Clinical trial NCT00975221: Efficacy and Safety Study of Cinacalcet for the Treatment of Hypercalcemia in Patients With Primary Hyperparathyroidism Unable to Undergo Parathyroidectomy
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hyperparathyroidism, Primary
Hypercalcemia
Keywords: Primary hyperparathyroidism
Parathyroidectomy
Hypercalcemia
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2009-09-11
Enrollment: 67
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is designed to demonstrate the efficacy and to assess the safety of cinacalcet for the reduction of hypercalcemia in patients with primary hyperparathyroidism for whom parathyroidectomy is indicated on the basis of an elevated corrected total serum calcium, but who are unable to undergo parathyroidectomy.

Detailed description: 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). Participants who complete 28 weeks on study will continue into an open-label safety extension phase for 24 weeks of investigational cinacalcet treatment.

Eligibility criteria: Inclusion Criteria:

* age ≥ 18 years
* diagnosis of primary hyperparathyroidism (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 parathyroid horone (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

Primary outcomes:
measure: Percentage of Participants With Mean Corrected Total Serum Calcium Concentration ≤ 10.3 mg/dL (2.57 mmol/L) During the EAP
timeFrame: Efficacy assessment phase (study visits at Weeks 16, 20, 24, and 28)
Secondary outcomes:
measure: Percentage of Participants With a ≥ 1 mg/dL (0.25 mmol/L) Decrease From Baseline in Mean Corrected Total Serum Calcium Concentration During the EAP
timeFrame: Baseline and the EAP (mean of Weeks 16, 20, 24, and 28)
measure: Percent Change From Baseline in Corrected Total Serum Calcium Concentration During the EAP
timeFrame: Baseline and the EAP (mean of Weeks 16, 20, 24, and 28)
measure: Percent Change From Baseline in Plasma Parathyroid Hormone Level During the EAP
timeFrame: Baseline and the EAP (mean of Weeks 16, 20, 24, and 28)
Other outcomes:
Locations:
city: Lake Forest
country: United States
facility: Research Site
state: California
city: Lancaster
country: United States
facility: Research Site
state: California
city: Los Gatos
country: United States
facility: Research Site
state: California
city: Mission Viejo
country: United States
facility: Research Site
state: California
city: Orange
country: United States
facility: Research Site
state: California
city: San Diego
country: United States
facility: Research Site
state: California
city: Aurora
country: United States
facility: Research Site
state: Colorado
city: Washington
country: United States
facility: Research Site
state: District of Columbia
city: Aventura
country: United States
facility: Research Site
state: Florida
city: Clearwater
country: United States
facility: Research Site
state: Florida
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Pembroke Pines
country: United States
facility: Research Site
state: Florida
city: Weston
country: United States
facility: Research Site
state: Florida
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Indianapolis
country: United States
facility: Research Site
state: Indiana
city: Kenner
country: United States
facility: Research Site
state: Louisiana
city: New Orleans
country: United States
facility: Research Site
state: Louisiana
city: Detroit
country: United States
facility: Research Site
state: Michigan
city: New York
country: United States
facility: Research Site
state: New York
city: Morehead City
country: United States
facility: Research Site
state: North Carolina
city: Columbus
country: United States
facility: Research Site
state: Ohio
city: Randwick
country: Australia
facility: Research Site
state: New South Wales
city: St Leonards
country: Australia
facility: Research Site
state: New South Wales
city: Footscray
country: Australia
facility: Research Site
state: Victoria
city: Geelong
country: Australia
facility: Research Site
state: Victoria
city: Nedlands
country: Australia
facility: Research Site
state: Western Australia
city: Calgary
country: Canada
facility: Research Site
state: Alberta
city: London
country: Canada
facility: Research Site
state: Ontario
city: Oakville
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Szeged
country: Hungary
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Coimbra
country: Portugal
facility: Research Site
city: Lisboa
country: Portugal
facility: Research Site
city: Lisboa
country: Portugal
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Rostov-na-Dony
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Yaroslavl
country: Russian Federation
facility: Research Site
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Khan A, Bilezikian J, Bone H, Gurevich A, Lakatos P, Misiorowski W, Rozhinskaya L, Trotman ML, Toth M. Cinacalcet normalizes serum calcium in a double-blind randomized, placebo-controlled study in patients with primary hyperparathyroidism with contraindications to surgery. Eur J Endocrinol. 2015 May;172(5):527-35. doi: 10.1530/EJE-14-0877. Epub 2015 Jan 30.