Effectiveness of Paricalcitol in Reducing Parathyroid Hormone (PTH) Levels in X-linked Hypophosphatemic Rickets

NCT00417612 | Completed Phase 3 Results DMC

• 3 other identifiers: 0607001636P50AR0540861P50AR054086-01
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the effectiveness of paricalcitol, a form of synthetic vitamin D, in lowering parathyroid hormone (PTH) levels and reducing disease symptoms in children and adults with X-linked hypophosphatemic (XLH) rickets.

Conditions

Hypophosphatemia, Familial; Hyperparathyroidism

Keywords

Rickets, Hypophosphatemia; Rickets, Vitamin D-Resistant; Rickets, X-linked hypophosphatemic

Outcome Measures

Primary Outcomes (3)

• Area Under the Curve for Parathyroid Hormone (PTHauc) Measurement

  Mean area under the curve for parathyroid hormone levels (PTHauc) sampled during a 26 hour study period, for Paricalcitol (Active Drug) and Placebo groups at Baseline and Month 12 .

  Measured at baseline and Month 12

• Area Under the Curve for Parathyroid Hormone (PTH; Percentage Decrease)

  Mean PTHauc (% decrease) for Paricalcitol (Active Drug) and Placebo from Baseline to Month 12.

  Measured at baseline and Month 12

• Reduction of Parathyroid Hormone Area Under the Curve (PTHauc) of 20% or Greater

  Clinically significant reduction of Mean PTHauc (% decrease \>/= 20) for Paricalcitol (Active Drug) and Placebo from Baseline to Month 12.

  Measured at baseline and Month 12

Secondary Outcomes (6)

• Static Parameters of Serum Alkaline Phosphatase at Baseline and 1 Year for Paricalcitol and Placebo Arms.

  Measured at baseline and Month 12

• Serum Calcium

  Measured at baseline and Month 12

• Bone Scan Severity Score

  Measured at baseline and Month 12

• Percent Change in Urinary Calcium Excretion From Baseline to 1 Year

  Measured at baseline and Month 12

• Serum Intact Fibroblast Growth Factor 23 (FGF23)

  Measured at baseline and Month 12

Study Arms (2)

1

EXPERIMENTAL

Participants given active drug, paricalcitol (Zemplar), in effort to reduce PTH level

Drug: Paricalcitol

2

PLACEBO COMPARATOR

Participants given placebo capsule to match for comparison

Other: Placebo

Interventions

Paricalcitol DRUG

Paricalcitol given first as a dose of 2 capsules once per day. Dose titration as needed per biochemical results at outpatient visits.

Also known as: Zemplar

1

Placebo OTHER

Placebo sugar pill

2

Eligibility Criteria

• Age: 9 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of XLH rickets
• Fasting serum calcium of 10.7 mg/dl or less
• Fasting PTH greater than 40 nleq/ml and less than 120 nleq/ml in the mid-molecule PTH assay at screening (upper limit of normal is 25 nleq/ml)
• Willing and able to participate in the trial
• Taking stable dose of standard therapy for XLH rickets for at least 2 months prior to study entry

You may not qualify if:

• Parent or guardian willing to provide informed consent, if applicable
• Concomitant kidney failure (estimated creatinine clearance less than 60 cc/min or serum creatinine greater than 1.5 mg/dl)
• Serum 25-hydroxy vitamin D less than 20 ng/ml. Participants meeting this criterion will receive vitamin D3 supplementation for 3 months and then be rescreened.
• Unable to comply with protocol and appropriate follow-up visits
• Treatment with agents that may affect skeletal metabolism, such as glucocorticoids and anticonvulsants

Sponsors & Collaborators

• Yale University: lead
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): collaborator

Study Sites (1)

Yale University School of Medicine

New Haven, Connecticut, 06520, United States

Location

Related Publications (3)

• Brown AJ, Dusso AS, Slatopolsky E. Vitamin D analogues for secondary hyperparathyroidism. Nephrol Dial Transplant. 2002;17 Suppl 10:10-9. doi: 10.1093/ndt/17.suppl_10.10.

  PMID: 12386264 BACKGROUND

• McElduff A, Posen S. Parathyroid hormone sensitivity in familial X-linked hypophosphatemic rickets. J Clin Endocrinol Metab. 1989 Aug;69(2):386-9. doi: 10.1210/jcem-69-2-386.

  PMID: 2753981 BACKGROUND

• Carpenter TO, Olear EA, Zhang JH, Ellis BK, Simpson CA, Cheng D, Gundberg CM, Insogna KL. Effect of paricalcitol on circulating parathyroid hormone in X-linked hypophosphatemia: a randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab. 2014 Sep;99(9):3103-11. doi: 10.1210/jc.2014-2017. Epub 2014 Jul 16.

  PMID: 25029424 DERIVED

MeSH Terms

Conditions

Hypophosphatemia, Familial; Hyperparathyroidism; Rickets; Hypophosphatemia; Rickets, Hypophosphatemic; Familial Hypophosphatemic Rickets

Interventions

paricalcitol

Condition Hierarchy (Ancestors)

Renal Tubular Transport, Inborn Errors; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Metal Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Phosphorus Metabolism Disorders; Parathyroid Diseases; Endocrine System Diseases; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Calcium Metabolism Disorders; Vitamin D Deficiency; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders

Results Point of Contact

• Title: Dr. Thomas O. Carpenter
• Organization: Yale University School of Medicine

thomas.carpenter@yale.edu

203-785-6526

Study Officials

• Thomas O. Carpenter, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics

Study Record Dates

• First Submitted: December 28, 2006
• First Posted: January 1, 2007
• Study Start: January 1, 2007
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2012
• Last Updated: March 17, 2020
• Results First Posted: October 28, 2014

Record last verified: 2020-03

Locations

US (1)