CompletedNCT00626275Updated Jul 1, 2015Results posted

Study Evaluating the Analgesic Efficacy and Safety of ADL5859 in Participants With Rheumatoid Arthritis

A Phase 2 interventional study of ADL5859 and Naproxen in Rheumatoid Arthritis, sponsored by Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA). Completed at 8 sites in United States. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2015-07-01.

Sponsored by Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 46
Allocation: Randomized
Ages: 18 Years to 75 Years
Sex: All

Study 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.

Read the 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.

Conditions studied

Rheumatoid Arthritis

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Keywords

Rheumatoid arthritis
arthritis

In context

Arthritis

3,554 studies on the registry are indexed under Arthritis; 317 are open to participants now.

This study's enrollment of 46 is below the median of 90 across 2,377 interventional studies indexed under Arthritis.

Browse Arthritis studies →

Lead sponsor

Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) is the lead sponsor of 65 studies on the registry; none are open to participants now.

Of its 6 completed or terminated interventional studies of FDA-regulated products, 5 (83%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 75 Years
Sexes eligible: All
Accepts 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

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

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 46 participants (actual)

Study arms

Experimental
ADL5859 -- 200 mg (Part A)
ADL5859: 200 milligrams (mg), capsules, administered orally as a single dose during 1 of 3 Treatment Periods in Part A of the study
Drug: ADL5859
Active comparator
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
Drug: Naproxen
Placebo comparator
Placebo (Part A)
Matching placebo, capsules, administered orally, as a single dose during 1 of 3 Treatment Periods in Part A of the study
Drug: Placebo
Experimental
ADL5859 - 100 mg (Part B)
ADL5859: 100 mg, capsules, administered orally, twice daily (BID) for 2 weeks during Part B of the study
Drug: ADL5859
Placebo comparator
Placebo (Part B)
Matching placebo, capsules, administered orally, BID for 2 weeks during Part B of the study
Drug: Placebo

Interventions

DrugADL5859
Also known as: ADL-5859
DrugNaproxen
Also known as: Naprosyn
DrugPlacebo
Also known as: Lactose Monohydrate National Formulary (NF)
DrugADL5859
Also known as: ADL-5859
DrugPlacebo
Also known as: Lactose Monohydrate NF

What researchers measure

Primary outcomes

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
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

Secondary outcomes

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
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
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
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
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
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
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
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
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
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
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

Results

Posted Jul 1, 2015

Participant flow

Part A - Treatment Period 1

Participant flow — Part A - Treatment Period 1
Milestone	Part A, Sequence 1: Placebo First, Then ADL5859, Then Naproxen	Part A Sequence 2: ADL5859 First, Then Naproxen, Then Placebo	Part A Sequence 3: Naproxen First, Then Placebo, Then ADL5859	Part A Sequence 4: Naproxen First, Then ADL5859, Then Placebo	Part A Sequence 5: Placebo First, Then Naproxen, Then ADL5859	Part A Sequence 6: ADL5859 First, Then Placebo, Then Naproxen
Started	7	7	7	8	9	8
Received at least 1 dose of study drug	7	7	7	8	9	8
Completed	6	7	6	8	9	8
Not completed	1	0	1	0	0	0
Withdrew: Adverse event	1	0	0	0	0	0
Withdrew: Withdrawal by subject	0	0	1	0	0	0

Part A - Washout Period 1

Participant flow — Part A - Washout Period 1
Milestone	Part A, Sequence 1: Placebo First, Then ADL5859, Then Naproxen	Part A Sequence 2: ADL5859 First, Then Naproxen, Then Placebo	Part A Sequence 3: Naproxen First, Then Placebo, Then ADL5859	Part A Sequence 4: Naproxen First, Then ADL5859, Then Placebo	Part A Sequence 5: Placebo First, Then Naproxen, Then ADL5859	Part A Sequence 6: ADL5859 First, Then Placebo, Then Naproxen
Started	6	7	6	8	9	8
Completed	6	7	6	8	9	8
Not completed	0	0	0	0	0	0

Part A - Treatment Period 2

Participant flow — Part A - Treatment Period 2
Milestone	Part A, Sequence 1: Placebo First, Then ADL5859, Then Naproxen	Part A Sequence 2: ADL5859 First, Then Naproxen, Then Placebo	Part A Sequence 3: Naproxen First, Then Placebo, Then ADL5859	Part A Sequence 4: Naproxen First, Then ADL5859, Then Placebo	Part A Sequence 5: Placebo First, Then Naproxen, Then ADL5859	Part A Sequence 6: ADL5859 First, Then Placebo, Then Naproxen
Started	6	7	6	8	9	8
Received at least 1 dose of study drug	6	7	6	8	9	8
Completed	6	7	6	8	9	8
Not completed	0	0	0	0	0	0

Part A - Washout Period 2

Participant flow — Part A - Washout Period 2
Milestone	Part A, Sequence 1: Placebo First, Then ADL5859, Then Naproxen	Part A Sequence 2: ADL5859 First, Then Naproxen, Then Placebo	Part A Sequence 3: Naproxen First, Then Placebo, Then ADL5859	Part A Sequence 4: Naproxen First, Then ADL5859, Then Placebo	Part A Sequence 5: Placebo First, Then Naproxen, Then ADL5859	Part A Sequence 6: ADL5859 First, Then Placebo, Then Naproxen
Started	6	7	6	8	9	8
Completed	6	7	6	8	9	8
Not completed	0	0	0	0	0	0

Part A - Treatment Period 3

Participant flow — Part A - Treatment Period 3
Milestone	Part A, Sequence 1: Placebo First, Then ADL5859, Then Naproxen	Part A Sequence 2: ADL5859 First, Then Naproxen, Then Placebo	Part A Sequence 3: Naproxen First, Then Placebo, Then ADL5859	Part A Sequence 4: Naproxen First, Then ADL5859, Then Placebo	Part A Sequence 5: Placebo First, Then Naproxen, Then ADL5859	Part A Sequence 6: ADL5859 First, Then Placebo, Then Naproxen
Started	6	7	6	8	9	8
Received at least 1 dose of study drug	6	7	6	8	9	8
Completed	6	7	6	8	9	8
Not completed	0	0	0	0	0	0

Re-randomization Period for Part B

Participant flow — Re-randomization Period for Part B
Milestone	Part B: ADL5859 100 mg	Part B: Placebo
Started	20	24
Completed	20	24
Not completed	0	0

Part B

Participant flow — Part B
Milestone	Part B: ADL5859 100 mg	Part B: Placebo
Started	20	24
Completed	19	23
Not completed	1	1
Withdrew: Lost to follow-up	1	0
Withdrew: Withdrawal by subject	0	1

Outcome measures

PrimaryPart 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
Reported as:: Least squares mean · units on a scale

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
units on a scale	Placebo (Part A)	Naproxen - 500 mg (Part A)	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	1.12 ± 0.240	1.95 ± 0.240	1.20 ± 0.242

SecondaryPart 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
Reported as:: Mean · units on a scale

Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain
units on a scale	Placebo (Part A)	Naproxen - 500 mg (Part A)	ADL5859 - 200 mg (Part A)
ELEPI, Baseline	6.36 ± 1.873	6.20 ± 1.471	6.363 ± 1.806
ELEPI, 2 hr Post Dose	5.47 ± 1.854	4.71 ± 1.973	5.45 ± 1.649
ELEPI, 4 hr Post Dose	5.16 ± 2.174	4.24 ± 1.760	5.00 ± 2.035
ELEPI, 6 hr Post Dose	4.93 ± 2.517	4.00 ± 1.871	4.95 ± 2.124
LEPI, Baseline	6.18 ± 2.059	5.78 ± 1.845	5.68 ± 1.840
LEPI, 1 hr Post Dose	5.38 ± 2.124	5.00 ± 1.719	5.34 ± 1.584
LEPI, 2 hr Post Dose	5.24 ± 2.013	4.33 ± 1.822	4.91 ± 1.507
LEPI, 3 hr Post Dose	4.67 ± 2.089	4.04 ± 1.858	4.73 ± 1.590
LEPI, 4 hr Post Dose	4.76 ± 2.036	3.93 ± 1.737	4.70 ± 1.593
LEPI, 5 hr Post Dose	4.71 ± 2.117	3.98 ± 1.685	4.73 ± 1.921
LEPI, 6 hr Post Dose	4.49 ± 2.149	3.89 ± 1.774	4.77 ± 1.696
LEPI, 12 hr Post Dose	5.11 ± 2.037	3.78 ± 1.813	4.76 ± 1.817
OPI, Baseline	6.20 ± 1.89	6.13 ± 1.753	5.77 ± 1.710
OPI, 6 hr Post Dose	4.80 ± 2.282	4.04 ± 1.833	4.91 ± 1.815
OPI, 12 hr Post Dose	5.03 ± 1.993	3.73 ± 1.880	4.89 ± 1.955

SecondaryPart B: Mean Daily LEPI Scores for Weeks 1 and 2

Time frame:: Baseline through Week 1 and Week 1 through Week 2
Reported as:: Mean · units on a scale

Part B: Mean Daily LEPI Scores for Weeks 1 and 2
units on a scale	Placebo (Part B)	ADL5859 - 100 mg (Part B)
Over Week 1	4.28 ± 1.691	4.17 ± 1.667
Over Week 2	4.23 ± 2.090	4.13 ± 1.756

SecondaryPart 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
Reported as:: Mean · units on a scale

Part A: Pain Intensity Difference Between Baseline and the Value at Each Scheduled Time Point for Overall Pain
units on a scale	Placebo (Part A)	Naproxen - 500 mg (Part A)	ADL5859 - 200mg (Part A)
Change From Baseline 6 Hours Post Dose	1.40 ± 2.240	2.09 ± 1.917	0.86 ± 2.120
Change From Baseline 12 Hours Post Dose	1.16 ± 1.911	3.73 ± 1.880	0.92 ± 2.278

SecondaryPart 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
Reported as:: Mean · units on a scale

Part A: Average Difference Between Baseline and Postdose Evoked Lower Extremity Pain Over the 4 Hours After Dosing
units on a scale	Placebo (Part A)	Naproxen - 500 mg (Part A)	ADL5859 - 200 mg (Part A)
Part A: Average Difference Between Baseline and Postdose Evoked Lower Extremity Pain Over the 4 Hours After Dosing	1.04 ± 1.437	1.72 ± 1.753	1.14 ± 1.553

SecondaryPart 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
Reported as:: Mean · units on a scale

Part A: Mean Peak Difference in ELEPI According to the NPRS Scale
units on a scale	Placebo (Part A)	Naproxen - 500 mg (Part A)	ADL5859 - 200 mg (Part A)
Part A: Mean Peak Difference in ELEPI According to the NPRS Scale	1.82 ± 1.874	2.49 ± 1.740	1.84 ± 1.725

SecondaryPart 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
Reported as:: Number · Percentage of Participants

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 of Participants	Placebo (Part A)	Naproxen - 500 mg (Part A)	ADL5859 - 200 mg (Part A)
2 Hours Post-Dose, 25% Reduction	28.9	46.7	22.7
4 Hours Post-Dose, 25% Reduction	40.0	60.0	36.4
6 Hours Post-Dose, 25% Reduction	42.2	64.4	45.5
2 Hours Post-Dose, 50% Reduction	4.4	24.4	4.5
4 Hours Post-Dose, 50% Reduction	22.2	31.1	15.9
6 Hours Post-Dose, 50% Reduction	26.7	33.3	18.2
2 Hours Post-Dose, 75% Reduction	0	6.7	0
4 Hours Post-Dose, 75% Reduction	0	8.9	6.8
6 Hours Post-Dose, 75% Reduction	6.7	11.1	6.8

SecondaryPart 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
Reported as:: Number · Participants

Part B: Participants' Global Evaluation of Study Medication
Participants	Placebo (Part B)	ADL5859 - 100 mg (Part B)
Week 1 - Excellent (n=23, 20)	2	3
Week 1 - Very good (n=23, 20)	5	7
Week 1 - Good (n=23, 20)	6	4
Week 1 - Fair (n=23, 20)	6	4
Week 1 - Poor (n=23, 20)	4	2
Week 2 - Excellent (n=24, 19)	2	4
Week 2 - Very Good (n=24, 19)	5	4
Week 2 - Good (n=24, 19)	7	3
Week 2 - Fair (n=24, 19)	5	5
Week 2 - Poor (n=24, 19)	5	3

SecondaryPart 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
Reported as:: Mean · units on a scale

Part B: Mean Daily Average LEPI Scores Over the Last 24 Hours at Week 1 and Week 2
units on a scale	Placebo (Part B)	ADL5859 - 100 mg (Part B)
Week 1	4.66 ± 1.872	4.26 ± 1.741
Week 2	4.57 ± 2.197	4.25 ± 1.777

SecondaryPart 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
Reported as:: Mean · units on a scale

Part B: Mean Daily Average Overall Pain Intensity Scores Over Week 1, Over Week 2, and Over a 2-Week Period
units on a scale	Placebo (Part B)	ADL5859 - 100 mg (Part B)
Change from Baseline to Week 1	4.26 ± 2.050	4.26 ± 1.939
Change from Week 1 to Week 2	4.33 ± 2.426	4.06 ± 1.955
Change from Baseline to Week 2	4.33 ± 2.125	4.21 ± 1.805

SecondaryPart 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
Reported as:: Number · Percentage of Participants

Part B: Percentage of Participants Using Rescue Medication
Percentage of Participants	Placebo (Part B)	ADL5859 - 100 mg (Part B)
Part B: Percentage of Participants Using Rescue Medication	45.8	40.0

SecondaryPart 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
Reported as:: Number · participants

Part A: Participant's Global Evaluation of Study Medication
participants	Placebo (Part A)	Naproxen - 500 mg (Part A)	ADL5859 - 200 mg (Part A)
Excellent	1	6	1
Very Good	9	12	8
Good	15	15	12
Fair	12	9	15
Poor	8	3	8

PrimaryPart 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
Reported as:: Least squares mean · units on a scale

Part B: The Mean of Daily Average "Now" Lower Extremity Pain Intensity (LEPI) Score During the 2-Week Period
units on a scale	Placebo (Part B)	ADL5859 - 100 mg (Part B)
Part B: The Mean of Daily Average "Now" Lower Extremity Pain Intensity (LEPI) Score During the 2-Week Period	4.23 ± 0.339	4.21 ± 0.371

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Placebo (Part A)	—	0/46 (0%)	8/46 (17.4%)
Naproxen - 500 mg (Part A)	—	0/46 (0%)	7/46 (15.2%)
ADL5859 - 200 mg (Part A)	—	0/46 (0%)	8/46 (17.4%)
Placebo (Part B)	—	0/24 (0%)	10/24 (41.7%)
ADL5859 - 100 mg (Part B)	—	0/20 (0%)	10/20 (50%)

Most frequent other events

Showing 10 of 36

Most frequent other events
Event	Placebo (Part A)	Naproxen - 500 mg (Part A)	ADL5859 - 200 mg (Part A)	Placebo (Part B)	ADL5859 - 100 mg (Part B)
DiarrheaGastrointestinal disorders	1/46	0/46	0/46	2/24	2/20
NauseaGastrointestinal disorders	0/46	0/46	1/46	1/24	2/20
ConstipationGastrointestinal disorders	0/46	0/46	0/46	0/24	2/20
HeadacheNervous system disorders	1/46	0/46	1/46	2/24	1/20
Orthostatic HypotensionVascular disorders	2/46	2/46	3/46	1/24	1/20
Urinary Tract InfectionInfections and infestations	0/46	0/46	1/46	0/24	1/20
Abdominal DistensionGastrointestinal disorders	0/46	0/46	0/46	0/24	1/20
Abdominal TendernessGastrointestinal disorders	0/46	0/46	0/46	0/24	1/20
Influenza-like DisorderGeneral disorders	0/46	0/46	0/46	0/24	1/20
Haematocrit DecreasedInvestigations	0/46	0/46	0/46	0/24	1/20

Baseline characteristics

All participants who received at least 1 dose of study drug

Age, Continuous
Age, Continuous(years)	All Treated Participants
Mean	54.6 ± 8.91

Sex: Female, Male
Sex: Female, Male(Participants)	All Treated Participants
Female	36
Male	10

Study locations

8 sites

New England Research Associates
Trumbull, Connecticut 06611, United States
Covance Clinical Research Unit Inc.
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

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jul 1, 2015, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00626275
Lead sponsor: Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Responsible party: Sponsor
First posted: Feb 29, 2008
Start date: Oct 2007
Primary completion: Sep 2008
Completion: Sep 2008
Results posted: Jul 1, 2015
Last update: Jul 1, 2015

Study contacts

Bruce Berger, MD

study director · Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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