ClinicalTrials.gov
ClinicalTrials.gov Menu

Effect Of Pregabalin Treatment In Patients With Diabetic Nerve Pain Who Currently Use A Non-Steroid Anti-Inflammatory Drug (NSAID) For Another Pain

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01455415
Recruitment Status : Completed
First Posted : October 20, 2011
Results First Posted : April 23, 2015
Last Update Posted : April 23, 2015
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition: Painful Diabetic Peripheral Neuropathy
Interventions: Drug: pregabalin
Drug: placebo

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
501 participants were screened, of whom 197 were withdrawn before randomization. 304 were randomized, of whom 3 discontinued before being treated. Participants were randomized at 47 centers in 3 countries: US (43), Czech Republic (3), and Italy (1). 4 centers received study drug but did not randomize participants.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants completed daily pain and sleep diary from Visit 1 (Screening) to Visit 9. Participants with a mean pain score ≥ 4 (moderate to severe pain) and those having completed ≥ 4 daily pain dairies over past 7 days and having a mean score of ≥ 4 at Visit 2 (Baseline) were randomized.

Reporting Groups
  Description
Pregabalin/Placebo Participants were randomized to double-blind treatment with pregabalin for 6 weeks (150 - 300 mg/day) in period 1 followed by placebo in period 2. There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.
Placebo/Pregablin Participants were randomized to double-blind treatment with placebo for 6 weeks in period 1 followed by pregabalin in period 2 (150 - 300 mg/day). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.

Participant Flow for 4 periods

Period 1:   Period 1
    Pregabalin/Placebo   Placebo/Pregablin
STARTED   154 [1]   147 [1] 
COMPLETED   135   123 
NOT COMPLETED   19   24 
Adverse Event (AE) Related to Study Drug                9                6 
Lost To Follow-up Related to Study Drug                3                3 
Drug Error not Associated to AE                0                1 
AE Not Related to Study Drug                2                6 
Withdrawal by Subject                4                5 
Unspecified Reason                1                1 
Protocol Violation                0                2 
[1] Started=Treated

Period 2:   Washout
    Pregabalin/Placebo   Placebo/Pregablin
STARTED   135   123 
COMPLETED   127   116 
NOT COMPLETED   8   7 
AE Related to Study Drug                2                0 
Lost to Follow-up                1                0 
Drug Error not Associated to AE                2                1 
AE Not Related to Study Drug                2                3 
Unspecified Reason                1                2 
Protocol Violation                0                1 

Period 3:   Period 2
    Pregabalin/Placebo   Placebo/Pregablin
STARTED   127   116 
COMPLETED   114   106 
NOT COMPLETED   13   10 
AE Related to Study Drug                1                2 
Lost to Follow-up                2                1 
AE Not Related to Study Drug                2                1 
Lack of Efficacy                2                0 
Withdrawal by Subject                2                3 
Unspecified Reason                2                3 
Protocol Violation                2                0 

Period 4:   Follow-up
    Pregabalin/Placebo   Placebo/Pregablin
STARTED   114   106 
COMPLETED   111   104 
NOT COMPLETED   3   2 
AE Related to Study Drug                0                1 
Lack of Efficacy                0                1 
Withdrawal by Subject                2                0 
Unspecified Reason                1                0 



  Baseline Characteristics

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.
Intent-to-Treat Population (ITT) included all randomized participants with at least one dose of study drug. The ITT population was analyzed according to what the randomization schedule intended for the participants to take in each period.

Reporting Groups
  Description
Pregabalin/Placebo Participants were randomized to double-blind treatment with pregabalin for 6 weeks (150 - 300 mg/day) in period 1 followed by placebo in period 2. There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.
Placebo/Pregablin Participants were randomized to double-blind treatment with placebo for 6 weeks in period 1 followed by pregabalin in period 2 (150 - 300 mg/day). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.
Total Total of all reporting groups

Baseline Measures
   Pregabalin/Placebo   Placebo/Pregablin   Total 
Overall Participants Analyzed 
[Units: Participants]
 154   147   301 
Age 
[Units: Years]
Mean (Standard Deviation)
 59.4  (9.8)   58.4  (9.5)   58.9  (9.7) 
Gender 
[Units: Participants]
     
Female   65   72   137 
Male   89   75   164 


  Outcome Measures

1.  Primary:   Average Diabetic Peripheral Neuropathy (DPN) Pain Based on a Numeric Rating Scale (NRS) Over the Last 7 Days of Each Treatment Period (Week 6 of Each Treatment Period)   [ Time Frame: End of Period (includes both Visits 5 and 9) ]
  Hide Outcome Measure 1

Measure Type Primary
Measure Title Average Diabetic Peripheral Neuropathy (DPN) Pain Based on a Numeric Rating Scale (NRS) Over the Last 7 Days of Each Treatment Period (Week 6 of Each Treatment Period)
Measure Description The daily pain diary consisted of an 11-point numeric scale ranging from 0 (“no pain”) to 10 (“worst possible pain”). Participants described their pain during the past 24 hours by having chosen the appropriate number between 0 and 10. Self assessment was performed daily in the evening before bedtime on a telephone via interactive voice recognition system (IVRS) (time window for completion between 6.00 pm to midnight). The endpoint mean pain score was defined as the mean of the last 7 daily diary pain ratings while taking study drug in each treatment period - period 1 and period 2, respectively. A rating of 1 - 3 was considered as mild pain; 4 - 6 as moderate pain; and 7 - 10 as severe pain.
Time Frame End of Period (includes both Visits 5 and 9)  

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.
The ITT population included all randomized participants with at least one dose of study drug. The ITT population was analyzed according to what the randomization schedule intended for the participants to take in each period.

Reporting Groups
  Description
Pregabalin The below tables included data from participants while receiving pregabalin in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6- week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period. There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.
Placebo The below table included data from participants while receiving placebo in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period. There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.

Measured Values
   Pregabalin   Placebo 
Participants Analyzed   272   276 
Average Diabetic Peripheral Neuropathy (DPN) Pain Based on a Numeric Rating Scale (NRS) Over the Last 7 Days of Each Treatment Period (Week 6 of Each Treatment Period) 
[Units: Units on a scale]
Least Squares Mean (Standard Error)
 4.980  (0.127)   5.018  (0.126) 


Statistical Analysis 1 for Average Diabetic Peripheral Neuropathy (DPN) Pain Based on a Numeric Rating Scale (NRS) Over the Last 7 Days of Each Treatment Period (Week 6 of Each Treatment Period)
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Repeated measure mixed effects model
P Value [4] 0.7174
Mean Difference (Final Values) [5] -0.038
95% Confidence Interval -0.248 to 0.171
Standard Error of the mean (0.106)
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  A longitudinal analysis was done using a repeated measure linear mixed effects model including visit, treatment, an indicator variable for Week 6, and treatment by visit and by the indicator variable interaction as fixed effect factors and participant within sequence and within-participant error (estimated by using an unstructured covariance structure) as random factors. The treatment differences were tested using within-participant variability as the error term.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  The Kenward-Roger method was used to estimate denominator degrees of freedom.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Primary analysis was two-sided and performed at the 0.05 significance level.
[5] Other relevant estimation information:
  No text entered.



2.  Secondary:   Percentage of Participants Achieving 30% Reduction in Mean DPN Pain Score From Baseline at the End of Each Treatment Period (Week 6 of Each Treatment Period)   [ Time Frame: End of Period (includes both Visits 5 and 9) ]

3.  Secondary:   Percentage of Participants Achieving 50% Reduction in Mean DPN Pain Score From Baseline at the End of Each Treatment Period (Week 6 of Each Treatment Period)   [ Time Frame: End of Period (includes both Visits 5 and 9) ]

4.  Secondary:   Brief Pain Inventory-Short Form (BPI-sf) Score for Pain-Severity Domain at the End of Each Treatment Period (Week 6 of Each Treatment Period)   [ Time Frame: End of Period (includes both Visits 5 and 9) ]

5.  Secondary:   BPI-sf Score for Pain-Interference Domain at the End of Each Treatment Period (Week 6 of Each Treatment Period)   [ Time Frame: End of Period (includes both Visits 5 and 9) ]

6.  Secondary:   Mean Sleep Interference Rating Score at the End of Each Treatment Period (Week 6 of Each Treatment Period)   [ Time Frame: End of Period (includes both Visits 5 and 9) ]

7.  Secondary:   Hospital Anxiety and Depression Scale - Anxiety (HADS-A) Total Score at the End of Each Treatment Period (Week 6 of Each Treatment Period)   [ Time Frame: End of Period (includes both Visits 5 and 9) ]

8.  Secondary:   HADS-D Total Score at the End of Each Treatment Period (Week 6 of Each Treatment Period)   [ Time Frame: End of Period (includes both Visits 5 and 9) ]

9.  Secondary:   Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) Total Quality of Life (TQOL) Score at the End of Each Treatment Period (Week 6 of Each Treatment Period)   [ Time Frame: End of Period (includes both Visits 5 and 9) ]

10.  Secondary:   Norfolk QOL-DN Symptoms Domain Score at the End of Each Treatment Period (Week 6 of Each Treatment Period)   [ Time Frame: End of Period (includes both Visits 5 and 9) ]

11.  Secondary:   Norfolk QOL-DN Activities of Daily Living Domain Score at the End of Each Treatment Period (Week 6 of Each Treatment Period)   [ Time Frame: End of Period (includes both Visits 5 and 9) ]

12.  Secondary:   Norfolk QOL-DN Physical Functioning / Large Fiber Domain Score at the End of Each Treatment Period (Week 6 of Each Treatment Period)   [ Time Frame: End of Period (includes both Visits 5 and 9) ]

13.  Secondary:   Norfolk QOL-DN Small Fiber Domain Score at the End of Each Treatment Period (Week 6 of Each Treatment Period)   [ Time Frame: End of Period (includes both Visits 5 and 9) ]

14.  Secondary:   Norfolk QOL-DN Autonomic Domain Score at the End of Each Treatment Period (Week 6 of Each Treatment Period)   [ Time Frame: End of Period (includes both Visits 5 and 9) ]

15.  Secondary:   Euro QoL-5 Dimensions (EQ-5D) Mobility Domain Score at the End of Each Treatment Period (Week 6 of Each Treatment Period)   [ Time Frame: End of Period (includes both Visits 5 and 9) ]

16.  Secondary:   EQ-5D Self-Care Domain Score at the End of Each Treatment Period (Week 6 of Each Treatment Period)   [ Time Frame: End of Period (includes both Visits 5 and 9) ]

17.  Secondary:   EQ-5D Usual Activities Domain Score at the End of Each Treatment Period (Week 6 of Each Treatment Period)   [ Time Frame: End of Period (includes both Visits 5 and 9) ]

18.  Secondary:   EQ-5D Pain / Discomfort Domain Score at the End of Each Treatment Period (Week 6 of Each Treatment Period)   [ Time Frame: End of Period (includes both Visits 5 and 9) ]

19.  Secondary:   EQ-5D Anxiety / Depression Domain Score at the End of Each Treatment Period (Week 6 of Each Treatment Period)   [ Time Frame: End of Period (includes both Visits 5 and 9) ]

20.  Secondary:   EQ-5D Dolan 1997 Index Summary Score at the End of Each Treatment Period (Week 6 of Each Treatment Period)   [ Time Frame: End of Period (includes both Visits 5 and 9) ]

21.  Secondary:   EQ-5D Dolan 2002 Index Summary Score at the End of Each Treatment Period (Week 6 of Each Treatment Period)   [ Time Frame: End of Period (includes both Visits 5 and 9) ]

22.  Secondary:   Patient Global Impression of Change (PGIC) Score at the End of Period 1 (Week 6) - Original Scores   [ Time Frame: End of Period 1 (V5) ]

23.  Secondary:   PGIC Score at the End of Period 1 (Week 6) - Categorized Scores   [ Time Frame: End of Period 1 (V5) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

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
No text entered.


  More Information

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: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
phone: 1-800-718-1021
e-mail: ClinicalTrials.gov_Inquiries@pfizer.com


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01455415     History of Changes
Other Study ID Numbers: A0081268
2011-002743-10 ( EudraCT Number )
First Submitted: October 17, 2011
First Posted: October 20, 2011
Results First Submitted: October 30, 2014
Results First Posted: April 23, 2015
Last Update Posted: April 23, 2015