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

NCT01020487 | Completed Phase 3 Results

• 2 other identifiers: M10-1492010-019439-37
• Study Type: interventional
• Target: 47
• Locations: 0 countries
• Sites: N/A

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.

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

Outcome Measures

Primary Outcomes (3)

• Part 1: Paricalcitol Maximum Observed Plasma Concentration (Cmax)

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

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

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

• 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.

  12-week double-blind treatment period

Secondary Outcomes (5)

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

  Week 12

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

  Baseline and Weeks 2, 4, 8 and 12

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

  Week 12

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

  Week 12

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

  Baseline and Weeks 4, 8 and 12

Study Arms (3)

Part 1: Paricalcitol

EXPERIMENTAL

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

Drug: Paricalcitol

Part 2: Placebo

PLACEBO COMPARATOR

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.

Drug: Paricalcitol; Drug: Placebo

Part 2: Paricalcitol

EXPERIMENTAL

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.

Drug: Paricalcitol

Interventions

Paricalcitol DRUG

Paricalcitol capsules taken with water.

Also known as: Zemplar

Part 1: Paricalcitol; Part 2: Paricalcitol; Part 2: Placebo

Placebo DRUG

Placebo capsules taken with water

Part 2: Placebo

Eligibility Criteria

• Age: 10 Years - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AbbVie (prior sponsor, Abbott): lead

Related Publications (1)

• 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.

  PMID: 28332096 RESULT

Related Links

• Related Info

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Interventions

paricalcitol

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Global Medical Services
• Organization: AbbVie (prior sponsor, Abbott)

800-633-9110

Study Officials

• Deepa Chand, MD

  AbbVie

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2009
• First Posted: November 24, 2009
• Study Start: February 1, 2010
• Primary Completion: May 1, 2014
• Study Completion: December 1, 2014
• Last Updated: July 2, 2018
• Results First Posted: March 29, 2017

Record last verified: 2017-02