Clinical trial NCT00667576: Dose-response Study of Paricalcitol Injection in Chronic Kidney Disease Patients Receiving Hemodialysis
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Kidney Disease on Hemodialysis
Secondary Hyperparathyroidism
Keywords: chronic kidney disease
secondary hyperparathyroidism
hemodialysis
paricalcitol
maxacalcitol
Lead sponsor: Abbott
Sponsor class: INDUSTRY
Collaborators: name: Abbott Japan Co.,Ltd
First posted: 2008-04-28
Enrollment: 153
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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).

Eligibility criteria: 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)

Primary outcomes:
measure: Percentage of Subjects With ≥ 50% Decrease From Baseline in Intact Parathyroid Hormone (iPTH) Serum Level
timeFrame: Baseline to Week 13 (Final Visit)
Secondary outcomes:
measure: Mean Change From Baseline in Intact Parathyroid Hormone (iPTH) Level
timeFrame: Baseline to Week 13 (Final Visit)
measure: Percentage of Subjects With Intact Parathyroid Hormone (iPTH) ≤ 180 Picograms/Milliliter (pg/mL)
timeFrame: Baseline to Week 13 (Final Visit)
measure: Percentage of Subjects With 2 or More Decreases of ≥ 50% From Baseline in Intact Parathyroid Hormone (iPTH) Level
timeFrame: Through Week 13
measure: Duration of 2 Consecutive Decreases of ≥ 50% From Baseline in Intact Parathyroid Hormone (iPTH) Values
timeFrame: Through Week 13
measure: Duration of 2 Consecutive Intact Parathyroid Hormone (iPTH) Values ≤ 180 pg/mL
timeFrame: Through Week 13
Other outcomes:
measure: Percentage of Subjects With Hypercalcemia
timeFrame: Through Week 13
measure: Percentage of Subjects With Hyperphosphatemia
timeFrame: Through Week 13
Locations:
city: Tokyo
country: Japan
state: Metropolis
city: Aichi
country: Japan
state: Prefecture
city: Chiba
country: Japan
state: Prefecture
city: Fukuoka
country: Japan
state: Prefecture
city: Hokkaido
country: Japan
state: Prefecture
city: Ibaragi
country: Japan
state: Prefecture
city: Kanagawa
country: Japan
state: Prefecture
city: Kumamoto
country: Japan
state: Prefecture
city: Nagano
country: Japan
state: Prefecture
city: Nagasaki
country: Japan
state: Prefecture
city: Osaka
country: Japan
state: Prefecture
city: Saitama
country: Japan
state: Prefecture
Study officials:
affiliation: Abbott
name: Ryotaro Matsuzawa
role: STUDY_DIRECTOR
References: