Protocol BCI-CH-126: A Study of the Safety and Tolerance of Daily Oral Doxercalciferol Therapy for Secondary Hyperparathyroidism in End Stage Renal Disease Patients on Chronic Peritoneal Dialysis

Hectorol® (doxercalciferol)

Drug Name	Generic Name	Therapeutic Area and FDA Approved Indications:	Approved U.S. Drug Label
Hectorol®	doxercalciferol capsules	Therapeutic Area: Chronic Kidney Disease FDA Approved Indications: Dialysis Patients: Hectorol® is indicated for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease on dialysis. Pre-Dialysis Patients: Hectorol® is indicated for the treatment of secondary hyperparathyroidism in patients with Stage 3 or Stage 4 chronic kidney disease.	Prescribing Info for Hectorol® Capsules

These results are supplied for informational purposes only. Prescribing decisions should be made based on the approved package insert.

PUBLICATION (REFERENCE)

Publications

NAME OF SPONSOR/COMPANY:

Genzyme Corporation, 500 Kendall Street, Cambridge, MA 02142
Bone Care International, Inc., Middleton, WI 53652 (Bone Care was acquired by Genzyme Corporation July 2005)

TITLE OF STUDY:

Protocol BCI-CH-126: A Study of the Safety and Tolerance of Daily Oral Doxercalciferol Therapy for Secondary Hyperparathyroidism in End Stage Renal Disease Patients on Chronic Peritoneal Dialysis

INVESTIGATORS AND STUDY CENTER(S):

This was a multi-center study conducted at two study sites in the U.S.

STUDIED PERIOD:

First patient enrolled: 28 July 1999
Last patient completed: 03 May 2000

PHASE OF DEVELOPMENT:

Phase 4

OBJECTIVES:

To establish the safety and tolerance of oral Hectorol® as a therapy for secondary hyperparathyroidism in patients with Stage 5 Chronic Kidney Disease on peritoneal dialysis.

METHODOLOGY:

This was a Phase 4, open-label study conducted at two centers. The study consisted of three periods: a 4-week Baseline Period, a 12-week treatment period, and a 2-week post-treatment period.

NUMBER OF PATIENTS (PLANNED AND ANALYZED):

No. Enrolled: 11
No. Treated: 11
No. Completed: 9
The study was terminated prematurely due to difficulty in subject enrollment.

DIAGNOSIS AND MAIN CRITERIA FOR INCLUSION:

Subjects included in the study were at least 18 years old with Stage 5 Chronic Kidney Disease on peritoneal dialysis for at least three months, and had a history of plasma intact parathyroid hormone (iPTH) levels ≥ 400 pg/mL.

TEST PRODUCT, DOSE, AND MODE OF ADMINISTRATION:

Doxercalciferol: 0.5 mcg soft gelatin capsules
Dose: 2.5 mcg daily
Doses were administered orally before breakfast.

DURATION OF TREATMENT:

18 weeks (4-week baseline period; 12-week treatment period; 2-week post-treatment period)

REFERENCE THERAPY, DOSE AND MODE OF ADMINISTRATION:

Not applicable

CRITERIA FOR EVALUATION:

Criteria for Evaluation - Efficacy:
There were no efficacy criteria pre-defined for this study.

Criteria for Evaluation - Safety:
Safety was evaluated based on adverse events, vital sign assessments, serum calcium, and phosphorus.

STATISTICAL METHODS:

Statistical Methods - Efficacy:
No statistical analyses were conducted.

Statistical Methods - Safety:
All adverse events were recorded and their frequencies determined. Baseline values for serum calcium and phosphorus were defined as the average of the data collected at Weeks -2, -1, and 0. For each parameter, the significance of the change from baseline was assessed at each time point using a paired t-test.

SUMMARY / CONCLUSIONS:

Summary / Conclusions - Demographics:
Of the 11 subjects enrolled, 45.5% (5/11) were men, 81.8% (9/11) were Caucasian, and 18.2 % (2/11) were African American. The mean age was 49 years (range, 26 to 78 years).

Summary / Conclusions - Efficacy:
No efficacy analyses were performed, though iPTH levels decreased in all patients treated with doxercalciferol.

Summary / Conclusions - Safety Results:
A total of 25 treatment emergent adverse events occurred in 10 (91%) patients treated with study drug. A majority of adverse events were mild to moderate in intensity. Other than the expected events of over-suppression of iPTH and hypercalcemia, the remaining adverse events were judged to be not related or probably not related to study drug by the Investigator.

Four treatment emergent serious adverse events occurred in two patients. The serious adverse events were assessed as severe in intensity. All serious events were assessed as not related or probably not related to study drug by the Investigator. One subject died of unknown causes two months after completing the study. The death was considered not related to study drug by the Investigator.

Mean serum calcium (corrected for albumin) increased from 8.8 mg/dL at baseline to 9.0 mg/dL at Week 12, which was statistically significant (p = 0.0174). A mean decrease in mean phosphorus of 0.3 mg/dl from a mean of 5.0 mg/dl at baseline was observed at Week 12. This mean decrease was not statistically significant (p=0.1378). No clinically significant changes in other chemistry and hematology laboratory parameters were seen during the course of the study.

CONCLUSION:

Limited analyses for safety were conducted because the study was terminated prematurely due to difficulty in subject enrollment. Eleven subjects were dosed, and nine subjects completed this open-label study. Analysis of the preliminary safety data provided by this study did not provide any additional information beyond the potential of hypercalcemia and of iPTH over-suppression for Hectorol® (doxercalciferol capsules).