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Safety and Efficacy of Paricalcitol Capsules in Decreasing Serum Parathyroid Hormone Levels in Children Aged 10-16 With Chronic Kidney Disease (CKD)

Primary Purpose

Chronic Kidney Disease Stage 3 and 4

Status

Completed

Phase

Phase 3

Locations

Study Type

Interventional

Intervention

Paricalcitol

Placebo

About this trial

This is an interventional treatment trial for Chronic Kidney Disease Stage 3 and 4 focused on measuring Reduction of parathyroid hormone levels in pediatric patients with Chronic Kidney Disease Stage 3 and 4

Eligibility Criteria

10 Years - 16 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Subject has chronic kidney disease Stage 3 or 4 as determined by estimated glomerular filtration rate (15 to 59 mL/min/1.73 m²) at Screening.
Subject is not expected to begin dialysis for at least 6 months (in the opinion of the investigator).
For entry into the Washout Period (for subjects who are currently on a vitamin D receptor activator [VDRA] and need to complete a 2 to 4 week washout), the subject must satisfy the following criteria based on the Screening laboratory values:
- estimated glomerular filtration rate between 15 to 59 mL/min/1.73 m².
- iPTH measurement that is greater than or equal to 60 pg/mL (Stage 3 subjects) or greater than or equal to 90 pg/mL (Stage 4 subjects).
- An adjusted serum calcium value greater than or equal to 8.2 mg/dL (2.05 mmol/L) to less than or equal to 10.5 mg/dL (2.63 mmol/L).
- A serum phosphorus value greater than or equal to 2.0 mg/dL (0.65 mmol/L but less than or equal to 6.0 mg/dL (1.94 mmol/L).
For entry into the Treatment Phase (vitamin D receptor activator naïve subjects and those that have completed a 4 week washout), the subject must have:
- iPTH measurement that is greater than or equal to 75 pg/mL (Stage 3 subjects) or greater than or equal to 110 pg/mL (Stage 4 subjects).
- An adjusted serum calcium value greater than or equal to 8.4 mg/dL (2.10 mmol/L) but less than or equal to 10.2 mg/dL (2.55 mmol/L).
- A serum phosphorus value greater than or equal to 2.5 mg/dL (0.81 mmol/L) but less than or equal to 5.8 mg/dL (1.87 mmol/L).
- Must have 25-hydroxyvitamin D levels ≥ 30 ng/mL prior to washout, if not VDRA naïve, or treatment in Part II of the study.

Exclusion Criteria:

All subjects that have had a small bowel transplant will be excluded from the study.
Subject has had acute kidney failure within 12 weeks of the Screening Phase (defined as an acute rise in serum creatinine).
Subject has had symptomatic or significant hypocalcemia requiring active vitamin D therapy (for example, calcitriol, paricalcitol, doxercalciferol or alfacalcidol) within 6 months prior to the Screening Phase.
Subject has a history of active kidney stones (6 months prior to screening).
Subject has chronic gastrointestinal disease, which in the investigator's opinion may cause significant gastrointestinal malabsorption.
Subject is taking maintenance calcitonin, bisphosphonates, cinacalcet, glucocorticoids in an equivalent dose of greater than 5 mg prednisone daily, or other drugs known to affect calcium or bone metabolism within 4 weeks prior to treatment.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Experimental

Arm Label

Part 1: Paricalcitol

Part 2: Placebo

Part 2: Paricalcitol

Arm Description

Participants received a single 3 µg dose of paricalcitol capsules on Study Day 1.

Participants received placebo capsules three times a week (TIW) for 12 weeks during the double-blind treatment phase. From Weeks 12 to 24 participants received open-label paricalcitol at an initial dose of 1 µg three times a week. Doses could be increased in 1 μg increments every 4 weeks based on chemistry evaluations to target Kidney Disease Outcomes Quality Initiatives (KDOQI) target levels.

Participants received paricalcitol three times a week for 12 weeks during the double-blind treatment period and during the open-label period (Weeks 12-24). The initial dose of paricalcitol was 1 µg TIW. Doses could be increased in 1 μg increments every 4 weeks based on chemistry evaluations to target KDOQI target levels.

Outcomes

Primary Outcome Measures

Part 1: Paricalcitol Maximum Observed Plasma Concentration (Cmax)

Part 1: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞)

Part 2: Percentage of Participants Achieving Two Consecutive Reductions at Least 30% From Baseline in iPTH

The primary efficacy endpoint was the percentage of participants who achieved two consecutive ≥ 30% reductions from baseline in intact parathyroid hormone (iPTH) levels during the 12 week double-blind portion of the study regardless of CKD stage.

Secondary Outcome Measures

Part 2: Percentage of Participants Achieving a Final iPTH Within KDOQI Target Ranges

The Kidney Disease Outcomes Quality Initiatives (KDOQI) Pediatric Subcommittee on Practice Guidelines for Bone Metabolism and Disease in Children with CKD target range for intact parathyroid hormone (iPTH) is as follows:: CKD Stage 3: 35 - 69 pg/mL; CKD Stage 4: 70 - 110 pg/mL.

Part 2: Change From Baseline in iPTH to Each Post-baseline Visit

Part 2: Percentage of Participants Achieving Final Calcium Levels Within KDOQI Target Ranges

KDOQI recommends serum calcium is maintained within age appropriate normal ranges: Age 6 - 12: 9.4 - 10.2 mg/dL (2.35 - 2.55 mmol/L); Age 13 - 20: 8.8 - 10.2 mg/dL (2.20 - 2.55 mmol/L).

Part 2: Percentage of Participants Achieving Final Phosphorus Levels Within KDOQI Target Ranges

The KDOQI target ranges of serum phosphorus are to maintain at or above age appropriate lower limits and no higher than the age-appropriate upper limits: Age 6 - 12: 3.6 - 5.8 mg/dL (1.16 - 1.87 mmol/L); Age 13 - 20: 2.3 - 4.5 mg/dL (0.74 - 1.45 mmol/L).

Part 2: Change From Baseline in First Morning Void (FMV) Urinary Albumin to Creatinine Ratio (UACR)

The mean change from Baseline in FMV UACR on a log scale to each post baseline visit.

Full Information

NCT ID

NCT01020487

First Posted

November 13, 2009

Last Updated

June 1, 2018

Sponsor

AbbVie (prior sponsor, Abbott)

1. Study Identification

Unique Protocol Identification Number

NCT01020487

Brief Title

Safety and Efficacy of Paricalcitol Capsules in Decreasing Serum Parathyroid Hormone Levels in Children Aged 10-16 With Chronic Kidney Disease (CKD)

Official Title

A Phase 3, Prospective, Randomized, Double-blind, Placebo-controlled Multicenter Study to Evaluate the Pharmacokinetics, Safety and Efficacy of Paricalcitol Capsules in Decreasing Serum Intact Parathyroid Hormone Levels in Pediatric Subjects Ages 10 to 16 Years With Moderate to Severe Chronic Kidney Disease

Study Type

Interventional

2. Study Status

Record Verification Date

February 2017

Overall Recruitment Status

Completed

Study Start Date

February 2010 (undefined)

Primary Completion Date

May 2014 (Actual)

Study Completion Date

December 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AbbVie (prior sponsor, Abbott)

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

Part 1: To determine the safety, tolerability, and pharmacokinetics of a single dose of 3 μg paricalcitol capsules in children ages 10 to 16 years with moderate to severe chronic kidney disease (CKD Stages 3 and 4). Part 2: To determine the safety and efficacy of paricalcitol capsules as compared to placebo in decreasing serum intact parathyroid hormone (iPTH) in children ages 10 to 16 years with moderate to severe chronic kidney disease with an initial 12 weeks of double-blinded study drug followed by a minimum of 12 weeks of open-label active drug.

Detailed Description

The study consists of two parts. Part 1 is an open-label single-dose, non-fasting, multicenter study to evaluate the pharmacokinetics (PK) of paricalcitol capsules in 12 children ages 10 to 16 years with CKD Stages 3 and 4. Part 2 of this study will be conducted as a 12 week randomized double-blind, placebo-controlled study, followed by 12 weeks open-label treatment. Participants active or enrolled under amendment 5 will enter a follow-up period and have study visits every 4 weeks until the final participant reaches Week 24.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Kidney Disease Stage 3 and 4

Keywords

Reduction of parathyroid hormone levels in pediatric patients with Chronic Kidney Disease Stage 3 and 4

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

47 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part 1: Paricalcitol

Arm Type

Experimental

Arm Description

Participants received a single 3 µg dose of paricalcitol capsules on Study Day 1.

Arm Title

Part 2: Placebo

Arm Type

Placebo Comparator

Arm Description

Arm Title

Part 2: Paricalcitol

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Paricalcitol

Other Intervention Name(s)

Zemplar

Intervention Description

Paricalcitol capsules taken with water.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo capsules taken with water

Primary Outcome Measure Information:

Title

Part 1: Paricalcitol Maximum Observed Plasma Concentration (Cmax)

Time Frame

Blood samples were collected at hour 0, 1, 2, 4, 6, 8, 12, 24, 36, and 48 hours after dosing.

Title

Part 1: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞)

Time Frame

Blood samples were collected at hour 0, 1, 2, 4, 6, 8, 12, 24, 36, and 48 hours after dosing.

Title

Part 2: Percentage of Participants Achieving Two Consecutive Reductions at Least 30% From Baseline in iPTH

Description

Time Frame

12-week double-blind treatment period

Secondary Outcome Measure Information:

Title

Part 2: Percentage of Participants Achieving a Final iPTH Within KDOQI Target Ranges

Description

Time Frame

Week 12

Title

Part 2: Change From Baseline in iPTH to Each Post-baseline Visit

Time Frame

Baseline and Weeks 2, 4, 8 and 12

Title

Part 2: Percentage of Participants Achieving Final Calcium Levels Within KDOQI Target Ranges

Description

KDOQI recommends serum calcium is maintained within age appropriate normal ranges: Age 6 - 12: 9.4 - 10.2 mg/dL (2.35 - 2.55 mmol/L); Age 13 - 20: 8.8 - 10.2 mg/dL (2.20 - 2.55 mmol/L).

Time Frame

Week 12

Title

Part 2: Percentage of Participants Achieving Final Phosphorus Levels Within KDOQI Target Ranges

Description

Time Frame

Week 12

Title

Part 2: Change From Baseline in First Morning Void (FMV) Urinary Albumin to Creatinine Ratio (UACR)

Description

The mean change from Baseline in FMV UACR on a log scale to each post baseline visit.

Time Frame

Baseline and Weeks 4, 8 and 12

10. Eligibility

Sex

All

Minimum Age & Unit of Time

10 Years

Maximum Age & Unit of Time

16 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Subject has chronic kidney disease Stage 3 or 4 as determined by estimated glomerular filtration rate (15 to 59 mL/min/1.73 m²) at Screening. Subject is not expected to begin dialysis for at least 6 months (in the opinion of the investigator). For entry into the Washout Period (for subjects who are currently on a vitamin D receptor activator [VDRA] and need to complete a 2 to 4 week washout), the subject must satisfy the following criteria based on the Screening laboratory values: estimated glomerular filtration rate between 15 to 59 mL/min/1.73 m². iPTH measurement that is greater than or equal to 60 pg/mL (Stage 3 subjects) or greater than or equal to 90 pg/mL (Stage 4 subjects). An adjusted serum calcium value greater than or equal to 8.2 mg/dL (2.05 mmol/L) to less than or equal to 10.5 mg/dL (2.63 mmol/L). A serum phosphorus value greater than or equal to 2.0 mg/dL (0.65 mmol/L but less than or equal to 6.0 mg/dL (1.94 mmol/L). For entry into the Treatment Phase (vitamin D receptor activator naïve subjects and those that have completed a 4 week washout), the subject must have: iPTH measurement that is greater than or equal to 75 pg/mL (Stage 3 subjects) or greater than or equal to 110 pg/mL (Stage 4 subjects). An adjusted serum calcium value greater than or equal to 8.4 mg/dL (2.10 mmol/L) but less than or equal to 10.2 mg/dL (2.55 mmol/L). A serum phosphorus value greater than or equal to 2.5 mg/dL (0.81 mmol/L) but less than or equal to 5.8 mg/dL (1.87 mmol/L). Must have 25-hydroxyvitamin D levels ≥ 30 ng/mL prior to washout, if not VDRA naïve, or treatment in Part II of the study. Exclusion Criteria: All subjects that have had a small bowel transplant will be excluded from the study. Subject has had acute kidney failure within 12 weeks of the Screening Phase (defined as an acute rise in serum creatinine). Subject has had symptomatic or significant hypocalcemia requiring active vitamin D therapy (for example, calcitriol, paricalcitol, doxercalciferol or alfacalcidol) within 6 months prior to the Screening Phase. Subject has a history of active kidney stones (6 months prior to screening). Subject has chronic gastrointestinal disease, which in the investigator's opinion may cause significant gastrointestinal malabsorption. Subject is taking maintenance calcitonin, bisphosphonates, cinacalcet, glucocorticoids in an equivalent dose of greater than 5 mg prednisone daily, or other drugs known to affect calcium or bone metabolism within 4 weeks prior to treatment.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Deepa Chand, MD

Organizational Affiliation

AbbVie

Official's Role

Study Director

12. IPD Sharing Statement

Citations:

PubMed Identifier

28332096

Citation

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.

Results Reference

result

Links:

URL

http://www.rxabbvie.com

Description

Related Info

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Safety and Efficacy of Paricalcitol Capsules in Decreasing Serum Parathyroid Hormone Levels in Children Aged 10-16 With Chronic Kidney Disease (CKD)

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