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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ADL5859 -- 200 mg (Part A) | Experimental | ADL5859: 200 milligrams (mg), capsules, administered orally as a single dose during 1 of 3 Treatment Periods in Part A of the study |
|
| Naproxen -- 500 mg (Part A) | Active Comparator | Naproxen: 500 mg, capsules, administered orally as a single dose during 1 of 3 Treatment Periods in Part A of the study |
|
| Placebo (Part A) | Placebo Comparator | Matching placebo, capsules, administered orally, as a single dose during 1 of 3 Treatment Periods in Part A of the study |
|
| ADL5859 - 100 mg (Part B) | Experimental | ADL5859: 100 mg, capsules, administered orally, twice daily (BID) for 2 weeks during Part B of the study |
|
| Placebo (Part B) | Placebo Comparator | Matching placebo, capsules, administered orally, BID for 2 weeks during Part B of the study |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ADL5859 | Drug |
|
| |
| Naproxen |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline through 6 hours post dose |
| 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. | Baseline through 2 Weeks |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Bruce Berger, MD | Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| New England Research Associates | Trumbull | Connecticut | 06611 | United States | ||
| Covance Clinical Research Unit Inc. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Part A, Sequence 1: Placebo First, Then ADL5859, Then Naproxen | Eligible participants were randomized to 1 of 6 treatment sequences. Each treatment sequence had 3 treatment periods, each separated by a washout period of at least 48 hours and up to 1 week between doses. During each treatment period of Part A, participants received a single dose of study medication (placebo, then ADL5859 200 milligrams (mg), then naproxen 500 mg). Part A, Treatment Period 1: matching placebo, capsules, administered orally, as a single dose; Part A, Treatment Period 2: ADL5859 200 mg, capsules, administered orally as a single dose; and Part A, Treatment Period 3: naproxen 500 mg, capsules, administered orally as a single dose |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Part A - Treatment Period 1 |
|
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| Drug |
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| Placebo | Drug |
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| ADL5859 | Drug |
|
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| Placebo | Drug |
|
|
| Baseline up to 12 hours post dose |
| 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. | Baseline through Week 1 and Week 1 through Week 2 |
| 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. | Baseline, 6 and 12 hours post dose |
| 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. | Baseline, 4 hours post dose |
| 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. | Baseline, 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 | 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. | Up to 2, 4, and 6 hours post dosing |
| 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). | Up to Week 1 and Week 2 |
| 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 | Week 1 and Week 2 |
| 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 | Baseline through Week 1, Week 1 through Week 2, and Baseline through Week 2 |
| 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. | Baseline through Week 2 |
| 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. | 6 hours post dose during Treatment Periods 1, 2, and 3 of Part A |
| Daytona Beach |
| Florida |
| 32117 |
| United States |
| The Center for Rheumatology and Bone Research | Wheaton | Maryland | 20901 | United States |
| Heartland Clinical Research, Inc. | Omaha | Nebraska | 68134 | United States |
| Advanced Biomedical Research of America | Las Vegas | Nevada | 89123 | United States |
| Winthrop University Hospital, Clinical Trials Center | Mineola | New York | 11501 | United States |
| University Hospitals Case Medical Center, Division of Rheumatology, Rheumatology Clinical Research Unit | Beachwood | Ohio | 44122 | United States |
| Altoona Center for Clinical Research | Duncansville | Pennsylvania | 16635-8406 | United States |
| FG001 | Part A Sequence 2: ADL5859 First, Then Naproxen, Then Placebo | Eligible participants were randomized to 1 of 6 treatment sequences. Each treatment sequence had 3 treatment periods, each separated by a washout period of at least 48 hours and up to 1 week between doses. During each treatment period of Part A, participants received a single dose of study medication (ADL5859 200 mg, then naproxen 500 mg, then placebo). Part A, Treatment Period 1: ADL5859 200 mg, capsules, administered orally as a single dose; Part A, Treatment Period 2: naproxen 500 mg, capsules, administered orally as a single dose; and Part A, Treatment Period 3: matching placebo, capsules, administered orally, as a single dose. |
| FG002 | Part A Sequence 3: Naproxen First, Then Placebo, Then ADL5859 | Eligible participants were randomized to 1 of 6 treatment sequences. Each treatment sequence had 3 treatment periods, each separated by a washout period of at least 48 hours and up to 1 week between doses. During each treatment period of Part A, participants received a single dose of study medication (naproxen 500 mg, then placebo, then ADL5859 200 mg). Part A, Treatment Period 1: naproxen 500 mg, capsules, administered orally as a single dose; Part A, Treatment Period 2: matching placebo, capsules, administered orally, as a single dose; and Part A, Treatment Period 3: ADL5859 200 mg, capsules, administered orally as a single dose. |
| FG003 | Part A Sequence 4: Naproxen First, Then ADL5859, Then Placebo | Eligible participants were randomized to 1 of 6 treatment sequences. Each treatment sequence had 3 treatment periods, each separated by a washout period of at least 48 hours and up to 1 week between doses. During each treatment period of Part A, participants received a single dose of study medication (naproxen 500 mg, then ADL5859 200 mg, then placebo). Part A, Treatment Period 1: naproxen 500 mg, capsules, administered orally as a single dose; Part A, Treatment Period 2: ADL5859 200 mg, capsules, administered orally as a single dose; and Part A, Treatment Period 3: matching placebo, capsules, administered orally, as a single dose. |
| FG004 | Part A Sequence 5: Placebo First, Then Naproxen, Then ADL5859 | Eligible participants were randomized to 1 of 6 treatment sequences. Each treatment sequence had 3 treatment periods, each separated by a washout period of at least 48 hours and up to 1 week between doses. During each treatment period of Part A, participants received a single dose of study medication (placebo, then naproxen 500 mg, then ADL5859 200 mg). Part A, Treatment Period 1: matching placebo, capsules, administered orally, as a single dose; Part A, Treatment Period 2: naproxen 500 mg, capsules, administered orally as a single dose; and Part A, Treatment Period 3: ADL5859 200 mg, capsules, administered orally as a single dose. |
| FG005 | Part A Sequence 6: ADL5859 First, Then Placebo, Then Naproxen | Eligible participants were randomized to 1 of 6 treatment sequences. Each treatment sequence had 3 treatment periods, each separated by a washout period of at least 48 hours. During each treatment period of Part A, participants received a single dose of study medication (ADL5859 200 mg, then placebo, then naproxen 500 mg). Part A, Treatment Period 1: ADL5859 200 mg, capsules, administered orally as a single dose; Part A, Treatment Period 2: matching placebo, capsules, administered orally, as a single dose; and Part A, Treatment Period 3: naproxen 500 mg, capsules, administered orally as a single dose. |
| FG006 | Part B: ADL5859 100 mg | ADL5859: 100 mg, capsules, administered orally, twice daily (BID) for 2 weeks during Part B of the study |
| FG007 | Part B: Placebo | Matching placebo, capsules, administered orally, BID for 2 weeks during Part B of the study |
| Received at Least 1 Dose of Study Drug |
|
| COMPLETED |
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| NOT COMPLETED |
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|
| Part A - Washout Period 1 |
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| Part A - Treatment Period 2 |
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| Part A - Washout Period 2 |
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| Part A - Treatment Period 3 |
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| Re-randomization Period for Part B |
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| Part B |
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|
All participants who received at least 1 dose of study drug
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| 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 | 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. | Participants in Part A who received at least 1 dose of study drug and had at least 1 pain intensity assessment post dose. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline through 6 hours post dose |
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| 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. | Participants in Part A who received at least 1 dose of study drug and had at least 1 pain intensity assessment post dose. | Posted | Mean | Standard Deviation | units on a scale | Baseline up to 12 hours post dose |
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| 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. | Participants in Part B who received at least 1 dose of study drug and had at least 1 pain intensity assessment post dose. | Posted | Mean | Standard Deviation | units on a scale | Baseline through Week 1 and Week 1 through Week 2 |
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| 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. | Participants in Part A who received at least 1 dose of study drug and had at least 1 pain intensity assessment post dose. | Posted | Mean | Standard Deviation | units on a scale | Baseline, 6 and 12 hours post dose |
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| 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. | Participants in Part A who received at least 1 dose of study drug and had at least 1 pain intensity assessment post dose | Posted | Mean | Standard Deviation | units on a scale | Baseline, 4 hours post dose |
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| 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. | Participants in Part A who received at least 1 dose of study drug and had at least 1 pain intensity assessment post dose. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Up to 6 hours post dose |
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| 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. | Participants in Part A who received at least 1 dose of study drug and had at least 1 pain intensity assessment post dose. | Posted | Number | Percentage of Participants | Up to 2, 4, and 6 hours post dosing |
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| 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). | Participants in Part B who received at least 1 dose of study drug and had at least 1 pain intensity assessment post dose. | Posted | Number | Participants | Up to Week 1 and Week 2 |
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| 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 | Participants in Part B who received at least 1 dose of study drug and had at least 1 pain intensity assessment post dose. | Posted | Mean | Standard Deviation | units on a scale | Week 1 and Week 2 |
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| 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 | Participants in Part B who received at least 1 dose of study drug and had at least 1 pain intensity assessment post dose. | Posted | Mean | Standard Deviation | units on a scale | Baseline through Week 1, Week 1 through Week 2, and Baseline through Week 2 |
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| 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. | Participants in Part B who received at least 1 dose of study drug and had at least 1 pain intensity assessment post dose. | Posted | Number | Percentage of Participants | Baseline through Week 2 |
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| 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. | Participants in Part A who received at least 1 dose of study drug and had at least 1 pain intensity assessment post dose. | Posted | Number | participants | 6 hours post dose during Treatment Periods 1, 2, and 3 of Part A |
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| 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. | Participants in Part B who received at least 1 dose of study drug and had at least 1 pain intensity assessment post dose. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline through 2 Weeks |
|
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Analysis Population:
All participants who received at least 1 dose of study drug
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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 (Part A) | Matching placebo, capsules, administered orally, as a single dose during 1 of 3 Treatment Periods in Part A of the study | 0 | 46 | 8 | 46 | ||
| EG001 | Naproxen - 500 mg (Part A) | Naproxen: 500 mg, capsules, administered orally as a single dose during 1 of 3 Treatment Periods in Part A of the study | 0 | 46 | 7 | 46 | ||
| EG002 | ADL5859 - 200 mg (Part A) | ADL5859: 200 mg, capsules, administered orally as a single dose during 1 of 3 Treatment Periods in Part A of the study | 0 | 46 | 8 | 46 | ||
| EG003 | Placebo (Part B) | Matching placebo, capsules, administered orally, BID for 2 weeks during Part B of the study | 0 | 24 | 10 | 24 | ||
| EG004 | ADL5859 - 100 mg (Part B) | ADL5859: 100 mg, capsules, administered orally, BID for 2 weeks during Part B of the study | 0 | 20 | 10 | 20 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Tachycardia | Cardiac disorders | MedDRA (11.1) |
| ||
| Vision Blurred | Eye disorders | MedDRA (11.1) |
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| Diarrhea | Gastrointestinal disorders | MedDRA (11.1) |
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| Dry Mouth | Gastrointestinal disorders | MedDRA (11.1) |
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| Dyspepsia | Gastrointestinal disorders | MedDRA (11.1) |
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| Food Poisoning | Gastrointestinal disorders | MedDRA (11.1) |
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| Nausea | Gastrointestinal disorders | MedDRA (11.1) |
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| Feeling hot | General disorders | MedDRA (11.1) |
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| Pain | General disorders | MedDRA (11.1) |
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| Urinary Tract Infection | Infections and infestations | MedDRA (11.1) |
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| Heart Rate Increase | Investigations | MedDRA (11.1) |
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| Musculoskeletal Chest Pain | Musculoskeletal and connective tissue disorders | MedDRA (11.1) |
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| Dizziness | Nervous system disorders | MedDRA (11.1) |
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| Dysgeusia | Nervous system disorders | MedDRA (11.1) |
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| Headache | Nervous system disorders | MedDRA (11.1) |
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| Migraine | Nervous system disorders | MedDRA (11.1) |
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| Abnormal Dreams | Psychiatric disorders | MedDRA (11.1) |
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| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA (11.1) |
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| Hypotension | Vascular disorders | MedDRA (11.1) |
| ||
| Orthostatic Hypotension | Vascular disorders | MedDRA (11.1) |
| ||
| Phlebitis | Vascular disorders | MedDRA (11.1) |
| ||
| Abdominal Distension | Gastrointestinal disorders | MedDRA (11.1) |
| ||
| Abdominal Tenderness | Gastrointestinal disorders | MedDRA (11.1) |
| ||
| Constipation | Gastrointestinal disorders | MedDRA (11.1) |
| ||
| Chest Discomfort | General disorders | MedDRA (11.1) |
| ||
| Influenza-like Disorder | General disorders | MedDRA (11.1) |
| ||
| Blood Glucose Increased | Investigations | MedDRA (11.1) |
| ||
| Haematocrit Decreased | Investigations | MedDRA (11.1) |
| ||
| Haemoglobin Decreased | Investigations | MedDRA (11.1) |
| ||
| Red Blood Cell Count Decreased | Investigations | MedDRA (11.1) |
| ||
| Joint Swelling | Musculoskeletal and connective tissue disorders | MedDRA (11.1) |
| ||
| Muscle Spasms | Musculoskeletal and connective tissue disorders | MedDRA (11.1) |
| ||
| Somnolence | Nervous system disorders | MedDRA (11.1) |
| ||
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (11.1) |
| ||
| Rash | Skin and subcutaneous tissue disorders | MedDRA (11.1) |
| ||
| Skin Lesion | Skin and subcutaneous tissue disorders | MedDRA (11.1) |
|
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Vice President, Clinical Research | Cubist Pharmaceuticals | 1.781.860.8660 |
| ID | Term |
|---|---|
| D001172 | Arthritis, Rheumatoid |
| D001168 | Arthritis |
| ID | Term |
|---|---|
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C532570 | N,N-diethyl-4-(5-hydroxyspiro(chromene-2,4'-piperidine)-4-yl)benzamide |
| D009288 | Naproxen |
| ID | Term |
|---|---|
| D009280 | Naphthaleneacetic Acids |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
Not provided
Not provided
| Withdrawal by Subject |
|
Naproxen: 500 mg, capsules, administered orally as a single dose during 1 of 3 Treatment Periods in Part A of the study |
| OG002 | ADL5859 - 200 mg (Part A) | ADL5859: 200 mg, capsules, administered orally as a single dose during 1 of 3 Treatment Periods in Part A of the study |
|
|
|
|
|
|
ADL5859: 200 mg, capsules, administered orally as a single dose during 1 of 3 Treatment Periods in Part A of the study
|
|
| OG002 | ADL5859 - 200 mg (Part A) | ADL5859: 200 mg, capsules, administered orally as a single dose during 1 of 3 Treatment Periods in Part A of the study |
|
|
|
|
|
|
|
|
| Units | Counts |
|---|---|
| Participants |
|
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