A Randomized Open-Label Study to Evaluate the Safety and Efficacy of Denosumab and Ibandronate in Postmenopausal Women Sub-Optimally Treated with Daily or Weekly Bisphosphonates./ Estudio abierto aleatorizado para evaluar la seguridad y eficacia de denosumab e ibandronato en mujeres posmenopáusicas infratratadas con bisfosfonatos diarios o semanales.

• Register: EUCTR
• Last refreshed on: 26 June 2012
• Main ID: EUCTR2009-010726-19-ES
• Date of registration: 21/08/2009
• Prospective Registration: Yes
• Primary sponsor: Amgen Inc
• Public title: A Randomized Open-Label Study to Evaluate the Safety and Efficacy of Denosumab and Ibandronate in Postmenopausal Women Sub-Optimally Treated with Daily or Weekly Bisphosphonates./ Estudio abierto aleatorizado para evaluar la seguridad y eficacia de denosumab e ibandronato en mujeres posmenopáusicas infratratadas con bisfosfonatos diarios o semanales.
• Scientific title: A Randomized Open-Label Study to Evaluate the Safety and Efficacy of Denosumab and Ibandronate in Postmenopausal Women Sub-Optimally Treated with Daily or Weekly Bisphosphonates./ Estudio abierto aleatorizado para evaluar la seguridad y eficacia de denosumab e ibandronato en mujeres posmenopáusicas infratratadas con bisfosfonatos diarios o semanales.
• Date of first enrolment: 02/11/2009
• Target sample size: 800
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-010726-19
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

Estonia, France, Italy, Spain

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects will meet all of the following inclusion criteria prior to enrollment:

Ambulatory, postmenopausal women (based on medical history) 55 years or older at screening
-- Postmenopause will be defined as no vaginal bleeding or spotting for at least 12 months
- If the subject is 55 - 60 years old and there is uncertainty regarding menopausal status, confirmation of serum FSH (> or = 50 mIU/mL) and serum estradiol (< or = 20 pg/mL) must be obtained
- If the subject is greater than 60 years old, evaluation of FSH and estradiol levels is not needed to confirm menopausal status.

Have received their first prescription of daily or weekly bisphosphonate therapy at least 6 months but no more than 18 months prior to screening.

May have received:
-- raloxifene, calcitonin, prior to initiation of bisphosphonate therapy.
-- calcium, and vitamin D.
-- Hormone replacement therapy (e.g. estrogen use for mitigation of menopausal symptoms).

Subject has:
-- Stopped bisphosphonate therapy (is denoted as non-persistent) at least one month before the screening visit, or
-- Demonstrated low adherence to therapy assessed by a score of less than 6 on the OS-MMAS.

Screening BMD (g/cm2) values, at the lumbar spine OR total hip, that occur within the following ranges, based on the particular scanner that is used:

Lumbar spine: GE Lunar: 0.700 < or = BMD < or = 0.940; Hologic: 0.607< or = BMD < or = 0.827.
Total hip: GE Lunar: 0.504 < or = BMD < or = 0.756; Hologic: 0.454 < or = BMD < or = 0.698.

Both the initial and the repeat DXA scan of the lumbar spine OR the total hip must meet the above eligibility criteria.

At least 2 lumbar vertebrae must be evaluable by DXA.

At least one hip must be evaluable by DXA (eg, no history of either bilateral hip replacement or pins in both hips).

Provide signed informed consent before any study-specific procedures are conducted.
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Subjects meeting any of the following c.riteria are not eligible for participation in the study:

Any disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures.

Current use of medications prescribed for osteoporosis treatment other than oral daily or weekly bisphosphonate.

Contraindicated to receive oral ibandronate 150 mg PO QM, including.
-- Hypersensitivity to ibandronate 150 mg PO QM or other constituents of ibandronate 150 mg PO QM tablets.
-- Abnormalities of the esophagus, which delay esophageal emptying such as stricture or achalasia.
-- Inability to stand or sit upright for at least 60 minutes.

Administration of any of the following treatments within 3 months of screening:
-- Tibolone.
-- Anabolic steroids or testosterone.
-- Glucocorticosteroids (> or = 5 mg prednisone equivalent per day for more than 10 days or a total cumulative dose of > or = 50 mg).

Vitamin D deficiency [25(OH) vitamin D level < 20 ng/mL (<49.9 nmol/L)] - Repletion will be allowed and subjects may be re-screened.

Evidence of any of the following per subject report, chart review or central laboratory result:
-- Significantly impaired renal function as determined by estimated Glomerular Filtration Rate less that 30mL/min/1.73 m2.
-- Current hypo- or hypercalcemia based on the central laboratory reference ranges.
-- Active gastric or duodenal ulcer; or any history of significant gastrointestinal bleed requiring hospitalization or transfusion.
-- Known to have tested positive for human immunodeficiency virus, hepatitis C virus, or hepatitis B surface antigen.
-- Malignancy (except fully resected cutaneous basal cell or squamous cell carcinoma, cervical or breast ductal carcinoma in situ) within the last 5 years
-- Any metabolic bone disease or secondary cause of bone loss that is not controlled and may interfere with the interpretation of the findings.

Previous participation in clinical trials with denosumab 60 mg SC Q6M (regardless of treatment).

Received any solid organ or bone marrow transplant.

Any laboratory abnormality which, in the opinion of the investigator, will prevent the subject from completing the study or interfere with the interpretation of the study results.

Known sensitivity to mammalian cell derived drug products.

Known intolerance to calcium supplements.

Currently enrolled in or has not yet completed at least 1 month since ending other investigational device or drug trial(s).

Any physical or psychiatric disorder which, in the opinion of the investigator, will prevent the subject from completing the study or interfere with the interpretation of the study results.

Evidence of alcohol or substance-abuse within the last 12 months which the investigator believes would interfere with understanding or completing the study.


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

Health Condition(s) or Problem(s) studied

Postmenopausal osteoporosis / Osteoporosis posmenopáusica
MedDRA version: 9.1 Level: LLT Classification code 10031285 Term: Osteoporosis postmenopausal

Intervention(s)

Product Name: Denosumab
Product Code: AMG 162
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Denosumab
CAS Number: 615258-40-7
Current Sponsor code: AMG 162
Other descriptive name: ABX1-6 CHO OPG Ligand mAb IgG2:Human Monoclonal Antibody to RANKL
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 60-

Trade Name: BONVIVA 150 mg, comprimidos recubiertos con película
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: IBANDRONICO ACIDO
Other descriptive name: IBANDRONIC ACID
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Primary Outcome(s)

Primary end point(s): Percent change from baseline in BMD at the total hip at 12 months.

Secondary Objective: To evaluate the effects of transitioning to denosumab 60 mg SC Q6M in comparison to transitioning to ibandronate 150 mg PO QM on

-- Serum type 1 C-Telopeptide-1 (sCTX-1) levels at 1 month (in a subset of subjects)
-- BMD at the femoral neck at 12 months
-- BMD at the lumbar spine at 12 months

Main Objective: To evaluate the change in total hip Bone Mineral Density (BMD) at 12 months in postmenopausal women transitioning from previous daily or weekly bisphosphonate therapy to denosumab 60 mg SC Q6M compared to that in subjects transitioning to ibandronate 150mg PO QM.

Safety Objectives: To evaluate safety and tolerability measured by evaluating adverse events, antidenosumab antibodies and laboratory analytes over 12 months.

Secondary ID(s)

20080562

2009-010726-19-FR