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 of Osteoporosis in Postmenopausal Women Previously Treated with an Oral Bisphosphonate

• Conditions: Postmenopausal Osteoporosis; MedDRA version: 12.0Level: LLTClassification code 10031282Term: Osteoporosis

• Registration Number: EUCTR2009-014729-18-PL
• Lead Sponsor: Merck & Co. Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-11-20
• Last Update Posted: 15 May 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 520

Inclusion Criteria

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.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.
8.The patient agrees not to use medications for the treatment of osteoporosis (except as provided through this study) for the duration of her participation in the trial.

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

1.Has received the following agents with action on bone (all time periods are relative to V1):
(a)IV bisphosphonates 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 (e.g., Genistein, Diadzein, IsofemTM) used to treat osteoporosis within the prior 6 months
2.Has used estrogen ± progestin, raloxifene, tamoxifen, tibolone or another selective estrogen receptor modulator (SERM) within the 6 months prior to V1, or calcitonin within the prior 30 days.
3.Has used either pioglitazone hydrochloride, or rosiglitazone maleate, within the 6 months prior to V1.
4.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.Anticipates the use of any of the following potent inhibitors or potent inducers of CYP3A4 within 2 weeks prior to randomization or during the study:
Inhibitors
(a)grapefruit juice
(b)systemically administered azole antifungals such as ketoconazole, fluconazole, itraconazole, miconazole, posaconozole, ravuconazole, and voriconazole,
(c)nefazodone,
(d)the macrolide antibiotics clarithromycin, dirithromycin, erythromycin, and troleandomycin. Azithromycin use is permitted,
(e)protease inhibitors
Inducers
(f)rifampin,
(g)rifabutin,
(h)orally administered dexamethasone,
(i)phenytoin,
(j)any barbiturate, e.g., phenobarbital or primidone,
(k)St. John's Wort.
6.Primary parathyroid disease, or secondary hyperparathyroidism with an elevated PTH.
7.Prior total thyroidectomy.
8.History of Paget's disease of bone.
9.HIV positive or is known to have an AIDS-related illness.
10.History of malignancy = 5 years prior to signing informed consent, except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer.
11.Evidence of a metabolic bone disorder other than osteopenia or osteoporosis.
12.History of recent major upper gastrointestinal (GI) mucosal erosive disease as defined by (a) significant upper GI bleeding within the previous year resulting in hospitalization and/or transfusion; (b) recurrent ulcer disease documented by radiographic or endoscopic means (2 episodes in the last 2 years, or any documented ulcer in the preceding 3 months); (c) uncontrolled dyspepsia being treated on a daily basis; (d) esophageal or gastric variceal disease; or (e) esophageal stricture, achalasia, or severe esophageal motor dysfunction.
13.Myocardial infarction, unstable angina, stroke or revascularization condition within the 3 months prior to V1.
14.The patient has had untreated malabsorption syndrome within the 4 y

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified