A Study to Evaluate the Effect of Analgesics on a Walking Model of Knee Pain (0000-105)(COMPLETED)

Study Overview
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Brief Summary
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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.

Official Title
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A Double-Blind, Placebo-Controlled, 3-Period Crossover Study to Evaluate the Analgesic Effects of Naproxen and Ultracet in a Walking Model of Osteoarthritis Knee Pain

Conditions
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Osteoarthritis

Intervention / Treatment
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* Drug: Naproxen
* Drug: Placebo
* Drug: Ultracet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has osteoarthritis of the knee and primary source of pain is knee Females must not be pregnant or nursing and must agree to use birth control throughout the study Is willing to limit alcohol and caffeine intake Is willing to abstain from smoking during study visits Must be able to walk on a treadmill at a pace of at least 1 mile/hour Exclusion Criteria: Has a medical/arthritic disease that would interfere with evaluation Is unable to take naproxen or Ultracet Has congestive heart failure or angina Has a history of stroke Has a history of uncontrolled high blood pressure Has a history of cancer Regularly uses a walker or cane

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Placebo, Naproxen, Ultracet<br>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. | Drug: Naproxen<br>* 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.<br>Drug: Placebo<br>* 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.<br>Drug: Ultracet<br>* 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.<br>|
| Experimental: Naproxen, Ultracet, Placebo<br>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. | Drug: Naproxen<br>* 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.<br>Drug: Placebo<br>* 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.<br>Drug: Ultracet<br>* 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.<br>|
| Experimental: Ultracet, Placebo, Naproxen<br>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. | Drug: Naproxen<br>* 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.<br>Drug: Placebo<br>* 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.<br>Drug: Ultracet<br>* 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.<br>|
| Experimental: Placebo, Ultracet, Naproxen<br>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. | Drug: Naproxen<br>* 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.<br>Drug: Placebo<br>* 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.<br>Drug: Ultracet<br>* 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.<br>|
| Experimental: Naproxen, Placebo, Ultracet<br>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. | Drug: Naproxen<br>* 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.<br>Drug: Placebo<br>* 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.<br>Drug: Ultracet<br>* 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.<br>|
| Experimental: Ultracet, Naproxen, Placebo<br>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. | Drug: Naproxen<br>* 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.<br>Drug: Placebo<br>* 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.<br>Drug: Ultracet<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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. | 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 |