NCT00620113

Efficacy and Safety of Odanacatib (MK-0822) in Participants With Involutional Osteoporosis (MK-0822-022)

Completed Phase 2 Results posted Last updated 27 August 2018

What this trial tests

Phase 2 trial testing Odanacatib in Osteoporosis Postmenopausal in 287 participants. Completed in 29 May 2009.

Timeline

3 December 2007

Primary endpoint
29 May 2009

29 May 2009

Quick facts

Lead sponsor	Merck Sharp & Dohme LLC
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	287
Start date	3 December 2007
Primary completion	29 May 2009
Estimated completion	29 May 2009

Drugs / interventions tested

• Odanacatib — full drug profile →
• Vitamin D3 (cholecalciferol) — full drug profile →
• Calcium carbonate (calcium carbonate) — full drug profile →
• Placebo

Conditions studied

• Osteoporosis Postmenopausal — all drugs for Osteoporosis Postmenopausal →

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

Adults 45 to 85, any sex, with Osteoporosis Postmenopausal. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percent Change From Baseline to Week 52 in Lumbar Spine Bone Mineral Density (BMD) at Lumbar Vertebrae 1 to 4 (L1-L4) Primary · Baseline (Observation visit to Wk 0 treatment visit), Week 52

BMD (g/cm2) data was measured by dual-energy X-ray absorptiometry (DXA) at lumbar spine vertebrae 1 through 4 (L1-L4) from anterior view at the Observation visit (up to 5 weeks before Treatment Period), Week 0 (start of Treatment Period) and Week 52 (end of Treatment Period) or at discontinuation. Baseline was defined as the average of the 2 values collected at the Observation visit and Week 0 visit. Percent change from baseline in BMD = (\[BMD at Week 52 visit\] - \[baseline BMD\] ÷ baseline BMD) × 100. Measurements were performed using the Hologic Quantitative Digital Radiography (QDR) Serie

Group	Value	95% CI
Placebo	0.55	-0.32 – 1.42
Odanacatib 10 mg	4.09	3.24 – 4.93
Odanacatib 25 mg	5.67	4.81 – 6.54
Odanacatib 50 mg	5.94	5.07 – 6.82

Percent Change From Baseline to Week 52 in Total Hip BMD Secondary · Baseline (Observation visit to Wk 0 treatment visit), Week 52

BMD (g/cm2) data was measured by DXA for total hip at the Observation visit (up to 5 weeks before Treatment Period), Week 0 (start of Treatment Period) and Week 52 (end of Treatment Period) or at discontinuation. Baseline was defined as the average of the 2 values collected at the Observation visit and Week 0 visit. Percent change from baseline in BMD = (\[BMD at Week 52 visit\] - \[baseline BMD\] ÷ baseline BMD) × 100. Measurements were performed using the Hologic QDR Series densitometer, and by same machine and under same scan mode throughout the study period. BMD data was centrally judged.

Group	Value	95% CI
Placebo	-0.35	-1.00 – 0.29
Odanacatib 10 mg	1.31	0.68 – 1.94
Odanacatib 25 mg	1.85	1.20 – 2.50
Odanacatib 50 mg	2.70	2.05 – 3.36

Number of Participants That Experienced an Adverse Event (AE) Primary · From first dose up to Post-Study (up to 54 weeks)

An AE was defined as any unfavorable and unintended change in the structure (sign), function (symptoms), or chemistry of the body (laboratory data) temporally associated with the use of the SPONSOR's products (including placebo), whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product was also an AE. The number of participants that experienced at least one AE was reported for each treatment arm.

Group	Value	95% CI
Placebo	57
Odanacatib 10 mg	63
Odanacatib 25 mg	62
Odanacatib 50 mg	58

Number of Participants That Discontinued Study Drug Due to an AE Primary · From first dose up to end of treatment (up to 52 weeks)

An AE was defined as any unfavorable and unintended change in the structure (sign), function (symptoms), or chemistry of the body (laboratory data) temporally associated with the use of the SPONSOR's products (including placebo), whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product was also an AE. The number of participants that discontinued study drug due to an AE was reported for each treatment ar

Group	Value	95% CI
Placebo	3
Odanacatib 10 mg	2
Odanacatib 25 mg	1
Odanacatib 50 mg	1

Percent Change From Baseline to Week 52 in Femoral Neck BMD Secondary · Baseline (Observation visit to Wk 0 treatment visit), Week 52

BMD (g/cm2) data was measured by DXA at the femoral neck subregion of the hip at the Observation visit (up to 5 weeks before Treatment Period), Week 0 (start of Treatment Period) and Week 52 (end of Treatment Period) or at discontinuation. Baseline was defined as the average of the 2 values collected at the Observation visit and Week 0 visit. Percent change from baseline in BMD = (\[BMD at Week 52 visit\] - \[baseline BMD\] ÷ baseline BMD) × 100. Measurements were performed using the Hologic QDR Series densitometer, and by same machine and under same scan mode throughout the study period. BMD

Group	Value	95% CI
Placebo	-0.72	-1.58 – 0.13
Odanacatib 10 mg	1.51	0.67 – 2.35
Odanacatib 25 mg	1.14	0.27 – 2.00
Odanacatib 50 mg	2.35	1.47 – 3.23

Percent Change From Baseline to Week 52 in Trochanter BMD Secondary · Baseline (Observation visit to Wk 0 treatment visit), Week 52

BMD (g/cm2) data was measured by DXA at the trochanter subregion of the hip (near bony protrusions along outside edge of femur) at the Observation visit (up to 5 weeks before Treatment Period), Week 0 (start of Treatment Period) and Week 52 (end of Treatment Period) or at discontinuation. Baseline was defined as the average of the 2 values collected at the Observation visit and Week 0 visit. Percent change from baseline in BMD = (\[BMD at Week 52 visit\] - \[baseline BMD\] ÷ baseline BMD) × 100. Measurements were performed using the Hologic QDR Series densitometer, and by same machine and unde

Group	Value	95% CI
Placebo	-0.28	-1.31 – 0.76
Odanacatib 10 mg	2.16	1.14 – 3.17
Odanacatib 25 mg	3.56	2.52 – 4.60
Odanacatib 50 mg	4.38	3.33 – 5.44

Percent Change From Baseline to Week 52 in Urinary N-telopeptides/Creatinine (u-NTx/Cre) Ratio Secondary · Baseline (Wk 0), Week 52

The u-NTx/Cre ratio is a biochemical marker index of bone resorption. Urine samples were collected from second void morning urine specimens to assess the u-NTx/Cre ratio. Percent change from baseline in biomarker = (\[biomarker value at Week 52 visit\] - \[baseline biomarker value\] ÷ baseline biomarker value) × 100. All measurements of bone biochemical markers were centrally performed.

Group	Value	95% CI
Placebo	-7.84	-21.19 – 7.76
Odanacatib 10 mg	-43.59	-51.26 – -34.71
Odanacatib 25 mg	-52.16	-58.73 – -44.54
Odanacatib 50 mg	-58.48	-64.42 – -51.54

Percent Change From Baseline to Week 52 in Serum C-Telopeptides of Type 1 Collagen (s-CTx) Level Secondary · Baseline (Wk 0), Week 52

s-CTx is a biochemical marker index of bone resorption. Blood samples were collected in the morning and in fasting state for measurement of s-CTx. Percent change from baseline in biomarker = (\[biomarker value at Week 52 visit\] - \[baseline biomarker value\] ÷ baseline biomarker value) × 100. All measurements of bone biochemical markers were centrally performed.

Group	Value	95% CI
Placebo	-10.95	-32.05 – 16.72
Odanacatib 10 mg	-49.68	-60.92 – -35.20
Odanacatib 25 mg	-71.64	-78.04 – -63.39
Odanacatib 50 mg	-71.36	-78.02 – -62.68

Percent Change From Baseline to Week 52 in Urinary Deoxypyridinoline/Creatinine Ratio (u-DPD/Cre) Secondary · Baseline (Wk 0), Week 52

The u-DPD/Cre ratio is a biochemical marker index of bone resorption. Urine samples were collected from second void morning urine specimens to assess the u-DPD/Cre ratio. Percent change from baseline in biomarker = (\[biomarker value at Week 52 visit\] - \[baseline biomarker value\] ÷ baseline biomarker value) × 100. All measurements of bone biochemical markers were centrally performed.

Group	Value	95% CI
Placebo	16.45	-1.24 – 37.30
Odanacatib 10 mg	-10.32	-23.11 – 4.61
Odanacatib 25 mg	-21.00	-32.39 – -7.69
Odanacatib 50 mg	-26.46	-37.51 – -13.46

Percent Change From Baseline to Week 52 in Serum Bone Specific Alkaline Phosphatase (s-BSAP) Level Secondary · Baseline (Wk 0), Week 52

s-BSAP is a biochemical marker index of bone formation. Blood samples were collected in the morning and in fasting state for measurement of s-BSAP. Percent change from baseline in biomarker = (\[biomarker value at Week 52 visit\] - \[baseline biomarker value\] ÷ baseline biomarker value) × 100. All measurements of bone biochemical markers were centrally performed.

Group	Value	95% CI
Placebo	-9.91	-17.02 – -2.20
Odanacatib 10 mg	-7.44	-14.31 – -0.02
Odanacatib 25 mg	-22.47	-28.32 – -16.14
Odanacatib 50 mg	-25.43	-31.26 – -19.12

Percent Change From Baseline to Week 52 in Serum N-Terminal Propeptides of Type 1 Collagen (s-P1NP) Level Secondary · Baseline (Wk 0), Week 52

s-P1NP is a biochemical marker index of bone formation. Blood samples were collected in the morning and in fasting state for measurement of s- P1NP. Percent change from baseline in biomarker = (\[biomarker value at Week 52 visit\] - \[baseline biomarker value\] ÷ baseline biomarker value) × 100. All measurements of bone biochemical markers were centrally performed.

Group	Value	95% CI
Placebo	-20.14	-32.74 – -5.18
Odanacatib 10 mg	-25.75	-36.81 – -12.76
Odanacatib 25 mg	-48.99	-56.71 – -39.90
Odanacatib 50 mg	-47.00	-55.28 – -37.19

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose up to Post-Study (up to 54 weeks). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo

Serious: 5/73 (7%)

Deaths: —

Odanacatib 10 mg

Serious: 6/74 (8%)

Deaths: —

Odanacatib 25 mg

Serious: 4/70 (6%)

Deaths: —

Odanacatib 50 mg

Serious: 4/69 (6%)

Deaths: —

Serious adverse events (18 terms)

Reaction	System	Placebo	Odanacatib 10 mg	Odanacatib 25 mg	Odanacatib 50 mg
Vertigo	Ear and labyrinth disorders	—	—	—	—
Spinal compression fracture	Injury, poisoning and procedural complications	—	—	—	—
Angina pectoris	Cardiac disorders	—	—	—	—
Myocardial ischaemia	Cardiac disorders	—	—	—	—
Cataract	Eye disorders	—	—	—	—
Ileus	Gastrointestinal disorders	—	—	—	—
Intestinal obstruction	Gastrointestinal disorders	—	—	—	—
Cellulitis	Infections and infestations	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—
Radius fracture	Injury, poisoning and procedural complications	—	—	—	—
Foot deformity	Musculoskeletal and connective tissue disorders	—	—	—	—
Adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—
Lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—
Cerebellar haemorrhage	Nervous system disorders	—	—	—	—
Intraneural cyst	Nervous system disorders	—	—	—	—
Subarachnoid haemorrhage	Nervous system disorders	—	—	—	—
Transient ischaemic attack	Nervous system disorders	—	—	—	—
Neurosis	Psychiatric disorders	—	—	—	—

Other adverse events (23 terms — click to expand)

Reaction	System	Placebo	Odanacatib 10 mg	Odanacatib 25 mg	Odanacatib 50 mg
Nasopharyngitis	Infections and infestations	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—
Osteoarthritis	Musculoskeletal and connective tissue disorders	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—
Cystitis	Infections and infestations	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—
Stomatitis	Gastrointestinal disorders	—	—	—	—
Pharyngitis	Infections and infestations	—	—	—	—
Joint sprain	Injury, poisoning and procedural complications	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—
Periarthritis	Musculoskeletal and connective tissue disorders	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—
Headache	Nervous system disorders	—	—	—	—
Abdominal discomfort	Gastrointestinal disorders	—	—	—	—
Gastritis	Gastrointestinal disorders	—	—	—	—
Periodontitis	Gastrointestinal disorders	—	—	—	—
Bronchitis	Infections and infestations	—	—	—	—
Gastroenteritis	Infections and infestations	—	—	—	—
Contusion	Injury, poisoning and procedural complications	—	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—	—
Spinal osteoarthritis	Musculoskeletal and connective tissue disorders	—	—	—	—
Eczema	Skin and subcutaneous tissue disorders	—	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—	—

Most-reported serious reactions: Vertigo, Spinal compression fracture, Angina pectoris, Myocardial ischaemia, Cataract, Ileus, Intestinal obstruction, Cellulitis.

Data from ClinicalTrials.gov NCT00620113 adverse events section.

Sponsor's own description

The purpose of this study is to assess the dose-response on the percent change from baseline in lumbar spine bone mineral density (BMD) at lumbar vertebrae 1 to 4 (L1- L4) when odanacatib (MK-0822) 10 mg, 25 mg, 50 mg or placebo is orally administered once weekly for 52 weeks to Japanese involutional osteoporosis participants. The study will also assess safety and tolerability of odanacatib (10, 25, and 50 mg) in these participants.

The study will enroll approximately 280 participants and randomly assign them to 3 different doses of odanacatib or placebo for 52 weeks, along with supplemental vitamin D3 and calcium carbonate. The primary efficacy hypothesis is that a dose-response relationship on the percent change from baseline in lumbar spine BMD (L1- L4) is seen when odanacatib 10, 25, 50 mg or placebo is orally administered once weekly for 52 weeks to involutional osteoporosis participants. The primary safety hypothesis is that odanacatib will be safe and well tolerated over 52 weeks to involutional osteoporosis participants.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Cathepsin K Inhibitors as Potential Drugs for the Treatment of Osteoarthritis.
   Brizuela L, Buchet R, Bougault C, Mebarek S. · · 2025 · cited 3× · PMID 40243480 · DOI 10.3390/ijms26072896