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

• INCLUSION CRITERIA:

  1. Chronological age: 18-70 years

  2. Diagnosis of a genetic form of FGF23-mediated hypophosphatemia:

     1. X-linked hypophosphatemic rickets (XLH)
     2. Autosomal dominant hypophosphatemic rickets (ADHR)
     3. Autosomal recessive hypophosphatemic rickets (ARHR)

     Or, diagnosis of a non-genetic form of FGF23-mediated hypophosphatemia, i.e. tumor-induced osteomalacia (TIO)

  3. Ability to understand and provide informed consent
  4. Ability to complete the protocol scheduled assessments and medication regimen
  5. Women of child-bearing potential (not surgically sterile via tubal ligation, bilateral oophorectomy or hysterectomy, or who are not postmenopausal for greater than or equal to 1 year) must agree to practice adequate contraception that may include, but is not limited to, abstinence, monogamous relationship with vasectomized partner, barrier methods such as condoms, diaphragms, spermicides, intrauterine devices, and licensed hormonal methods for the duration of the treatment portion of the study.

EXCLUSION CRITERIA:

1. Chronic or recurrent hypocalcemia defined by a serum calcium < 8.4 mg/dL (2.1 mmol/L)
2. Tertiary hyperparathyroidism as evidenced by concurrent PTH and calcium levels above the upper limit of normal
3. History of parathyroid surgery and/or hypoparathyroidism
4. Hypercalciuria as defined as > 4 mg/kg/day (0.1 mmol/kg/day) on optimized conventional therapy (as determined during SOC optimization phase)
5. Moderate to severe hepatic insufficiency as defined by total bilirubin > 2 mg/dL and serum albumin < 3 g/dL and International Normalized Ratio (INR) > 2 OR presence of ascites or hepatic encephalopathy.
6. A calculated eGFR < 50 mL/min/1.73 m(2), using the CKD-EPI equation
7. History of a non-febrile seizure disorder
8. History of a clinically significant cardiac arrhythmia
9. History of chronic gastrointestinal disease
10. Current therapy (at the time of informed consent) bisphosphonates, calcitonin, diuretics or medications that may have a significant drug interaction with cinacalcet
11. Known hypersensitivity to cinacalcet or any of its constituents
12. Positive pregnancy test or lactation
13. Use of another investigational agent (i.e., in the context of a clinical trial, use of an investigational product that may have impact on the study) within the last 3 months