The primary objective of the study is to evaluate the effect of denosumab 60mg every 6 months (Q6M) compared with Actonel 150mg monthly (QM) on total hip Bone Mineral Density (BMD) at 12 months in postmenopausal women transitioning from previous…
ID
Source
Brief title
Condition
- Bone disorders (excl congenital and fractures)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective of the study is to evaluate the effect of denosumab 60mg
every 6 months (Q6M) compared with Actonel 150mg monthly (QM) on total hip Bone
Mineral Density (BMD) at 12 months in postmenopausal women transitioning from
previous alendronate therapy
Secondary outcome
To evaluate the effect of denosumab 60mg Q6M en Actonel 150 mg QM on CTX (
C-terminal telopeptide) , a subset of subjects, at 1 month . Further to
evaluateBMD at the femoral neck at 12 months and the BMD at the lumbar spine at
12 months.
And to evaluate safety objectives as the effect and tolerability of denosumab
60mg Q6M and Actonel 150 mg QM , measured by evaluating adverse events and
laboratory parameters over 12 months.
Background summary
protocol 20080099 is a Randomized Phase 3b Open-Label Study to Evaluate the
Safety and Efficacy of Denosumab and Monthly Actonel® Therapies in
Postmenopausal Women Transitioned from Weekly or Daily Alendronate Therapys.
Bisphosphonates (BPs) are currently the most commonly utilized treatment
forosteoporosis in Europe. Alendronate is generally prescribed as a first line
therapy. However difficult dosing regimens and multiple sie-effects limit drug
adherence. Most patients, who discontinue BP therapy, do so within the first
year of treatment. Poor adherence is common and is associated with poor
outcomes and increased treatment costs and is likely associated with a lack of
effectiveness.
Study objective
The primary objective of the study is to evaluate the effect of denosumab 60mg
every 6 months (Q6M) compared with Actonel 150mg monthly (QM) on total hip Bone
Mineral Density (BMD) at 12 months in postmenopausal women transitioning from
previous alendronate therapy,who have a low adherence to or stopped previously
with alendronate.
Study design
The study consist of two parts.
Firts part is to define of the patient is eligible for the study. Second part
is the studyphase and the study conduct is 12 months. The total study period is
13 months, and the first month is the screeningperiod. As a result of a
positive outcome of the screening the patient will be allocated to one of the
arms.
Approximately 800 subjects will be randomized across approximately 75 sites in
a 1:1 ratio to either open label :
• Denosumab 60 mg ( subcutane injection every 6 months during 12 months
or
• Actonel® 150 mg oral ( one 75 mg tablet on reach of 2 consecutive days each
month during 12 months
Patienten zullen ook calcium- en vitamine D-supplementen krijgen die men
dagelijks moet innemen.
In total 800 patients are participating in this trial. There is a sub-study ,
called CTX sub-study for bone turnovermarkers. 250 patients of 800 patients
will be approached by selected centers. This means these patients have 1
addditional vist and have to perform additional bloodassessments to assess
bonemarkers.
Intervention
denosumab 60mg SC every 6 months (Q6M) and Actonel 150mg monthly (QM)
Study burden and risks
Load for patients
The following procedures will be performed per visit schedule outlined in
Appendix A, page 59 of the protocol:Physical examination, vital signs, DXA,
hematology,serum chemistry and anti denosumab antibody and serum CTX for the
subgroup. Adverse events and concomitant medications will be recorded through
participation.
The patients have to visit 4 times the site(inclusive screeningvisit) during
the 12 months. For patients, participating the sub-study have to vperform in
total 5 visit. At a maximum 28 out of the 100 patients in The Netherlands
will partcipate at the CTX study. These patients will be approached by two
sites.
More than 13,500 patients have been treated with denosumab in clinical
studies. Denosumab has been generally well tolerated.
The following adverse events occurred slightly more frequently (at least 1%
more) in patients receiving denosumab than placebo in patients participating in
completed large clinical studies:
• Very common adverse events: joint pain, pain in extremity
• Common adverse events: reports of high cholesterol, muscle and bone pain,
dizziness, cough, osteoarthritis, cataracts, eczema, muscle pain, difficulty
emptying the bladder and decreased skin sensation.
Temporary lowering of blood calcium levels below normal has been observed very
rarely in subjects treated with denosumab,The risk of this happening may be
higher in subjects with severe kidney disease.
Skin infections such as cellulitis by denosumab does not appear to increase the
occurrence of infection when compared to placebo,, in one large study, skin
infections that required hospitalization were observed more in patients treated
with denosumab than in placebo. Skin infections leading to hospitalization
were observed uncommonly in patients receiving denosumab .Some patients
receiving bisphosphonates for treatment of bone loss or spread of cancer to
their bones may experience osteonecrosis.Osteonecrosis has been reported in
patients with cancer involving the bones who received denosumab.
The development of antibodies to denosumab in patients has been uncommon and
has had no clinical effects and has not reduced the effect of denosumab on
bones. Refer herwith also to section potential risks and discomforts of the
patient informed consent
Minervum 7061
4800DH Breda
NL
Minervum 7061
4800DH Breda
NL
Listed location countries
Age
Inclusion criteria
1. Ambulatory, postmenopausal women (based) on medical history) aged 55 years or older at screening :
-postmenopause will be defined as no vaginal bleeding or spotting for a least 12 months
2. received at least 1 prescription of oral alendronate therapy (weekly or dialy) as a first treatment for post menopausal osteoporosis in the 18 months prior to screening. Use of raloxifene, calcitonin or HRT prior to alendronate treatment will be allowed. Prior and/or current use of vitamin D and calcium will be allowed.
3,Subject has demonstrated 1 of the following :
-has stopped oral alendronate therapy (is denoted as non-persistent) at least one month before the screening visit
-is still taking oral alendronate therapy but demonstrates low adherence to therapy assessed by a score of less than 6 on the Osteoporosis Specific Morisky Medication Adherence Scale(OS-MMAS)
4.Provide signed informed consent before any study-specific procedures are conducted
Exclusion criteria
1. any prior or current use of medications prescribed for osteoporosis treatment other than: oral daily or weekly alendronate, calcium and vitamin D
prior use of raloxifene, calcitonin or HRT before alendronate therapy was initiated will be allowed. Use of these therapies must have stopped prior to initiating oral alendronate and their current use is not allowed.;Any prior or current use of medications prescribed for osteoporosis treatment other than:
-oral daily or weekly alendronate, calcium and vitamin D
prior use of raloxifene, calcitonin, or HRT before alendronate therapy was initiated will be allowed. Use of these therapies must have stopped prior to initiating oral alendronate and their currentn use is not allowed
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2009-010587-42-NL |
| ClinicalTrials.gov | NCTnummernognietbekend |
| CCMO | NL28193.068.09 |