Safety And Efficacy Study Of Once Daily Controlled Release Pregabalin In The Treatment Of Patients With Postherpetic Neuralgia

Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to explore the safety and efficacy of a new once a day pregabalin formulation versus placebo for patients with post herpetic neuralgia (Shingles)

Official Title
-----------------
A Phase 3 Double-blind, Randomized, Placebo-controlled, Safety And Efficacy Study Of Once Daily Controlled Release Pregabalin In The Treatment Of Patients With Postherpetic Neuralgia (Protocol A0081224)

Conditions
-----------------
Post Herpetic Neuralgia

Intervention / Treatment
-----------------
* Drug: Pregabalin
* Drug: placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients must have pain present for more than 3 months after the healing of the herpes zoster skin rash. At screening (V1) and enrollment (V2), patients must have a score of greater than or equal to 4 on the Pain Numeric Rating Scale (1 week recall period). At enrollment (V2), at least 4 pain diaries must be completed satisfactorily within the last 7 days and the average pain score must be greater than or equal to 4. Male or female of any race, at least 18 years of age, and using appropriate methods of contraception Exclusion Criteria: Creatinine clearance <30 mL/min (estimated from serum creatinine). Skin conditions in the affected dermatome that could alter sensation Pregabalin use in the last 30 days. Subjects taking pregabalin in the last 30 days should be washed out of pregabalin for at least 30 days prior to screening visit. Patients who had not responded to pregabalin

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pregablain CR tablet 82.5 to 660mg<br> | Drug: Pregabalin<br>* Tablets, 82.5 to 660mg, once per day. Duration: 19 weeks<br>|
| Placebo Comparator: Placebo<br> | Drug: placebo<br>* Placebo, 82.5 to 660mg, once per day. Duration: 13 weeks<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Loss of Therapeutic Response. | Loss of Therapeutic Response (LTR) is defined as <30% pain response relative to the single blind phase baseline or patient discontinuation due to lack of efficacy or adverse events in the double blind phase of the study. For the calculation of <30% pain response relative to baseline, baseline will be defined as the mean of the last 7 observations prior to the start of SB treatment, which will be compared with the 7 days rolling average of pain response in DB phase. Participants may be discontinued due to lack of efficacy in this study at the discretion of the study physician. | 13 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants With Secondary LTR Based on 5 Day Rolling Average Diary Results | A secondary LTR endpoint (S-LTR) was defined as the 5 day rolling average pain score during DB, compared to the 5 day randomization baseline pain score. As a secondary endpoint, S-LTR was defined as: At least a 30% increase in the 5 days rolling average pain score during DB relative to the 5 Day randomization baseline pain score A 5 days rolling average pain score ≥4. Participants who discontinue due to lack of efficacy or adverse events in the DB phase of the study will also be counted as an LTR. | 13 Weeks | 
| Percentage of Participants With 30% Reduction in the Mean Pain Score. | The 30% pain responders were defined as participants with at least a 30% reduction in the mean pain score from SB baseline to DB endpoint. | 13 Weeks | 
| Percentage of Participants With 50% Reduction in the Mean Pain Score. | The 50% pain responders were defined as participants with at least a 50% reduction in the mean pain score from SB baseline to DB endpoint. | 13 Weeks | 
| Change From Baseline to Endpoint in Weekly Mean Pain Score. | The pain numeric rating scale (NRS Pain) consists of an 11 point NRS ranging from 0 (no pain) to 10 (worst possible pain). A rating of 1-3 is considered mild pain; 4-6, moderate pain; and 7-10, severe pain | SB Baseline (Enrollment) to Week 19 and DB Baseline (Week 6) to Week 19 | 
| Change in the Weekly NRS-Pain (1-Week Recall). | The pain numeric rating scale (NRS Pain) consists of an 11 point NRS ranging from 0 (no pain) to 10 (worst possible pain). A rating of 1-3 is considered mild pain; 4-6, moderate pain; and 7-10, severe pain. Participants were asked to rate their pain over the past week. | SB Baseline (Enrollment) to Week 19 and DB Baseline (Week 6) to Week 19 | 
| Change in the Medical Outcomes Study-Sleep Scale (MOS-SS). | The MOS-SS is a validated self administered questionnaire consisting of 12 items that assess key constructs of sleep. The scale has been found reliable and valid with good overall measurement properties. 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 assessing sleep over the past week. Scores are transformed (actual raw score minus lowest possible score divided by possible raw score range multiplied by 100); total score range = 0 to 100; higher score indicates greater intensity of attribute. | SB Baseline (BL) (Enrollment) to Week 19 and DB Baseline (Week 6) to Week 19 | 
| Change in the MOS-SS-Quantity of Sleep. | The MOS-SS is a validated self administered questionnaire consisting of 12 items that assess key constructs of sleep. The scale has been found reliable and valid with good overall measurement properties. 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 assessing sleep over the past week. The item Quantity of sleep of MOS-SS is presented here. | SB Baseline (BL) (Enrollment) to Week 19 and DB Baseline (Week 6) to Week 19 | 
| The MOS-SS-Optimal Sleep. | The MOS-SS is a validated self administered questionnaire consisting of 12 items that assess key constructs of sleep. The scale has been found reliable and valid with good overall measurement properties. 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 assessing sleep over the past week. The optimal sleep score is a dichotomous 'Yes' or 'No' rating, where 'Yes' indicates optimal sleep (average 7-8 hours per night) and 'No' indicates not optimal sleep. The percentage of participants with optimal sleep is presented here. | Week 6 and Week 19 | 
| Percentage of Participants With Change in the Patient Global Impression of Change (PGIC) Score | The PGIC is a participant-rated instrument that has been used in chronic pain and fibromyalgia studies to rate change in a patient's overall status. This single item instrument uses a 7 point Likert scale, anchored by (1) very much improved, to (7) very much worse. | Week 19 | 
| Change in the Short Form 36 Health Survey (SF-36) | The SF 36 is a self administered, validated questionnaire that measures each of the following 8 health aspects: Physical functioning, role limitations due to physical problems, social functioning, bodily pain, mental health, role limitations due to emotional problems, vitality, and general health perception over the past week. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning) where, higher scores indicate a better health related quality of life. | Week 19 | 
| Change in Mean Daily Sleep Interference Scores | The pain related sleep interference item rating scale is scored on an 11 point numeric rating scale (NRS Sleep). It is self administered by the subject in order to rate how pain has interfered with their sleep during the past 24 hours, ranging from 0 (pain does not interfere with sleep) to 10 (completely interferes (unable to sleep due to pain)). Participants are to describe how their pain has interfered with their sleep during the past 24 hours by choosing the appropriate number on the numeric rating scale. | Week 19 | 
| Change in Hospital Anxiety and Depression Scales (HADS) | The HADS is a self administered questionnaire that was designed to screen for the presence of a mood disorder in medically ill patients. To distinguish psychiatric presentations from physical illness, the items focus on subjective disturbance of mood rather than physical signs. The HADS contains 14 items rated on 4 point Likert type scales. Two subscales assess depression and anxiety. Each subscale consists of 7 statements, rated on a scale of 0 to 3 (0 = No anxiety or depression, to 3 = Severe feelings of anxiety or depression). Separate scores are calculated for each subscale ranging from 0 to 21. Higher scores denote greater severity of depression or anxiety | Week 19 | 
| Change in the Brief Pain Inventory (BPI-sf) | The BPI sf is a self-administered questionnaire developed to assess the severity of pain and the impact of pain on daily functions during a 24 hour period prior to evaluation. The BPI sf consists of 5 questions. Questions 1, 2, 3, and 4 measure pain on an 11 point scale from 0 (no pain) to 10 (worst pain possible). Question 5 consists of 7 item subsets which measure the level of interference of pain on daily functions on an 11 point scale from 0 (Does not interfere) to 10 (Completely interferes). | Week 19 | 
| Percentage of Participants With Benefit From Treatment, Satisfaction With Treatment and Willingness to Continue Treatement (BSW) | The BSW is administered by the study physician or designated site personnel and consists of three single item measures designed to capture the patient's perception of the effect of treatment in terms of the relative benefit, their satisfaction, and their intention or willingness to continue on therapy. | Week 19 | 
| Number of Participants With Adverse Events | An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. A serious adverse event is any untoward medical occurrence at any dose that: Results in death; Is life-threatening (immediate risk of death); Requires inpatient hospitalization or prolongation of existing hospitalization; Results in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); or Results in congenital anomaly/birth defect. The study physician used the adjective severe to those AEs that interfere significantly with participant's usual function. | Baseline to Week 20 | 
| Percentage of Participants With Suicidal Behaviour/Ideation | Percentage of participants with suicidal behavior/ideation were noted as Baseline, Weeks 6, 11, 15, 19 and 20. | Baseline, Weeks 6, 11, 15, 19 and 20 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Control Release Pregabalin in Post Herpetic Neuralgia