Open-label Dose-titration Study of the Tolerability and Efficacy of Cinacalcet to Treat Fibroblast Growth Factor 23 (FGF23)-Mediated Hypophosphatemia
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.
Up to 17 subjects with FGF23-mediated hypophosphatemia will be treated.
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 their MTD. At
the end of the cinacalcet treatment phase of the study, cinacalcet will be discontinued and
standard of care (SOC) medications will be adjusted/restarted on an individualized basis.
Subjects will continue in this final SOC safety follow-up period for up to 4 weeks until
their SOC medications have been re-equilibrated.
Whether or not a subject discontinued the study due to a toxicity, related serious adverse
event (SAE), or related intolerable adverse event (AE).
- Maximum tolerated dose of cinacalcet
- Serum calcium levels
- Urine calcium levels
- Adverse events
- Time from cinacalcet discontinuation to return to pre-treatment standard of care dosage
- Pharmacodynamic assessments
- Serum: FGF23, intact parathyroid hormone, calcium, creatinine, phosphorus
- Urine: phosphorus, creatinine, calcium.
- Tubular maximum reabsorption of phosphate/glomerular filtration rate
- Tubular reabsorption of phosphate
- Change in oral phosphate and calcitriol intake required to maintain adequate phosphorus
and calcium serum levels
- Serum osteocalcin and alkaline phosphatase
- Serum intact parathyroid hormone (PTH)
- Twice-Daily Dosing at MTD
- Time from cinacalcet discontinuation of twice-daily dosing to return to pre-treatment
standard of care dosage levels
- Dental Evaluation
- Visible Plaque Index (VPI)
- Gingival Bleeding Index (GBI)
- Position of Gingival Margin (PGM)
- Relative Attachment Level (RAL)
- Periodontal Probing Pocket Depth (PPD)
- Gingival Crevicular Fluid (GCF) Biomarkers
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Evaluate the tolerability of cinacalcet in individuals with FGF23-mediated hypophosphatemia
Rachel I Gafni, M.D.
National Institute of Dental and Craniofacial Research (NIDCR)
United States: Federal Government
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Bethesda, Maryland 20892|