Clinical Trial: Cinacalcet for Fibroblast Growth Factor 23 (FGF23)-Mediated Hypophosphatemia (Hypophosphatemic Rickets)

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: Open-label Dose-titration Study of the Tolerability and Efficacy of Cinacalcet to Treat Fibroblast Growth Factor 23 (FGF23)-Mediated Hypophosphatemia

Brief Summary:

Background:

  • Hypophosphatemia is a condition where a person has low levels of phosphorus in the blood. Low blood phosphorus can cause muscle and bone weakness (such as rickets) and teeth problems. One cause of the condition is having too much fibroblast growth factor 23 (FGF23). FGF23 is a hormone that causes the kidney to get rid of phosphorus in the urine. It can also prevent the body from making vitamin D, which helps the body absorb phosphorus in food.
  • Many people with low blood phosphorus take high doses of phosphorus and calcium medications. However, one side effect of these drugs is increased blood levels of parathyroid hormone (PTH). The drug cinacalcet can help lower PTH levels, which may decrease the amount of phosphorus lost in the urine and increase the phosphorus levels in the blood. Researchers want to see if cinacalcet can help blood phosphorus and decrease the amount of phosphorus supplements that people need to take.

Objectives:

- To see if cinacalcet can be a safe and effective treatment for people with low phosphorus conditions due to high FGF23.

Eligibility:

- Individuals between 18 and 70 years of age who have different forms of hypophosphatemic rickets and tumor-induced hypophosphatemia

Design:

  • Participants will have up to 25 study visits over about 28 weeks.
  • Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected.
  • Up to three

    Detailed Summary:

    OBJECTIVES:

    The primary objective of this protocol is to evaluate the tolerability of cinacalcet in individuals with fibroblast growth factor 23 (FGF23)-mediated hypophosphatemia, using an open-label, dose-titration study of once-daily dosing. Secondary objectives are to evaluate the pharmacodynamics of cinacalcet in this subject population and to explore the efficacy of cinacalcet by comparing a) level of oral phosphate required at baseline to the level required at maximum tolerated dose (MTD) and b) change in renal phosphate handling from baseline to MTD. Tertiary objectives are to evaluate tolerability, pharmacodynamics, and efficacy of twice daily dosing of each subject s MTD of cinacalcet after completion of the once-daily dose-titration phase. A final objective is to determine the length of time it takes for subjects to return to their pre-treatment steady state once treatment is complete.

    STUDY POPULATION:

    Up to 17 subjects with FGF23-mediated hypophosphatemia will be treated.

    DESIGN:

    This study is an open-label, dose-titration study of once-daily dosing of cinacalcet, with up to 4 escalating doses given at approximately 3 week intervals. After an initial standard of care optimization period of 2-9 weeks, subjects will proceed to the cinacalcet dose-titration period. Subjects who experience extended toxicity or study drug related serious adverse events or other related, intolerable adverse events will be down titrated to a lower dose of study medication. After subjects have achieved their own maximum tolerated dose (MTD) and completed the once-daily dosing phase, they will continue the study medication for approximately 3 additional weeks with twice daily dosing at the
    Sponsor: National Institute of Dental and Craniofacial Research (NIDCR)

    Current Primary Outcome: Evaluate the tolerability of cinacalcet in individuals with FGF23-mediated hypophosphatemia [ Time Frame: 4 years ]

    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    Original Secondary Outcome:

    • To explore the effectiveness of cinacalcet at decreaing renal phosphate wasting [ Time Frame: 4 years ]
    • Evaluate the pharmacodynamics of cinacalcet in this subject population. [ Time Frame: 4 years ]


    Information By: National Institutes of Health Clinical Center (CC)

    Dates:
    Date Received: December 11, 2012
    Date Started: November 16, 2012
    Date Completion:
    Last Updated: May 12, 2017
    Last Verified: July 7, 2015