Efficacy and Safety Study of Cinacalcet for the Treatment of Hypercalcemia in Subjects With PHPT Unable to Undergo Parathyroidectomy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00975221
First received: September 10, 2009
Last updated: February 25, 2014
Last verified: February 2014
  Purpose

This phase 3, randomized, double-blind, placebo-controlled study is designed to demonstrate the efficacy and to assess the safety of cinacalcet for the reduction of hypercalcemia in subjects with primary HPT for whom parathyroidectomy is indicated on the basis of an elevated corrected total serum calcium, but who are unable to undergo parathyroidectomy. The reasons a subject would be unable to undergo parathyroidectomy include failed parathyroidectomy, medical contraindication to surgery, or because together with their primary physician they decided it was inappropriate. The study will consist of a 30-day screening phase, a 12-week placebo-controlled dose-titration phase, and a 16 week placebo-controlled efficacy assessment phase (EAP). Subjects who complete 28 weeks on study will continue into an open-label safety extension phase for 24 weeks of investigational cinacalcet treatment.


Condition Intervention Phase
Hyperparathyroidism, Primary
Drug: cinacalcet HCl
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Double-blind Placebo-controlled Study to Evaluate the Efficacy and Safety of Cinacalcet for the Treatment of Hypercalcemia in Subjects With Primary Hyperparathyroidism Unable to Undergo Parathyroidectomy

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • to demonstrate the efficacy of cinacalcet for normalizing serum calcium in subjects with primary HPT who are unable to undergo parathyroidectomy [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • to demonstrate the efficacy of cinacalcet for reducing corrected total serum calcium and plasma PTH levels [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Enrollment: 67
Study Start Date: October 2009
Study Completion Date: March 2013
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: cinacalcet
Subjects will be randomized in a 1:1 ratio to cinacalcet or placebo stratified by bisphosphonate use
Drug: cinacalcet HCl
Subjects will be administered cinacalcet or placebo orally at a starting dose of 30 mg twice a day (BID) on day 1. Subjects will be eligible for a dose titration once every 3 weeks during the placebo-controlled dose titration phase based on corrected total serum calcium concentration and safety assessments obtained the previous week. Doses may be sequentially increased to 60 mg BID, 90 mg BID, and 90 mg 3 times a day (TID)
Other Names:
  • Sensipar
  • Mimpara
Placebo Comparator: Placebo
Subjects will be randomized in a 1:1 ratio to cinacalcet or placebo stratified by bisphosphonate use
Drug: Placebo
Subjects will be administered cinacalcet or placebo orally at a starting dose of 30 mg twice a day (BID) on day 1. Subjects will be eligible for a dose titration once every 3 weeks during the placebo-controlled dose titration phase based on corrected total serum calcium concentration and safety assessments obtained the previous week. Doses may be sequentially increased to 60 mg BID, 90 mg BID, and 90 mg 3 times a day (TID)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • age ≥18 years
  • diagnosis of primary HPT
  • subjects must have the following laboratory values:

    1. local/historical laboratory result showing a corrected total serum calcium > 1 mg/dL (0.25 mmol/L) above the upper limit of normal and

      ≤ 12.5 mg/dL (3.12 mmol/L) within the past 12 months, and

      • local/historical laboratory result showing a plasma PTH > 75% of upper limit of normal within the past 12 months, and
      • one central laboratory draw at the screen visit showing a corrected total serum calcium > 11.3 mg/dL (2.82 mmol/L) and ≤ 12.5 mg/dL (3.12 mmol/L), and
      • one central laboratory draw at the screen visit showing a plasma PTH > 55 pg/mL (5.8 pmol/L) OR
    2. two central laboratory draws performed during the screening period at least 7 days apart, showing a

      • corrected total serum calcium > 11.3 mg/dL (2.82 mmol/L) and ≤ 12.5 mg/dL (3.12 mmol/L), and
      • plasma PTH > 55 pg/mL (5.8 pmol/L)
  • not able to undergo parathyroidectomy for ≥ 1 of the following reasons:

    • failed parathyroidectomy
    • comorbid conditions contraindicating parathyroidectomy
    • parathyroidectomy not considered appropriate or is not feasible by primary physician and subject
  • before any study-specific procedure is performed, the appropriate written informed consent must be obtained

Exclusion Criteria:

  • symptoms attributable to hypercalcemia, requiring immediate medical intervention, as judged by the investigator (including acute kidney stone, nausea and vomiting requiring intravenous hydration, confusion, lethargy, stupor, or coma)
  • unstable medical condition, defined as having been hospitalized within 30 days before the date of informed consent, or otherwise unstable in the judgment of the investigator
  • administration of drugs that increase serum calcium concentration, including but not limited to thiazide diuretics or lithium
  • initiated bisphosphonate therapy or changed bisphosphonate dose within 12 weeks before the date of informed consent
  • current administration of drugs for ventricular arrhythmia
  • unable to provide informed consent, or is at risk for poor compliance with study procedures
  • currently enrolled in another investigational device or drug study(s), or completed such study within 30 days before the date of informed consent
  • known hypersensitivity to or unable to tolerate cinacalcet
  • received treatment with cinacalcet within 60 days before the date of informed consent
  • history of seizures or an adjustment of anti-seizure medication within 12 weeks before the date of informed consent
  • family history or diagnosis a genetic syndrome, such as familial benign hypocalciuric hypercalcemia (FBHH) or multiple endocrine neoplasia type 1 (MEN1) and type 2 (MEN2), where primary HPT is one of the clinical manifestations of familial benign hypocalciuric hypercalcemia (FBHH)
  • refused to use highly effective contraceptive measures (as determined by the investigator) throughout the study
  • pregnant or breastfeeding
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00975221

  Show 47 Study Locations
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00975221     History of Changes
Other Study ID Numbers: 20070277
Study First Received: September 10, 2009
Last Updated: February 25, 2014
Health Authority: Australia: Therapeutic Goods Administration
Hungary: National Institute of Pharmacy
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Portugal: Instituto Nacional da Farmácia e do Medicamento (INFARMED)
Russia: Federal Service for Surveillance in the field of Healthcare and Social Development (a body of the Ministry of Health)
Russia: Ministry of Health
United States: Food and Drug Administration
United States: Western Institutional Review Board

Keywords provided by Amgen:
Primary hyperparathyroidism
Parathyroidectomy
Hypercalcemia

Additional relevant MeSH terms:
Hypercalcemia
Hyperparathyroidism
Hyperparathyroidism, Primary
Calcium Metabolism Disorders
Metabolic Diseases
Water-Electrolyte Imbalance
Parathyroid Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on April 22, 2014