A Randomized, Double-blind, Placebo-Controlled, Phase 3 Study to Investigate the Use of NPSP558, a Recombinant Human Parathyroid Hormone [rhPTH(1-84)] for the Treatment of Adults with Hypoparathyroidism - CL1-11-040

• Conditions: Hypoparatthyroidism; MedDRA version: 12.0Level: LLTClassification code 10021041Term: Hypoparathyroidism

• Registration Number: EUCTR2008-005063-34-IT
• Lead Sponsor: PS PHARMACEUTICALS

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-06-18
• Last Update Posted: 28 August 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 84

Inclusion Criteria

1. Adult male/female 18-65 years of age. Those < 25 years old will be examined radiologically to ensure epiphyseal closure. 2. Hypoparathyroidism history for &#8805; 18 months post-diagnosis, inclusive of historical biochemical evidence of hypocalcemia and concomitant PTH unchanged in the serum < 15 pg/mL in the analysis carried out on 2 different dates at a distance of at least 21 days in the 12 months prior to the randomization. 3. Requirement for supplemental oral calcium treatment > 1000 mg per day over and above normal dietary calcium intake (see Appendix 2 for the table of the normal reference intake taken with the diet on the basis of age and gender). 4. Serum thyroid function tests within normal laboratory limits during screening. For patients undergoing replacement thyroid hormone treatment, the dose must have remained stable for at least 3 months before screening. 5. The stable serum magnesium levels must be within normal laboratory limits. The subjects with low levels of serum magnesium must be subject to integration to clinically appropriate levels until the serum magnesium returns to the normal range by the end of the optimization period; in addition, normal serum magnesium must be maintained for the entire study. 6. Serum 25-hydroxyvitamin D [25(OH)D] level &#8804; 120 ng/mL (normal range 20-80 ng/mL). The patients with low levels of 25(OH)D in the serum at screening will be subject to integration of Vitamin D during the optimization period. For the patients with levels of 25(OH)D in the serum > 80 ng/mL, the integration of Vitamin D during the optimization period will be stopped. The levels of 25(OH)D in the serum within the normal levels must be confirmed at the end of the optimization period. See Section 5.4.2. 7. Creatinine clearance > 30 mL/min on two separate measurements at screening OR creatinine clearance > 60 mL/min AND serum creatinine < 1.5 mg/dL at screening. 8. Capable of providing written informed consent. 9. Able to perform daily SC self-injections of the experimental drug (or have a designee perform injection) via multi-dose injection pen into the thigh. 10. Willingness and ability to understand and comply with the protocol. 11. With regard to the women patients: women who are postmenopausal for &#8805; 2 years and women who are surgically sterilized can be enrolled. Women of child-bearing potential (WOCBP) are excluded from the study.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Patients who have any of the following during the screening visit are not eligible for enrollment
in this study:
1. Hypoparathyroidism resulting from an 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`s disease, insulindependent
diabetes mellitus (IDDM) or poorly controlled Type II diabetes mellitus
(HbA1C > 8), severe and chronic cardiac, liver or renal disease, Cushing`s syndrome,
neuromuscular disease such as rheumatoid arthritis, myeloma, pancreatitis, malnutrition,
rickets, recent prolonged immobility, active malignancy, primary or secondary
hyperparathyroidism, a history of parathyroid carcinoma, hypopituitarism, acromegaly, or
multiple endocrine neoplasia types I and II.
3. To be eligible, patients with a history of thyroid cancer must be documented to be
disease-free for a period of at least 5 years.
4. Patients dependent on regular parenteral calcium infusions (eg calcium gluconate) to
maintain calcium homeostasis.
5. Patients that have undergone gastric resection or have active peptic ulcer disease
requiring medical therapy.
6. Use of prohibited medications such as loop diuretics, raloxifene hydrochloride, lithium,
estrogens, progestins, methotrexate, or systemic corticosteroids within respective
prohibited periods.
7. Previous treatment with PTH-like drugs, including PTH(1-84), PTH(1-34) or other
N-terminal fragments or analogs of PTH or PTH-related protein within the prohibited
period.
NPSP 558 CLINICAL PROTOCOL CL1-11-040 V5.0
AMENDMENT 4.0
CONFIDENTIAL 30
8. Other drugs known to influence calcium and bone metabolism, calcitonin, fluoride, or
cinacalcet hydrochloride within the prohibited period.
9. Use of oral bisphosphonates within the previous 6 months or IV bisphosphonate
preparations during the previous 12 months.
10. Seizure disorder/epilepsy with a history of a seizure within the previous 6 months.
11. Presence of open epiphyses.
12. Irradiation to the skeleton within 5 years.
13. Serum 25-hydroxyvitamin D levels > 120 ng/mL (normal 20 ? 80 ng/mL).
14. Any disease or condition in the opinion of the Investigator that has a high probability of
precluding the patient from completing the study or where the patient cannot or will not
appropriately comply with study requirements.
15. Participation in any other investigational trial in which receipt of investigational drug or
device occurred within 30 days prior to screening for this study.
16. Women of child-bearing potential unless surgically sterilized or are postmenopausal for
_ 2 years.
17. History of diagnosed drug or alcohol dependence within the previous 3 years.
18. Clinical history of renal calculi within the past 12 months.
19. History of gout.
20. 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?s disease.
21. Chronic/severe cardiac disease including but not limited to cardiac insufficiency,
arrhythmias, bradycardia (resting heart rate < 60 beats/minute), or hypotension (systolic
and diastolic blood pressures < 100 and 60 mmHg, respectively).
22. History of cerebrovascular accident (CVA).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified