Efficacy and Safety Study of Celecoxib and Pregabalin Compared With Celecoxib Monotherapy, in Patients With Chronic Low Back Pain Having a Neuropathic Component

Study Overview
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Brief Summary
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The purpose of this study is to determine if treatment with celecoxib and pregabalin together would prove to be more effective in relief of pain than treatment with celecoxib alone in people who have chronic low back pain with a probable neuropathic component.

Detailed Description
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The primary objective is to evaluate the efficacy of the concomitant use of pregabalin and celecoxib compared with celecoxib monotherapy for the symptomatic relief of pain in patients with chronic low back pain with a probable neuropathic component. The secondary objectives are: Demonstrate the additional benefit of adding pregabalin to celecoxib monotherapy. To evaluate the concomitant use of pregabalin and celecoxib compared to celecoxib monotherapy in a set of patient reported measures (sleep, depression, anxiety, impact of pain in daily functions, patient's global impression of change and patient's perception of the treatment). To evaluate the safety and tolerability of celecoxib and of the concomitant administration of pregabalin and celecoxib.

Official Title
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A Randomized Double Blind Placebo Controlled Parallel Group Study Of The Efficacy And Safety Of Concomitant Administration Of Celecoxib And Pregabalin Compared With Celecoxib Monotherapy, In Patients With Chronic Low Back Pain Having A Neuropathic Component

Conditions
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Chronic Low Back Pain With a Neuropathic Component

Intervention / Treatment
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* Drug: pregabalin and celecoxib
* Drug: Placebo and celecoxib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have Chronic low back pain with high probability of a significant neuropathic component for 4 years or less (but no less than 3 months) Subjects must be in generally good health, except for the presence of chronic low back pain with a neuropathic component. Subjects must be literate and have the ability (unaided) to understand and use the interactive voice response system (IVRS), have daily access to a telephone or the internet in order to complete the IVRS assessments each day, perform telephone or web visits and complete all required assessments/forms Exclusion Criteria: Subjects with past history of surgery for chronic low back pain. Subjects with past history of failure on pregabalin treatment and/or intolerance associated with pregabalin or gabapentin. Subjects with past history of intolerance associated with celecoxib or known hypersensitivity to celecoxib. Patients with anticipated need for treatment with opioid analgesics, anti-epileptic medications, SNRI antidepressants or tricyclic antidepressants to alleviate pain during the course of the study. Patients with chronic low back pain with a neuropathic component for more than 4 years. Patients with neurologic disorders unrelated to low back pain that may confuse or confound the assessment of neuropathic pain (eg, primary or secondary nerve diseases). Subjects considered at risk of suicide or self-harm based on investigator judgment and/or details of a risk assessment. Use of prohibited medications in the absence of appropriate washout periods. Patients with any severe pain associated with conditions other than chronic low back pain with a neuropathic component that may confound the assessment or self-evaluation of the pain due to chronic low back pain. Patients with diabetes with poor glycemic control (HbA1c >8%). Patients with any clinically significant or unstable medical or psychiatric condition or laboratory abnormality that, in the opinion of the investigator, would compromise participation in the study Patients who have participated in any previous clinical trial for pregabalin or have participated in 2 or more previous clinical trials for pain related to chronic low back pain. Patients who are likely to require surgery during the course of the study (except minor surgery, eg, for skin conditions) Patients with a history of Substance Abuse as defined by DSM-IV-TR diagnostic criteria

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>The group of patients who are randomized to receive concomitant treatment of pregabalin and celecoxib during the first study period. | Drug: pregabalin and celecoxib<br>* During the first study period subjects in Arm A will be administered a daily fixed dose of celecoxib 200 mg once daily and pregabalin 150 mg (75 mg BID) for one week (during Week 0) followed by pregabalin 300 mg (150 mg BID) daily for the remaining 4 weeks. During the second study period all subjects will be administered concomitant treatment of a daily fixed dose of celecoxib 200 mg once daily and pregabalin 300 mg (150 mg BID). Subjects in Arm B will be initiated on pregabalin 150 mg (75 mg BID) daily for one week, before pregabalin will up titrated to 300 mg (150 mg BID) daily. All subjects will complete a treatment taper (a) after completing the second study period or (b) after premature study discontinuation. During treatment taper, the pregabalin dose will be decreased to 150 mg (75 mg BID) daily and subjects will participate in a follow up visit for a final safety assessment.<br>|
| Other: Arm B<br>The group of patients who are randomized to receive celecoxib monotherapy during the first study period. | Drug: Placebo and celecoxib<br>* Subjects in Arm B will be administered a daily fixed dose celecoxib 200 mg and placebo of pregabalin for 5 weeks. During the second study period all subjects will be administered concomitant treatment of a daily fixed dose of celecoxib 200 mg once daily and pregabalin 300 mg (150 mg BID). Subjects in Arm B will be initiated on pregabalin 150 mg (75 mg BID) daily for one week, before pregabalin will up titrated to 300 mg (150 mg BID) daily. All subjects will complete a treatment taper (a) after completing the second study period or (b) after premature study discontinuation. During treatment taper, the pregabalin dose will be decreased to 150 mg (75 mg BID) daily and subjects will participate in a follow up visit for a final safety assessment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Weekly Mean Pain Numeric Rating Scale (NRS) Score at Week 5 (ie, Visit 4) Compared Between the Two Study Arms | The Daily Pain diary consists of an 11-point NRS ranging from 0 (no pain) to 10 (worst possible pain). Participants described their pain during the past 24 hours by choosing the appropriate number between 0 and 10: Select the number that best describes your pain during the past 24 hours from 0 to10 where 0 represents no pain and 10 represents the worst possible pain. | Baseline and Week 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Weekly Mean Pain NRS Score in Arm B, Compared Between Week 5 (Visit 4) and Week 10 (Visit 6). | The Daily Pain diary consists of an 11-point NRS ranging from 0 (no pain) to 10 (worst possible pain). Participants described their pain during the past 24 hours by choosing the appropriate number between 0 and 10: Select the number that best describes your pain during the past 24 hours from 0 to10 where 0 represents no pain and 10 represents the worst possible pain. | Week 5 and Week 10 | 
| Change From Baseline in the Weekly Mean Pain NRS Score at Week 10 (Visit 6) Compared Between the Two Study Arms | The Daily Pain diary consists of an 11-point NRS ranging from 0 (no pain) to 10 (worst possible pain). Participants described their pain during the past 24 hours by choosing the appropriate number between 0 and 10: Select the number that best describes your pain during the past 24 hours from 0 to10 where 0 represents no pain and 10 represents the worst possible pain. | Baseline and Week 10 | 
| Change From Baseline in Benefit, Satisfaction, and Willingness to Continue Measure Scores Compared Between Arms at Week 5 (Visit 4) and at Week 10 (Visit 6) | The BSW consists of 3, single-item measures designed to capture the participant's perception of the effect of treatment in terms of the relative benefit, their satisfaction, and their intention or willingness to continue on therapy. The BSW was administered by the investigator or designated site personnel in the local language as a standardized interview during the follow-up visits. The BSW can potentially be self-administered; however, this method of administration has not been tested. Participants completed this questionnaire at Visit 4 and Visit 6. | Week 5 and Week 10 | 
| Patient Global Impression of Change (PGIC) Compared Between Arms at Week 5 (Visit 4) and at Week 10 (Visit 6) | The PGIC is a single-item, self-rated instrument that measures change in the patient's overall status since starting study medication on a scale from 1 (very much improved) to 7 (very much worse), where lower scores indicate greater improvement. This scale was administered at Visit 4 and Visit 6. | Week 5 and Week 10 | 
| Percentage of Participants With PGIC for Each Arm Compared at Week 5 (Visit 4) and at Week 10 (Visit 6) | The PGIC is a single-item, self-rated instrument that measures change in the patient's overall status since starting study medication on a scale from 1 (very much improved) to 7 (very much worse), where lower scores indicate greater improvement. This scale was administered at Visit 4 and Visit 6. | Week 5 and Week 10 | 
| Change From Baseline in Weekly Mean of Daily Sleep Interference Rating Scale (SIRS) Compared Between Arms at Week 5 (Visit 4) and at Week 10 (Visit 6) | The Daily Sleep Interference Rating Scale (SIRS) consists of an 11-point NRS ranging from 0 (pain does not interfere with sleep) to 10 (pain completely interferes with sleep [unable to sleep due to pain]). Participants described how pain had interfered with their sleep during the past 24 hours: Select the number that best describes how your pain has interfered with your sleep during the past 24 hours on a scale from 0 to 10 where 0 represents 'does not interfere with sleep' and 10 represents 'completely interferes' which means you are unable to sleep due to pain. | Week 5 and Week 10 | 
| Change From Baseline in Hospital Anxiety and Depression Scale (HADS-A) Anxiety Scores at Week 5 (Visit 4) and Week 10 (Visit 6) | The HADS is a self-administered questionnaire measuring anxiety. Each subscale consists of 7 statements and the participants respond as to how each item applies to them on a scale of 0 to 3 (0 = No anxiety, to 3 = Severe feelings of anxiety). Separate scores are calculated for each subscale and a score (ranging from 0 to 21) is obtained for each subscale. The higher the score the more severe the anxiety. | Week 5 and Week 10 | 
| Change From Baseline in Hospital Anxiety and Depression Scale (HADS-D) Depression Scores at Week 5 (Visit 4) and Week 10 (Visit 6) | The HADS is a self-administered questionnaire measuring depression. Each subscale consists of 7 statements and the participants respond as to how each item applies to them on a scale of 0 to 3 (0 = No depression, to 3 = Severe feelings of depression). Separate scores are calculated for each subscale and a score (ranging from 0 to 21) is obtained for each subscale. The higher the score the more severe the depression. | Week 5 and Week 10 | 
| Percentage of Days in Mild, Moderate and Severe Pain at Period 1 and Period 2 | Period 1 indicates from Visit 2 (baseline) to Visit 4 (Week 5). Period 2 indicates from Visit 4 (Week 5) to Visit 6 (Week 10). A rating of 0 is considered no pain; 1-3 is considered mild pain; 4-6, moderate pain; and 7-10, severe pain. | Period 1 and Period 2 | 
| Change From Baseline in Brief Pain Inventory Short Form (BPI sf) - Pain Severity Index Score at Week 5 and Week 10 | BPI-sf is a self-administered questionnaire developed to assess the severity of pain and the impact of pain on daily functions during the past 24 hours. The Pain severity domain: The BPI severity domain includes pain at its 'worst,' 'least,' 'average,' and 'now' (current pain) on 0-10 NRS scales and takes the mean of these 4 items. Scores range from 0 (no pain) to 10 (pain as bad as you can imagine), therefore higher scores indicate greater pain severity. | Week 5 and Week 10 | 
| Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale - Sleep Disturbance Subscale at Week 5 and Week 10 | The MOS-Sleep Scale is a self-administered questionnaire consisting of 12 items that assess key constructs of sleep. Instrument scoring yields 7 subscales (sleep disturbance, snoring, awaken short of breath or with a headache, quantity of sleep, optimal sleep, sleep adequacy, and somnolence) as well as a 9-item overall sleep problems index. With the exception of sleep adequacy, optimal sleep, and quantity, higher scores reflect greater impairment in the MOS-Sleep subscales. Sleep Disturbance: Range=0 to 100; higher scores indicate greater sleep disturbance. Negative changes indicate improvement. | Week 5 and Week 10 | 
| Percentage of Participants With >= 30% Reduction From Baseline in the Weekly Mean Pain NRS Score at Week 5 and Week 10 | The Daily Pain diary consists of an 11-point NRS ranging from 0 (no pain) to 10 (worst possible pain). Participants described their pain during the past 24 hours by choosing the appropriate number between 0 and 10: Select the number that best describes your pain during the past 24 hours from 0 to10 where 0 represents no pain and 10 represents the worst possible pain. | Week 5 and Week 10 | 
| Percentage of Participants With >= 50% Reduction From Baseline in the Weekly Mean Pain NRS Score at Week 5 and Week 10 | The Daily Pain diary consists of an 11-point NRS ranging from 0 (no pain) to 10 (worst possible pain). Participants described their pain during the past 24 hours by choosing the appropriate number between 0 and 10: Select the number that best describes your pain during the past 24 hours from 0 to10 where 0 represents no pain and 10 represents the worst possible pain. | Week 5 and Week 10 |