A Phase IIb, Randomized, Double-Blind, Placebo- and Active-Controlled, Dose-Range-Finding Study to Evaluate the Effects of MK-5442 on Bone Mineral Density (BMD) in the Treatment ofOsteoporosis in Postmenopausal Women Previously Treated with an Oral Bisphosphonate
- Conditions
- Postmenopausal Osteoporosis
- Registration Number
- EUCTR2009-014729-18-DK
- Lead Sponsor
- Merck & Co., Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 480
1.The patient is a woman 45 to 85 years of age, inclusive.
2.The patient has been postmenopausal for =5 years, defined as no menses for at least 5 years, OR at least 5 years status post bilateral oophorectomy.
3.The patient is currently taking alendronate for treatment of osteoporosis
(either 70 mg once weekly with or without vitamin D3, or 10 mg daily), and has taken alendronate during the 12 consecutive months prior to Visit 1 (and no other bisphosphonate). In addition, the patient has taken bisphosphonates for treatment of osteoporosis for at least 3 years within the 4 years prior to screening (i.e. while in the 1st year prior to screening the bisphosphonate must be alendronate, for the 2nd, 3rd, and 4th years prior to screening the patient could have taken any one or combination of oral bisphosphonates for at least 2 of those 3 years).
4.Patients must have been approximately 80% compliant with either once-weekly or daily alendronate during the 12 consecutive months prior to Visit 1, and therefore, to the best of their recollection, may not have missed a total of more than 12 weekly doses during the past year, or a total of more than 73 daily doses during that time.
5.The patient has, at screening either: (1) an areal BMD T-score = -2.5 at one or more of the lumbar spine, femoral neck, trochanter, or total hip, and a BMD T-score at all of these sites that is = -4.0, with or without a history of a prior vertebral or non-vertebral fragility fracture; OR (2) an areal BMD T-score = -1.5 at one or more of these 4 sites, and a BMD T-score at all of these sites that is = -4.0, and at least one prior vertebral or non-vertebral fragility fracture documented by medical record, or detected on the screening spine radiographs by the local radiologist. Only the T-scores provided by the central imaging vendor can be used to determine eligibility. Hip BMD measurements should be performed on the left hip only, unless the left hip is not evaluable.
6.Patient has no increased risk of bone cancer due to any reason, such as a history of skeletal malignancy at any time, or a history of therapeutic irradiation.
7.Patient's weight or body mass index (BMI) at screening does not preclude the acquisition of DXA and CT images of good quality.
8.The patient has a 25-hydroxyvitamin D level as measured by the central laboratory of =15 ng/mL. Note: If the 25-hydroxyvitamin D level is =9 and <15 ng/mL, she may enter if her alkaline phosphatase and PTH levels, as measured by the central laboratory, are normal. Note: Patients with a serum 25-hydroxyvitamin D level (as measured by the central laboratory) that does not qualify for this study may have it retested once during the screening period.
9.The patient has a serum PTH value at screening that does not exceed the upper limit of normal (as measured by the central laboratory). Note: Patients with a serum PTH value above the upper limit of normal as measured by the central laboratory may have their serum PTH retested once during the screening period if the investigator believes the elevation is due to a low 25-hydroxyvitamin D. In that case, the patient should be supplemented with vitamin D before the PTH retest.
10.During the run-in period, patient took the placebo for MK-5442, and the calcium supplement (if dispensed during the run-in period), on at least 11 of the 14 days (i.e., approximately 80% of the time) following the dosing instructions described in Section 3.2.5. Patients
1.The patient has received the following agents with action on bone (all time periods are relative to Visit 1):
(a)IV bisphosphonates (e.g., zoledronic acid) at any time in the past
(b)fluoride treatment at a dose greater than 1 mg/day for more than 2 weeks at any time in the past,
(c)strontium at any time in the past,
(d)growth hormone at any time in the past,
(e)any cathepsin K inhibitor, such as MK-0822/odanacatib, at any time in the past,
(f)use of denosumab or any other RANK-L inhibitor at any time in the past,
(g)oral bisphosphonates other than alendronate within the past 12 months
(h)PTH (1-34, or 1-84) at any time within the prior 24 months,
(i)cyclosporin for more than 2 weeks within the prior 6 months,
(j)heparin within the prior 2 weeks,
(k)anabolic steroids or glucocorticoids (=5 mg/day prednisone or equivalent) for more than 2 weeks in the prior 6 months,
(l)prescription soy isoflavones used to treat osteoporosis within the prior 6 months
2.The patient has used estrogen selective estrogen receptor modulator (SERM) within the 6 months prior to Visit 1, or calcitonin within the prior 30 days.
3.The patient has used either pioglitazone hydrochloride, or rosiglitazone maleate, within the 6 months prior to Visit 1.
4.The patient is currently taking vitamin A (excluding beta carotene) >10,000 IU daily, or vitamin D >5,000 IU daily, and is not willing to reduce her vitamin A dose to
=10,000 IU daily, and her vitamin D dose to an equivalent of =2000 IU daily (including the weekly vitamin D supplementation being provided for this study) during the study.
5.Patient anticipates the use of any potent inhibitors or potent inducers of CYP3A4 within 2 weeks prior to randomization or during the study.
6.The patient has primary parathyroid disease, or secondary hyperparathyroidism with an elevated PTH. (Note: patients with a history of primary hyperparathyroidism and with curative partial parathyroidectomy =2 years prior to the screening visit are not excluded).
7.The patient has had prior total thyroidectomy (patient with a hemithyroidectomy may be included).
8.Patient has any history of Paget's disease of bone.
9.Patient is known to be HIV positive or is known to have an AIDS-related illness.
10.Patient has a history of malignancy = 5 years prior to signing the informed consent, except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer.
11.The patient has evidence of a metabolic bone disorder other than osteopenia or osteoporosis.
12.The patient has a history of recent major upper gastrointestinal (GI) mucosal erosive disease.
13.The patient has had a myocardial infarction, unstable angina, stroke or revascularization condition within the 3 months prior to Visit 1.
14.The patient has had untreated malabsorption syndrome within the 4 years prior to the screening visit.
15.Patient has a history of nephrolithiasis at any time in the past.
16.Patient has new-onset diabetes or poorly controlled hyperglycemia.
17.Patient has a history of osteonecrosis of the jaw, or is contemplating or planning a dental extraction, or implantation of a dental prosthetic anchor during the entire duration of study.
18.The patient has a total serum calcium value outside the normal range.
19.The patient has an abnormal TSH.
20. Patient has an unexplained elevation in alkaline phosphatase above the upper limit of normal for the central laboratory at the screening visit.
21.T
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: 1. Objective: To assess the effect of switching alendronate therapy to 5, 7.5, or <br> 10 mg MK-5442 daily compared to continued alendronate therapy on <br> lumbar spine areal BMD over 12 months.<br><br>2. Objective: To assess the safety and tolerability of 5, 7.5, and 10 mg MK 5442 <br> daily compared to placebo over 12 months.<br>;Secondary Objective: ;Primary end point(s): Areal BMD, Safety
- Secondary Outcome Measures
Name Time Method