A Study to Assess Safety and Efficacy of Odanacatib (MK-0822) in Men With Osteoporosis (MK-0822-053)

Phase 3

Completed

• Conditions: Osteoporosis
• Interventions: Drug: Placebo for Odanacatib; Drug: Odanacatib; Dietary Supplement: Vitamin D3; Dietary Supplement: Calcium carbonate

• Registration Number: NCT01120600
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

The purpose of this study is to test the hypothesis that treatment with odanacatib will result in increased bone mineral density (BMD) compared to treatment with placebo. This study will also evaluate the safety and efficacy of odanacatib for male osteoporosis participants.

Detailed Description

The original study was divided into two parts, with the primary analysis of endpoints to occur at 24 months and participants will then remain in the study for an additional 12 months (Part 2). Amendment 1 of the protocol removed the additional 12 month period and the Month 36 BMD analysis was deleted.

Study Timeline

• Study First Submitted: 2010-05-07
• Study First Submitted QC: 2010-05-07
• Study First Posted: 2010-05-11
• Study Start: 2010-06-09
• Primary Completion: 2013-07-22
• Study Completion: 2013-07-22
• Results First Submitted: 2017-11-08
• Results First Submitted QC: 2017-11-08
• Results First Posted: 2017-12-06
• Status Verified: 2018-07
• Last Update Submitted: 2018-07-30
• Last Update Posted: 2018-08-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 294

Inclusion Criteria

• Is a male between 40 and 95 years of age
• Has osteoporosis
• Has anatomy suitable for dual energy x-ray absorptiometry (DXA) scan of the lumbar spine and and hip
• Is ambulatory

Exclusion Criteria

• Is currently on oral bisphosphonates or other treatment for osteoporosis
• Had previous hip fragility fracture and is a candidate for standard of care therapy
• Has had a fragility fracture (vertebral or non-vertebral fractures indicating reduced bone strength) within 12 months
• Has had more then one previous vertebral fracture
• Has been diagnosed with metabolic bone disorder other than osteoporosis
• Is Vitamin D deficient
• Has a history of renal stones
• Has active parathyroid disease
• Has history of thyroid disease not well controlled by medication
• Is diagnosed with secondary osteoporosis
• Has a daily calcium intake of <1,200 mg and is unwilling to take study prescribed supplements or increase dietary intake, such that his daily calcium intake is at least 1200 mg
• Has a history of malignancy ≤5 years prior to signing informed consent
• Has been diagnosed with hypogonadism due to causes that affect multiple organ and body systems

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Odanacatib 50 mg once weekly	Vitamin D3	Participants will receive one Odanacatib 50 mg tablet once weekly. In addition, they will receive a weekly dose 5600 IU of open-label Vitamin D3 as well as a sufficient supply of open-label calcium carbonate so that their total daily calcium intake from both dietary and supplemental sources is approximately 1200 mg.
Odanacatib 50 mg once weekly	Calcium carbonate	Participants will receive one Odanacatib 50 mg tablet once weekly. In addition, they will receive a weekly dose 5600 IU of open-label Vitamin D3 as well as a sufficient supply of open-label calcium carbonate so that their total daily calcium intake from both dietary and supplemental sources is approximately 1200 mg.
Placebo once weekly	Vitamin D3	Participants will receive one Placebo tablet once weekly. In addition, they will receive a weekly dose 5600 IU of open-label Vitamin D3 as well as a sufficient supply of open-label calcium carbonate so that their total daily calcium intake from both dietary and supplemental sources is approximately 1200 mg.
Placebo once weekly	Calcium carbonate	Participants will receive one Placebo tablet once weekly. In addition, they will receive a weekly dose 5600 IU of open-label Vitamin D3 as well as a sufficient supply of open-label calcium carbonate so that their total daily calcium intake from both dietary and supplemental sources is approximately 1200 mg.
Placebo once weekly	Placebo for Odanacatib	Participants will receive one Placebo tablet once weekly. In addition, they will receive a weekly dose 5600 IU of open-label Vitamin D3 as well as a sufficient supply of open-label calcium carbonate so that their total daily calcium intake from both dietary and supplemental sources is approximately 1200 mg.
Odanacatib 50 mg once weekly	Odanacatib	Participants will receive one Odanacatib 50 mg tablet once weekly. In addition, they will receive a weekly dose 5600 IU of open-label Vitamin D3 as well as a sufficient supply of open-label calcium carbonate so that their total daily calcium intake from both dietary and supplemental sources is approximately 1200 mg.

Primary Outcome Measures

Name	Time	Method
Percentage Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Month 24	Baseline and Month 24	Lumbar spine BMD was assessed by dual energy X-ray absorptiometry (DXA) at Baseline and at Month 24.
Number of Participants Who Discontinued Treatment Due to an AE	Up to 24 months after first dose of study drug	An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug.
Number of Participants Who Experienced an Adverse Event (AE)	Up to 24 months (plus 14 days) after first dose of study drug	An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug.

Secondary Outcome Measures

Name	Time	Method
Percentage Change From Baseline in Femoral Neck BMD at Month 24	Baseline and Month 24	Femoral Neck BMD was assessed by DXA at Baseline and at Month 24.
Percentage Change From Baseline in Trochanter BMD at Month 24	Baseline and Month 24	Trochanter BMD was assessed by DXA at Baseline and at Month 24.
Percentage Change From Baseline in Serum C-Telopeptides of Type 1 Collagen (s-CTx) at Month 24	Baseline and Month 24	Serum samples were collected to evaluate biochemical markers for s-CTx, which were measured at Baseline and at Month 24.
Percentage Change From Baseline in Serum N-Terminal Propeptides of Type I Collagen (s-P1NP) at Month 24	Baseline and Month 24	Serum samples were collected to evaluate biochemical markers for s-P1NP, which were measured at Baseline and at Month 24.
Percentage Change From Baseline in Total Hip BMD at Month 24	Baseline and Month 24	Total hip BMD was assessed by DXA at Baseline and at Month 24.
Percentage Change From Baseline in Serum Bone-Specific Alkaline Phosphatase (s-BSAP) at Month 24	Baseline and Month 24	Serum samples were collected to evaluate biochemical markers for s-BSAP, which were measured at Baseline and at Month 24.
Percentage Change From Baseline in Urine Collagen N-Telopeptide/Creatinine Ratio (U-NTx/Cr) at Month 24	Baseline and Month 24	Urine samples were collected to evaluate biochemical markers for u-NTx/Cr, which were measured at Baseline and at Month 24.