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CompletedNCT00975221Updated Oct 17, 2018Results posted

Efficacy and Safety Study of Cinacalcet for the Treatment of Hypercalcemia in Patients With Primary Hyperparathyroidism Unable to Undergo Parathyroidectomy

A Phase 3 interventional study of Cinacalcet and Placebo in Hyperparathyroidism, Primary and Hypercalcemia, sponsored by Amgen. Completed at 47 sites in 7 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-10-17.

Sponsored by Amgen · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
67
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Hyperparathyroidism, Primary
  • Hypercalcemia

Keywords

  • Primary hyperparathyroidism
  • Parathyroidectomy
  • Hypercalcemia
03

In context

Hyperparathyroidism, Primary

105 studies on the registry are indexed under Hyperparathyroidism, Primary; 23 are open to participants now.

This study's enrollment of 67 is close to the median of 67 across 57 interventional studies indexed under Hyperparathyroidism, Primary.

Browse Hyperparathyroidism, Primary studies →

Lead sponsor

Amgen is the lead sponsor of 1,044 studies on the registry; 51 are open to participants now.

Of its 246 completed or terminated interventional studies of FDA-regulated products, 164 (67%) have results posted.

Browse Amgen studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
67 participants (actual)

Study arms

  • Experimental
    Cinacalcet

    Participants received cinacalcet at a starting dose of 30 mg orally BID and were eligible for a dose titration once every 3 weeks during the 12-week dose-titration phase based on corrected total serum calcium concentration and safety assessments. Participants continued to receive cinacalcet for another 16 weeks during the efficacy assessment phase and then continued into the open-label extension phase and received cinacalcet at a starting dose of 30 mg BID for 24 weeks. The dose of cinacalcet could have been increased or decreased as needed to maintain a corrected total serum calcium concentration within the normal range through Week 52.

    Drug: Cinacalcet

  • Placebo comparator
    Placebo

    Participants received placebo orally twice a day (BID) for 12 weeks during the dose titration phase and for another 16 weeks during the efficacy assessment phase. Participants then continued into the open-label extension phase and received cinacalcet at a starting dose of 30 mg BID for 24 weeks. The dose of cinacalcet could have been increased or decreased as needed to maintain a corrected total serum calcium concentration within the normal range through Week 52.

    Drug: Cinacalcet · Drug: Placebo

Interventions

  • DrugCinacalcet

    Administered orally at a starting dose of 30 mg twice a day (BID). Participants 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).

    Also known as: Sensipar, Mimpara

  • DrugPlacebo

    Administered orally following the same tiitration regimen as the experimental arm.

06

What researchers measure

Primary outcomes

  1. Percentage of Participants With Mean Corrected Total Serum Calcium Concentration ≤ 10.3 mg/dL (2.57 mmol/L) During the EAP

    Time frame: Efficacy assessment phase (study visits at Weeks 16, 20, 24, and 28)

Secondary outcomes

  1. 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

    Time frame: Baseline and the EAP (mean of Weeks 16, 20, 24, and 28)

  2. Percent Change From Baseline in Corrected Total Serum Calcium Concentration During the EAP

    Time frame: Baseline and the EAP (mean of Weeks 16, 20, 24, and 28)

  3. Percent Change From Baseline in Plasma Parathyroid Hormone Level During the EAP

    Time frame: Baseline and the EAP (mean of Weeks 16, 20, 24, and 28)

07

Results

Posted Jan 25, 2016

Participant flow

The study was conducted at 29 centers in United States, Australia, Canada, Hungary, Poland, Portugal, and Russian Federation. The first participant enrolled on 10 March 2010 and the last participant enrolled on 28 December 2011.

Titration Phase (Weeks 1-12)
Participant flow — Titration Phase (Weeks 1-12)
MilestonePlaceboCinacalcet
Started3433
Received study drug3433
Completed3129
Not completed34
Withdrew: Withdrawal by subject23
Withdrew: Requirement for alternative therapy10
Withdrew: Other01
Efficacy Assessment Phase (Weeks 13-28)
Participant flow — Efficacy Assessment Phase (Weeks 13-28)
MilestonePlaceboCinacalcet
Started3029
Completed3028
Not completed01
Withdrew: Lost to follow-up01
Open-label Extension Phase (Weeks 29-52)
Participant flow — Open-label Extension Phase (Weeks 29-52)
MilestonePlaceboCinacalcet
Started2928
Completed2727
Not completed21
Withdrew: Adverse event11
Withdrew: Withdrawal by subject10

Outcome measures

PrimaryPercentage of Participants With Mean Corrected Total Serum Calcium Concentration ≤ 10.3 mg/dL (2.57 mmol/L) During the EAP
Time frame:
Efficacy assessment phase (study visits at Weeks 16, 20, 24, and 28)
Reported as:
Number · percentage of participants
Percentage of Participants With Mean Corrected Total Serum Calcium Concentration ≤ 10.3 mg/dL (2.57 mmol/L) During the EAP
percentage of participantsPlaceboCinacalcet
Percentage of Participants With Mean Corrected Total Serum Calcium Concentration ≤ 10.3 mg/dL (2.57 mmol/L) During the EAP0.075.8
Statistical analysis
  • Placebo vs Cinacalcet · Cochran-Mantel-Haenszel · p = <0.001 · Cochran-mantel-haenszel (cmh) statistic: 39.866
SecondaryPercentage of Participants With a ≥ 1 mg/dL (0.25 mmol/L) Decrease From Baseline in Mean Corrected Total Serum Calcium Concentration During the EAP
Time frame:
Baseline and the EAP (mean of Weeks 16, 20, 24, and 28)
Reported as:
Number · percentage of participants
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
percentage of participantsPlaceboCinacalcet
Percentage of Participants With a ≥ 1 mg/dL (0.25 mmol/L) Decrease From Baseline in Mean Corrected Total Serum Calcium Concentration During the EAP5.984.8
Statistical analysis
  • Placebo vs Cinacalcet · Cochran-Mantel-Haenszel · p = <0.001 · Cmh statistic: 40.953
SecondaryPercent Change From Baseline in Corrected Total Serum Calcium Concentration During the EAP
Time frame:
Baseline and the EAP (mean of Weeks 16, 20, 24, and 28)
Reported as:
Least squares mean · percent change
Percent Change From Baseline in Corrected Total Serum Calcium Concentration During the EAP
percent changePlaceboCinacalcet
Percent Change From Baseline in Corrected Total Serum Calcium Concentration During the EAP-1.66 ± 0.99-15.21 ± 1.00
Statistical analysis
  • Placebo vs Cinacalcet · ANCOVA · p = <0.001 · Ls mean treatment difference: -13.55 · 95% CI -16.23 to -10.88Treatment difference: cinacalcet-placebo
SecondaryPercent Change From Baseline in Plasma Parathyroid Hormone Level During the EAP
Time frame:
Baseline and the EAP (mean of Weeks 16, 20, 24, and 28)
Reported as:
Least squares mean · percent change
Percent Change From Baseline in Plasma Parathyroid Hormone Level During the EAP
percent changePlaceboCinacalcet
Percent Change From Baseline in Plasma Parathyroid Hormone Level During the EAP-1.01 ± 4.05-23.80 ± 4.18
Statistical analysis
  • Placebo vs Cinacalcet · ANCOVA · p = <0.001 · Ls mean treatment difference: -22.79 · 95% CI -34.01 to -11.57Treatment difference: cinacalcet-placebo

Adverse events

Collected over 60 Weeks. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Double-blind Phase: Placebo—4/34 (11.8%)15/34 (44.1%)
Double-blind Phase: Cinacalcet—3/33 (9.1%)25/33 (75.8%)
Open-label Phase: Previous Placebo—7/29 (24.1%)15/29 (51.7%)
Open-label Phase: Previous Cinacalcet—1/28 (3.6%)10/28 (35.7%)
Most frequent serious events
Showing 10 of 18
Most frequent serious events
EventDouble-blind Phase: PlaceboDouble-blind Phase: CinacalcetOpen-label Phase: Previous PlaceboOpen-label Phase: Previous Cinacalcet
Neuropathy peripheralNervous system disorders0/340/330/291/28
Hyperparathyroidism primaryEndocrine disorders1/340/331/290/28
Abdominal painGastrointestinal disorders0/340/331/290/28
CholelithiasisHepatobiliary disorders0/340/331/290/28
Infective exacerbation of chronic obstructive airways diseaseInfections and infestations0/340/331/290/28
Urinary tract infectionInfections and infestations0/340/331/290/28
Vertebrobasilar insufficiencyNervous system disorders0/340/331/290/28
AnxietyPsychiatric disorders0/340/331/290/28
Pulmonary embolismRespiratory, thoracic and mediastinal disorders0/340/331/290/28
Aortic aneurysmVascular disorders1/340/331/290/28
Most frequent other events
Showing 10 of 33
Most frequent other events
EventDouble-blind Phase: PlaceboDouble-blind Phase: CinacalcetOpen-label Phase: Previous PlaceboOpen-label Phase: Previous Cinacalcet
NauseaGastrointestinal disorders6/349/336/291/28
Muscle spasmsMusculoskeletal and connective tissue disorders0/346/334/292/28
DiarrhoeaGastrointestinal disorders4/344/331/291/28
HeadacheNervous system disorders2/344/332/292/28
Abdominal pain upperGastrointestinal disorders2/342/333/291/28
Oedema peripheralGeneral disorders0/342/333/291/28
Urinary tract infectionInfections and infestations1/343/330/291/28
ArthralgiaMusculoskeletal and connective tissue disorders0/343/330/290/28
Back painMusculoskeletal and connective tissue disorders2/343/332/290/28
Pain in extremityMusculoskeletal and connective tissue disorders2/343/330/291/28

Baseline characteristics

Age, Continuous
Age, Continuous(years)PlaceboCinacalcetTotal
Mean75.0 ± 8.969.5 ± 13.072.3 ± 11.4
Sex: Female, Male
Sex: Female, Male(Participants)PlaceboCinacalcetTotal
Female272552
Male7815
Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)PlaceboCinacalcetTotal
Black or African American145
Hispanic or Latino011
White or Caucasian332861
Albumin-corrected Calcium
Albumin-corrected Calcium(mg/dL)PlaceboCinacalcetTotal
Mean11.80 ± 0.4811.73 ± 0.4511.77 ± 0.46
Intact Parathyroid Hormone (iPTH)
Intact Parathyroid Hormone (iPTH)(pg/mL)PlaceboCinacalcetTotal
Mean238.6 ± 212.2179.0 ± 98.0209.7 ± 168.4
Bisphosphonate Use
Bisphosphonate Use(participants)PlaceboCinacalcetTotal
Yes10919
No242448
08

Study locations

47 sites
  • Research Site
    Lake Forest, California 92630, United States
  • Research Site
    Lancaster, California 93534, United States
  • Research Site
    Los Gatos, California 95032, United States
  • Research Site
    Mission Viejo, California 92691, United States
  • Research Site
    Orange, California 92869, United States
  • Research Site
    San Diego, California 92124, United States
  • Research Site
    Aurora, Colorado 80045, United States
  • Research Site
    Washington D.C., District of Columbia 20010, United States
  • Research Site
    Aventura, Florida 33180, United States
  • Research Site
    Clearwater, Florida 33756, United States
  • Research Site
    Jacksonville, Florida 32204, United States
  • Research Site
    Miami, Florida 33145, United States
  • Research Site
    Pembroke Pines, Florida 33028, United States
  • Research Site
    Weston, Florida 33331, United States
  • Research Site
    Atlanta, Georgia 30322, United States
  • Research Site
    Indianapolis, Indiana 46202, United States
  • Research Site
    Kenner, Louisiana 70065, United States
  • Research Site
    New Orleans, Louisiana 70121, United States
  • Research Site
    Detroit, Michigan 48236, United States
  • Research Site
    New York, New York 10032, United States
  • Research Site
    Morehead City, North Carolina 28557, United States
  • Research Site
    Columbus, Ohio 43210-1296, United States
  • Research Site
    Randwick, New South Wales 2031, Australia
  • Research Site
    St Leonards, New South Wales 2065, Australia
  • Research Site
    Footscray, Victoria 3011, Australia
  • Research Site
    Geelong, Victoria 3220, Australia
  • Research Site
    Nedlands, Western Australia 6009, Australia
  • Research Site
    Calgary, Alberta T2N 4Z6, Canada
  • Research Site
    London, Ontario N6A 4V2, Canada
  • Research Site
    Oakville, Ontario L6J 1X8, Canada
  • Research Site
    Toronto, Ontario M5C 2T2, Canada
  • Research Site
    Budapest, 1083, Hungary
  • Research Site
    Budapest, 1088, Hungary
  • Research Site
    Budapest, 1113, Hungary
  • Research Site
    Szeged, 6720, Hungary
  • Research Site
    Warsaw, 01-809, Poland
  • Research Site
    Warsaw, 02-097, Poland
  • Research Site
    Warsaw, 02-507, Poland
  • Research Site
    Coimbra, 3000-075, Portugal
  • Research Site
    Lisbon, 1350-179, Portugal
  • Research Site
    Lisbon, 1649-035, Portugal
  • Research Site
    Moscow, 117036, Russia
  • Research Site
    Moscow, 119034, Russia
  • Research Site
    Moscow, 129110, Russia
  • Research Site
    Rostov-na-Dony, 344022, Russia
  • Research Site
    Saint Petersburg, 197341, Russia
  • Research Site
    Yaroslavl, 150003, Russia
09

References and documents

Publications

  • 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. PubMed 25637076 ↗
10

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Ran from Mar 2010 to primary completion in Jul 2012, 28 months.

Results were first posted in Jan 2016, 3 years 6 months after primary completion. A results delay was requested in Dec 2013.

How these figures are worked out, and which studies are left out of them.

Registered
Sep 10, 2009
First posted
Sep 11, 2009
StartActual
Mar 10, 2010
Primary completionActual
Jul 12, 2012
CompletionActual
Dec 21, 2012
Results delay requested
Dec 19, 2013
Results first posted
Jan 25, 2016
Last update
Oct 17, 2018
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Oct 17, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00975221
Lead sponsor
Amgen
Responsible party
Sponsor
First posted
Sep 11, 2009
Start date
Mar 10, 2010
Primary completion
Jul 12, 2012
Completion
Dec 21, 2012
Results posted
Jan 25, 2016
Last update
Oct 17, 2018

Study contacts

MD
study director · Amgen

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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