Evaluate Safety and Efficacy of Paricalcitol in Reducing Serum Intact Parathyroid Hormone in Chronic Kidney Disease

A Phase 3b, Randomized, Active-Controlled, Single-Blind, Multicenter Study to Evaluate the Safety and Efficacy of Paricalcitol Injection in Reducing Serum Intact Parathyroid Hormone Levels in Chronic Kidney Disease Stage 5 Subjects Receiving Hemodialysis

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01071070

Enrollment

216

Registered

2010-02-19

Start date

2009-11-30

Completion date

2010-11-30

Last updated

2012-01-26

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Kidney Disease

Keywords

Chronic Kidney Disease, Secondary hyperparathyroidism

Brief summary

Evaluate Safety and Efficacy of Paricalcitol in Reducing Serum Intact Parathyroid Hormone in Chronic Kidney Disease

Detailed description

Evaluate the safety and efficacy of paricalcitol injection with two different dosing regimens (currently approved dosing regimen used in the US package insert versus dosing based on a formula of iPTH/80 that was approved and used in the EU package insert) in Chronic Kidney Disease (CKD) Stage 5 subjects with secondary hyperparathyroidism receiving hemodialysis.

Interventions

DRUGparicalcitol

Initiation dosing based on 2 approved package inserts , followed by a dose adjusted by limited chemistry test value. See Arm Description for additional details.

Study design

Allocation

RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

SINGLE (Subject)

Eligibility

Sex/Gender

ALL

Age

20 Years to No maximum

Healthy volunteers

Inclusion criteria

1. Subject is a Chinese male or female greater than or equal to 20 years old. 2. Subject is diagnosed with Chronic Kidney Disease Stage 5 and must be on maintenance hemodialysis three times a week for at least 2 months prior to the Screening Visit and expected to remain on hemodialysis for the duration of the study. 3. For entry into the Treatment Phase, the subject must have: * Intact parathyroid hormone greater than or equal to 300 pg/mL * Serum calcium less than 10.2 mg/dL (2.55 mmol/L) * Calcium-phosphorus product less than 65 mg\^2/dL\^2

Exclusion criteria

1. Subject has a history of an allergic reaction or significant sensitivity to vitamin D or vitamin D related compounds. 2. Subject received a partial parathyroidectomy within one year prior to the Screening Phase. 3. Subject with New York Heart Association (NYHA) Class III or IV. 4. Subject has taken aluminum-containing phosphate binders for greater than 3 weeks in the last 3 months prior to the Screening Phase, or requires such medications for greater than 3 weeks in the study. 5. Subject has a current malignancy (with the exception of basal or squamous cell carcinoma of the skin), or clinically significant liver disease, in the opinion of the Investigator. 6. Subject has a history of drug or alcohol abuse within 6 months prior to the Screening Phase. 7. Subject is known to be human immunodeficiency virus (HIV) positive. 8. Subject has evidence of poor compliance with diet, medication or hemodialysis that may interfere, in the Investigator's opinion, with adherence to the protocol.

Design outcomes

Primary

Measure	Time frame	Description
The Achievement of Two Consecutive Greater Than or Equal to 30% Decreases From Baseline Intact Parathyroid Hormone Levels	Baseline to 12 Weeks	The number of participants who achieved (Yes) or did not achieve (No) two consecutive decreases of greater than or equal to 30% from baseline in intact parathyroid hormone (iPTH) values

Secondary

Measure	Time frame	Description
The Change From Baseline to the Final Observation in Intact Parathyroid Hormone Value	Baseline to 12 Weeks	—
The Change From Baseline to the Final Observation in Calcium	Baseline to 12 Weeks	—
The Change From Baseline to the Final Observation in Calcium-phosphorus Product	Baseline to 12 Weeks	—
The Proportion of Subjects Achieving a Final Intact Parathyroid Hormone Value Between 150 and 300 pg/mL	Baseline to 12 Weeks	The number of subjects with (Yes) or without (No) final intact parathyroid hormone (iPTH) values between 150 and 300 pg/mL
The Change From Baseline to the Final Observation in the Vital Sign of Diastolic Blood Pressure	Baseline to 12 Weeks	—
The Change From Baseline to the Final Observation in the Vital Sign of Heart Rate	Baseline to 12 Weeks	—
The Proportion of Subjects With 2 Consecutive Calcium Measurements Greater Than 11.0 mg/dL (2.75 mmol/L)	Baseline to 12 weeks	The number of subjects with (Yes) or without (No) two consecutive calcium measurements greater than 11.0 mg/dL (2.75 mmol/L)
The Change From Baseline to the Final Observation in the Vital Sign of Systolic Blood Pressure	Baseline to 12 Weeks	—

Countries

China

Participant flow

Recruitment details

Participants were enrolled in the study at investigative sites in China. Recruitment began in October 2009 and ended in July 2010. The study population consisted of participants with Stage 5 chronic kidney disease who were receiving hemodialysis.

Pre-assignment details

If subjects were receiving vitamin D receptor (VDR) activators, they participated in a Washout Phase for 2 weeks prior to entering into the Screening Phase in order to wash out any VDR activators and their potential hysteresis or carryover effects.

Participants by arm

Arm	Count
Group 1 Initial dosing based on a formula of intact parathyroid hormone value/80 (where intact parathyroid hormone value is the baseline value in pg/mL).	108
Group 2 Dose determined by US paricalcitol injection package insert dosing instructions (starting dose at 0.04 microgram/kg)	108
Total	216

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	0	3
Overall Study	Hypercalcemia	1	0
Overall Study	Missed 3 consecutive doses of study drug	2	0
Overall Study	Withdrawal by Subject	1	0

Baseline characteristics

Characteristic	Total	Group 1	Group 2
Age Continuous	50.6 years STANDARD_DEVIATION 13.09	50.5 years STANDARD_DEVIATION 13.55	50.8 years STANDARD_DEVIATION 12.67
Age, Customized < 65 years	184 Participants	91 Participants	93 Participants
Age, Customized >=65 years	32 Participants	17 Participants	15 Participants
Region of Enrollment China	216 participants	108 participants	108 participants
Sex: Female, Male Female	77 Participants	41 Participants	36 Participants
Sex: Female, Male Male	139 Participants	67 Participants	72 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	29 / 108	19 / 108
serious Total, serious adverse events	0 / 108	3 / 108

Outcome results

Primary

The Achievement of Two Consecutive Greater Than or Equal to 30% Decreases From Baseline Intact Parathyroid Hormone Levels

The number of participants who achieved (Yes) or did not achieve (No) two consecutive decreases of greater than or equal to 30% from baseline in intact parathyroid hormone (iPTH) values