Dose-response Study of Paricalcitol Injection in Chronic Kidney Disease Patients Receiving Hemodialysis

Secondary Hyperparathyroidism Clinical Trial

Official title:

Late Phase 2 Study of Paricalcitol Injection: Dose-response Study of Paricalcitol Injection in Chronic Kidney Disease Subjects Receiving Hemodialysis With Secondary Hyperparathyroidism (Examination of Initial Dose and Incremental Dose)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00667576
• Other study ID #: M10-309
• Status: Completed
• Phase: Phase 2
• First received: April 24, 2008
• Last updated: January 18, 2012
• Start date: April 2008
• Est. completion date: March 2009

Study information

• Verified date: January 2012
• Source: Abbott
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial Summary

The purpose of this study was to investigate the initial dose and dose adjustment range for paricalcitol injection in patients with chronic kidney disease on hemodialysis who have secondary hyperparathyroidism.

Description:

This multicenter, randomized, open-label trial consisted of 4 dose-adjustment regimens for paricalcitol injection (initial doses and dose adjustment ranges were 2 ± 1 µg, 2 ± 2 µg, 4 ± 1 µg, and 4 ± 2 µg) and 1 maxacalcitol regimen (initial dose and dose adjustment range was 5 µg ± 2.5 µg or 10 µg ± 2.5 µg) as a reference group. Subjects who met the inclusion criteria were randomized equally to 1 of the treatment groups with iPTH values at screening (< 500 pg/mL or ≥ 500 pg/mL) as a dynamic allocation factor. Study drugs were administered 3 times weekly (every other day) from the venous end of the hemodialysis circuit just before completion of the dialysis session. The initial doses were continued for 2 weeks, followed by dose adjustments (increase, maintenance, decrease, suspension, or resumption) by 1 µg or 2 µg units for the paricalcitol groups and by 2.5 µg units for the maxacalcitol group based on iPTH, calcium (adjusted), and phosphorus values every 2 weeks.

Subjects in the paricalcitol groups were to be suspended from treatment if their iPTH value decreased to < 60 pg/mL in accordance with the guidelines proposed by the Japanese Society of Dialysis Therapy for the treatment of secondary hyperparathyroidism in chronic dialysis patients (control goal value of 60-180 pg/mL for iPTH). The dose adjustment criteria based on iPTH values for the maxacalcitol group were set according to the prescribing information for maxacalcitol (suspended when iPTH decreased to ≤ 150 pg/mL).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 153
• Est. completion date: March 2009
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

• Diagnosed with chronic kidney disease receiving hemodialysis 3 times a week for at least 3 months prior to obtaining the informed consent and scheduled to be receiving the same hemodialysis during the study period.

• Using dialysate with constant concentration of calcium for 4 weeks prior to obtaining informed consent and phosphate binder with constant dose regimen for 2 weeks prior to obtaining informed consent.

• Intact parathyroid hormone level (iPTH) = 300 pg/mL

• Calcium (adjusted) 8.4-10.2 milligrams/deciliter (mg/dL)

• Phosphorus = 6.5 mg/dL

• Age = 20 years

Exclusion Criteria:

• History of allergic reaction or significant sensitivity to vitamin D or vitamin D related compounds

• Parathyroidectomy or ethanol infusion within past year

• Progressive malignancy or clinically significant hepatic diseases, severe cerebral/cardiovascular diseases, severe hypertension, or uncontrolled diabetes mellitus

• Drug or alcohol abuse within past 6 months

• Taking calcitonin, maintenance intravenous or oral glucocorticoids, cinacalcet, bisphosphonates, selective estrogen-receptor modulator (SERM), vitamin D compounds (other than study drug), or other drugs that may affect calcium or bone metabolism (other than estrogen or progestin, vitamin K2)

• Will need to take chronic dose (= 2 consecutive weeks) of cytochrome P450 (CYP3A) inhibitors (e.g., clarithromycin, grapefruit products) or inducers (e.g., carbamazepine, rifampicin)

• Taking aluminum containing products (2 weeks prior to consent)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Kidney Disease on Hemodialysis
• Hyperparathyroidism
• Hyperparathyroidism, Secondary
• Kidney Diseases
• Neoplasm Metastasis
• Renal Insufficiency, Chronic
• Secondary Hyperparathyroidism

Intervention

Drug:
• Maxacalcitol
Study drug was administered 3 times per week (no more frequently than every other day) intravenously immediately before the completion of hemodialysis. The initial dosage was administered for 2 weeks, with subsequent dosage adjustment based on the subject's iPTH, calcium (adjusted), and phosphorus levels every 2 weeks. Total duration of treatment was 12 weeks.
• Paricalcitol
Study drug was administered 3 times per week (no more frequently than every other day) intravenously immediately before the completion of hemodialysis. The initial dosage was administered for 2 weeks, with subsequent dosage adjustment based on the subject's iPTH, calcium (adjusted), and phosphorus levels every 2 weeks. Total duration of treatment was 12 weeks.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Abbott	Abbott Japan Co.,Ltd

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Subjects With = 50% Decrease From Baseline in Intact Parathyroid Hormone (iPTH) Serum Level		Baseline to Week 13 (Final Visit)	No
Secondary	Mean Change From Baseline in Intact Parathyroid Hormone (iPTH) Level		Baseline to Week 13 (Final Visit)	No
Secondary	Percentage of Subjects With Intact Parathyroid Hormone (iPTH) = 180 Picograms/Milliliter (pg/mL)		Baseline to Week 13 (Final Visit)	No
Secondary	Percentage of Subjects With 2 or More Decreases of = 50% From Baseline in Intact Parathyroid Hormone (iPTH) Level		Through Week 13	No
Secondary	Duration of 2 Consecutive Decreases of = 50% From Baseline in Intact Parathyroid Hormone (iPTH) Values		Through Week 13	No
Secondary	Duration of 2 Consecutive Intact Parathyroid Hormone (iPTH) Values = 180 pg/mL		Through Week 13	No