Efficacy and Safety of Odanacatib in Postmenopausal Women Previously Treated With Oral Bisphosphonate (MK-0822-076)

Osteoporosis Clinical Trial

Official title:

A Phase III Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Effects of Odanacatib (MK-0822) on Bone Mineral Density (BMD) and Overall Safety in the Treatment of Osteoporosis in Postmenopausal Women Previously Treated With an Oral Bisphosphonate

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01803607
• Other study ID #: 0822-076
• Status: Terminated
• Phase: Phase 3
• Start date: March 14, 2013
• Est. completion date: November 11, 2014

Study information

• Verified date: August 2019
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess to what extent sequential treatment with odanacatib results in incremental gains in bone mineral density (BMD) over time in female participants who have received at least 3 years of bisphosphonate therapy. It was hypothesized that odanacatib treatment would increase femoral neck BMD relative to placebo after 24 months.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 135
• Est. completion date: November 11, 2014
• Est. primary completion date: November 11, 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 60 Years and older

Eligibility

Inclusion Criteria:

• Postmenopausal for =5 years (defined as no menses for at least 5 years or at least 5 years post bilateral oophorectomy).

• Prior or current treatment with oral bisphosphonate therapy (i.e., alendronate, risedronate, ibandronate) for postmenopausal osteoporosis for =3 years.

• BMD T-score at any hip site (femoral neck, trochanter, or total hip) =-2.5 and >-3.5 as assessed by dual-energy X-ray absorptiometry (DXA) without a history of a prior fragility fracture. For participants with a history of a prior fragility fracture (except hip fracture), BMD T-score can be =-1.5 and >-3.5 at any hip site.

• Serum 25-hydroxyvitamin D level of =20 and =60 ng/mL within 90 days of the time of randomization.

Exclusion Criteria:

• Evidence of a metabolic bone disorder other than osteopenia or osteoporosis

• History or current evidence of hip fracture.

• 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.

• Active parathyroid disease. Participant with a documented history of parathyroid disease can be considered for inclusion if she has normal parathyroid hormone (PTH) at screening.

• History of thyroid disease not adequately controlled by medication.

• Current treatment with anti-seizure medication, with indices of calcium metabolism not within normal limits.

• Prior treatment with strontium-containing products; intravenous bisphosphonates; cathepsin K inhibitors; RANK ligand inhibitors; fluoride treatment at a dose greater than 1 mg/day for more than 2 weeks.

• Use of following medications within the 6 months prior to the screening visit:

activated vitamin D; estrogen, with or without progestin, at a dose high enough to have systemic effects; raloxifene or other selective estrogen receptor modulator (SERM), tibolone or any aromatase inhibitor; sub-cutaneous calcitonin (Note: use of intranasal calcitonin is allowed at any time); anabolic steroid; PTH (1-34 or 1-84); growth hormone; systemic glucocorticoids (=5 mg/day of prednisone or equivalent) for more than 2 weeks; cyclosporine for more than 2 weeks.

• Concurrent use of cancer chemotherapy or heparin; protease inhibitors for human immunodeficiency virus (HIV) treatment; and vitamin A (excluding beta carotene) >10,000 IU daily, unless willing to discontinue this dose during the study.

• Current treatment with cytochrome P450 3A4 (CYP3A4) inducers or treatment with CYP3A4 inducer within 4 weeks of screening.

Related Conditions & MeSH terms

• Osteoporosis

Intervention

Drug:
• odanacatib
odanacatib 50 mg oral tablet

Other:
• placebo to odanacatib
dose-matched placebo to odanacatib, oral tablet

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change From Baseline to Month 12 in Femoral BMD	Dual-energy X-ray absorptiometry (DXA) was used to determine the change from baseline in femoral neck BMD at Month 12.	Baseline and Month 12
Secondary	Percent Change From Baseline to Month 24 in Femoral Neck BMD: Within-Group Comparison of Odanacatib	DXA was used to determine the within-group change from baseline in femoral neck BMD at Month 24.	Baseline and Month 24
Secondary	Percent Change From Baseline to Month 12 in Trochanter, Total Hip, and Lumbar Spine BMD	DXA was used to determine the change from baseline in trochanter, total hip, and lumbar spine BMD at Month 12.	Baseline and Month 12
Secondary	Change From Baseline in Serum C-telopeptides of Type 1 Collagen (s-CTx)	s-CTx is a biochemical marker of bone resorption. At baseline and Month 12, s-CTx was measured and expressed in ng/mL and results are expressed as percentage change from baseline.	Baseline and Month 12
Secondary	Change From Baseline in Urine C-telopeptides of Type I Collagen (u-CTx)	u-CTx is a biochemical marker of bone resorption. At baseline and Month 12, u-CTx was measured and expressed in ug/mL and results are expressed as percentage change from baseline.	Baseline and Month 12
Secondary	Change From Baseline in Urine N-telopeptides of Type 1 Collagen Corrected for Creatinine (u-NTx/Cr)	The u-NTx/Cr ratio is a biochemical marker of bone resorption. u-NTx/Cr was measured at baseline and Month 12 and expressed in nM:mM and results are expressed as percentage change from baseline.	Baseline and Month 12
Secondary	Change From Baseline in Serum Bone Specific Alkaline Phosphatase (s-BSAP)	s-BSAP is a biochemical marker of bone resorption. s-BSAP was measured and expressed in ng/mL at Baseline and Month 12, and results are shown as percentage change from baseline.	Baseline and Month 12
Secondary	Change From Baseline in Serum N-terminal Propeptide of Type 1 Collagen (s-P1NP)	s-P1NP is a biochemical marker of bone resorption. s-P1NP was measured and expressed as ng/mL at Baseline and Month 12, and results are expressed as percentage change from baseline.	Baseline and Month 12