A Study to Examine the Effects of an Experimental Drug on Postmenopausal Osteoporosis (MK-0822-004 AM2; EXT1(AM1); EXT2(AM2); EXT3)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00112437
First received: June 2, 2005
Last updated: August 6, 2014
Last verified: August 2014
  Purpose

This is a 2-year study to examine the effects of a new experimental medication (MK0822) on postmenopausal osteoporosis. This study will enroll approximately 375 postmenopausal women, and randomly assign them to 4 different doses of MK0822or to placebo. Measurements performed during the study include: bone mineral density scans, spine x-rays, laboratory blood and urine tests, height measurements and optional bone biopsies (at the end of 2 years).


Condition Intervention Phase
Osteoporosis
Drug: MK0822
Dietary Supplement: Vitamin D3
Dietary Supplement: Calcium Carbonate
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety, Tolerability, and Efficacy of MK0822 in the Treatment of Postmenopausal Women With Osteoporosis

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Percentage Change From Baseline in Lumbar Spine Bone Mineral Density at 12 Months [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
    Percentage change in lumbar spine Bone Mineral Density (relative to baseline) at 12 Months.

  • Percentage Change From Baseline in Lumbar Spine Bone Mineral Density at 24 Months [ Time Frame: Baseline and 24 months ] [ Designated as safety issue: No ]
    Percentage change in lumbar spine Bone Mineral Density (relative to baseline) at 24 Months.

  • Percentage Change From Baseline in Lumbar Spine Bone Mineral Density at 36 Months [ Time Frame: Baseline and 36 months ] [ Designated as safety issue: No ]
    Percentage change in lumbar spine Bone Mineral Density (relative to baseline) at 36 Months.


Secondary Outcome Measures:
  • Percentage Change in Total Hip Bone Mineral Density at 12 Months [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
    Percentage change in total hip Bone Mineral Density (relative to baseline) at 12 Months

  • Percentage Change in Femoral Neck Bone Mineral Density at 12 Months [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
    Percentage change in femoral neck Bone Mineral Density (relative to baseline) at 12 Months

  • Percentage Change in Trochanter Bone Mineral Density at 12 Months [ Time Frame: Baseline and 12 Months ] [ Designated as safety issue: No ]
    Percentage change in Trochanter Bone Mineral Density (relative to baseline) at 12 Months

  • Percentage Change in Total Body Bone Mineral Density at 12 Months [ Time Frame: Baseline and 12 Months ] [ Designated as safety issue: No ]
    Percentage change in total body Bone Mineral Density (relative to baseline) at 12 Months

  • Percentage Change in Distal Forearm Bone Mineral Density at 12 Months [ Time Frame: Baseline and 12 Months ] [ Designated as safety issue: No ]
    Percentage change in Distal Forearm Bone Mineral Density (relative to baseline) at 12 Months

  • Percentage Change in Biochemical Marker of Bone Turnover (Urinary N-telopeptides of Type I Collagen (u-NTx)) at 12 Months [ Time Frame: Baseline and 12 Months ] [ Designated as safety issue: No ]
    Back-transformation (geometric mean) of the Least Squares (LS) Mean of the log-values Percentage change from baseline, in Biochemical Marker of Bone turnover (urinary N-telopeptides of Type I collagen (u-NTx)) at 12 Months

  • Percentage Change in Biochemical Marker of Bone Turnover (Serum C-telopeptides of Type 1 Collagen (s-CTx)) at 12 Months [ Time Frame: Baseline and 12 Months ] [ Designated as safety issue: No ]
    Back-transformation (geometric mean) of the Least Squares (LS) Mean of the log-values Percentage change from baseline in Biochemical Marker of Bone turnover (serum C-telopeptides of Type 1 collagen (s-CTx)) at 12 Months.

  • Percentage Change in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines (u-DPyr)) at 12 Months [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
    Back-transformation (geometric mean) of the Least Squares Mean of the log-values Percentage change in Biochemical Marker of Bone turnover (urinary total deoxypyridinolines (u-DPyr)) (relative to baseline) at 12 Months

  • Percentage Change in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase (s-BSAP)) at 12 Months [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
    Back-transformation (geometric mean) of the Least Squares Mean of the log-values Percentage change from baseline, in Biochemical Marker of Bone turnover (serum bone-specific alkaline phosphatase (s-BSAP)), at 12 Months

  • Percentage Change in Biochemical Marker of Bone Turnover (Serum N-terminal Propeptide of Type 1 Collagen (s-P1NP)) at 12 Months [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
    Back-transformation (geometric mean) of the Least Squares Mean of the log-values Percentage change in Biochemical Marker of Bone turnover (serum N-terminal propeptide of Type 1 collagen (s-P1NP) (relative to baseline) at 12 Months

  • Percentage Change in Total Hip Bone Mineral Density at 24 Months [ Time Frame: Baseline and 24 months ] [ Designated as safety issue: No ]
    Percentage change in total hip Bone Mineral Density (relative to baseline) at 24 Months

  • Percentage Change in Femoral Neck Bone Mineral Density at 24 Months [ Time Frame: Baseline and 24 months ] [ Designated as safety issue: No ]
    Percentage change in femoral neck Bone Mineral Density (relative to baseline) at 24 Months

  • Percentage Change in Tronchanter Bone Mineral Density at 24 Months [ Time Frame: Baseline and 24 months ] [ Designated as safety issue: No ]
    Percentage change in trochanter Bone Mineral Density (relative to baseline) at 24 Months

  • Percentage Change in Total Body Bone Mineral Density at 24 Months [ Time Frame: Baseline and 24 months ] [ Designated as safety issue: No ]
    Percentage change in total body Bone Mineral Density (relative to baseline) at 24 Months

  • Percentage Change in Distal Forearm Bone Mineral Density at 24 Months [ Time Frame: Baseline and 24 months ] [ Designated as safety issue: No ]
    Percentage change in Distal Forearm Bone Mineral Density (relative to baseline) at 24 Months

  • Percentage Change in Biochemical Marker of Bone Turnover (Urinary N-telopeptides of Type I Collagen (u-NTx)) at 24 Months [ Time Frame: Baseline and 24 months ] [ Designated as safety issue: No ]
    Back-transformation (geometric mean) of the Least Squares Mean of the log-values Percentage change from baseline, in Biochemical Marker of Bone turnover (urinary N-telopeptides of Type I collagen (u- NTx)) (relative to baseline) at 24 Months

  • Percentage Change in Biochemical Marker of Bone Turnover (Serum C-telopeptides of Type 1 Collagen (s-CTx)) at 24 Months [ Time Frame: Baseline and 24 months ] [ Designated as safety issue: No ]
    Back-transformation (geometric mean) of the Least Squares Mean of the log-values Percentage change from baseline, in Biochemical Marker of Bone turnover (serum C-telopeptides of Type 1 collagen (s-CTx)) (relative to baseline) at 24 Months

  • Percentage Change in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines (u-DPyr)) at 24 Months [ Time Frame: Baseline and 24 months ] [ Designated as safety issue: No ]
    Back-transformation (geometric mean) of the Least Squares Mean of the log-values Percentage change from baseline, in Biochemical Marker of Bone turnover (urinary total deoxypyridinolines (u-DPyr)) (relative to baseline) at 24 Months

  • Percentage Change in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase (s-BSAP)) at 24 Months [ Time Frame: Baseline and 24 months ] [ Designated as safety issue: No ]
    Back-transformation (geometric mean) of the Least Squares Mean of the log-values Percentage change from baseline, in Biochemical Marker of Bone turnover (serum bone-specific alkaline phosphatase (s-BSAP)) (relative to baseline) at 24 Months

  • Percentage Change in Biochemical Marker of Bone Turnover (Serum N-terminal Propeptide of Type 1 Collagen (s-P1NP)) at 24 Months [ Time Frame: Baseline and 24 months ] [ Designated as safety issue: No ]
    Back-transformation (geometric mean) of the Least Squares Mean of the log-values Percentage change from baseline, in Biochemical Marker of Bone turnover (serum N-terminal propeptide of Type 1 collagen (s-P1NP)) (relative to baseline) at 24 Months

  • Percentage Change From Baseline in Total Hip Bone Mineral Density at 36 Months [ Time Frame: Baseline and 36 months ] [ Designated as safety issue: No ]
    Percentage change in Total Hip Bone Mineral Density (relative to baseline) at 36 Months

  • Percentage Change From Baseline in Femoral Neck Bone Mineral Density at 36 Months [ Time Frame: Baseline and 36 months ] [ Designated as safety issue: No ]
    Percentage change in Femoral Neck Bone Mineral Density (relative to baseline) at 36 Months

  • Percentage Change From Baseline in Trochanter Bone Mineral Density at 36 Months [ Time Frame: Baseline and 36 months ] [ Designated as safety issue: No ]
    Percentage change in Trochanter Bone Mineral Density (relative to baseline) at 36 Months

  • Percentage Change From Baseline in Total Body Bone Mineral Density at 36 Months [ Time Frame: Baseline and 36 months ] [ Designated as safety issue: No ]
    Percentage change in Total Body Bone Mineral Density (relative to baseline) at 36 Months

  • Percentage Change From Baseline in Distal Forearm Bone Mineral Density at 36 Months [ Time Frame: Baseline and 36 months ] [ Designated as safety issue: No ]
    Percentage change in Distal Forearm Bone Mineral Density (relative to baseline) at 36 Months

  • Geometric Mean Percentage Change From Baseline, in Biochemical Marker of Bone Turnover (Urinary N-telopeptides of Type I Collagen [u-NTx]) at 36 Months [ Time Frame: Baseline and 36 months ] [ Designated as safety issue: No ]
    Geometric Mean Percentage change from baseline, in Biochemical Marker of Bone turnover (urinary N-telopeptides of Type I collagen [u-NTx]) at 36 Months

  • Geometric Mean Percentage Change From Baseline, in Biochemical Marker of Bone Turnover (Serum C-telopeptides of Type 1 Collagen [s-CTx]) at 36 Months [ Time Frame: Baseline and 36 months ] [ Designated as safety issue: No ]
    Geometric Mean Percentage change from baseline, in Biochemical Marker of Bone turnover (serum C-telopeptides of Type 1 collagen [s-CTx]) at 36 Months

  • Geometric Mean Percentage Change From Baseline, in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 36 Months [ Time Frame: Baseline and 36 months ] [ Designated as safety issue: No ]
    Geometric Mean Percentage change from baseline, in Biochemical Marker of Bone turnover (urinary total deoxypyridinolines [u-DPyr]) at 36 Months

  • Geometric Mean Percentage Change From Baseline, in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 36 Months [ Time Frame: Baseline and 36 months ] [ Designated as safety issue: No ]
    Geometric Mean Percentage change from baseline, in Biochemical Marker of Bone turnover (serum bone-specific alkaline phosphatase [s-BSAP]) at 36 Months

  • Percentage Change in Biochemical Marker of Bone Turnover (Serum N-terminal Propeptide of Type 1 Collagen [s-P1NP]) at 36 Months [ Time Frame: Baseline and 36 months ] [ Designated as safety issue: No ]
    Geometric Mean Percentage change from baseline, in Biochemical Marker of Bone turnover (serum N-terminal propeptide of Type 1 collagen [s-P1NP]) at 36 Months

  • Geometric Mean Percentage Change From Baseline, in Biochemical Marker of Bone Turnover (Serum Bone Tartrate-resistant Acid Phosphatase Isoform 5b) [TRAP 5-b]) at 36 Months [ Time Frame: Baseline and 36 months ] [ Designated as safety issue: No ]
    Geometric Mean Percentage change from baseline, in Biochemical Marker of Bone turnover (serum Bone tartrate-resistant acid phosphatase isoform 5b [TRAP 5-b]) at 36 Months

  • Geometric Mean Percentage Change From Baseline, in Biochemical Marker of Bone Turnover (Serum Cross-Linked Carboxyterminal Telopeptides of Type I Collagen [1-CTP]) at 36 Months [ Time Frame: Baseline and 36 months ] [ Designated as safety issue: No ]
    Geometric mean Percentage change from baseline, in Biochemical Marker of bone turnover (serum Cross-Linked Carboxyterminal Telopeptides of Type I Collagen [1-CTP]) at 36 Months


Enrollment: 399
Study Start Date: June 2005
Estimated Study Completion Date: December 2015
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Dietary Supplement: Vitamin D3
Vitamin D3, two 2800 IU weekly throughout the study
Other Name: Vitamin D3
Dietary Supplement: Calcium Carbonate
Patient who have a calcium intake less than 1000 mg/day will receive daily calcium supplements providing 500 mg of elemental calcium.
Other Name: Calcium Carbonate
Drug: Placebo
Placebo to MK0822 3 mg, 10 mg, 25 mg, or 50 once weekly for 24 months
Experimental: MK0822 3 mg Drug: MK0822
MK0822 3 mg, once weekly for 24 months
Other Name: MK0822
Dietary Supplement: Vitamin D3
Vitamin D3, two 2800 IU weekly throughout the study
Other Name: Vitamin D3
Dietary Supplement: Calcium Carbonate
Patient who have a calcium intake less than 1000 mg/day will receive daily calcium supplements providing 500 mg of elemental calcium.
Other Name: Calcium Carbonate
Experimental: MK0822 10 mg Drug: MK0822
MK0822 10 mg, once weekly for 24 months
Other Name: MK0822
Dietary Supplement: Vitamin D3
Vitamin D3, two 2800 IU weekly throughout the study
Other Name: Vitamin D3
Dietary Supplement: Calcium Carbonate
Patient who have a calcium intake less than 1000 mg/day will receive daily calcium supplements providing 500 mg of elemental calcium.
Other Name: Calcium Carbonate
Experimental: MK0822 25 mg Drug: MK0822
MK0822 25 mg, once weekly for 24 months
Other Name: MK0822
Dietary Supplement: Vitamin D3
Vitamin D3, two 2800 IU weekly throughout the study
Other Name: Vitamin D3
Dietary Supplement: Calcium Carbonate
Patient who have a calcium intake less than 1000 mg/day will receive daily calcium supplements providing 500 mg of elemental calcium.
Other Name: Calcium Carbonate
Experimental: MK0822 50 mg Drug: MK0822
MK0822 50 mg, once weekly for 24 months
Other Name: MK0822
Dietary Supplement: Vitamin D3
Vitamin D3, two 2800 IU weekly throughout the study
Other Name: Vitamin D3
Dietary Supplement: Calcium Carbonate
Patient who have a calcium intake less than 1000 mg/day will receive daily calcium supplements providing 500 mg of elemental calcium.
Other Name: Calcium Carbonate

Detailed Description:

Study Extension:

Participants who completed 24 months of the base study were invited to continue in three extensions: MK0822-004-10, which extended the study to 36 months, MK0822-004-20 (NCT00112437) which extended the study to 60 months, and MK0822-004-30 (NCT00112437), which extended the study to 120 months.

  • In the first extension, participants were re-randomized to 50 mg MK0822 or placebo OW for 12 months.
  • In the second extension, participants who were initially randomized to MK0822 3 mg or placebo OW in the base study received MK0822 50 mg weekly in Years 4&5; all other participants remained on the same treatment they were during Year 3.
  • In the third extension, all participants received odanacatib weekly in Years 6-10.

Study arms for extensions include only 50 mg MK0822 and placebo for the first two extensions and 50 mg MK0822 only for the third extension.

Extension Studies:

MK0822-004-10 (NCT00112437) Extension: Patient has participated in and completed 24 months of treatment in the base study

MK0822-004-20 (NCT00112437) Extension: Patient participated in and completed 36 months of treatment in base and extension studies.

MK0822-004-30 (NCT00112437) Extension: Patient participated in and completed 60 months of treatment in the base and extension studies.

  Eligibility

Ages Eligible for Study:   45 Years to 85 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Postmenopausal for 5 or more years, defined as no menses for at least 5 years OR at least 5 years status post bilateral oophorectomy
  • Bone mineral density T-score at the hip or spine of -2.0 or less
  • Spinal anatomy suitable for dual-energy x-ray absorptiometry (DXA). At the lumbar spine, there is no evidence of vertebral fracture in at least 3 vertebrae in the L1 to L4 region on baseline spine films. (Significant scoliosis, bony trauma, degenerative joint disease, and sequelae of orthopedic procedures that result in anatomy that is unsuitable for accurate bone densitometry must be absent from the lumbar spine.)
  • At least one hip must be evaluable by DXA (e.g., contain no hardware from orthopedic procedures)
  • In a state of general health allowing for successful completion of the trial
  • Agreement to not use any medications to treat osteoporosis during the study

Exclusion Criteria:

  • History of prior osteoporotic fracture (unless declined treatment with or was ineligible for osteoporosis therapy)
  • Past treatment with osteoporosis medications, steroids, hormone replacement, as well as various other medications that affect bone may be exclusionary. (Different exclusion criteria apply to each bone active drug. For example, any prior use of intravenous (IV) bisphosphonates is not permitted. By contrast, prior use of hormone replacement for several years is permitted if it has not occurred within the past 6 months. Please ask the study doctor for details)
  • Significant clinical or laboratory abnormalities at the screening visit for the study that, in the opinion of the investigator, could complicate interpretation of the study results or pose additional risk to the patient (for example, patients who are non-ambulatory should be excluded for this reason)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00112437

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Monitor Merck Sharp & Dohme Corp.
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00112437     History of Changes
Other Study ID Numbers: 0822-004, 2005_023
Study First Received: June 2, 2005
Results First Received: April 13, 2010
Last Updated: August 6, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Osteoporosis
Osteoporosis, Postmenopausal
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Calcium, Dietary
Cholecalciferol
Vitamin D
Ergocalciferols
Calcium Carbonate
Vitamins
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions
Antacids
Molecular Mechanisms of Pharmacological Action
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on August 21, 2014