Clinical trial NCT01020487: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Kidney Disease Stage 3 and 4
Keywords: Reduction of parathyroid hormone levels in pediatric patients with Chronic Kidney Disease Stage 3 and 4
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2009-11-24
Enrollment: 47
Sex: ALL
Minimum age (years): 10
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Part 1: Paricalcitol Maximum Observed Plasma Concentration (Cmax)
timeFrame: Blood samples were collected at hour 0, 1, 2, 4, 6, 8, 12, 24, 36, and 48 hours after dosing.
measure: Part 1: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞)
timeFrame: Blood samples were collected at hour 0, 1, 2, 4, 6, 8, 12, 24, 36, and 48 hours after dosing.
measure: Part 2: Percentage of Participants Achieving Two Consecutive Reductions at Least 30% From Baseline in iPTH
timeFrame: 12-week double-blind treatment period
Secondary outcomes:
measure: Part 2: Percentage of Participants Achieving a Final iPTH Within KDOQI Target Ranges
timeFrame: Week 12
measure: Part 2: Change From Baseline in iPTH to Each Post-baseline Visit
timeFrame: Baseline and Weeks 2, 4, 8 and 12
measure: Part 2: Percentage of Participants Achieving Final Calcium Levels Within KDOQI Target Ranges
timeFrame: Week 12
measure: Part 2: Percentage of Participants Achieving Final Phosphorus Levels Within KDOQI Target Ranges
timeFrame: Week 12
measure: Part 2: Change From Baseline in First Morning Void (FMV) Urinary Albumin to Creatinine Ratio (UACR)
timeFrame: Baseline and Weeks 4, 8 and 12
Other outcomes:
Locations:
Study officials:
affiliation: AbbVie
name: Deepa Chand, MD
role: STUDY_DIRECTOR
References:
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.