Efficacy and Safety of Paricalcitol on the Treatment of Secondary Hyperparathyroidism in Calcitriol Resistant Dialysis Subjects - Full Text View

Sponsors and Collaborators:	Abbott Statistika Consultoria Ltda
Information provided by:	Abbott
ClinicalTrials.gov Identifier:	NCT00664430

Purpose

The primary objective of this study is to evaluate the efficacy and safety of paricalcitol in moderate to severe SHPT subjects under hemodialysis who are calcitriol-resistant.

Condition	Intervention	Phase
Secondary Hyperparathyroidism Dialysis	Drug: Calcitriol Drug: Paricalcitol	Phase IV

Drug Information available for: Calcitriol 19-Nor-1alpha,25-dihydroxyvitamin D2

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study
Official Title:	Efficacy and Safety of Paricalcitol on the Treatment of Moderate to Severe Secondary Hyperparathyroidism in Calcitriol Resistant Dialysis Subjects

Further study details as provided by Abbott:

Primary Outcome Measures:

Efficacy will be assessed on visit 15 by the proportion of subjects who reduce PTH levels in 50% relative to visit 4 values. For subjects who do not perform visit 4, the reduction of the PTH levels in 50% will be assessed relative to visit 5 values. [ Time Frame: As soon as the subjects reduce PTH levels in 50% according to the protocol ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Adverse events occurrence will be considered secondary safety variable. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	100
Study Start Date:	January 2009
Estimated Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A There will be only one arm constituted by subjects with confirmed calcitriol resistance. To confirm this resistance, subjects will begin a controlled calcitriol therapy period. After this period, those who fail to reduce PTH (according to parameters in protocol) will initiate paricalcitol therapy.	Drug: Calcitriol Initial doses determined according to K/DOQI guideline. During therapy, calcitriol dose may be modified by 0.5 - 1 mcg at two to four weeks' intervals. Drug: Paricalcitol Dose calculated by 0.04 to 0.1 microgram per kilogram (mcg/kg). Paricalcitol will be administered intravenously after the subjects' dialysis. The paricalcitol dose will be titrated every 2 weeks until iPTH presents a reduction or up to 4 months, after which it will be adjusted monthly based on serum PTH, calcium, phosphorus and albumin measurements. Dosing may be modified by 2-4 mcg increments at two to four weeks' intervals.

Arms

Assigned Interventions

A

There will be only one arm constituted by subjects with confirmed calcitriol resistance. To confirm this resistance, subjects will begin a controlled calcitriol therapy period. After this period, those who fail to reduce PTH (according to parameters in protocol) will initiate paricalcitol therapy.

Drug: Calcitriol

Initial doses determined according to K/DOQI guideline. During therapy, calcitriol dose may be modified by 0.5 - 1 mcg at two to four weeks' intervals.

Drug: Paricalcitol

Dose calculated by 0.04 to 0.1 microgram per kilogram (mcg/kg). Paricalcitol will be administered intravenously after the subjects' dialysis. The paricalcitol dose will be titrated every 2 weeks until iPTH presents a reduction or up to 4 months, after which it will be adjusted monthly based on serum PTH, calcium, phosphorus and albumin measurements. Dosing may be modified by 2-4 mcg increments at two to four weeks' intervals.

Detailed Description:

Additional information for Arm Type, which is being reported as "Other". There will be only one arm constituted by subjects with confirmed calcitriol resistance. To confirm this resistance, subjects will begin a controlled calcitriol therapy period. After this period, those who fail to reduce PTH (according to parameters in protocol) will initiate paricalcitol therapy.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Male and female subjects > 18 years of age, with CKD stage V;
Subjects with diagnosis of calcitriol resistance defined as: Episodes of hypercalcemia and/or hyperphosphatemia (defined as an episode of calcium or phosphorus above Upper Limit of Normal or documented by medical history stating that the treatment with calcitriol was discontinued due to hypercalcemia and/or hyperphosphatemia) that precludes treatment continuation and/or persistent PTH above 600pg/mL during the calcitriol therapy;
PTH value at screening visit between 600 pg/mL and 2000 pg/mL;
Stable clinical conditions;
Subject has voluntarily consented to participate in the study, by signing and dating an informed consent form, approved by an Institutional Review Board (IRB)/Independent Ethics Committee (IEC), after the nature of the study has been explained and all his questions about the study have been elucidated. The informed consent must be signed before any study-specific procedures are performed.

Exclusion Criteria:

Previous parathyroidectomy;
Presence of hypercalcemia (corrected Ca* > 10,5 mg/dL) and/or hyperphosphatemia (P > 6.0 mg/dL) and/or Ca x P product > 60, at screening visit;
Severe and/or unstable clinical conditions, e.g., congestive heart failure, advanced cancer, advanced HIV disease, severe endocrinopathies, uncompensated diabetes mellitus, life-threatening cardiac arrhythmias, etc;
Abnormal liver tests (> 1.5 times above upper limit of normal);
Pregnant or breast-feeding women;
Evidence of vitamin D toxicity;
Known hypersensitivity to any study drug components.
- Corrected calcium will be calculated by: [4 - subject's serum albumin (g/dL)] x 0.8 + subject's serum calcium value

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00664430

Contacts

Contact: Lino Rodrigues, MD	(55 11) 5536-7092	lino.rodrigues@abbott.com
Contact: Paulo E M Covizzi, PharmD	(55 11) 5536-7231	paulo.covizzi@abbott.com

Locations

Brazil
Fundação Oswaldo Ramos / Hospital do Rim e Hipertensão - Universidade Federal de São Paulo/ Escola Paulista de Medicina	Recruiting
Sao Paulo, Brazil
Contact: Aluízio Barbosa de Carvalho, Physician 55-11-5087 8000 (8202) aluizio@uol.com.br
Principal Investigator: Aluízio Barbosa de Carvalho, Physician
Hospital das Clínicas da Universidade de São Paulo	Recruiting
Sao Paulo, Brazil
Contact: Vanda Jorgetti, Physician 55-11-3068-9428 vandajor@usp.br
Principal Investigator: Vanda Jorgetti, Physician

Sponsors and Collaborators

Abbott

Statistika Consultoria Ltda

More Information

No publications provided

Responsible Party:	Abbott Laboratorios do Brasil Ltda. ( Lino Rodrigues Júnior )
Study ID Numbers:	W10-131
Study First Received:	April 21, 2008
Last Updated:	April 27, 2009
ClinicalTrials.gov Identifier:	NCT00664430 History of Changes
Health Authority:	Brazil: Ethics Committee; Brazil: National Health Surveillance Agency

Keywords provided by Abbott:

Dialysis
Calcitriol Resistant
Secondary Hyperparathyroidism

Study placed in the following topic categories:

Parathyroid Diseases
Endocrine System Diseases
Trace Elements
Bone Density Conservation Agents
Cardiovascular Agents
Calcitriol
Calcium, Dietary

Hyperparathyroidism, Secondary
Hyperparathyroidism
Vitamins
Neoplasm Metastasis
Vasoconstrictor Agents
Endocrinopathy
Micronutrients

Additional relevant MeSH terms:

Parathyroid Diseases
Molecular Mechanisms of Pharmacological Action
Growth Substances
Calcium Channel Agonists
Physiological Effects of Drugs
Endocrine System Diseases
Bone Density Conservation Agents
Cardiovascular Agents
Pharmacologic Actions
Calcitriol
Membrane Transport Modulators

Hyperparathyroidism, Secondary
Neoplastic Processes
Neoplasms
Pathologic Processes
Hyperparathyroidism
Therapeutic Uses
Vitamins
Vasoconstrictor Agents
Neoplasm Metastasis
Micronutrients

ClinicalTrials.gov processed this record on May 07, 2009