A Study to Assess the Efficacy and Safety of Twice-Daily Dose Regimens of an Oral Calcimimetic Agent AMG 073 (Cinacalcet) in Primary Hyperparathyroidism (PHPT)

NCT00936650 | Completed Phase 2

• 1 other identifier: 990120
• Study Type: interventional
• Target: 78
• Locations: 0 countries
• Sites: N/A

Brief Summary

This randomized, placebo-controlled study in patients with primary HPT was designed to evaluate the efficacy, safety, pharmacokinetics, and health-related quality of life (HRQOL) of AMG 073 when administered 2 times a day (BID). The study consisted of 3 phases: a 12-week dose-titration phase, a 12-week maintenance phase, and a 28-week follow-up phase.

Conditions

Hyperparathyroidism, Primary

Keywords

Hyperparathyroidism, Primary; cinacalcet

Outcome Measures

Primary Outcomes (1)

• Proportion of subjects with the mean of the maintenance phase serum calcium measurements ≤ 10.3 mg/dL and with a mean decrease of at least 0.5 mg/dL

  24 weeks

Secondary Outcomes (6)

• The change from baseline and percent change from baseline in maintenance phase mean for the following variables: serum BALP, serum 1,25(OH)2D3, serum NTx, serum phosphorus, urinary calcium/creatinine ratio, urinary DPD/creatinine ratio, and urinary NTx/c

  24 weeks

• The internal consistency reliability, discriminant validity, criterion validity, and responsiveness of the Medical Outcomes Short Form-36 (SF-36), Brief Symptom Inventory (BSI), and Visual Analogue Scale (VAS)

  52 weeks

• Change from baseline in serum calcium, percent change from baseline in serum calcium, and the proportion of subjects maintaining a 12-week maintenance phase mean reduction of serum calcium from baseline of at least 0.5 mg/dL

  24 weeks

• Change from baseline in iPTH, percent change from baseline in PTH, the proportion with baseline > 65 pg/mL who decrease to ≤ 65 pg/mL, and the proportion of all subjects with iPTH ≤ 65 pg/mL

  24 weeks

• The percent change from baseline in BMD at weeks 24 and 52 as assessed by DXA scans of proximal femur (total femur and femoral neck), lumbar spine (L1-L4), forearm (ultra distal radius and 1/3 radius), and total body

  52 weeks

Study Arms (2)

cinacalcet

EXPERIMENTAL

Drug: cinacalcet

placebo

PLACEBO COMPARATOR

Drug: placebo

Interventions

placebo DRUG

Subjects were titrated to doses of 30, 40, or 50 mg BID every 4 weeks in a 12 week titration period, depending on their serum calcium concentration. The dose was kept constant for the ensuing 40 weeks except for dose reductions for hypocalcemia.

placebo

cinacalcet DRUG

Subjects were titrated to doses of 30, 40, or 50 mg BID every 4 weeks in a 12 week titration period, depending on their serum calcium concentration. The dose was kept constant for the ensuing 40 weeks except for dose reductions for hypocalcemia.

cinacalcet

Eligibility Criteria

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

You may qualify if:

• Men or women ≥ 18 years of age at screening
• Using, in the opinion of the principal investigator, effective contraceptive measures
• Plasma iPTH concentration \> 45 pg/mL on at least 2 occasions at least 7 days apart during the 12 months preceding day 0 (at least 1 of these determinations should have been made during screening by the central lab) and serum calcium concentration \> 10.3 mg/dL and ≤ 12.5 mg/dL on at least 2 occasions at least 7 days apart
• Acceptable renal function, with an estimated creatinine clearance \> 50 mL/min as determined by the Cockroft and Gault equation
• Acceptable hepatic function, defined as serum aspartate aminotransferase, alanine aminotansferase, and total bilirubin ≤ 2 times the upper limit of normal according to the range provided by the central laboratory

You may not qualify if:

• Chest x-ray within the previous 12 months without evidence of an active infectious, inflammatory, or malignant process
• Subject or legally acceptable representative gave informed consent for participation in the study
• Unstable medical condition, defined as having been hospitalized within 30 days before day 0
• Pregnant or nursing
• Body habitus that precluded accurate DXA measurements
• Therapy within 21 days before day 0 with systemic glucocorticoids, lithium, tricyclic antidepressants with the exception of amitriptyline and nortryptiline, thioridazine, haloperidol, flecainide or other drugs with a narrow therapeutic index that are primarily metabolized by hepatic cytochrome P450 (CYP) 2D6, drugs that affect renal tubular calcium handling (eg, thiazide or loop diuretics), or calcitonin
• Received, within 90 days before day 0, therapy with bisphosphonates, with fluoride, or changes in thyroid replacement therapy
• Dose changes in selective estrogen receptor modulators (SERMs), or significant changes in doses of estrogen within 90 days before day 0. If a subject had discontinued estrogen or SERM therapy, they must have been off treatment for at least 90 days before day 0
• Alcohol abuse, or use of illicit drugs, within 12 months before day 0
• Myocardial infarction (MI) within 6 months before day 0
• Ventricular rhythm disturbance requiring current treatment
• Seizures within 12 months before day 0
• History (within 5 years) of malignancy of any type, other than nonmelanomatous skin cancers or in situ cervical cancer
• Within the past 5 years, evidence of treatment for and/or active sarcoidosis, tuberculosis, or other diseases known to cause hypercalcemia
• History of familial hypocalciuric hypercalcemia (FHH)

Sponsors & Collaborators

• Amgen: lead

Related Publications (1)

• Peacock M, Bilezikian JP, Klassen PS, Guo MD, Turner SA, Shoback D. Cinacalcet hydrochloride maintains long-term normocalcemia in patients with primary hyperparathyroidism. J Clin Endocrinol Metab. 2005 Jan;90(1):135-41. doi: 10.1210/jc.2004-0842. Epub 2004 Nov 2.

  PMID: 15522938 RESULT

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Hyperparathyroidism, Primary

Interventions

Cinacalcet

Condition Hierarchy (Ancestors)

Hyperparathyroidism; Parathyroid Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: June 4, 2009
• First Posted: July 10, 2009
• Study Start: November 1, 1999
• Primary Completion: March 1, 2001
• Study Completion: June 1, 2001
• Last Updated: May 8, 2013

Record last verified: 2013-05