Use of NPSP558 in the Treatment of Hypoparathyroidism

NCT00732615 | Completed Phase 3 Results DMC

• 2 other identifiers: CL1-11-0402008-005063-34
• Study Type: interventional
• Target: 124
• Locations: 8 countries
• Sites: 31

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.

Conditions

Hypoparathyroidism

Keywords

Hypoparathyroidism

Outcome Measures

Primary Outcomes (1)

• The Percentage of Subjects Who Met the Triple Efficacy Endpoint Criteria at Week 24.

  The triple efficacy endpoint criteria were defined as at least a 50% reduction from the baseline in oral calcium dose and at least a 50% reduction from the baseline in active vitamin D dose and an albumin-corrected total serum calcium concentration that was maintained or normalized compared to the baseline value (≥ 7.5 mg/dL) and did not exceed the upper limit of the laboratory normal range. The analysis of primary efficacy endpoint was based on investigator prescribed data.

  Week 24 of dosing

Secondary Outcomes (3)

• Percentage Changes From Baseline in Daily Calcium Dose at Week 24.

  24 Weeks

• Proportion of Subjects Who Achieved Independence From Active Vitamin D and an Oral Calcium Dose of ≤ 500 mg/Day at Week 24.

  24 Weeks

• Percentage of Subjects With Any Clinical Symptoms of Hypocalcemia During Weeks 16-24.

  8 Weeks

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Sterile water for injection

Drug: Placebo

50, 75, 100 mcg NPSP558

EXPERIMENTAL

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

Drug: NPSP558

Interventions

Placebo DRUG

Placebo for subcutaneous injection

Placebo

NPSP558 DRUG

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

50, 75, 100 mcg NPSP558

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Shire: lead

Study Sites (31)

Mayo Clinic-Scottsdale

Scottsdale, Arizona, 85259, United States

Location

Advance Medical Research LLC

Lakewood, California, 90712, United States

Location

Diabetes Associates

Orange, California, 92868, United States

Location

University of California-San Francisco VA Medical Center

San Francisco, California, 94127, United States

Location

Palm Springs Research Institute

Hialeah, Florida, 33012, United States

Location

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Indiana University School of Medicine

Indianapolis, Indiana, 46202, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Michigan Bone and Mineral Clinic PC

Detroit, Michigan, 48236, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

University Physicians Group

Staten Island, New York, 10301, United States

Location

Physicians East

Greenville, North Carolina, 27834, United States

Location

University of Cincinnati Bone Health and Osteoporosis Center

Cincinnati, Ohio, 45219, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Cetero Research DGD Research Inc.

San Antonio, Texas, 78229, United States

Location

Hillcrest Family Health Center

Waco, Texas, 76708, United States

Location

The Vancouver Clinic

Vancouver, Washington, 98664, United States

Location

Chetre Hospitalier Universitaire de Liege

Liège, BE-4000, Belgium

Location

Heritage Medical Research Clinic

Calgary, Alberta, T2N 4Z6, Canada

Location

Capital District Health Authority, QEII Health Sciences Centre

Halifax, Nova Scotia, B3H 2Y9, Canada

Location

Oakville Bone Center

Oakville, Ontario, L6J 1X8, Canada

Location

Aarhus University Hospital

Aarhus, DK-8000, Denmark

Location

Odense University Hospital

Odense, DK-5000, Denmark

Location

Hôpital Européen Georges Pompidou

Paris, F-75015, France

Location

Semmelweis University Medical School

Budapest, Hungary

Location

University of Pécs, School of Medicine

Pécs, Hungary

Location

University of Szeged

Szeged, Hungary

Location

University Hospital of Careggi

Florence, I - 50134, Italy

Location

Royal Liverpool University Hospital

Liverpool, L69 3GA, United Kingdom

Location

Related Publications (6)

• 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.

  PMID: 36018496 DERIVED

• 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.

  PMID: 35974422 DERIVED

• 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.

  PMID: 35696069 DERIVED

• 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.

  PMID: 32738041 DERIVED

• 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.

  PMID: 29099947 DERIVED

• 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.

  PMID: 24622413 DERIVED

MeSH Terms

Conditions

Hypoparathyroidism

Condition Hierarchy (Ancestors)

Parathyroid Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2008
• First Posted: August 12, 2008
• Study Start: December 18, 2008
• Primary Completion: September 28, 2011
• Study Completion: September 28, 2011
• Last Updated: June 3, 2021
• Results First Posted: March 6, 2015

Record last verified: 2021-05

Locations

IT (1); GB (1); US (19); BE (1); FR (1); DK (2); HU (3); CA (3)