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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Cubist Pharmaceuticals LLC
ClinicalTrials.gov Identifier:
NCT00626275
First received: February 22, 2008
Last updated: June 4, 2015
Last verified: June 2015
Results First Received: April 27, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Crossover Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Rheumatoid Arthritis
Interventions: Drug: ADL5859
Drug: Naproxen
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
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

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.

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.

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.

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.

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.

Part B: ADL5859 100 mg ADL5859: 100 mg, capsules, administered orally, twice daily (BID) for 2 weeks during Part B of the study
Part B: Placebo Matching placebo, capsules, administered orally, BID for 2 weeks during Part B of the study

Participant Flow for 7 periods

Period 1:   Part A - Treatment Period 1
    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     Part B: ADL5859 100 mg     Part B: Placebo  
STARTED     7     7     7     8     9     8     0     0  
Received at Least 1 Dose of Study Drug     7     7     7     8     9     8     0     0  
COMPLETED     6     7     6     8     9     8     0     0  
NOT COMPLETED     1     0     1     0     0     0     0     0  
Adverse Event                 1                 0                 0                 0                 0                 0                 0                 0  
Withdrawal by Subject                 0                 0                 1                 0                 0                 0                 0                 0  

Period 2:   Part A - Washout Period 1
    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     Part B: ADL5859 100 mg     Part B: Placebo  
STARTED     6     7     6     8     9     8     0     0  
COMPLETED     6     7     6     8     9     8     0     0  
NOT COMPLETED     0     0     0     0     0     0     0     0  

Period 3:   Part A - Treatment Period 2
    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     Part B: ADL5859 100 mg     Part B: Placebo  
STARTED     6     7     6     8     9     8     0     0  
Received at Least 1 Dose of Study Drug     6     7     6     8     9     8     0     0  
COMPLETED     6     7     6     8     9     8     0     0  
NOT COMPLETED     0     0     0     0     0     0     0     0  

Period 4:   Part A - Washout Period 2
    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     Part B: ADL5859 100 mg     Part B: Placebo  
STARTED     6     7     6     8     9     8     0     0  
COMPLETED     6     7     6     8     9     8     0     0  
NOT COMPLETED     0     0     0     0     0     0     0     0  

Period 5:   Part A - Treatment Period 3
    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     Part B: ADL5859 100 mg     Part B: Placebo  
STARTED     6     7     6     8     9     8     0     0  
Received at Least 1 Dose of Study Drug     6     7     6     8     9     8     0     0  
COMPLETED     6     7     6     8     9     8     0     0  
NOT COMPLETED     0     0     0     0     0     0     0     0  

Period 6:   Re-randomization Period for Part B
    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     Part B: ADL5859 100 mg     Part B: Placebo  
STARTED     0     0     0     0     0     0     20     24  
COMPLETED     0     0     0     0     0     0     20     24  
NOT COMPLETED     0     0     0     0     0     0     0     0  

Period 7:   Part B
    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     Part B: ADL5859 100 mg     Part B: Placebo  
STARTED     0     0     0     0     0     0     20     24  
COMPLETED     0     0     0     0     0     0     19     23  
NOT COMPLETED     0     0     0     0     0     0     1     1  
Lost to Follow-up                 0                 0                 0                 0                 0                 0                 1                 0  
Withdrawal by Subject                 0                 0                 0                 0                 0                 0                 0                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who received at least 1 dose of study drug

Reporting Groups
  Description
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.

Baseline Measures
    All Treated Participants  
Number of Participants  
[units: participants]
  46  
Age  
[units: years]
Mean (Standard Deviation)
  54.6  (8.91)  
Gender  
[units: participants]
 
Female     36  
Male     10  



  Outcome Measures
  Show All Outcome Measures

1.  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   [ Time Frame: Baseline through 6 hours post dose ]

2.  Primary:   Part B: The Mean of Daily Average "Now" Lower Extremity Pain Intensity (LEPI) Score During the 2-Week Period   [ Time Frame: Baseline through 2 Weeks ]

3.  Secondary:   Part A: Pain Intensity Score (NPRS Score) for Overall Pain, for Lower Extremity Pain, and for Evoked (by Treadmill Walking) Lower Extremity Pain   [ Time Frame: Baseline up to 12 hours post dose ]

4.  Secondary:   Part B: Mean Daily LEPI Scores for Weeks 1 and 2   [ Time Frame: Baseline through Week 1 and Week 1 through Week 2 ]

5.  Secondary:   Part A: Pain Intensity Difference Between Baseline and the Value at Each Scheduled Time Point for Overall Pain   [ Time Frame: Baseline, 6 and 12 hours post dose ]

6.  Secondary:   Part A: Average Difference Between Baseline and Postdose Evoked Lower Extremity Pain Over the 4 Hours After Dosing   [ Time Frame: Baseline, 4 hours post dose ]

7.  Secondary:   Part A: Mean Peak Difference in ELEPI According to the NPRS Scale   [ Time Frame: Baseline, Up to 6 hours post dose ]

8.  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   [ Time Frame: Up to 2, 4, and 6 hours post dosing ]

9.  Secondary:   Part B: Participants’ Global Evaluation of Study Medication   [ Time Frame: Up to Week 1 and Week 2 ]

10.  Secondary:   Part B: Mean Daily Average LEPI Scores Over the Last 24 Hours at Week 1 and Week 2   [ Time Frame: Week 1 and Week 2 ]

11.  Secondary:   Part B: Mean Daily Average Overall Pain Intensity Scores Over Week 1, Over Week 2, and Over a 2-Week Period   [ Time Frame: Baseline through Week 1, Week 1 through Week 2, and Baseline through Week 2 ]

12.  Secondary:   Part B: Percentage of Participants Using Rescue Medication   [ Time Frame: Baseline through Week 2 ]

13.  Secondary:   Part A: Participant’s Global Evaluation of Study Medication   [ Time Frame: 6 hours post dose during Treatment Periods 1, 2, and 3 of Part A ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Vice President, Clinical Research
Organization: Cubist Pharmaceuticals
phone: 1.781.860.8660



Responsible Party: Cubist Pharmaceuticals LLC
ClinicalTrials.gov Identifier: NCT00626275     History of Changes
Other Study ID Numbers: 33CL232
Study First Received: February 22, 2008
Results First Received: April 27, 2015
Last Updated: June 4, 2015
Health Authority: United States: Food and Drug Administration