Principal Investigator: Raoul  Nelson
Keywords: Hectorol , Chronic Kidney Disease , Secondary Hyperparathyroidism Department: Pediatric Administration
IRB Number: 00102348
Specialty: Pediatrics, General
Sub Specialties:
Recruitment Status: Recruiting

Contact Information

Richard Drake

Brief Summary

The primary objective of this study is to evaluate the effect of Hectorol® capsules in reducing
elevated levels of intact parathyroid hormone (iPTH)

The secondary objectives are:
• To evaluate the safety profile of Hectorol® capsules versus Rocaltrol® (calcitriol) capsules
• To determine the pharmacokinetics profile of 1,25-dihydroxyvitamin D2 after
administration of Hectorol®.

This is a randomized, multinational, open-label, parallel group, active comparator study in
patients aged 5 -18 years with CKD Stages 3 and 4 and SHPT not yet on dialysis. The study will
include a Screening Period (4 days to 4 weeks), a Primary Efficacy Period (12 weeks), and a
Safety Continuation Period (12 weeks). Eligible patients will be randomized either to the
Hectorol® or Rocaltrol® treatment groups in a 2:1 ratio and will be stratified by age and CKD
Stage at baseline as follows:
• At least 30% of patients < 12 years of age and at least 30% of patients ≥ 12 years of age
• At least 30% of patients with Stage 3 (GFR = 30 – 59 ml/min/1.73m2) CKD and at least
30% of patients with Stage 4 (GFR = 15 – 29 ml/min/1.73m2) CKD
All patients will be treated with either Hectorol® or Rocaltrol® from randomization until Week 24,
which represents the end of treatment visit.

The Rocaltrol® active comparator treatment group is included for qualitative comparison purposes only. No formal statistical comparison between the Hectorol® and Rocaltrol® treatment group will be made.

Hectorol® and Rocaltrol® dosing will be adjusted to the iPTH plasma levels measured bi-weekly
in all patients. For this pediatric study, the starting dose of Hectorol and all potential titration
increases are less than those used in adults and have been modeled to provide weekly exposures
comparable to those predicted in adults. The starting dose and titration instructions for Rocaltrol®
capsules will follow the pediatric pre-dialysis SHPT label instructions (3)

Inclusion Criteria

01. Male or female aged 5 to 18 years old.                                                                                             

02. Weight ≥15 kg.

03. CKD Stage 3 or 4 not yet on dialysis, defined as GFR between 15 and 59 mL/min/1.73 m2
(established by Schwartz equation) at the Week -2 visit

04. iPTH value >100 pg/mL for CKD Stage 3 or >160 pg/mL for CKD Stage 4, at the Week -2

05. Written informed consent, signed by the patient’s parent / legal guardian.

06. Written assent, for patients capable of understanding the purpose of the study.

Exclusion Criteria

01. The patient has a serum 25-hydroxyvitamin D level <30 ng/mL at screening*.

02. The patient has a corrected calcium ≥10 mg/dL at the Week -2 visit.

03. A serum phosphorus >4.5 mg/dL for children 13 to 18 years of age; >5.8 mg/dL for
children 5 to 12 years of age at the Week -2 visit.

04. The patient is anticipated to require maintenance hemodialysis within 3 months.

05. The patient used cinacalcet or vitamin D sterol therapies such as calcitriol, doxercalciferol,
or paricalcitol within 14 days prior to the baseline visit.

06. The patient has a history of, or active symptomatic heart disease within 12 months prior to
the baseline (Week 0) visit.

07. The patient currently has a chronic gastrointestinal disease (i.e., malabsorption, severe
chronic diarrhea, chronic ulcerative colitis, or ileostomy).

08. The patient currently has primary hyperparathyroidism or has had a total

09. The patient has an active malignancy.

10. The patient is unable to swallow a capsule in size similar to the Hectorol® and Rocaltrol®

11. The patient has a history of sensitivity or allergy to doxercalciferol, calcitriol or other
vitamin D analogs.

12. The patient has a history of or active ethanol or drug dependence or abuse, excluding
tobacco use.

13. The patient has taken other investigational drugs within 1 month or 5 half-lives, whichever
is longer, prior to screening.

14. The patient is medically unstable or is not otherwise suitable for study participation, in the
opinion of the Investigator.

15. The patient, in the opinion of the Investigator, is unable to adhere to the requirements of
the study.

16. Pregnant or breast-feeding female.

17. Female patient who is sexually active and unwilling to abstain from sexual intercourse or
is not protected by a highly effective contraceptive method of birth control.

Exclusion criteria related to the active comparator and/or mandatory background

18. All contraindications of Rocaltrol® and warning/precaution of Rocaltrol® use as per the US
Rocaltrol® Labeling (Rocaltrol® package insert) (3).

Exclusion criteria related to the current knowledge of Sanofi compound

19. The patient currently uses aluminum or magnesium-based binders.
*Re-screening: Patients who failed screening because they were not vitamin D replete (defined as 25-OH vitamin D ≥30 ng/mL, see E01) may be re-screened for potential enrollment following
normalization of their vitamin D levels. Treatment considerations may be made at the
investigator’s discretion with possible reference to K/DOQI Clinical Practice Guidance for Bone
Metabolism and Disease in Children with Chronic Kidney Disease; 2005 (2).