalcet	15.1 ng/mL/(mgkg) Standard Deviation 16.6	17.8 ng/mL/(mgkg) Standard Deviation 10.0	—

SECONDARY outcome

Timeframe: Week 12

Population: 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.

Outcome measures

Outcome measures
Measure	Cohort 1 n=2 Participants 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 2 n=6 Participants 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.	Total Participants received cinacalcet administered daily for 24 weeks.
Dose- and Weight-Normalized Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Quantifiable Concentration (AUClast) for Cinacalcet	160 hr*ng/mL/(mgkg) Standard Deviation 195	176.8 hr*ng/mL/(mgkg) Standard Deviation 177	—

Adverse Events

Cohort 1

Serious events: 4 serious events

Other events: 5 other events

Deaths: 0 deaths

Cohort 2

Serious events: 5 serious events

Other events: 9 other events

Deaths: 0 deaths

Total

Serious events: 9 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

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.
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Restriction type: OTHER

Measure	Cohort 1 n=7 participants at risk 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 2 n=10 participants at risk 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.	Total n=17 participants at risk Participants received cinacalcet administered daily for 24 weeks.
Gastrointestinal disorders Diarrhoea	0.00% 0/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	10.0% 1/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.9% 1/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Ileus	14.3% 1/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.9% 1/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Complication associated with device	14.3% 1/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	10.0% 1/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	11.8% 2/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Adenovirus infection	0.00% 0/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	10.0% 1/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.9% 1/17 • 26 Weeks 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% 0/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	10.0% 1/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.9% 1/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Device related sepsis	14.3% 1/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.9% 1/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Influenza	14.3% 1/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.9% 1/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Upper respiratory tract infection	0.00% 0/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	10.0% 1/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.9% 1/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Overdose	14.3% 1/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.9% 1/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Peritoneal dialysis complication	0.00% 0/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	10.0% 1/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.9% 1/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Dehydration	0.00% 0/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	10.0% 1/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.9% 1/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Failure to thrive	0.00% 0/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	10.0% 1/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.9% 1/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	10.0% 1/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.9% 1/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Seizure	0.00% 0/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	10.0% 1/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.9% 1/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Product Issues Device malfunction	0.00% 0/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	10.0% 1/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.9% 1/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Hypertension	14.3% 1/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	10.0% 1/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	11.8% 2/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

Measure	Cohort 1 n=7 participants at risk 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 2 n=10 participants at risk 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.	Total n=17 participants at risk Participants received cinacalcet administered daily for 24 weeks.
Blood and lymphatic system disorders Anaemia	0.00% 0/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	10.0% 1/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.9% 1/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Ear and labyrinth disorders Ear pain	14.3% 1/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.9% 1/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Eye disorders Eye pain	14.3% 1/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.9% 1/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Constipation	0.00% 0/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	10.0% 1/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.9% 1/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Diarrhoea	14.3% 1/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	10.0% 1/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	11.8% 2/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Nausea	14.3% 1/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.9% 1/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Vomiting	28.6% 2/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	20.0% 2/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	23.5% 4/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Asthenia	0.00% 0/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	10.0% 1/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.9% 1/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Complication associated with device	14.3% 1/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.9% 1/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Pain	0.00% 0/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	10.0% 1/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.9% 1/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Pyrexia	14.3% 1/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	20.0% 2/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	17.6% 3/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Bronchitis	28.6% 2/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	11.8% 2/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Device related sepsis	14.3% 1/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.9% 1/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Laryngitis	0.00% 0/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	10.0% 1/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.9% 1/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Peritonitis	0.00% 0/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	10.0% 1/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.9% 1/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Pharyngitis	0.00% 0/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	10.0% 1/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.9% 1/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Upper respiratory tract infection	14.3% 1/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	30.0% 3/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	23.5% 4/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Viral infection	28.6% 2/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	11.8% 2/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Viral upper respiratory tract infection	14.3% 1/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.9% 1/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations Platelet count decreased	14.3% 1/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.9% 1/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Acidosis	14.3% 1/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.9% 1/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	10.0% 1/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.9% 1/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Hypophosphataemia	0.00% 0/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	10.0% 1/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.9% 1/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Lethargy	14.3% 1/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.9% 1/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Unresponsive to stimuli	0.00% 0/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	10.0% 1/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.9% 1/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Cough	14.3% 1/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	30.0% 3/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	23.5% 4/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Nasal congestion	14.3% 1/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.9% 1/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Dermatitis contact	0.00% 0/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	10.0% 1/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.9% 1/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Erythema	14.3% 1/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.9% 1/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Pruritus	14.3% 1/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.9% 1/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Surgical and medical procedures Catheter removal	14.3% 1/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.9% 1/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Hypertension	14.3% 1/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	10.0% 1/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	11.8% 2/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Hypotension	0.00% 0/7 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	10.0% 1/10 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.9% 1/17 • 26 Weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.