A Study to Evaluate the Safety of Paricalcitol Capsules in Pediatric Subjects Ages 10 to 16 With Stage 5 Chronic Kidney Disease Receiving Peritoneal Dialysis or Hemodialysis

• ClinicalTrials.gov Identifier: NCT01382212
• Recruitment Status: Completed
• First Posted: June 27, 2011
• Results First Posted: November 21, 2016
• Last Update Posted: July 2, 2018
• Sponsor: AbbVie (prior sponsor, Abbott)
• Information provided by (Responsible Party): AbbVie ( AbbVie (prior sponsor, Abbott) )

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: End-Stage Renal Disease; Secondary Hyperparathyroidism
• Intervention: Drug: paricalcitol
• Enrollment: 13

Participant Flow

Recruitment Details
Pre-assignment Details	A total of 26 subjects were screened and 13 pediatric subjects (between 10 and 16 years of age) were enrolled; 1 subject was 16 years of age at the time of Screening and turned 17 by the time treatment began.

Arm/Group Title	Paricalcitol
Arm/Group Description	Open-label paricalcitol (maximum dose of 16 µg), 3 times weekly (no more frequently than every other day) for 12 weeks.
Period Title: Overall Study
Started	13
Completed	11
Not Completed	2
Reason Not Completed
Kidney transplant	1
Withdrew consent	1

Baseline Characteristics

Arm/Group Title		Paricalcitol
Arm/Group Description		Open-label paricalcitol (maximum dose of 16 µg), 3 times weekly (no more frequently than every other day) for 12 weeks.
Overall Number of Baseline Participants		13
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	13 participants
		14.5 (1.76)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	13 participants
	Female	8 61.5%
	Male	5 38.5%

Outcome Measures

1. Primary Outcome

Title	Percentage of Subjects With Hypercalcemia
Description	The percentage of subjects with hypercalcemia, defined as at least 2 consecutive post-baseline corrected calcium values > 10.2 mg/dL (2.55 mmol/L).
Time Frame	Day 1 to Week 12

Outcome Measure Data

Analysis Population Description

All-treated data set: all subjects enrolled and administered at least 1 dose of paricalcitol

Arm/Group Title	Paricalcitol
Arm/Group Description:	Open-label paricalcitol (maximum dose of 16 µg), 3 times weekly (no more frequently than every other day) for 12 weeks.
Overall Number of Participants Analyzed	13
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	15.3; (1.9 to 45.4)

2. Secondary Outcome

Title	Percentage of Subjects With 2 Consecutive Intact Parathyroid Hormone (iPTH)/120 Between 150 and 300 pg/mL
Description	[Not Specified]
Time Frame	Baseline (last measurement collected prior to the first dose) to Week 12

Outcome Measure Data

Analysis Population Description

All-treated data set

Arm/Group Title	Paricalcitol
Arm/Group Description:	Open-label paricalcitol (maximum dose of 16 µg), 3 times weekly (no more frequently than every other day) for 12 weeks.
Overall Number of Participants Analyzed	13
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	38.5; (13.9 to 68.4)

3. Secondary Outcome

Title	Percentage of Subjects With 2 Consecutive iPTH Reductions of at Least 30% From Baseline
Description	[Not Specified]
Time Frame	Baseline (last measurement collected prior to the first dose) to Week 12

Outcome Measure Data

Analysis Population Description

All-treated data set

Arm/Group Title	Paricalcitol
Arm/Group Description:	Open-label paricalcitol (maximum dose of 16 µg), 3 times weekly (no more frequently than every other day) for 12 weeks.
Overall Number of Participants Analyzed	13
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	61.5; (31.6 to 86.1)

4. Secondary Outcome

Title	Hemoglobin: Mean Change From Baseline to Final Visit
Description	[Not Specified]
Time Frame	Baseline (last measurement collected prior to the first dose) to Final Visit (up to Week 12)

Outcome Measure Data

Analysis Population Description

All subjects in the all-treated data set with evaluable data

Arm/Group Title	Paricalcitol
Arm/Group Description:	Open-label paricalcitol (maximum dose of 16 µg), 3 times weekly (no more frequently than every other day) for 12 weeks.
Overall Number of Participants Analyzed	11
Mean (Standard Deviation); Unit of Measure: g/dL
	-0.1 (1.263)

5. Secondary Outcome

Title	Hematocrit: Mean Change From Baseline to Final Visit
Description	[Not Specified]
Time Frame	Baseline (last measurement collected prior to the first dose) to Final Visit (up to Week 12)

Outcome Measure Data

Analysis Population Description

All subjects in the all-treated data set with evaluable data

Arm/Group Title	Paricalcitol
Arm/Group Description:	Open-label paricalcitol (maximum dose of 16 µg), 3 times weekly (no more frequently than every other day) for 12 weeks.
Overall Number of Participants Analyzed	11
Mean (Standard Deviation); Unit of Measure: percent
	-1.08 (5.066)

6. Secondary Outcome

Title	Red Blood Cells: Mean Change From Baseline to Final Visit
Description	[Not Specified]
Time Frame	Baseline (last measurement collected prior to the first dose) to Final Visit (up to Week 12)

Outcome Measure Data

Analysis Population Description

All subjects in the all-treated data set with evaluable data

Arm/Group Title	Paricalcitol
Arm/Group Description:	Open-label paricalcitol (maximum dose of 16 µg), 3 times weekly (no more frequently than every other day) for 12 weeks.
Overall Number of Participants Analyzed	11
Mean (Standard Deviation); Unit of Measure: cells x 10^6/µL
	-0.09 (0.496)

7. Secondary Outcome

Title	White Blood Cells (WBC) and Platelet Count: Mean Change From Baseline to Final Visit
Description	[Not Specified]
Time Frame	Baseline (last measurement collected prior to the first dose) to Final Visit (up to Week 12)

Outcome Measure Data

Analysis Population Description

All subjects in the all-treated data set with evaluable data

Arm/Group Title	Paricalcitol
Arm/Group Description:	Open-label paricalcitol (maximum dose of 16 µg), 3 times weekly (no more frequently than every other day) for 12 weeks.
Overall Number of Participants Analyzed	11
Mean (Standard Deviation); Unit of Measure: cells x 10^3/µL
WBC	-0.06 (2.982)
Platelet Count	19.2 (47.03)

8. Secondary Outcome

Title	Neutrophils, Lymphocytes, Monocytes, Eosinophils, and Basophils: Mean Change From Baseline to Final Visit
Description	[Not Specified]
Time Frame	Baseline (last measurement collected prior to the first dose) to Final Visit (up to Week 12)

Outcome Measure Data

Analysis Population Description

All subjects in the all-treated data set with evaluable data

Arm/Group Title	Paricalcitol
Arm/Group Description:	Open-label paricalcitol (maximum dose of 16 µg), 3 times weekly (no more frequently than every other day) for 12 weeks.
Overall Number of Participants Analyzed	11
Mean (Standard Deviation); Unit of Measure: cells x 10^9/µL
Neutrophils	0.11 (2.6812)
Lymphocytes	-0.294 (0.597)
Monocytes	0.032 (0.1276)
Eosinophils	0.059 (0.1522)
Basophils	-0.01 (0.0322)

9. Secondary Outcome

Title	Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactic Dehydrogenase (LDH), and Bone-Specific Alkaline Phosphatase (BSAP): Mean Change From Baseline to Final Visit
Description	n=subjects with evaluable Baseline and Post-baseline data for each parameter.
Time Frame	Baseline (last measurement collected prior to the first dose) to Final Visit (up to Week 12)

Outcome Measure Data

Analysis Population Description

All subjects in the all-treated data set with evaluable data

Arm/Group Title	Paricalcitol
Arm/Group Description:	Open-label paricalcitol (maximum dose of 16 µg), 3 times weekly (no more frequently than every other day) for 12 weeks.
Overall Number of Participants Analyzed	11
Mean (Standard Deviation); Unit of Measure: U/L
ALT (n=11)	-4.55 (16.501)
AST (n=11)	-4.45 (12.25)
LDH (n=11)	-6.5 (33.22)
BSAP (n=9)	-49.4 (86.95)

10. Secondary Outcome

Title	Bilirubin, Blood Urea Nitrogen (BUN), Uric Acid, Magnesium, Glucose, Cholesterol, Triglycerides, High Sensitivity C-Reactive Protein (hsCRP), Inorganic Phosphate, Corrected Calcium, and Creatinine: Mean Change From Baseline to Final Visit
Description	n=subjects with evaluable Baseline and Post-baseline data for each parameter.
Time Frame	Baseline (last measurement collected prior to the first dose) to Final Visit (up to Week 12)

Outcome Measure Data

Analysis Population Description

All subjects in the all-treated data set with evaluable data

Arm/Group Title	Paricalcitol
Arm/Group Description:	Open-label paricalcitol (maximum dose of 16 µg), 3 times weekly (no more frequently than every other day) for 12 weeks.
Overall Number of Participants Analyzed	11
Mean (Standard Deviation); Unit of Measure: mg/dL
Total bilirubin (n=11)	0.032 (0.3165)
Direct Bilirubin (n=11)	0.013 (0.0785)
Indirect Bilirubin (n=9)	0.056 (0.3035)
BUN (n=11)	1.33 (11.614)
Uric Acid (n=11)	0.31 (1.245)
Magnesium (n=11)	0.082 (0.3649)
Glucose (n=11)	4.36 (10.172)
Cholesterol (n=11)	-16.4 (27.37)
Triglycerides (n=11)	9.2 (40.32)
hsCRP (n=11)	0.061 (0.1967)
Inorganic phosphate (n=13)	0.64 (1.188)
Corrected Calcium (n=7)	0.31 (0.421)
Creatinine (n=11)	0.48 (1.592)

11. Secondary Outcome

Title	Alkaline Phosphatase: Mean Change From Baseline to Final Visit
Description	[Not Specified]
Time Frame	Baseline (last measurement collected prior to the first dose) to Final Visit (up to Week 12)

Outcome Measure Data

Analysis Population Description

All subjects in the all-treated data set with evaluable data

Arm/Group Title	Paricalcitol
Arm/Group Description:	Open-label paricalcitol (maximum dose of 16 µg), 3 times weekly (no more frequently than every other day) for 12 weeks.
Overall Number of Participants Analyzed	11
Mean (Standard Deviation); Unit of Measure: IU/L
	-61.8 (117.34)

12. Secondary Outcome

Title	Sodium, Potassium, Chloride, Bicarbonate: Mean Change From Baseline to Final Visit
Description	[Not Specified]
Time Frame	Baseline (last measurement collected prior to the first dose) to Final Visit (up to Week 12)

Outcome Measure Data

Analysis Population Description

All subjects in the all-treated data set with evaluable data

Arm/Group Title	Paricalcitol
Arm/Group Description:	Open-label paricalcitol (maximum dose of 16 µg), 3 times weekly (no more frequently than every other day) for 12 weeks.
Overall Number of Participants Analyzed	11
Mean (Standard Deviation); Unit of Measure: mEq/L
Sodium	-0.5 (2.02)
Potassium	0.25 (0.746)
Chloride	0.5 (3.21)
Bicarbonate	-0.45 (3.446)

13. Secondary Outcome

Title	Total Protein and Albumin: Mean Change From Baseline to Final Visit
Description	n=subjects with evaluable Baseline and Post-baseline data for each parameter.
Time Frame	Baseline (last measurement collected prior to the first dose) to Final Visit (up to Week 12)

Outcome Measure Data

Analysis Population Description

All-treated data set

Arm/Group Title	Paricalcitol
Arm/Group Description:	Open-label paricalcitol (maximum dose of 16 µg), 3 times weekly (no more frequently than every other day) for 12 weeks.
Overall Number of Participants Analyzed	13
Mean (Standard Deviation); Unit of Measure: g/dL
Total protein (n=11)	0.15 (0.43)
Albumin (n=13)	0.04 (0.325)

14. Secondary Outcome

Title	Fibroblast Growth Factor-23 (FGF-23), 1,25-Hydroxy Vitamin D, 25-Hydroxy Vitamin D, and Intact Parathyroid Hormone (iPTH): Mean Change From Baseline to Final Visit
Description	n=subjects with evaluable Baseline and Post-baseline data for each parameter.
Time Frame	Baseline (last measurement collected prior to the first dose) to Final Visit (up to Week 12)

Outcome Measure Data

Analysis Population Description

All-treated data set

Arm/Group Title	Paricalcitol
Arm/Group Description:	Open-label paricalcitol (maximum dose of 16 µg), 3 times weekly (no more frequently than every other day) for 12 weeks.
Overall Number of Participants Analyzed	13
Mean (Standard Deviation); Unit of Measure: pg/mL
FGF-23 (n=10)	1990.7 (3317.7)
1,25-Hydroxy Vitamin D (n=11)	15.65 (29.296)
25-Hydroxy Vitamin D (n=11)	5.8 (10.38)
iPTH (n=13)	-437.5 (491.83)

15. Secondary Outcome

Title	Osteocalcin: Mean Change From Baseline to Final Visit
Description	[Not Specified]
Time Frame	Baseline (last measurement collected prior to the first dose) to Final Visit (up to Week 12)

Outcome Measure Data

Analysis Population Description

All subjects in the all-treated data set with evaluable data

Arm/Group Title	Paricalcitol
Arm/Group Description:	Open-label paricalcitol (maximum dose of 16 µg), 3 times weekly (no more frequently than every other day) for 12 weeks.
Overall Number of Participants Analyzed	10
Mean (Standard Deviation); Unit of Measure: ng/mL
	117.21 (223.07)

16. Secondary Outcome

Title	Number of Subjects With Adverse Events
Description	An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the subject and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent events (TEAEs/TESAEs) are defined as any event that began or worsened in severity after the first dose of study drug. For more details on adverse events please see the Adverse Event section.
Time Frame	From first dose of study drug until 30 days following last dose of study drug (up to 16 weeks).

Outcome Measure Data

Analysis Population Description

All-treated data set

Arm/Group Title	Paricalcitol
Arm/Group Description:	Open-label paricalcitol (maximum dose of 16 µg), 3 times weekly (no more frequently than every other day) for 12 weeks.
Overall Number of Participants Analyzed	13
Measure Type: Number; Unit of Measure: participants
Any TEAE	11
TESAE	2

17. Secondary Outcome

Title	Number of Subjects With Potentially Clinically Significant Electrocardiogram (ECG) Findings
Description	12-lead ECGs were recorded after the subject had been in the supine position for at least 5 minutes. The number of subjects with potentially clinically significant ECG findings, as determined by the investigator, is presented.
Time Frame	Baseline (Day 1) to Final Visit (up to Week 12)

Outcome Measure Data

Analysis Population Description

All-treated data set

Arm/Group Title	Paricalcitol
Arm/Group Description:	Open-label paricalcitol (maximum dose of 16 µg), 3 times weekly (no more frequently than every other day) for 12 weeks.
Overall Number of Participants Analyzed	13
Measure Type: Number; Unit of Measure: participants
	0

18. Secondary Outcome

Title	Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP): Mean Change From Baseline to Final Visit
Description	Blood pressure was measured after the subject had been sitting for at least 3 minutes.
Time Frame	Baseline (last measurement collected prior to the first dose) to Final Visit (up to Week 12)

Outcome Measure Data

Analysis Population Description

All-treated data set

Arm/Group Title	Paricalcitol
Arm/Group Description:	Open-label paricalcitol (maximum dose of 16 µg), 3 times weekly (no more frequently than every other day) for 12 weeks.
Overall Number of Participants Analyzed	13
Mean (Standard Deviation); Unit of Measure: mm Hg
SBP	7.5 (15.66)
DBP	3.7 (12.98)

19. Secondary Outcome

Title	Heart Rate: Mean Change From Baseline to Final Visit
Description	Heart rate was measured after the subject had been sitting for at least 3 minutes.
Time Frame	Baseline (last measurement collected prior to the first dose) to Final Visit (up to Week 12)

Outcome Measure Data

Analysis Population Description

All-treated data set

Arm/Group Title	Paricalcitol
Arm/Group Description:	Open-label paricalcitol (maximum dose of 16 µg), 3 times weekly (no more frequently than every other day) for 12 weeks.
Overall Number of Participants Analyzed	13
Mean (Standard Deviation); Unit of Measure: bpm
	1.8 (17.43)

20. Secondary Outcome

Title	Oral Body Temperature: Mean Change From Baseline to Final Visit
Description	[Not Specified]
Time Frame	Baseline (last measurement collected prior to the first dose) to Final Visit (up to Week 12)

Outcome Measure Data

Analysis Population Description

All-treated data set

Arm/Group Title	Paricalcitol
Arm/Group Description:	Open-label paricalcitol (maximum dose of 16 µg), 3 times weekly (no more frequently than every other day) for 12 weeks.
Overall Number of Participants Analyzed	13
Mean (Standard Deviation); Unit of Measure: degrees Celsius
	0.03 (0.338)

21. Secondary Outcome

Title	Number of Subjects With Potentially Clinically Significant Physical Examination Findings
Description	[Not Specified]
Time Frame	Baseline (Day 1) and Final Visit (up to Week 12)

Outcome Measure Data

Analysis Population Description

All-treated data set

Arm/Group Title	Paricalcitol
Arm/Group Description:	Open-label paricalcitol (maximum dose of 16 µg), 3 times weekly (no more frequently than every other day) for 12 weeks.
Overall Number of Participants Analyzed	13
Measure Type: Number; Unit of Measure: participants
	0

Adverse Events

Time Frame	Treatment-emergent adverse events were collected from first dose of study drug until 30 days following last dose of study drug (up to 16 weeks); serious adverse events were collected from the time when informed consent was obtained (up to 28 weeks).
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Paricalcitol
Arm/Group Description	Open-label paricalcitol (maximum dose of 16 μg), 3 times weekly (no more frequently than every other day) for 12 weeks.
All-Cause Mortality
	Paricalcitol
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Paricalcitol
	Affected / at Risk (%)
Total	2/13 (15.38%)
Injury, poisoning and procedural complications
PERITONEAL DIALYSIS COMPLICATION † 1	1/13 (7.69%)
Metabolism and nutrition disorders
FLUID OVERLOAD † 1	1/13 (7.69%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 17.1
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Paricalcitol
	Affected / at Risk (%)
Total	10/13 (76.92%)
Gastrointestinal disorders
ABDOMINAL PAIN † 1	1/13 (7.69%)
ABDOMINAL PAIN UPPER † 1	1/13 (7.69%)
DIARRHOEA † 1	1/13 (7.69%)
NAUSEA † 1	2/13 (15.38%)
VOMITING † 1	1/13 (7.69%)
General disorders
INFLUENZA LIKE ILLNESS † 1	1/13 (7.69%)
PYREXIA † 1	2/13 (15.38%)
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION † 1	1/13 (7.69%)
Injury, poisoning and procedural complications
ARTERIOVENOUS FISTULA SITE COMPLICATION † 1	1/13 (7.69%)
PROCEDURAL PAIN † 1	1/13 (7.69%)
PROCEDURAL VOMITING † 1	1/13 (7.69%)
Investigations
BLOOD CALCIUM INCREASED † 1	1/13 (7.69%)
HAEMOGLOBIN DECREASED † 1	1/13 (7.69%)
Metabolism and nutrition disorders
HYPERPHOSPHATAEMIA † 1	1/13 (7.69%)
Musculoskeletal and connective tissue disorders
BACK PAIN † 1	1/13 (7.69%)
PAIN IN EXTREMITY † 1	1/13 (7.69%)
Nervous system disorders
HEADACHE † 1	1/13 (7.69%)
Respiratory, thoracic and mediastinal disorders
COUGH † 1	2/13 (15.38%)
THROAT IRRITATION † 1	1/13 (7.69%)
Skin and subcutaneous tissue disorders
PRURITUS † 1	1/13 (7.69%)
Vascular disorders
HYPERTENSION † 1	1/13 (7.69%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 17.1

Limitations and Caveats

The sample size of the study was limited to 13 subjects and there was no comparator group, so the study was not designed to analyze efficacy.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.

Results Point of Contact

• Name/Title: Global Medical Information
• Organization: AbbVie
• Phone: 800-633-9110

Publications of Results:

Webb NJA, Lerner G, Warady BA, Dell KM, Greenbaum LA, Ariceta G, Hoppe B, Linde P, Lee HJ, Eldred A, Dufek MB. Efficacy and safety of paricalcitol in children with stages 3 to 5 chronic kidney disease. Pediatr Nephrol. 2017 Jul;32(7):1221-1232. doi: 10.1007/s00467-017-3579-6. Epub 2017 Mar 22.

• Responsible Party: AbbVie ( AbbVie (prior sponsor, Abbott) )
• ClinicalTrials.gov Identifier: NCT01382212
• Other Study ID Numbers: M11-612; 2013-002610-13 ( EudraCT Number )
• First Submitted: June 24, 2011
• First Posted: June 27, 2011
• Results First Submitted: September 16, 2016
• Results First Posted: November 21, 2016
• Last Update Posted: July 2, 2018