Hyperparathyroidism, Primary
Conditions
Keywords
Hyperparathyroidism, Primary, cinacalcet
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.
Interventions
DRUGplacebo
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.
DRUGcinacalcet
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.
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 |
| 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 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 |
| 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 |
Outcome results
None listed