Phase 2 N=412 Randomized Quadruple-blind Treatment

Determine the Efficacy, Safety and Tolerability of Denosumab (AMG 162) in the Treatment of Postmenopausal Women With Low Bone Mineral Density

Low Bone Mineral Density

Bottom Line

View on ClinicalTrials.gov: NCT00043186 ↗

Enrolled (actual)

412

Serious AEs

17.0%

Results posted

Jul 2010

Primary outcome: Primary: Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 for the Placebo and Denosumab Arms — -0.81; 4.41; 4.71; 6.69 Percent change — p=<0.001

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Placebo (Drug); Denosumab (Drug); Alendronate (Drug)
Age: Pediatric, Adult, Older Adult
Sex: Female
Sponsor: Amgen
Primary completion: Apr 2007

Outcome Measures

Outcome	Result	p-value
PRIMARY Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 for the Placebo and Denosumab Arms	-0.81; 4.41; 4.71; 6.69; 3.03; 4.55	<0.001 sig
SECONDARY Serum CTX Percent Change From Baseline at Month 12	-4.699; -61.366; -77.989; -87.238; -12.054; -70.757	<0.001 sig
SECONDARY Urine NTX/Creatinine Percent Change From Baseline at Month 12	24.300; -40.018; -54.688; -60.652; -2.027; -36.523	<0.001 sig
SECONDARY Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 for the Alendronate Arm	4.59	—
SECONDARY Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 24	-1.25; 7.42; 7.21; 8.83; 3.94; 7.19	<0.001 sig
SECONDARY Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 36	-1.80; 8.57; 9.17; 1.94; 7.99; 9.04	<0.001 sig
SECONDARY Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 42	1.09; 7.21; 10.04; 5.06; 9.46; 9.59	0.02 sig
SECONDARY Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 48	-2.39; 9.35; 9.93; 9.03; 10.10; 10.34	<0.001 sig
SECONDARY Serum CTX Percent Change From Baseline at Month 24	-5.940; -50.687; -74.078; -83.985; -8.467; -68.437	<0.001 sig
SECONDARY Serum CTX Percent Change From Baseline at Month 36	-16.577; -62.298; -53.643; 56.286; -57.500; -54.418	0.011 sig
SECONDARY Serum CTX Percent Change From Baseline at Month 42	-16.279; -63.543; -40.827; -62.334; -46.408; -57.255	<0.001 sig
SECONDARY Serum CTX Percent Change From Baseline at Month 48	-14.561; -40.016; -34.999; -52.656; -39.899; -51.494	0.015 sig
SECONDARY Urine NTX/Creatinine Percent Change From Baseline at Month 24	14.422; -19.699; -37.691; -49.907; 2.134; -32.303	<0.001 sig
SECONDARY Urine NTX/Creatinine Percent Change From Baseline at Month 36	0.508; -33.294; -47.752; 82.910; -44.301; -36.874	0.011 sig
SECONDARY Urine NTX/Creatinine Percent Change From Baseline at Month 42	-18.102; -40.741; -40.043; -58.893; -47.188; -39.269	0.053
SECONDARY Urine NTX/Creatinine Percent Change From Baseline at Month 48	-21.064; -23.311; -38.002; -50.864; -46.128; -40.375	0.010 sig
SECONDARY Total Hip Bone Mineral Density Percent Change From Baseline at Month 12	-0.56; 2.89; 2.45; 3.32; 1.94; 3.56	<0.001 sig
SECONDARY Total Hip Bone Mineral Density Percent Change From Baseline at Month 24	-1.92; 4.04; 3.55; 5.03; 2.62; 4.96	<0.001 sig
SECONDARY Total Hip Bone Mineral Density Percent Change From Baseline at Month 36	-2.84; 4.79; 4.41; -1.23; 4.31; 5.83	<0.001 sig
SECONDARY Total Hip Bone Mineral Density Percent Change From Baseline at Month 42	-1.96; 5.01; 3.98; 2.37; 4.54; 6.34	0.002 sig
SECONDARY Total Hip Bone Mineral Density Percent Change From Baseline at Month 48	-3.52; 5.45; 4.03; 3.86; 4.82; 6.06	<0.001 sig
SECONDARY Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 12	-1.97; 0.89; 0.40; 1.10; 0.94; 1.29	0.033 sig
SECONDARY Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 24	-2.78; 1.31; 0.62; 1.30; 2.48; 1.89	0.009 sig
SECONDARY Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 36	-3.64; 1.99; 1.06; 1.05; 2.08; 2.69	0.002 sig
SECONDARY Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 42	-6.59; 1.00; 0.82; -3.91; 1.29; -0.87	0.496
SECONDARY Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 48	-4.67; 1.04; 1.42; 1.77; 1.74; 1.71	<0.001 sig
SECONDARY Total Body Bone Mineral Density Percent Change From Baseline at Month 12	-0.21; 1.82; 1.80; 2.74; 0.55; 2.51	0.001 sig
SECONDARY Total Body Bone Mineral Density Percent Change From Baseline at Month 24	-1.64; 2.59; 2.91; 4.44; 0.89; 2.57	<0.001 sig
SECONDARY Total Body Bone Mineral Density Percent Change From Baseline at Month 36	-1.61; 3.14; 3.04; 2.34; 2.04; 2.80	<0.001 sig
SECONDARY Total Body Bone Mineral Density Percent Change From Baseline at Month 42	1.61; 1.90; 4.05; 8.85; 3.72; 4.92	0.949
SECONDARY Total Body Bone Mineral Density Percent Change From Baseline at Month 48	-2.54; 3.68; 3.38; 3.76; 3.42; 3.43	<0.001 sig
SECONDARY Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 12	-4.609; -62.716; -60.098; -70.256; -39.474; -65.215	<0.001 sig
SECONDARY Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 24	16.464; -41.225; -47.597; -57.905; -22.350; -43.448	<0.001 sig
SECONDARY Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 36	1.955; -39.012; -56.021; 22.343; -47.500; -42.541	0.049 sig
SECONDARY Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 42	1.288; -40.182; -40.819; -52.684; -53.763; -44.892	0.061
SECONDARY Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 48	18.122; -34.727; -45.779; -47.770; -46.286; -34.361	0.142

Summary

To determine the effect of denosumab treatment compared with placebo over 12 months on bone mineral density (BMD) of the lumbar spine in postmenopausal women with low BMD. The clinical hypothesis is that denosumab subcutaneous injections administered every 3 or 6 months for 12 months will significantly increase lumbar spine bone mineral density and will be well tolerated.

Eligibility Criteria

Inclusion Criteria

women not more than 80 years of age on date of randomization
≥ 1 year postmenopausal on date of randomization
ambulatory
if ≤ 60 years of age, or had or would require a bilateral oophorectomy, serum follicle stimulating hormone (FSH) > 50 mU/mL or serum estradiol 5 mg oral prednisone equivalent per day for > 10 days)
inhaled corticosteroids (> 2000 μg per day for > 10 days)
anabolic steroids or testosterone
administration of the following medications within the 3 months before the enrollment date
systemic hormone replacement therapy
selective estrogen receptor modulators
calcitonin
calcitriol
current hyper- or hypothyroidism (allowed if stable on thyroid replacement therapy and thyroid-stimulating hormone was within the normal range)
current hyper- or hypoparathyroidism
albumin-adjusted serum calcium 1 single, grade 1 vertebral fracture
currently enrolled in or had participated within the previous 30 days in other investigational device or drug trial(s) (For some trials, this may have been allowed after discussion and written approval from Amgen.)
known sensitivity to mammalian-derived drug preparations (eg, Herceptin®)
any organic or psychiatric disorder, serum chemistry, or hematology that, in the opinion of the investigator, could have prevented the subject from completing the study or have interfered with the interpretation of the study results
self-reported alcohol or drug abuse within the previous 12 months
any disorder that compromised the ability to give truly informed consent for participation in the study
previous administration of denosumab
known sensitivity or contraindication to alendronate
known sensitivity or contraindication to tetracycline derivatives (subjects in the biopsy substudy only).

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00043186). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.