Use of NPSP558 in the Treatment of Hypoparathyroidism

NCT ID: NCT00732615

Last Updated: 2021-06-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 124 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-12-18
• Study Completion Date: 2011-09-28

Brief Summary

Use of PTH (1-84) a recombinant hormone in escalating doses for the treatment of adults with hypoparathyroidism. The use of PTH should result in a decrease of calcium and vitamin D supplements.

Detailed Description

Patients with a history of hypoparathyroidism will be randomized to receive placebo or study drug for 24 weeks, which will be injected daily in either thigh. During that time they will be monitored for safety (specifically, calcium levels in the blood and urine). In addition, the patients' intake of Vitamin D and calcium will be measured.

Conditions

Hypoparathyroidism

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Sterile water for injection

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo for subcutaneous injection

50, 75, 100 mcg NPSP558

Initial dose of 50mcg, to be titrated up to 75mcg and then 100mcg dependent upon response

Group Type: EXPERIMENTAL

NPSP558

Intervention Type: DRUG

Parathyroid hormone 50, 75, or 100 mcg injectable subcutaneously daily

Interventions

Placebo

Placebo for subcutaneous injection

Intervention Type: DRUG

NPSP558

Parathyroid hormone 50, 75, or 100 mcg injectable subcutaneously daily

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Adult males or females 18 to 85 years of age (prior to screening)
• History of hypoparathyroidism for ≥ 18 months
• Requirement for vitamin D metabolite/analog therapy with calcitriol ≥0.25 μg per day or alphacalcidol ≥0.50 μg per day prior to randomization. Requirement for supplemental oral calcium treatment ≥ 1000 mg per day over and above normal dietary calcium intake
• Serum thyroid function tests within normal laboratory limits at screening
• Serum magnesium levels within laboratory normal limits
• Serum 25-hydroxyvitamin D [25(OH)D] level ≤ 1.5-fold the laboratory upper limit of normal
• Creatinine clearance > 30 mL/min on two separate measurements OR creatinine clearance > 60 mL/min AND serum creatinine < 1.5 mg/dL
• With regard to female patients: women who are postmenopausal and women who are surgically sterilized can be enrolled. Women of childbearing potential must have a negative pregnancy test at Randomization and be willing to use two medically acceptable methods of contraception for the duration of the study.

Exclusion Criteria

Patients who have any of the following during the screening visit are not eligible for enrollment in this study:

• Known history of hypoparathyroidism resulting from an activating mutation in the CaSR gene or impaired responsiveness to PTH (pseudohypoparathyroidism)
• Any disease that might affect calcium metabolism or calcium-phosphate homeostasis other than hypoparathyroidism, such as active hyperthyroidism, Paget's disease, insulin dependent 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
• Patients with a history of thyroid cancer must be documented to be disease-free for a period of at least 5 years
• Patients dependent on regular parenteral calcium infusions (eg calcium gluconate) to maintain calcium homeostasis
• Patients that have undergone gastric resection or have active peptic ulcer disease requiring medical therapy
• Use of prohibited medications such as loop and thiazide diuretics, raloxifene hydrochloride, lithium, estrogens and progestins for hormone replacement therapy,methotrexate, or systemic corticosteroids within respective prohibited periods
• 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 6 months prior to screening
• Other drugs known to influence calcium and bone metabolism, such as calcitonin, fluoride tablets, or cinacalcet hydrochloride within the prohibited period
• Use of oral bisphosphonates within the previous 6 months or IV bisphosphonate preparations within the previous 12 months prior to screening
• Seizure disorder/epilepsy with a history of a seizure within the previous 6 months prior to screening
• Presence of open epiphyses
• Irradiation (radiotherapy) to the skeleton within 5 years
• Serum 25-hydroxyvitamin D levels greater than 1.5-fold the laboratory upper limit of normal
• Participation in any other investigational trial in which receipt of investigational drug or device occurred within 6 months prior to screening for this study
• Pregnant or lactating women
• History of diagnosed drug or alcohol dependence within the previous 3 years
• Clinical history of renal calculi within the past 12 months
• History of gout
• 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
• 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)
• History of cerebrovascular accident (CVA).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shire

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

Mayo Clinic-Scottsdale

Scottsdale, Arizona, United States

Advance Medical Research LLC

Lakewood, California, United States

Diabetes Associates

Orange, California, United States

University of California-San Francisco VA Medical Center

San Francisco, California, United States

Palm Springs Research Institute

Hialeah, Florida, United States

Mayo Clinic Jacksonville

Jacksonville, Florida, United States

University of Chicago Medical Center

Chicago, Illinois, United States

Indiana University School of Medicine

Indianapolis, Indiana, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Michigan Bone and Mineral Clinic PC

Detroit, Michigan, United States

Mayo Clinic Rochester

Rochester, Minnesota, United States

Columbia University Medical Center

New York, New York, United States

University Physicians Group

Staten Island, New York, United States

Physicians East

Greenville, North Carolina, United States

University of Cincinnati Bone Health and Osteoporosis Center

Cincinnati, Ohio, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Cetero Research DGD Research Inc.

San Antonio, Texas, United States

Hillcrest Family Health Center

Waco, Texas, United States

The Vancouver Clinic

Vancouver, Washington, United States

Chetre Hospitalier Universitaire de Liege

Liège, , Belgium

Heritage Medical Research Clinic

Calgary, Alberta, Canada

Capital District Health Authority, QEII Health Sciences Centre

Halifax, Nova Scotia, Canada

Oakville Bone Center

Oakville, Ontario, Canada

Aarhus University Hospital

Aarhus, , Denmark

Odense University Hospital

Odense, , Denmark

Hôpital Européen Georges Pompidou

Paris, , France

Semmelweis University Medical School

Budapest, , Hungary

University of Pécs, School of Medicine

Pécs, , Hungary

University of Szeged

Szeged, , Hungary

University Hospital of Careggi

Florence, , Italy

Royal Liverpool University Hospital

Liverpool, , United Kingdom

Countries

United States; Belgium; Canada; Denmark; France; Hungary; Italy; United Kingdom

References

Ayodele O, Rejnmark L, Mu F, Lax A, Berman R, Swallow E, Gosmanova EO. Five-Year Estimated Glomerular Filtration Rate in Adults with Chronic Hypoparathyroidism Treated with rhPTH(1-84): A Retrospective Cohort Study. Adv Ther. 2022 Nov;39(11):5013-5024. doi: 10.1007/s12325-022-02292-1. Epub 2022 Aug 26.

Reference Type: DERIVED

PMID: 36018496 (View on PubMed)

Rejnmark L, Ayodele O, Lax A, Mu F, Swallow E, Gosmanova EO. The risk of chronic kidney disease development in adult patients with chronic hypoparathyroidism treated with rhPTH(1-84): A retrospective cohort study. Clin Endocrinol (Oxf). 2023 Apr;98(4):496-504. doi: 10.1111/cen.14813. Epub 2022 Aug 28.

Reference Type: DERIVED

PMID: 35974422 (View on PubMed)

Ayodele O, Mu F, Berman R, Swallow E, Rejnmark L, Gosmanova EO, Kaul S. Lower Risk of Cardiovascular Events in Adult Patients with Chronic Hypoparathyroidism Treated with rhPTH(1-84): A Retrospective Cohort Study. Adv Ther. 2022 Aug;39(8):3845-3856. doi: 10.1007/s12325-022-02198-y. Epub 2022 Jun 11.

Reference Type: DERIVED

PMID: 35696069 (View on PubMed)

Chen KS, Gosmanova EO, Curhan GC, Ketteler M, Rubin M, Swallow E, Zhao J, Wang J, Sherry N, Krasner A, Bilezikian JP. Five-year Estimated Glomerular Filtration Rate in Patients With Hypoparathyroidism Treated With and Without rhPTH(1-84). J Clin Endocrinol Metab. 2020 Oct 1;105(10):e3557-65. doi: 10.1210/clinem/dgaa490.

Reference Type: DERIVED

PMID: 32738041 (View on PubMed)

Vokes TJ, Mannstadt M, Levine MA, Clarke BL, Lakatos P, Chen K, Piccolo R, Krasner A, Shoback DM, Bilezikian JP. Recombinant Human Parathyroid Hormone Effect on Health-Related Quality of Life in Adults With Chronic Hypoparathyroidism. J Clin Endocrinol Metab. 2018 Feb 1;103(2):722-731. doi: 10.1210/jc.2017-01471.

Reference Type: DERIVED

PMID: 29099947 (View on PubMed)

Mannstadt M, Clarke BL, Vokes T, Brandi ML, Ranganath L, Fraser WD, Lakatos P, Bajnok L, Garceau R, Mosekilde L, Lagast H, Shoback D, Bilezikian JP. Efficacy and safety of recombinant human parathyroid hormone (1-84) in hypoparathyroidism (REPLACE): a double-blind, placebo-controlled, randomised, phase 3 study. Lancet Diabetes Endocrinol. 2013 Dec;1(4):275-83. doi: 10.1016/S2213-8587(13)70106-2. Epub 2013 Oct 7.

Reference Type: DERIVED

PMID: 24622413 (View on PubMed)

Other Identifiers

2008-005063-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CL1-11-040

Identifier Type: -

Identifier Source: org_study_id