Rheumatoid Arthritis
Conditions
Keywords
Rheumatoid arthritis, arthritis
Brief summary
The purpose of this study is to evaluate the effectiveness of ADL5859 in relieving pain associated with rheumatoid arthritis (RA) compared with placebo and naproxen (similar to Aleve®). A second objective is to see whether the effect of ADL5859 differs after a single dose compared with multiple doses.
Detailed description
This Phase 2a study was conducted in 2 parts. Part A was a randomized, single-dose, double-blind, placebo- and active-controlled, 3-way crossover phase during which participants were administered study medication in the clinical facility. Part B was a 14-day, randomized, double-blind, placebo-controlled, parallel-group, multiple-dose phase in which participants self-administered study medication at home.
Interventions
Sponsors
Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Male and female participants between 18 and 75 years of age, inclusive * Have a documented history of rheumatoid arthritis (diagnosed according to American College of Rheumatology criteria) * Have painful rheumatoid arthritis with pain predominantly in the lower extremities (that is, hip, knees, ankles, and/or feet) * Have an evoked lower extremity pain intensity (ELEPI) score of 5 or higher on a numeric pain rating scale (NPRS) completed on Day 1 of Part A before dosing (after resting for 45 minutes and then walking for at least 10 minutes on a treadmill) and then have a minimum ELEPI score of 4 on other visits during Part A * If receiving disease modifying antirheumatic drugs, have a stable dose regimen for at least 30 days before study entry (90 days before study entry for biologic therapy) * If biologic therapy has been recently discontinued, Enbrel™ or Orencia™ must have been discontinued at least 30 days before study entry, and Humira™, Remicade™, and Rituxan™ must have been discontinued at least 60 days before study entry * For male participants, be surgically sterile or agree to use an appropriate method of contraception * For female participants of child bearing potential, be surgically sterile or using an insertable, injectable, transdermal, or combination oral contraceptive deemed highly effective by the US Food and Drug Administration (FDA) through the completion of the study and have negative findings on a urine pregnancy test before administration of study medication (women who are postmenopausal \[no menses for at least 2 years\] are also eligible to participate) * Have a body weight of at least 45 kilograms (kg) * Be able to understand and comply with the protocol requirements (such as repeated treadmill walking and diary completion via the interactive voice response system), instructions, and protocol-specified restrictions.
Exclusion criteria
* Have an overall pain intensity (OPI) score equal to 10 at screening or before the first dose of study medication in Part A * Have a pain intensity score for the upper body (that is, back, neck, fingers, wrists, elbows, and/or shoulders) above 7 on a numeric pain rating scale (NPRS) before study medication administration * Have a history of headache requiring prescription treatment within 6 months of study entry * Have significant renal disease (as indicated by blood urea nitrogen or serum creatinine ≥ 2 times the upper limit of normal) or have significant hepatic disease (as indicated by liver function test results ≥ 2 times the upper limit of normal) * Have evidence of symptomatic orthostatic hypotension * Have a history of a seizure disorder, including febrile seizures * Have, as determined by the investigator or the sponsor's medical monitor, a history or clinical manifestations of significant renal, hepatic, cardiovascular, metabolic, neurologic, psychiatric, or other conditions that would affect study participation * Are taking cytochrome P450 (CYP) 3A4/5 or P glycoprotein (P gp) transporter inhibitors * Have taken oral steroids within 30 days of study entry or intra articular steroids within 60 days of study entry (inhaled or topical steroids or stable oral dose ≤ 10 mg is permitted) * Have a history or presence of allergy or intolerance to nonsteroidal anti-inflammatory drugs or acetaminophen, or have a history of drug or other allergy that, in the opinion of the investigator, contraindicates participation in the study * Have a history of alcoholism or drug addiction or abuse within 5 years before the scheduled administration of study medication * Have participated in a trial of any investigational medication within 30 days before study drug administration
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Average Difference Between Baseline and Post Dose Evoked (by Treadmill Walking) Lower-Extremity Pain Intensity Scores (AELEPID) Over the 6 Hours After Dosing | Baseline through 6 hours post dose | Approximately 1 hour before baseline and again approximately 45 minutes before the 2-, 4-, and 6-hour time points, participants rested for 45 minutes, then they started the treadmill walk at 15 minutes before baseline and at the 2-, 4-, and 6-hour time points. After the treadmill walk, participants were asked to rate their lower extremity pain on an 11 point Numeric Pain Rating Scale (NPRS), with 0 indicating No Pain and 10 indicating Worst Possible Pain. The average difference between baseline and 6 hours post dose evoked lower-extremity pain intensity scores (AELEPID-6) is presented for each treatment group. Difference = predose (baseline) NPRS score - NPRS score 6 hours post dose. Least square (LS) means and standard errors (SE) were calculated from an analysis-of-covariance (ANCOVA) model with fixed effects for sequence, treatment, period, predose evoked lower extremity pain intensity as a covariate, and a random effect for participant nested within sequence. |
| Part B: The Mean of Daily Average Now Lower Extremity Pain Intensity (LEPI) Score During the 2-Week Period | Baseline through 2 Weeks | Participants assessed their Now LEPI 3 times each day (morning, midday, and evening at approximately 10 AM, 2 PM, and 8 PM) and before taking any rescue medication. At each time point, participants were asked to rate their lower extremity pain on an 11-point Numeric Pain Rating Scale (NPRS), with 0 indicating No Pain and 10 indicating Worst Possible Pain. If a scheduled pain assessment was taken within 4 hours of rescue medication, the observed pain score was replaced by the pain score obtained right before the rescue medication was taken. LS means and SE were calculated from an analysis-of-covariance model with effect for treatment and baseline Now LEPI (before dosing for Treatment Period 1 of Part A) as a covariate. Participants with no postbaseline assessments were excluded from the baseline summary. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Pain Intensity Difference Between Baseline and the Value at Each Scheduled Time Point for Overall Pain | Baseline, 6 and 12 hours post dose | Overall Pain Intensity (OPI) was assessed by the participant using the 11-point Numeric Pain Rating Scale (NPRS), with 0 indicating No Pain and 10 indicating Worst Possible Pain. OPI was assessed at 15 minutes before dosing for baseline and at 6 and 12 hours after dosing. Difference = predose (baseline) OPI score - OPI score 6 and 12 hours post dose. |
| Part A: Average Difference Between Baseline and Postdose Evoked Lower Extremity Pain Over the 4 Hours After Dosing | Baseline, 4 hours post dose | Evoked Lower Extremity Pain Intensity (ELEPI) was assessed using the 11-point Numeric Pain Rating Scale (NPRS), with 0 indicating No Pain and 10 indicating Worst Possible Pain. Approximately 1 hour before dosing and approximately 45 minutes before the 2-, 4-, and 6-hour time points, the participant rested for 45 minutes, then he or she started a treadmill walk at 15 minutes before dosing for baseline and at the 2-, 4-, and 6-hour time points, and then assessed ELEPI. Difference = predose (baseline) ELEPI score - ELEPI score 4 hours post dose. |
| Part A: Mean Peak Difference in ELEPI According to the NPRS Scale | Baseline, Up to 6 hours post dose | Evoked Lower Extremity Pain Intensity (ELEPI) was assessed using the 11-point NPRS. Participants were asked to rate their lower extremity pain on an 11 point NPRS, with 0 indicating No Pain and 10 indicating Worst Possible Pain. If a scheduled pain assessment was taken within 4 hours of rescue medication, the observed pain score was replaced by the pain score obtained right before the rescue medication was taken. Approximately 1 hour before dosing and approximately 45 minutes before the 2-, 4-, and 6-hour time points, the participant rested for 45 minutes, then he or she started a treadmill walk at 15 minutes before dosing for baseline and at the 2-, 4-, and 6-hour time points, and then assessed ELEPI. Peak ELEPID was defined as the maximum of ELEPIDs recorded at 2, 4, and 6 hours post dose. Difference = predose (baseline) NPRS score - peak NPRS score up to 6 hours post dose. |
| Part A: Percentage of Participants in Each Treatment Group Achieving a 25%, 50%, or 75% Reduction From Baseline in Evoked Lower Extremity Pain Intensity Scores | Up to 2, 4, and 6 hours post dosing | Percentage was measured by identifying the number of participants who achieved the desired percentage Reduction From Baseline in ELEPI Score at either 2, 4, and 6 hours post dose and was divided the by the number of total participants in the given group and then multiplied by 100 to equate to a percentage. |
| Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | Baseline up to 12 hours post dose | Overall Pain Intensity (OPI), Now Lower Extremity Pain Intensity (LEPI), and Evoked Lower Extremity Pain Intensity (ELEPI) were assessed using the 11-point Numeric Pain Rating Scale (NPRS), with 0 indicating No Pain and 10 indicating Worst Possible Pain. OPI was assessed at 15 minutes before dosing for baseline and at 6 and 12 hours (hr) after dosing. At 15 minutes before dosing, during Period 1 only, participants were also asked to assess their average LEPI over the last 24 hours as a baseline measurement. Now LEPI was assessed at 15 minutes before dosing for baseline and at the 1-, 2-, 3-, 4-, 5-, 6-, and 12-hour time points. Approximately 1 hour before dosing and approximately 45 minutes before the 2-, 4-, and 6-hour time points, the participant rested for 45 minutes, then (after the Now LEPI assessment) he or she started a treadmill walk at 15 minutes before dosing for baseline and at the 2-, 4-, and 6-hour time points, and then assessed ELEPI. |
| Part B: Mean Daily Average LEPI Scores Over the Last 24 Hours at Week 1 and Week 2 | Week 1 and Week 2 | Each day during Part B, participants rated their Lower Extremity Pain Intensity over the last 24 hours on an 11-point NPRS, with 0 indicating No Pain and 10 indicating Worst Possible Pain |
| Part B: Mean Daily Average Overall Pain Intensity Scores Over Week 1, Over Week 2, and Over a 2-Week Period | Baseline through Week 1, Week 1 through Week 2, and Baseline through Week 2 | During Part B, participants returned to the clinic for 2 additional visits at approximately weekly intervals for assessments of Overall Pain Index (OPI). Participants rated their OPI on an 11-point Numeric Pain Rating Scale (NPRS) with 0 indicating No Pain and 10 indicating Worst possible pain |
| Part B: Percentage of Participants Using Rescue Medication | Baseline through Week 2 | The percentage of participants who took at least 1 dose of rescue medication during 2-week treatment period of Part B is presented. |
| Part A: Participant's Global Evaluation of Study Medication | 6 hours post dose during Treatment Periods 1, 2, and 3 of Part A | For each treatment period during Part A, each participant's global evaluation (overall impression) of study medication was obtained 6 hours after dosing. Scores were recorded on the Case Report Form (CRF) on a 5 point scale ranging from excellent to poor. Participant counts per score were reported once in Part A. |
| Part B: Participants' Global Evaluation of Study Medication | Up to Week 1 and Week 2 | For Part B, each participant's global evaluation (overall impression) of study medication was obtained at each weekly visit. Scores were recorded on the Case Report Form (CRF) on a 5 point scale ranging from excellent to poor. Participant counts per score were reported at Week 1 (Day 7) and Week 2 (Day 14). |
| Part B: Mean Daily LEPI Scores for Weeks 1 and 2 | Baseline through Week 1 and Week 1 through Week 2 | Participants assessed their Now LEPI 3 times each day (morning, midday, and evening at approximately 10 AM, 2 PM, and 8 PM) and before taking any rescue medication. At each time point, participants were asked to rate their lower extremity pain on an 11 point Numeric Pain Rating Scale (NPRS), with 0 indicating No Pain and 10 indicating Worst Possible Pain. If a scheduled pain assessment was taken within 4 hours of rescue medication, the observed pain score was replaced by the pain score obtained right before the rescue medication was taken. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Treated Participants All participants who received at least 1 dose of study drug during any sequence of Part A of the study. Baseline measures reported in aggregate for all participants to avoid double counting of Parts A and B. | 46 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Part A - Treatment Period 1 | Adverse Event | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part A - Treatment Period 1 | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Part B | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Part B | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | All Treated Participants |
|---|---|
| Age, Continuous | 54.6 years STANDARD_DEVIATION 8.91 |
| Sex: Female, Male Female | 36 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 8 / 46 | 7 / 46 | 8 / 46 | 10 / 24 | 10 / 20 |
| serious Total, serious adverse events | 0 / 46 | 0 / 46 | 0 / 46 | 0 / 24 | 0 / 20 |
Outcome results
Primary
Part A: Average Difference Between Baseline and Post Dose Evoked (by Treadmill Walking) Lower-Extremity Pain Intensity Scores (AELEPID) Over the 6 Hours After Dosing
Approximately 1 hour before baseline and again approximately 45 minutes before the 2-, 4-, and 6-hour time points, participants rested for 45 minutes, then they started the treadmill walk at 15 minutes before baseline and at the 2-, 4-, and 6-hour time points. After the treadmill walk, participants were asked to rate their lower extremity pain on an 11 point Numeric Pain Rating Scale (NPRS), with 0 indicating No Pain and 10 indicating Worst Possible Pain. The average difference between baseline and 6 hours post dose evoked lower-extremity pain intensity scores (AELEPID-6) is presented for each treatment group. Difference = predose (baseline) NPRS score - NPRS score 6 hours post dose. Least square (LS) means and standard errors (SE) were calculated from an analysis-of-covariance (ANCOVA) model with fixed effects for sequence, treatment, period, predose evoked lower extremity pain intensity as a covariate, and a random effect for participant nested within sequence.
Time frame: Baseline through 6 hours post dose
Population: Participants in Part A who received at least 1 dose of study drug and had at least 1 pain intensity assessment post dose.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Part A) | Part A: Average Difference Between Baseline and Post Dose Evoked (by Treadmill Walking) Lower-Extremity Pain Intensity Scores (AELEPID) Over the 6 Hours After Dosing | 1.12 units on a scale | Standard Error 0.24 |
| Naproxen - 500 mg (Part A) | Part A: Average Difference Between Baseline and Post Dose Evoked (by Treadmill Walking) Lower-Extremity Pain Intensity Scores (AELEPID) Over the 6 Hours After Dosing | 1.95 units on a scale | Standard Error 0.24 |
| ADL5859 - 200 mg (Part A) | Part A: Average Difference Between Baseline and Post Dose Evoked (by Treadmill Walking) Lower-Extremity Pain Intensity Scores (AELEPID) Over the 6 Hours After Dosing | 1.20 units on a scale | Standard Error 0.242 |
Primary
Part B: The Mean of Daily Average Now Lower Extremity Pain Intensity (LEPI) Score During the 2-Week Period
Participants assessed their Now LEPI 3 times each day (morning, midday, and evening at approximately 10 AM, 2 PM, and 8 PM) and before taking any rescue medication. At each time point, participants were asked to rate their lower extremity pain on an 11-point Numeric Pain Rating Scale (NPRS), with 0 indicating No Pain and 10 indicating Worst Possible Pain. If a scheduled pain assessment was taken within 4 hours of rescue medication, the observed pain score was replaced by the pain score obtained right before the rescue medication was taken. LS means and SE were calculated from an analysis-of-covariance model with effect for treatment and baseline Now LEPI (before dosing for Treatment Period 1 of Part A) as a covariate. Participants with no postbaseline assessments were excluded from the baseline summary.
Time frame: Baseline through 2 Weeks
Population: Participants in Part B who received at least 1 dose of study drug and had at least 1 pain intensity assessment post dose.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Part A) | Part B: The Mean of Daily Average Now Lower Extremity Pain Intensity (LEPI) Score During the 2-Week Period | 4.23 units on a scale | Standard Error 0.339 |
| Naproxen - 500 mg (Part A) | Part B: The Mean of Daily Average Now Lower Extremity Pain Intensity (LEPI) Score During the 2-Week Period | 4.21 units on a scale | Standard Error 0.371 |
Secondary
Part A: Average Difference Between Baseline and Postdose Evoked Lower Extremity Pain Over the 4 Hours After Dosing
Evoked Lower Extremity Pain Intensity (ELEPI) was assessed using the 11-point Numeric Pain Rating Scale (NPRS), with 0 indicating No Pain and 10 indicating Worst Possible Pain. Approximately 1 hour before dosing and approximately 45 minutes before the 2-, 4-, and 6-hour time points, the participant rested for 45 minutes, then he or she started a treadmill walk at 15 minutes before dosing for baseline and at the 2-, 4-, and 6-hour time points, and then assessed ELEPI. Difference = predose (baseline) ELEPI score - ELEPI score 4 hours post dose.
Time frame: Baseline, 4 hours post dose
Population: Participants in Part A who received at least 1 dose of study drug and had at least 1 pain intensity assessment post dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Part A) | Part A: Average Difference Between Baseline and Postdose Evoked Lower Extremity Pain Over the 4 Hours After Dosing | 1.04 units on a scale | Standard Deviation 1.437 |
| Naproxen - 500 mg (Part A) | Part A: Average Difference Between Baseline and Postdose Evoked Lower Extremity Pain Over the 4 Hours After Dosing | 1.72 units on a scale | Standard Deviation 1.753 |
| ADL5859 - 200 mg (Part A) | Part A: Average Difference Between Baseline and Postdose Evoked Lower Extremity Pain Over the 4 Hours After Dosing | 1.14 units on a scale | Standard Deviation 1.553 |
Secondary
Part A: Mean Peak Difference in ELEPI According to the NPRS Scale
Evoked Lower Extremity Pain Intensity (ELEPI) was assessed using the 11-point NPRS. Participants were asked to rate their lower extremity pain on an 11 point NPRS, with 0 indicating No Pain and 10 indicating Worst Possible Pain. If a scheduled pain assessment was taken within 4 hours of rescue medication, the observed pain score was replaced by the pain score obtained right before the rescue medication was taken. Approximately 1 hour before dosing and approximately 45 minutes before the 2-, 4-, and 6-hour time points, the participant rested for 45 minutes, then he or she started a treadmill walk at 15 minutes before dosing for baseline and at the 2-, 4-, and 6-hour time points, and then assessed ELEPI. Peak ELEPID was defined as the maximum of ELEPIDs recorded at 2, 4, and 6 hours post dose. Difference = predose (baseline) NPRS score - peak NPRS score up to 6 hours post dose.
Time frame: Baseline, Up to 6 hours post dose
Population: Participants in Part A who received at least 1 dose of study drug and had at least 1 pain intensity assessment post dose.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Part A) | Part A: Mean Peak Difference in ELEPI According to the NPRS Scale | 1.82 units on a scale | Standard Deviation 1.874 |
| Naproxen - 500 mg (Part A) | Part A: Mean Peak Difference in ELEPI According to the NPRS Scale | 2.49 units on a scale | Standard Deviation 1.74 |
| ADL5859 - 200 mg (Part A) | Part A: Mean Peak Difference in ELEPI According to the NPRS Scale | 1.84 units on a scale | Standard Deviation 1.725 |
Secondary
Part A: Pain Intensity Difference Between Baseline and the Value at Each Scheduled Time Point for Overall Pain
Overall Pain Intensity (OPI) was assessed by the participant using the 11-point Numeric Pain Rating Scale (NPRS), with 0 indicating No Pain and 10 indicating Worst Possible Pain. OPI was assessed at 15 minutes before dosing for baseline and at 6 and 12 hours after dosing. Difference = predose (baseline) OPI score - OPI score 6 and 12 hours post dose.
Time frame: Baseline, 6 and 12 hours post dose
Population: Participants in Part A who received at least 1 dose of study drug and had at least 1 pain intensity assessment post dose.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Part A) | Part A: Pain Intensity Difference Between Baseline and the Value at Each Scheduled Time Point for Overall Pain | Change From Baseline 6 Hours Post Dose | 1.40 units on a scale | Standard Deviation 2.24 |
| Placebo (Part A) | Part A: Pain Intensity Difference Between Baseline and the Value at Each Scheduled Time Point for Overall Pain | Change From Baseline 12 Hours Post Dose | 1.16 units on a scale | Standard Deviation 1.911 |
| Naproxen - 500 mg (Part A) | Part A: Pain Intensity Difference Between Baseline and the Value at Each Scheduled Time Point for Overall Pain | Change From Baseline 6 Hours Post Dose | 2.09 units on a scale | Standard Deviation 1.917 |
| Naproxen - 500 mg (Part A) | Part A: Pain Intensity Difference Between Baseline and the Value at Each Scheduled Time Point for Overall Pain | Change From Baseline 12 Hours Post Dose | 3.73 units on a scale | Standard Deviation 1.88 |
| ADL5859 - 200 mg (Part A) | Part A: Pain Intensity Difference Between Baseline and the Value at Each Scheduled Time Point for Overall Pain | Change From Baseline 6 Hours Post Dose | 0.86 units on a scale | Standard Deviation 2.12 |
| ADL5859 - 200 mg (Part A) | Part A: Pain Intensity Difference Between Baseline and the Value at Each Scheduled Time Point for Overall Pain | Change From Baseline 12 Hours Post Dose | 0.92 units on a scale | Standard Deviation 2.278 |
Secondary
Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain
Overall Pain Intensity (OPI), Now Lower Extremity Pain Intensity (LEPI), and Evoked Lower Extremity Pain Intensity (ELEPI) were assessed using the 11-point Numeric Pain Rating Scale (NPRS), with 0 indicating No Pain and 10 indicating Worst Possible Pain. OPI was assessed at 15 minutes before dosing for baseline and at 6 and 12 hours (hr) after dosing. At 15 minutes before dosing, during Period 1 only, participants were also asked to assess their average LEPI over the last 24 hours as a baseline measurement. Now LEPI was assessed at 15 minutes before dosing for baseline and at the 1-, 2-, 3-, 4-, 5-, 6-, and 12-hour time points. Approximately 1 hour before dosing and approximately 45 minutes before the 2-, 4-, and 6-hour time points, the participant rested for 45 minutes, then (after the Now LEPI assessment) he or she started a treadmill walk at 15 minutes before dosing for baseline and at the 2-, 4-, and 6-hour time points, and then assessed ELEPI.
Time frame: Baseline up to 12 hours post dose
Population: Participants in Part A who received at least 1 dose of study drug and had at least 1 pain intensity assessment post dose.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | LEPI, 1 hr Post Dose | 5.38 units on a scale | Standard Deviation 2.124 |
| Placebo (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | ELEPI, 4 hr Post Dose | 5.16 units on a scale | Standard Deviation 2.174 |
| Placebo (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | LEPI, 6 hr Post Dose | 4.49 units on a scale | Standard Deviation 2.149 |
| Placebo (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | LEPI, 2 hr Post Dose | 5.24 units on a scale | Standard Deviation 2.013 |
| Placebo (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | ELEPI, 2 hr Post Dose | 5.47 units on a scale | Standard Deviation 1.854 |
| Placebo (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | LEPI, 5 hr Post Dose | 4.71 units on a scale | Standard Deviation 2.117 |
| Placebo (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | LEPI, 3 hr Post Dose | 4.67 units on a scale | Standard Deviation 2.089 |
| Placebo (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | OPI, Baseline | 6.20 units on a scale | Standard Deviation 1.89 |
| Placebo (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | LEPI, 4 hr Post Dose | 4.76 units on a scale | Standard Deviation 2.036 |
| Placebo (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | ELEPI, 6 hr Post Dose | 4.93 units on a scale | Standard Deviation 2.517 |
| Placebo (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | OPI, 12 hr Post Dose | 5.03 units on a scale | Standard Deviation 1.993 |
| Placebo (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | ELEPI, Baseline | 6.36 units on a scale | Standard Deviation 1.873 |
| Placebo (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | LEPI, Baseline | 6.18 units on a scale | Standard Deviation 2.059 |
| Placebo (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | OPI, 6 hr Post Dose | 4.80 units on a scale | Standard Deviation 2.282 |
| Placebo (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | LEPI, 12 hr Post Dose | 5.11 units on a scale | Standard Deviation 2.037 |
| Naproxen - 500 mg (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | LEPI, 12 hr Post Dose | 3.78 units on a scale | Standard Deviation 1.813 |
| Naproxen - 500 mg (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | ELEPI, Baseline | 6.20 units on a scale | Standard Deviation 1.471 |
| Naproxen - 500 mg (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | ELEPI, 2 hr Post Dose | 4.71 units on a scale | Standard Deviation 1.973 |
| Naproxen - 500 mg (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | ELEPI, 4 hr Post Dose | 4.24 units on a scale | Standard Deviation 1.76 |
| Naproxen - 500 mg (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | ELEPI, 6 hr Post Dose | 4.00 units on a scale | Standard Deviation 1.871 |
| Naproxen - 500 mg (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | LEPI, Baseline | 5.78 units on a scale | Standard Deviation 1.845 |
| Naproxen - 500 mg (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | LEPI, 1 hr Post Dose | 5.00 units on a scale | Standard Deviation 1.719 |
| Naproxen - 500 mg (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | LEPI, 2 hr Post Dose | 4.33 units on a scale | Standard Deviation 1.822 |
| Naproxen - 500 mg (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | LEPI, 3 hr Post Dose | 4.04 units on a scale | Standard Deviation 1.858 |
| Naproxen - 500 mg (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | LEPI, 4 hr Post Dose | 3.93 units on a scale | Standard Deviation 1.737 |
| Naproxen - 500 mg (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | LEPI, 5 hr Post Dose | 3.98 units on a scale | Standard Deviation 1.685 |
| Naproxen - 500 mg (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | LEPI, 6 hr Post Dose | 3.89 units on a scale | Standard Deviation 1.774 |
| Naproxen - 500 mg (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | OPI, Baseline | 6.13 units on a scale | Standard Deviation 1.753 |
| Naproxen - 500 mg (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | OPI, 6 hr Post Dose | 4.04 units on a scale | Standard Deviation 1.833 |
| Naproxen - 500 mg (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | OPI, 12 hr Post Dose | 3.73 units on a scale | Standard Deviation 1.88 |
| ADL5859 - 200 mg (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | LEPI, 1 hr Post Dose | 5.34 units on a scale | Standard Deviation 1.584 |
| ADL5859 - 200 mg (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | OPI, 6 hr Post Dose | 4.91 units on a scale | Standard Deviation 1.815 |
| ADL5859 - 200 mg (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | LEPI, 6 hr Post Dose | 4.77 units on a scale | Standard Deviation 1.696 |
| ADL5859 - 200 mg (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | LEPI, Baseline | 5.68 units on a scale | Standard Deviation 1.84 |
| ADL5859 - 200 mg (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | ELEPI, 6 hr Post Dose | 4.95 units on a scale | Standard Deviation 2.124 |
| ADL5859 - 200 mg (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | LEPI, 12 hr Post Dose | 4.76 units on a scale | Standard Deviation 1.817 |
| ADL5859 - 200 mg (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | ELEPI, 4 hr Post Dose | 5.00 units on a scale | Standard Deviation 2.035 |
| ADL5859 - 200 mg (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | ELEPI, Baseline | 6.363 units on a scale | Standard Deviation 1.806 |
| ADL5859 - 200 mg (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | OPI, Baseline | 5.77 units on a scale | Standard Deviation 1.71 |
| ADL5859 - 200 mg (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | LEPI, 3 hr Post Dose | 4.73 units on a scale | Standard Deviation 1.59 |
| ADL5859 - 200 mg (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | ELEPI, 2 hr Post Dose | 5.45 units on a scale | Standard Deviation 1.649 |
| ADL5859 - 200 mg (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | LEPI, 4 hr Post Dose | 4.70 units on a scale | Standard Deviation 1.593 |
| ADL5859 - 200 mg (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | LEPI, 2 hr Post Dose | 4.91 units on a scale | Standard Deviation 1.507 |
| ADL5859 - 200 mg (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | OPI, 12 hr Post Dose | 4.89 units on a scale | Standard Deviation 1.955 |
| ADL5859 - 200 mg (Part A) | Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain | LEPI, 5 hr Post Dose | 4.73 units on a scale | Standard Deviation 1.921 |
Secondary
Part A: Participant's Global Evaluation of Study Medication
For each treatment period during Part A, each participant's global evaluation (overall impression) of study medication was obtained 6 hours after dosing. Scores were recorded on the Case Report Form (CRF) on a 5 point scale ranging from excellent to poor. Participant counts per score were reported once in Part A.
Time frame: 6 hours post dose during Treatment Periods 1, 2, and 3 of Part A
Population: Participants in Part A who received at least 1 dose of study drug and had at least 1 pain intensity assessment post dose.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Part A) | Part A: Participant's Global Evaluation of Study Medication | Fair | 12 participants |
| Placebo (Part A) | Part A: Participant's Global Evaluation of Study Medication | Good | 15 participants |
| Placebo (Part A) | Part A: Participant's Global Evaluation of Study Medication | Excellent | 1 participants |
| Placebo (Part A) | Part A: Participant's Global Evaluation of Study Medication | Very Good | 9 participants |
| Placebo (Part A) | Part A: Participant's Global Evaluation of Study Medication | Poor | 8 participants |
| Naproxen - 500 mg (Part A) | Part A: Participant's Global Evaluation of Study Medication | Good | 15 participants |
| Naproxen - 500 mg (Part A) | Part A: Participant's Global Evaluation of Study Medication | Excellent | 6 participants |
| Naproxen - 500 mg (Part A) | Part A: Participant's Global Evaluation of Study Medication | Very Good | 12 participants |
| Naproxen - 500 mg (Part A) | Part A: Participant's Global Evaluation of Study Medication | Fair | 9 participants |
| Naproxen - 500 mg (Part A) | Part A: Participant's Global Evaluation of Study Medication | Poor | 3 participants |
| ADL5859 - 200 mg (Part A) | Part A: Participant's Global Evaluation of Study Medication | Poor | 8 participants |
| ADL5859 - 200 mg (Part A) | Part A: Participant's Global Evaluation of Study Medication | Fair | 15 participants |
| ADL5859 - 200 mg (Part A) | Part A: Participant's Global Evaluation of Study Medication | Excellent | 1 participants |
| ADL5859 - 200 mg (Part A) | Part A: Participant's Global Evaluation of Study Medication | Good | 12 participants |
| ADL5859 - 200 mg (Part A) | Part A: Participant's Global Evaluation of Study Medication | Very Good | 8 participants |
Secondary
Part A: Percentage of Participants in Each Treatment Group Achieving a 25%, 50%, or 75% Reduction From Baseline in Evoked Lower Extremity Pain Intensity Scores
Percentage was measured by identifying the number of participants who achieved the desired percentage Reduction From Baseline in ELEPI Score at either 2, 4, and 6 hours post dose and was divided the by the number of total participants in the given group and then multiplied by 100 to equate to a percentage.
Time frame: Up to 2, 4, and 6 hours post dosing
Population: Participants in Part A who received at least 1 dose of study drug and had at least 1 pain intensity assessment post dose.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Part A) | Part A: Percentage of Participants in Each Treatment Group Achieving a 25%, 50%, or 75% Reduction From Baseline in Evoked Lower Extremity Pain Intensity Scores | 2 Hours Post-Dose, 50% Reduction | 4.4 Percentage of Participants |
| Placebo (Part A) | Part A: Percentage of Participants in Each Treatment Group Achieving a 25%, 50%, or 75% Reduction From Baseline in Evoked Lower Extremity Pain Intensity Scores | 6 Hours Post-Dose, 75% Reduction | 6.7 Percentage of Participants |
| Placebo (Part A) | Part A: Percentage of Participants in Each Treatment Group Achieving a 25%, 50%, or 75% Reduction From Baseline in Evoked Lower Extremity Pain Intensity Scores | 6 Hours Post-Dose, 50% Reduction | 26.7 Percentage of Participants |
| Placebo (Part A) | Part A: Percentage of Participants in Each Treatment Group Achieving a 25%, 50%, or 75% Reduction From Baseline in Evoked Lower Extremity Pain Intensity Scores | 4 Hours Post-Dose, 50% Reduction | 22.2 Percentage of Participants |
| Placebo (Part A) | Part A: Percentage of Participants in Each Treatment Group Achieving a 25%, 50%, or 75% Reduction From Baseline in Evoked Lower Extremity Pain Intensity Scores | 2 Hours Post-Dose, 25% Reduction | 28.9 Percentage of Participants |
| Placebo (Part A) | Part A: Percentage of Participants in Each Treatment Group Achieving a 25%, 50%, or 75% Reduction From Baseline in Evoked Lower Extremity Pain Intensity Scores | 4 Hours Post-Dose, 75% Reduction | 0 Percentage of Participants |
| Placebo (Part A) | Part A: Percentage of Participants in Each Treatment Group Achieving a 25%, 50%, or 75% Reduction From Baseline in Evoked Lower Extremity Pain Intensity Scores | 6 Hours Post-Dose, 25% Reduction | 42.2 Percentage of Participants |
| Placebo (Part A) | Part A: Percentage of Participants in Each Treatment Group Achieving a 25%, 50%, or 75% Reduction From Baseline in Evoked Lower Extremity Pain Intensity Scores | 4 Hours Post-Dose, 25% Reduction | 40.0 Percentage of Participants |
| Placebo (Part A) | Part A: Percentage of Participants in Each Treatment Group Achieving a 25%, 50%, or 75% Reduction From Baseline in Evoked Lower Extremity Pain Intensity Scores | 2 Hours Post-Dose, 75% Reduction | 0 Percentage of Participants |
| Naproxen - 500 mg (Part A) | Part A: Percentage of Participants in Each Treatment Group Achieving a 25%, 50%, or 75% Reduction From Baseline in Evoked Lower Extremity Pain Intensity Scores | 4 Hours Post-Dose, 50% Reduction | 31.1 Percentage of Participants |
| Naproxen - 500 mg (Part A) | Part A: Percentage of Participants in Each Treatment Group Achieving a 25%, 50%, or 75% Reduction From Baseline in Evoked Lower Extremity Pain Intensity Scores | 2 Hours Post-Dose, 25% Reduction | 46.7 Percentage of Participants |
| Naproxen - 500 mg (Part A) | Part A: Percentage of Participants in Each Treatment Group Achieving a 25%, 50%, or 75% Reduction From Baseline in Evoked Lower Extremity Pain Intensity Scores | 4 Hours Post-Dose, 25% Reduction | 60.0 Percentage of Participants |
| Naproxen - 500 mg (Part A) | Part A: Percentage of Participants in Each Treatment Group Achieving a 25%, 50%, or 75% Reduction From Baseline in Evoked Lower Extremity Pain Intensity Scores | 6 Hours Post-Dose, 25% Reduction | 64.4 Percentage of Participants |
| Naproxen - 500 mg (Part A) | Part A: Percentage of Participants in Each Treatment Group Achieving a 25%, 50%, or 75% Reduction From Baseline in Evoked Lower Extremity Pain Intensity Scores | 2 Hours Post-Dose, 50% Reduction | 24.4 Percentage of Participants |
| Naproxen - 500 mg (Part A) | Part A: Percentage of Participants in Each Treatment Group Achieving a 25%, 50%, or 75% Reduction From Baseline in Evoked Lower Extremity Pain Intensity Scores | 6 Hours Post-Dose, 50% Reduction | 33.3 Percentage of Participants |
| Naproxen - 500 mg (Part A) | Part A: Percentage of Participants in Each Treatment Group Achieving a 25%, 50%, or 75% Reduction From Baseline in Evoked Lower Extremity Pain Intensity Scores | 2 Hours Post-Dose, 75% Reduction | 6.7 Percentage of Participants |
| Naproxen - 500 mg (Part A) | Part A: Percentage of Participants in Each Treatment Group Achieving a 25%, 50%, or 75% Reduction From Baseline in Evoked Lower Extremity Pain Intensity Scores | 4 Hours Post-Dose, 75% Reduction | 8.9 Percentage of Participants |
| Naproxen - 500 mg (Part A) | Part A: Percentage of Participants in Each Treatment Group Achieving a 25%, 50%, or 75% Reduction From Baseline in Evoked Lower Extremity Pain Intensity Scores | 6 Hours Post-Dose, 75% Reduction | 11.1 Percentage of Participants |
| ADL5859 - 200 mg (Part A) | Part A: Percentage of Participants in Each Treatment Group Achieving a 25%, 50%, or 75% Reduction From Baseline in Evoked Lower Extremity Pain Intensity Scores | 6 Hours Post-Dose, 25% Reduction | 45.5 Percentage of Participants |
| ADL5859 - 200 mg (Part A) | Part A: Percentage of Participants in Each Treatment Group Achieving a 25%, 50%, or 75% Reduction From Baseline in Evoked Lower Extremity Pain Intensity Scores | 2 Hours Post-Dose, 25% Reduction | 22.7 Percentage of Participants |
| ADL5859 - 200 mg (Part A) | Part A: Percentage of Participants in Each Treatment Group Achieving a 25%, 50%, or 75% Reduction From Baseline in Evoked Lower Extremity Pain Intensity Scores | 2 Hours Post-Dose, 75% Reduction | 0 Percentage of Participants |
| ADL5859 - 200 mg (Part A) | Part A: Percentage of Participants in Each Treatment Group Achieving a 25%, 50%, or 75% Reduction From Baseline in Evoked Lower Extremity Pain Intensity Scores | 4 Hours Post-Dose, 25% Reduction | 36.4 Percentage of Participants |
| ADL5859 - 200 mg (Part A) | Part A: Percentage of Participants in Each Treatment Group Achieving a 25%, 50%, or 75% Reduction From Baseline in Evoked Lower Extremity Pain Intensity Scores | 6 Hours Post-Dose, 75% Reduction | 6.8 Percentage of Participants |
| ADL5859 - 200 mg (Part A) | Part A: Percentage of Participants in Each Treatment Group Achieving a 25%, 50%, or 75% Reduction From Baseline in Evoked Lower Extremity Pain Intensity Scores | 4 Hours Post-Dose, 50% Reduction | 15.9 Percentage of Participants |
| ADL5859 - 200 mg (Part A) | Part A: Percentage of Participants in Each Treatment Group Achieving a 25%, 50%, or 75% Reduction From Baseline in Evoked Lower Extremity Pain Intensity Scores | 2 Hours Post-Dose, 50% Reduction | 4.5 Percentage of Participants |
| ADL5859 - 200 mg (Part A) | Part A: Percentage of Participants in Each Treatment Group Achieving a 25%, 50%, or 75% Reduction From Baseline in Evoked Lower Extremity Pain Intensity Scores | 4 Hours Post-Dose, 75% Reduction | 6.8 Percentage of Participants |
| ADL5859 - 200 mg (Part A) | Part A: Percentage of Participants in Each Treatment Group Achieving a 25%, 50%, or 75% Reduction From Baseline in Evoked Lower Extremity Pain Intensity Scores | 6 Hours Post-Dose, 50% Reduction | 18.2 Percentage of Participants |
Secondary
Part B: Mean Daily Average LEPI Scores Over the Last 24 Hours at Week 1 and Week 2
Each day during Part B, participants rated their Lower Extremity Pain Intensity over the last 24 hours on an 11-point NPRS, with 0 indicating No Pain and 10 indicating Worst Possible Pain
Time frame: Week 1 and Week 2
Population: Participants in Part B who received at least 1 dose of study drug and had at least 1 pain intensity assessment post dose.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Part A) | Part B: Mean Daily Average LEPI Scores Over the Last 24 Hours at Week 1 and Week 2 | Week 1 | 4.66 units on a scale | Standard Deviation 1.872 |
| Placebo (Part A) | Part B: Mean Daily Average LEPI Scores Over the Last 24 Hours at Week 1 and Week 2 | Week 2 | 4.57 units on a scale | Standard Deviation 2.197 |
| Naproxen - 500 mg (Part A) | Part B: Mean Daily Average LEPI Scores Over the Last 24 Hours at Week 1 and Week 2 | Week 1 | 4.26 units on a scale | Standard Deviation 1.741 |
| Naproxen - 500 mg (Part A) | Part B: Mean Daily Average LEPI Scores Over the Last 24 Hours at Week 1 and Week 2 | Week 2 | 4.25 units on a scale | Standard Deviation 1.777 |
Secondary
Part B: Mean Daily Average Overall Pain Intensity Scores Over Week 1, Over Week 2, and Over a 2-Week Period
During Part B, participants returned to the clinic for 2 additional visits at approximately weekly intervals for assessments of Overall Pain Index (OPI). Participants rated their OPI on an 11-point Numeric Pain Rating Scale (NPRS) with 0 indicating No Pain and 10 indicating Worst possible pain
Time frame: Baseline through Week 1, Week 1 through Week 2, and Baseline through Week 2
Population: Participants in Part B who received at least 1 dose of study drug and had at least 1 pain intensity assessment post dose.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Part A) | Part B: Mean Daily Average Overall Pain Intensity Scores Over Week 1, Over Week 2, and Over a 2-Week Period | Change from Baseline to Week 1 | 4.26 units on a scale | Standard Deviation 2.05 |
| Placebo (Part A) | Part B: Mean Daily Average Overall Pain Intensity Scores Over Week 1, Over Week 2, and Over a 2-Week Period | Change from Week 1 to Week 2 | 4.33 units on a scale | Standard Deviation 2.426 |
| Placebo (Part A) | Part B: Mean Daily Average Overall Pain Intensity Scores Over Week 1, Over Week 2, and Over a 2-Week Period | Change from Baseline to Week 2 | 4.33 units on a scale | Standard Deviation 2.125 |
| Naproxen - 500 mg (Part A) | Part B: Mean Daily Average Overall Pain Intensity Scores Over Week 1, Over Week 2, and Over a 2-Week Period | Change from Baseline to Week 1 | 4.26 units on a scale | Standard Deviation 1.939 |
| Naproxen - 500 mg (Part A) | Part B: Mean Daily Average Overall Pain Intensity Scores Over Week 1, Over Week 2, and Over a 2-Week Period | Change from Week 1 to Week 2 | 4.06 units on a scale | Standard Deviation 1.955 |
| Naproxen - 500 mg (Part A) | Part B: Mean Daily Average Overall Pain Intensity Scores Over Week 1, Over Week 2, and Over a 2-Week Period | Change from Baseline to Week 2 | 4.21 units on a scale | Standard Deviation 1.805 |
Secondary
Part B: Mean Daily LEPI Scores for Weeks 1 and 2
Participants assessed their Now LEPI 3 times each day (morning, midday, and evening at approximately 10 AM, 2 PM, and 8 PM) and before taking any rescue medication. At each time point, participants were asked to rate their lower extremity pain on an 11 point Numeric Pain Rating Scale (NPRS), with 0 indicating No Pain and 10 indicating Worst Possible Pain. If a scheduled pain assessment was taken within 4 hours of rescue medication, the observed pain score was replaced by the pain score obtained right before the rescue medication was taken.
Time frame: Baseline through Week 1 and Week 1 through Week 2
Population: Participants in Part B who received at least 1 dose of study drug and had at least 1 pain intensity assessment post dose.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Part A) | Part B: Mean Daily LEPI Scores for Weeks 1 and 2 | Over Week 1 | 4.28 units on a scale | Standard Deviation 1.691 |
| Placebo (Part A) | Part B: Mean Daily LEPI Scores for Weeks 1 and 2 | Over Week 2 | 4.23 units on a scale | Standard Deviation 2.09 |
| Naproxen - 500 mg (Part A) | Part B: Mean Daily LEPI Scores for Weeks 1 and 2 | Over Week 1 | 4.17 units on a scale | Standard Deviation 1.667 |
| Naproxen - 500 mg (Part A) | Part B: Mean Daily LEPI Scores for Weeks 1 and 2 | Over Week 2 | 4.13 units on a scale | Standard Deviation 1.756 |
Secondary
Part B: Participants' Global Evaluation of Study Medication
For Part B, each participant's global evaluation (overall impression) of study medication was obtained at each weekly visit. Scores were recorded on the Case Report Form (CRF) on a 5 point scale ranging from excellent to poor. Participant counts per score were reported at Week 1 (Day 7) and Week 2 (Day 14).
Time frame: Up to Week 1 and Week 2
Population: Participants in Part B who received at least 1 dose of study drug and had at least 1 pain intensity assessment post dose.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Part A) | Part B: Participants' Global Evaluation of Study Medication | Week 1 - Excellent (n=23, 20) | 2 Participants |
| Placebo (Part A) | Part B: Participants' Global Evaluation of Study Medication | Week 1 - Very good (n=23, 20) | 5 Participants |
| Placebo (Part A) | Part B: Participants' Global Evaluation of Study Medication | Week 1 - Good (n=23, 20) | 6 Participants |
| Placebo (Part A) | Part B: Participants' Global Evaluation of Study Medication | Week 1 - Fair (n=23, 20) | 6 Participants |
| Placebo (Part A) | Part B: Participants' Global Evaluation of Study Medication | Week 1 - Poor (n=23, 20) | 4 Participants |
| Placebo (Part A) | Part B: Participants' Global Evaluation of Study Medication | Week 2 - Excellent (n=24, 19) | 2 Participants |
| Placebo (Part A) | Part B: Participants' Global Evaluation of Study Medication | Week 2 - Very Good (n=24, 19) | 5 Participants |
| Placebo (Part A) | Part B: Participants' Global Evaluation of Study Medication | Week 2 - Good (n=24, 19) | 7 Participants |
| Placebo (Part A) | Part B: Participants' Global Evaluation of Study Medication | Week 2 - Fair (n=24, 19) | 5 Participants |
| Placebo (Part A) | Part B: Participants' Global Evaluation of Study Medication | Week 2 - Poor (n=24, 19) | 5 Participants |
| Naproxen - 500 mg (Part A) | Part B: Participants' Global Evaluation of Study Medication | Week 2 - Good (n=24, 19) | 3 Participants |
| Naproxen - 500 mg (Part A) | Part B: Participants' Global Evaluation of Study Medication | Week 1 - Excellent (n=23, 20) | 3 Participants |
| Naproxen - 500 mg (Part A) | Part B: Participants' Global Evaluation of Study Medication | Week 2 - Excellent (n=24, 19) | 4 Participants |
| Naproxen - 500 mg (Part A) | Part B: Participants' Global Evaluation of Study Medication | Week 1 - Very good (n=23, 20) | 7 Participants |
| Naproxen - 500 mg (Part A) | Part B: Participants' Global Evaluation of Study Medication | Week 2 - Poor (n=24, 19) | 3 Participants |
| Naproxen - 500 mg (Part A) | Part B: Participants' Global Evaluation of Study Medication | Week 1 - Good (n=23, 20) | 4 Participants |
| Naproxen - 500 mg (Part A) | Part B: Participants' Global Evaluation of Study Medication | Week 2 - Very Good (n=24, 19) | 4 Participants |
| Naproxen - 500 mg (Part A) | Part B: Participants' Global Evaluation of Study Medication | Week 1 - Fair (n=23, 20) | 4 Participants |
| Naproxen - 500 mg (Part A) | Part B: Participants' Global Evaluation of Study Medication | Week 2 - Fair (n=24, 19) | 5 Participants |
| Naproxen - 500 mg (Part A) | Part B: Participants' Global Evaluation of Study Medication | Week 1 - Poor (n=23, 20) | 2 Participants |
Secondary
Part B: Percentage of Participants Using Rescue Medication
The percentage of participants who took at least 1 dose of rescue medication during 2-week treatment period of Part B is presented.
Time frame: Baseline through Week 2
Population: Participants in Part B who received at least 1 dose of study drug and had at least 1 pain intensity assessment post dose.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Part A) | Part B: Percentage of Participants Using Rescue Medication | 45.8 Percentage of Participants |
| Naproxen - 500 mg (Part A) | Part B: Percentage of Participants Using Rescue Medication | 40.0 Percentage of Participants |