Hypoparathyroidism MedDRA version: 20.0 Level: PT Classification code 10051315 Term: Congenital hypoparathyroidism System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 20.0 Level: PT Classification code 10075900 Term: Primary hypoparathyroidism System Organ Class: 10014698 - Endocrine disorders MedDRA version: 20.0 Level: PT Classification code 10021041 Term: Hypoparathyroidism System Organ Class: 10014698 - Endocrine disorders
Conditions
Interventions
Trade Name: Natpara
Product Name: human recombinant parathyroid hormone
Product Code: rhPTH(1-84)
Pharmaceutical Form: Lyophilisate and solvent for solution for injection
INN or Proposed INN: RECOMBIN
Sponsors
Shire Human Genetic Therapies, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Has an understanding, ability, and willingness to fully comply with study procedures and restrictions. 2. Is able to voluntarily provide a signed and dated informed consent form before any study-related procedures are performed. 3. Is an adult male or female 18 to 85 years of age, inclusive. 4. In subjects 25 years of age or younger, has radiological evidence of epiphyseal closure based on X-ray of left wrist and left hand before randomization. 5. Has a history of hypoparathyroidism with onset 12 months or more before screening. The diagnosis of hypoparathyroidism is established based on hypocalcemia in the setting of inappropriately low serum PTH levels. 6. During the Week -3 screening visit, the subject reports by history at least 2 of the following symptoms related to hypoparathyroidism occurring within the 2 weeks before Week -3 visit: muscle cramps, muscle spasms or twitching, tingling, numbness, heaviness in arms or legs, physical fatigue, or slowed or confused thinking (brain fog). 7. Based on the results of the Hypoparathyroidism Symptom Diary (HPT-SD) administered during the first week of the screening period (from Week -3 to Week -2 visits), the subject reports at least 2 of the following symptoms that average at least moderate in intensity: muscle cramps, muscle spasms or twitching, tingling, numbness, heaviness in arms or legs, physical fatigue, or slowed or confused thinking (brain fog). Additionally, the sum score of the HPT-SD symptom subscale (items 1-7) measured during the first week of the screening period must be =6 (see Appendix 3). At least 4 responses must be entered for each symptom. 8. Must be treated with active vitamin D (calcitriol or alfacalcidol) alone or in conjunction with calcium supplements. ?If treated with active vitamin D alone, the subject must be taking =0.5 µg/day of calcitriol or =1.0 µg/day of alfacalcidol. If treated with 30 ml/min/1.73m2. 12. Prior to randomization, is able to perform daily SC self-injections of study medication (or have a designee perform injection) via a multidose injec
Exclusion criteria
Exclusion criteria: 1. History of hypoparathyroidism resulting from a known activating mutation in the CaSR gene or impaired responsiveness to PTH (pseudohypoparathyroidism). 2. Any disease that might affect calcium metabolism or calcium-phosphate homeostasis other than hypoparathyroidism, such as active hyperthyroidism; Paget disease; type 1 diabetes mellitus or poorly controlled type 2 diabetes mellitus; severe and chronic cardiac, liver, or renal disease; Cushing syndrome; rheumatoid arthritis; myeloma; active pancreatitis; malnutrition; rickets; recent prolonged immobility; active malignancy (other than low-risk well differentiated thyroid cancer); primary or secondary hyperparathyroidism; or documented parathyroid carcinoma within the previous 5 years, acromegaly, or multiple endocrine neoplasia types 1 and 2. 3. Albumin-corrected serum calcium level <1.875 mmol/L (7.5 mg/dL) or =2.56 mmol/L (10.3 mg/dL) at the Week -3screening visit. Results from a local laboratory may be used for this assessment. 4. Albumin-corrected serum calcium level =2.56 mmol/L (10.3 mg/dL) at the baseline (Week 0) visit. Results from a local laboratory may be used for this assessment. 5. Use of prohibited medications, such as loop and thiazide diuretics, phosphate binders (other than calcium carbonate), digoxin, lithium, methotrexate, or systemic corticosteroids, within respective prohibited periods. See Section 5 (Prior and Concomitant Treatment) for a list of prohibited and restricted medications 6. Participation in any other investigational study in which receipt of investigational drug or device occurred within 6 months before screening for this study. Prior treatment with PTH-like drugs (whether commercially available or through participation in an investigational study), including PTH(1-84), PTH(1-34), or other N-terminal fragments or analogs of PTH or PTH-related protein, within 3 months before screening. 7. Use of other drugs known to influence calcium and bone metabolism, such as calcitonin, fluoride tablets, or cinacalcet hydrochloride, within the prohibited period. 8. Use of oral bisphosphonates within the previous 6 months or intravenous bisphosphonate preparations within the previous 24 months before screening. 9. Nonhypocalcemic seizure disorder with a history of a seizure within the previous 6 months before screening. Subjects with a history of seizures that occur in the setting of hypocalcemia are allowed. 10. The subject is at increased baseline risk for osteosarcoma, such as those with Paget’s disease of bone or unexplained elevations of alkaline phosphatase, hereditary disorders predisposing to osteosarcoma, or with a prior history of external beam or implant radiation therapy involving the skeleton. 11. Any disease or condition that, in the opinion of the investigator, may require treatment or make the subject unlikely to fully complete the study, or any condition that presents undue risk from the investigational product or procedures. 12. Pregnant or lactating women. 13. History of diagnosed drug or alcohol dependence within the previous 3 years. 14. Disease processes that may adversely affect gastrointestinal absorption, including but not limited to short bowel syndrome, bowel resection, tropical sprue, celiac disease, ulcerative colitis, and Crohn disease. 15. Chronic or severe cardiac disease including but not limited to heart failure, arrhythmias, bradycardia (resting heart rate <50 beats/minute). 16. History of cerebrovascular accident.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To test the hypothesis that rhPTH(1-84) treatment can result in superior improvements in the symptoms of hypoparathyroidism assessed by the hypoparathyroidism Symptom Diary (HPT-SD) symptom subscale compared with standard therapy.;Secondary Objective: The key secondary objectives are to test the hypotheses that rhPTH(1-84) treatment can result in superior improvements in: Fatigue assessed by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) compared with standard therapy. The physical component summary (PCS) derived from the 36-Item Short Form Health Survey version 2 (SF-36v2) acute version compared with standard therapy.;Primary end point(s): Change in the HPT-SD symptom subscale score from baseline;Timepoint(s) of evaluation of this end point: Week 26 from baseline | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Change in FACIT-Fatigue score at Week 26 Change in the PCS derived from SF-36v2 scores at Week 26;Timepoint(s) of evaluation of this end point: Week 26 from baseline | — |
Countries
Belgium, Denmark, France, Germany, Italy, Netherlands, Norway, Portugal, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactElena Tokareva
Shire Human Genetic Therapies, Inc
Outcome results
None listed