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)

Sponsor

Amgen (Industry)

Overall Status

Completed

CT.gov ID

NCT00936650

Collaborator

(none)

Enrollment

Arms

Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hyperparathyroidism, Primary	Drug: placebo Drug: cinacalcet	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

78 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Double-Blind, Randomized, Placebo-Controlled, Multicenter Dose-Titration Study to Assess the Efficacy and Safety of Twice-Daily Dose Regimens of an Oral Calcimimetic Agent AMG 073 (Cinacalcet) in Primary Hyperparathyroidism (PHPT)

Study Start Date :

Nov 1, 1999

Actual Primary Completion Date :

Mar 1, 2001

Actual Study Completion Date :

Jun 1, 2001

Arms and Interventions

Arm	Intervention/Treatment
Experimental: cinacalcet	Drug: cinacalcet 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 Comparator: placebo	Drug: placebo 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.

Arm

Intervention/Treatment

Experimental: cinacalcet

Drug: cinacalcet

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 Comparator: placebo

Drug: placebo

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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]
The pharmacokinetic profile of AMG 073 as determined with population-based methods [24 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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
Laboratory test results within the central laboratory's normal range for hematology, urinalysis, and clinical chemistry parameters not mentioned specifically in other inclusion and exclusion criteria
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

Exclusion Criteria:

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)
Uncontrolled diabetes, as defined by hemoglobin A1c (HbA1c) ≥ 8.0
Gastrointestinal disorder that might have been associated with impaired absorption of orally dministered medications
Inability to swallow tablets
Known sensitivity to any of the products to be administered during the study
Psychiatric disorder that would have interfered with understanding and giving informed consent or compliance with protocol requirements
Other condition that might have reduced the chance of obtaining data (eg, known poor compliance) required by the protocol or that might have compromised the ability to give truly informed consent