A Study to Evaluate the Safety and Efficacy of Denosumab Compared With Zoledronic Acid in Postmenopausal Women With Osteoporosis Previously Treated With Oral Bisphosphonates

• Register: EUCTR
• Last refreshed on: 23 February 2015
• Main ID: EUCTR2012-001821-28-ES
• Date of registration: 02/10/2012
• Prospective Registration: Yes
• Primary sponsor: Amgen, Inc.
• Public title: A Study to Evaluate the Safety and Efficacy of Denosumab Compared With Zoledronic Acid in Postmenopausal Women With Osteoporosis Previously Treated With Oral Bisphosphonates
• Scientific title: A Randomized Double-blind Study to Evaluate the Safety and Efficacy of Denosumab Compared With Zoledronic Acid in Postmenopausal Women With Osteoporosis Previously Treated With Oral Bisphosphonates
• Date of first enrolment: 28/11/2012
• Target sample size: 620
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-001821-28
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Australia, Belgium, Canada, Denmark, Germany, Poland, Spain, United States

Contacts

• Name: IHQ Medical Info ? Clinical Trials
• Affiliation: Amgen (EUROPE) GmbH

• Name: IHQ Medical Info ? Clinical Trials
• Affiliation: Amgen (EUROPE) GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
- Subject or subject?s legally acceptable representative has provided informed consent prior to any study specific procedure(s)
- Ambulatory postmenopausal women. Ambulatory is defined as women who are able to walk, not bedridden; postmenopause is defined as no vaginal bleeding or spotting for at least 12 months prior to screening.
- Age 55 years or older
- Received oral bisphosphonate therapy for OP for at least 2 years immediately prior to screening visit
- Screening BMD (g/cm2) values at the lumbar spine, total hip or femoral neck; values of equal to or less than those listed in the protocol. Eligibility will be determined by a local reading of the DXAs at the investigator site. At least 2 lumbar vertebrae and one hip must be evaluable by DXA at the screening visit.
- Serum CTX value of <= 0.5 ng/mL at the screening visit as determined by central laboratory
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 180
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 440

Exclusion criteria:
- Height, weight or girth which may preclude accurate DXA measurements
- Received other OP treatment or bone active treatment with the following guidelines
.administration of denosumab or zoledronic acid at any time
.administration of the following within the last 5 years
..IV bisphosphonate other than zoledronic acid
..fluoride or strontium at doses approved for OP
..PTH or PTH derivatives within the last year
- Abnormalities of the following per central laboratory reference ranges:
.vitamin D deficiency (25[OH] vitamin D level < 20 ng/mL), repletion will be allowed and subjects may be re-screened
.hypercalcemia
.elevated transaminases >= 2.0 x upper limits of normal (ULN)
- Administration of any of the following treatment within 3 months of screening:
.any selective estrogen receptor modulator (estrogen agonist antagonist)
.tibolone
.anabolic steroids or testosterone
.glucocorticosteroids (>= 5 mg prednisone equivalent per day for more than 10 days or a total cumulative dose of >= 50 mg)
.systemic hormone replacement therapy (HRT) (subjects stable on HRT for more than 3 months prior is permitted)
.calcitonin
.other bone active drugs including anti-convulsants (except
benzodiazepines) and heparin
.cathepsin K inhibitor
.anti-sclerostin antibody
.chronic systemic ketoconazole, androgens, adrenocorticotrophic hormone, cinacalcet, aluminum, lithium, protease inhibitors, gonadotropin- releasing hormone agonists
- Evidence of history of any of the following:
.hyperthyroidism (stable on antithyroid therapy is allowed)
.hypothyroidism (stable on thyroid replacement therapy is allowed)
.hypo- or hyperparathyroidism
.hypo- or hypercalcemia based on the central laboratory reference ranges
.known to have tested positive for human immunodeficiency virus, hepatitis C virus, or hepatitis B surface antigen
.osteomalacia (chart review)
.osteonecrosis of the jaw (ONJ) or risk factors for ONJ such as invasive dental procedures (eg, tooth extraction, dental implants, oral surgery in the past 6 months), poor oral hygiene, periodontal and/or pre-existing dental disease
.recent tooth extraction (within 6 months of screening visit)
.Paget disease of bone (subject report or chart review)
.other bone diseases which affect bone metabolism (eg, osteopetrosis, osteogenesis imperfecta) (chart review)
- History of any solid organ or bone marrow transplant
- Malignancy (except nonmelanoma skin cancers, cervical or breast ductal carcinoma in situ) within the last 5 years
- Contraindicated or poorly tolerant of denosumab therapy; contraindications include
.hypocalcemia
.hypersensitivity to drug or any component of the drug
- Contraindicated or poorly tolerant of zoledronic acid therapy; contraindications include the following:
.hypocalcemia
.subjects with creatinine clearance of <35 mL/min and in those with evidence of acute renal impairment (calculated using Cockcroft Gault equation)
.hypersensitivity to any component of zoledronic acid solution
- Known intolerance to calcium or vitamin D supplements
- For women of child bearing potential: refusal to use 2 highly effective forms of contraception and to continue this practice for 7 months after last injection of study medication
- Self-reported alcohol or drug abuse within 12 months prior to screening
- Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(s)
- Other investigational procedures while pa

Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Therapeutic area: Body processes [G] - Bones and nerves physological processes [G11]

Post Menospausal Osteoporosis
MedDRA version: 15.0 Level: PT Classification code 10031282 Term: Osteoporosis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Intervention(s)

Trade Name: Prolia
Product Name: Denosumab
Product Code: AMG 162
Pharmaceutical Form: Solution for injection/infusion in pre-filled syringe
INN or Proposed INN: 615258-40-7
CAS Number: 615258-40-7
Other descriptive name: DENOSUMAB
Concentration unit: mg/l milligram(s)/litre
Concentration type: equal
Concentration number: 60-
Pharmaceutical form of the placebo: Solution for injection/infusion in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Trade Name: Zometa
Product Name: Zoledronic acid
Product Code: MO5BA08
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: ZOLEDRONIC ACID
CAS Number: 118072-93-8
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Concentrate for solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Month 12

Main Objective: The primary objective of this study is to evaluate if the effect of administering denosumab (60 mg subcutaneously [SC] every 6 months [Q6M]) is not inferior to that of zoledronic acid (5 mg
intravenously [IV] once yearly) in postmenopausal women with osteoporosis previously treated with oral bisphosphonates with respect to change in bone mineral density (BMD) by dual energy
x-ray absorptiometry (DXA) of lumbar spine at 12 months.

Primary end point(s): Primary Endpoint:
- percent change from baseline in lumbar spine BMD at month 12 (non-inferiority)

Secondary Objective: Compare the efficacy of administering denosumab (60 mg SC Q6M), with that of zoledronic acid
(5 mg IV once yearly), on the following:
- BMD by DXA of total hip at 12 months (non - inferiority)
- BMD by DXA of lumbar spine at 12 months (superiority)
- BMD by DXA of total hip at 12 months (superiority)

Secondary Outcome(s)

Secondary end point(s): Secondary Endpoints:
- percent change from baseline in total hip BMD at month 12 (non-inferiority)
- percent change from baseline in lumbar spine BMD at month 12 (superiority)
- percent change from baseline in total hip BMD at month 12 (superiority)

Timepoint(s) of evaluation of this end point: Month 12

Secondary ID(s)

2012-001821-28-DE

20110153

Source(s) of Monetary Support

Amgen Inc