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| ID | Type | Description | Link |
|---|---|---|---|
| 2008_566 | Other Identifier | Merck |
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This study will evaluate a walking model of osteoarthritis for use in testing of new therapeutic agents. The primary hypothesis is that participants treated with Naproxen or Ultracet will have lower Pain Intensity (PI) than those treated with Placebo during self-paced walks on Day 3 of treatment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo, Naproxen, Ultracet | Experimental | Participants were treated with Placebo for 3 days in Treatment Period 1, Naproxen for 3 days in Treatment Period 2, and Ultracet for 3 days in Treatment Period 3. The treatment periods were separated by a 4-6 day break. |
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| Naproxen, Ultracet, Placebo | Experimental | Participants were treated with Naproxen for 3 days in Treatment Period 1, Ultracet for 3 days in Treatment Period 2, and Placebo for 3 days in Treatment Period 3. The treatment periods were separated by a 4-6 day break. |
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| Ultracet, Placebo, Naproxen | Experimental | Participants were treated with Ultracet for 3 days in Treatment Period 1, Placebo for 3 days in Treatment Period 2, and Naproxen for 3 days in Treatment Period 3. The treatment periods were separated by a 4-6 day break. |
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| Placebo, Ultracet, Naproxen | Experimental | Participants were treated with Placebo for 3 days in Treatment Period 1, Ultracet for 3 days in Treatment Period 2, and Naproxen for 3 days in Treatment Period 3. The treatment periods were separated by a 4-6 day break. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Naproxen | Drug | Naproxen tablets 500 mg twice daily on Day 1, a first dose at t = 0 hrs, and a second dose at t = 12 hrs. Twice daily on Day 2 and 500 mg once daily on Day 3. Walking tests will be performed on Days 1 and 3 of the treatment period. |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Time Weighted Average (TWA) Pain Intensity (PI) on a Numeric Rating Scale (NRS) Due to Self-paced Walks on Day 3 | Baseline measurements of participant-specific knee PI were gathered pre-dose on Day 1 from the briskest possible self-pace constant walks on a treadmill over the course of a 20 minute interval. Over this interval PI readings were taken at time points 0,3,6,9,12,15,18 and 20 minutes, rated on an 11-point numeric rating scale (NRS), with 0: No Pain - 10: Worst Pain You Can Imagine. Following a single treatment on Day 3, PI was similarly measured over 20 minute self paced walks at 4 and 6 hrs post-dose. The difference between the TWA (0-20 minutes) PI determined at baseline, and the average of the two TWA (0-20 minutes) PI from the self-paced walks on Day 3 is reported as units on a scale. | Baseline and Day 3 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Time Weighted Average (TWA) Pain Intensity (PI) on a Numeric Rating Scale (NRS) Due to Self-paced Walks on Day 1 | Baseline measurements of participant-specific knee PI were gathered pre-dose on Day 1 from the briskest possible self-pace constant walks on a treadmill over the course of a 20 minute interval. Over this interval PI readings were taken at time points 0,3,6,9,12,15,18 and 20 minutes, rated on an 11-point numeric rating scale (NRS), with 0: No Pain - 10: Worst Pain You Can Imagine. Following the first treatment on Day 1, PI was similarly measured over 20 minute self-paced walks at 2, 4, and 6 hrs post-dose . The difference between the TWA (0-20 minutes) PI determined at baseline, and the average of the three TWA (0-20 minutes)PI from the self-paced walks on Day 1 is reported as units on a scale. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor | Merck Sharp & Dohme LLC | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20175977 | Derived | Peeva E, Beals CR, Bolognese JA, Kivitz AJ, Taber L, Harman A, Smugar SS, Moskowitz RW. A walking model to assess the onset of analgesia in osteoarthritis knee pain. Osteoarthritis Cartilage. 2010 May;18(5):646-53. doi: 10.1016/j.joca.2009.12.008. Epub 2010 Feb 6. |
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Inclusion criteria: Patient has osteoarthritis of the knee and primary source of pain is knee
Titration schedule for Ultracet® (Acetaminophen 325 mg and tramadol hydrochloride 37.5 mg): twice on Day 1, three times on Day 2, and twice on the morning of Day 3.
Naproxen tablets 500 mg twice daily on Days 1 and 2 and 500 mg once daily on Day 3.
First Patient Entered: 23 June 2008
Last Patient, Last Visit: 20 November 2008
2 sites
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo, Naproxen, Ultracet | Placebo in Treatment Period 1, Naproxen in Treatment Period 2, Ultracet in Treatment Period 3. |
| FG001 | Naproxen, Ultracet, Placebo | Naproxen in Treatment Period 1, Ultracet in Treatment Period 2, Placebo in Treatment Period 3. |
| FG002 | Ultracet, Placebo, Naproxen | Ultracet in Treatment Period 1, Placebo in Treatment Period 2, Naproxen in Treatment Period 3. |
| FG003 | Placebo, Ultracet, Naproxen | Placebo in Treatment Period 1, Ultracet in Treatment Period 2, Naproxen in Treatment Period 3. |
| FG004 | Naproxen, Placebo, Ultracet | Naproxen in Treatment Period 1, Placebo in Treatment Period 2, Ultracet inTreatment Period 3. |
| FG005 | Ultracet, Naproxen, Placebo | Ultracet in Treatment Period 1, Naproxen in Treatment Period 2, Placebo in Treatment Period 3. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Crossover Treatment 1 |
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| Break 1 (4-7 Days) |
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| Crossover Treatment 2 |
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| Break 2 (4-7 Days) |
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| Crossover Treatment 3 |
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| ID | Title | Description |
|---|---|---|
| BG000 | All Participants | All randomized participants |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in Time Weighted Average (TWA) Pain Intensity (PI) on a Numeric Rating Scale (NRS) Due to Self-paced Walks on Day 3 | Baseline measurements of participant-specific knee PI were gathered pre-dose on Day 1 from the briskest possible self-pace constant walks on a treadmill over the course of a 20 minute interval. Over this interval PI readings were taken at time points 0,3,6,9,12,15,18 and 20 minutes, rated on an 11-point numeric rating scale (NRS), with 0: No Pain - 10: Worst Pain You Can Imagine. Following a single treatment on Day 3, PI was similarly measured over 20 minute self paced walks at 4 and 6 hrs post-dose. The difference between the TWA (0-20 minutes) PI determined at baseline, and the average of the two TWA (0-20 minutes) PI from the self-paced walks on Day 3 is reported as units on a scale. | All treated participants who provided baseline and at least one on-treatment observation | Posted | Least Squares Mean | 95% Confidence Interval | units on a scale | Baseline and Day 3 |
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Adverse experiences (AEs) were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed.
AEs were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Patients were queried at each visit for any adverse experiences since the previous visit.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Participants treated with at least one dose of Placebo |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gout | Metabolism and nutrition disorders | MedDRA 11.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D010003 | Osteoarthritis |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
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| ID | Term |
|---|---|
| D009288 | Naproxen |
| C478659 | Ultracet |
| ID | Term |
|---|---|
| D009280 | Naphthaleneacetic Acids |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
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| Naproxen, Placebo, Ultracet | Experimental | Participants were treated with Naproxen for 3 days in Treatment Period 1, Placebo for 3 days in Treatment Period 2, and Ultracet for 3 days in Treatment Period 3. The treatment periods were separated by a 4-6 day break. |
|
| Ultracet, Naproxen, Placebo | Experimental | Participants were treated with Ultracet for 3 days in Treatment Period 1, Naproxen for 3 days in Treatment Period 2, and Placebo for 3 days in Treatment Period 3. The treatment periods were separated by a 4-6 day break. |
|
| Placebo | Drug | Placebo capsules twice daily on Day 1, a first dose at t = 0 hrs, and a second dose at t = 12 hrs. Three times daily on Day 2, and 2 capsules on the morning of Day 3. Walking tests will be performed on Days 1 and 3 of the treatment period. |
|
| Ultracet | Drug | Ultracet (tramadol/acetaminophen) 37.5/325 mg/mg capsules twice daily on Day 1, a first dose at t = 0 hrs, and a second dose at t = 12 hrs. Three times daily on Day 2, and two 37.5/325 mg capsules on the morning of Day 3. Walking tests will be performed on Days 1 and 3 of the treatment period. |
|
| Baseline and Day 1 |
| Change From Baseline in Time Weighted Average (TWA) Pain Intensity (PI) on a Numeric Rating Scale (NRS) Due to High-paced Walks on Day 1 | Baseline measurements of participant-specific knee PI were gathered pre-dose on Day 1 from the briskest possible self-pace constant walks on a treadmill over the course of a 20 minute interval. Over this interval PI readings were taken at time points 0,3,6,9,12,15,18 and 20 minutes,rated on an 11-point numeric rating scale (NRS), with 0: No Pain - 10: Worst Pain You Can Imagine. Following the first treatment on Day 1, PI was similarly measured over a 20 minute high-paced treadmill walk at 5 hrs post-dose. A high-paced walk is the highest pace that can be walked safely for at least 5 minutes that is at a 10-30% higher rate than a self-paced walk. The difference between the TWA (0-20 minutes) PI determined at baseline, and the TWA (0-20 minutes) PI of the high-paced walk on Day 1 is reported as units on a scale. | Baseline and Day 1 |
| Change From Baseline in Time Weighted Average (TWA) Pain Intensity (PI) on a Numeric Rating Scale (NRS) Due to High-paced Walks on Day 3 | Baseline measurements of participant-specific knee PI were gathered pre-dose on Day 1 from the briskest possible self-pace constant walks on a treadmill over the course of a 20 minute interval. Over this interval PI readings were taken at time points 0,3,6,9,12,15,18 and 20 minutes, rated on an 11-point numeric rating scale (NRS), with 0: No Pain - 10: Worst Pain You Can Imagine. Following a single treatment on Day 3, PI was similarly measured over a 20 minute high-paced treadmill walk, at 5 hrs post-dose. A high-paced walk is the highest pace that can be walked safely for at least 5 minutes that is at a 10-30% higher rate than a self-paced walk. The difference between the TWA (0-20 minutes) PI determined at baseline, and the TWA (0-20 minutes) PI of the high-paced walk on Day 3 is reported as units on a scale. | Baseline and Day 3 |
| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| Years |
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| Sex: Female, Male | Count of Participants | Participants |
|
| Placebo |
Participants treated with at least one dose of Placebo |
| OG001 | Naproxen | Participants treated with at least one dose of Naproxen |
| OG002 | Ultracet | Participants treated with at least one dose of Ultracet. |
|
|
|
| Secondary | Change From Baseline in Time Weighted Average (TWA) Pain Intensity (PI) on a Numeric Rating Scale (NRS) Due to Self-paced Walks on Day 1 | Baseline measurements of participant-specific knee PI were gathered pre-dose on Day 1 from the briskest possible self-pace constant walks on a treadmill over the course of a 20 minute interval. Over this interval PI readings were taken at time points 0,3,6,9,12,15,18 and 20 minutes, rated on an 11-point numeric rating scale (NRS), with 0: No Pain - 10: Worst Pain You Can Imagine. Following the first treatment on Day 1, PI was similarly measured over 20 minute self-paced walks at 2, 4, and 6 hrs post-dose . The difference between the TWA (0-20 minutes) PI determined at baseline, and the average of the three TWA (0-20 minutes)PI from the self-paced walks on Day 1 is reported as units on a scale. | All treated participants who provided baseline and at least one on-treatment observation | Posted | Least Squares Mean | 95% Confidence Interval | units on a scale | Baseline and Day 1 |
|
|
|
|
| Secondary | Change From Baseline in Time Weighted Average (TWA) Pain Intensity (PI) on a Numeric Rating Scale (NRS) Due to High-paced Walks on Day 1 | Baseline measurements of participant-specific knee PI were gathered pre-dose on Day 1 from the briskest possible self-pace constant walks on a treadmill over the course of a 20 minute interval. Over this interval PI readings were taken at time points 0,3,6,9,12,15,18 and 20 minutes,rated on an 11-point numeric rating scale (NRS), with 0: No Pain - 10: Worst Pain You Can Imagine. Following the first treatment on Day 1, PI was similarly measured over a 20 minute high-paced treadmill walk at 5 hrs post-dose. A high-paced walk is the highest pace that can be walked safely for at least 5 minutes that is at a 10-30% higher rate than a self-paced walk. The difference between the TWA (0-20 minutes) PI determined at baseline, and the TWA (0-20 minutes) PI of the high-paced walk on Day 1 is reported as units on a scale. | All treated participants who provided baseline and at least one on-treatment observation | Posted | Least Squares Mean | 95% Confidence Interval | units on a scale | Baseline and Day 1 |
|
|
|
|
| Secondary | Change From Baseline in Time Weighted Average (TWA) Pain Intensity (PI) on a Numeric Rating Scale (NRS) Due to High-paced Walks on Day 3 | Baseline measurements of participant-specific knee PI were gathered pre-dose on Day 1 from the briskest possible self-pace constant walks on a treadmill over the course of a 20 minute interval. Over this interval PI readings were taken at time points 0,3,6,9,12,15,18 and 20 minutes, rated on an 11-point numeric rating scale (NRS), with 0: No Pain - 10: Worst Pain You Can Imagine. Following a single treatment on Day 3, PI was similarly measured over a 20 minute high-paced treadmill walk, at 5 hrs post-dose. A high-paced walk is the highest pace that can be walked safely for at least 5 minutes that is at a 10-30% higher rate than a self-paced walk. The difference between the TWA (0-20 minutes) PI determined at baseline, and the TWA (0-20 minutes) PI of the high-paced walk on Day 3 is reported as units on a scale. | All treated participants who provided baseline and at least one on-treatment observation | Posted | Least Squares Mean | 95% Confidence Interval | units on a scale | Baseline and Day 3 |
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| 0 |
| 22 |
| 0 |
| 22 |
| EG001 | Naproxen | Participants treated with at least one dose of Naproxen | 0 | 22 | 0 | 22 |
| EG002 | Ultracet | Participants treated with at least one dose of Ultracet. Two participants were not treated due to discontinuation. | 0 | 20 | 2 | 20 |
| Somnolence | Nervous system disorders | MedDRA 11.1 | Systematic Assessment |
|
Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
| ANCOVA |
Baseline measurement included as covariate: Time-weighted average pain intensity during pretreatment walk |
| 0.001 |
1-sided, alpha = 0.05 |
| Mean Difference (Final Values) |
| -1.03 |
| 90 |
| -1.54 |
| -0.53 |
| No |
| Superiority or Other |
| ANCOVA |
Baseline measurement included as covariate: Time-weighted average pain intensity during pretreatment walk |
| 0.003 |
1-sided, alpha = 0.05 |
| Mean Difference (Final Values) |
| -1.15 |
| 90 |
| -1.81 |
| -0.49 |
| No |
| Superiority or Other |
| ANCOVA |
Baseline measurement included as covariate: Time-weighted average pain intensity during pretreatment walk |
| 0.007 |
1-sided, alpha = 0.05 |
| Mean Difference (Final Values) |
| -1.07 |
| 90 |
| -1.77 |
| -0.37 |
| No |
| Superiority or Other |