Post Herpetic Neuralgia
Conditions
Keywords
Control Release Pregabalin in Post Herpetic Neuralgia
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)
Interventions
DRUGPregabalin
Tablets, 82.5 to 660mg, once per day. Duration: 19 weeks
DRUGplacebo
Placebo, 82.5 to 660mg, once per day. Duration: 13 weeks
Sponsors
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Loss of Therapeutic Response. | 13 Weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With 30% Reduction in the Mean Pain Score. | 13 Weeks | 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. |
| Percentage of Participants With 50% Reduction in the Mean Pain Score. | 13 Weeks | 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. |
| Change From Baseline to Endpoint in Weekly Mean Pain Score. | SB Baseline (Enrollment) to Week 19 and DB Baseline (Week 6) to Week 19 | 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 |
| Change in the Weekly NRS-Pain (1-Week Recall). | SB Baseline (Enrollment) to Week 19 and DB Baseline (Week 6) to Week 19 | 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. |
| Change in the Medical Outcomes Study-Sleep Scale (MOS-SS). | SB Baseline (BL) (Enrollment) to Week 19 and DB Baseline (Week 6) to Week 19 | 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. |
| Change in the MOS-SS-Quantity of Sleep. | SB Baseline (BL) (Enrollment) to Week 19 and DB Baseline (Week 6) to Week 19 | 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. |
| The MOS-SS-Optimal Sleep. | Week 6 and Week 19 | 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. |
| Participants With Secondary LTR Based on 5 Day Rolling Average Diary Results | 13 Weeks | 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: 1. At least a 30% increase in the 5 days rolling average pain score during DB relative to the 5 Day randomization baseline pain score 2. 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. |
| Change in the Short Form 36 Health Survey (SF-36) | Week 19 | 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. |
| Change in Mean Daily Sleep Interference Scores | Week 19 | 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. |
| Change in Hospital Anxiety and Depression Scales (HADS) | Week 19 | 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 |
| Change in the Brief Pain Inventory (BPI-sf) | Week 19 | 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). |
| Percentage of Participants With Benefit From Treatment, Satisfaction With Treatment and Willingness to Continue Treatement (BSW) | Week 19 | 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. |
| Number of Participants With Adverse Events | Baseline to Week 20 | 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. |
| Percentage of Participants With Suicidal Behaviour/Ideation | Baseline, Weeks 6, 11, 15, 19 and 20 | Percentage of participants with suicidal behavior/ideation were noted as Baseline, Weeks 6, 11, 15, 19 and 20. |
| Percentage of Participants With Change in the Patient Global Impression of Change (PGIC) Score | Week 19 | 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. |
Countries
Bulgaria, Colombia, Croatia, Czechia, Denmark, Germany, Hong Kong, India, Poland, Russia, Serbia, Slovakia, South Africa, Sweden, Taiwan, Ukraine, United States
Participant flow
Recruitment details
A total of 129 centers in 17 countries screened subjects for the study, including 68 in the US, 6 in Bulgaria, 6 in Poland, 6 in Russia, 6 in the Ukraine, 5 in India, 5 in South Africa, 5 in Sweden, 4 in Slovakia, 3 in Colombia, 3 in Croatia, 3 in Germany, 2 in Denmark, 2 in Hong Kong, 2 in Serbia, 2 in Taiwan, and 1 in the Czech Republic.
Pre-assignment details
The study consisted of 4 phases: Baseline (1 week \[wk\]): to determine study entry criteria; Single Blind (SB) (6 wks): to determine optimized dose; Double Blind (DB) (13 wks): responders with at least 50% improvement in pain at SB were considered and randomized to pregabalin or matching placebo; and DB taper phase (1 wk).
Participants by arm
| Arm | Count |
|---|---|
| Pregabalin CR DB Possible doses for participants with normal creatinine clearance (CLcr) (≥60 mL/min) during the DB fixed dose phase were pregabalin CR 165 mg/day, 330 mg/day, 495 mg/day CR or 660 mg/day CR. Doses for participants with low CLcr (\>30 - \<60 mL/min) were pregabalin 82.5 mg/day, 165 mg/day, 247.5 mg/day, or 330 mg/day CR. | 208 |
| Placebo DB Participants received matching placebo | 205 |
| Total | 413 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double Blind Phase | Adverse event not related to study drug | 1 | 1 | 0 |
| Double Blind Phase | Adverse event related to study drug | 5 | 7 | 0 |
| Double Blind Phase | Death | 0 | 1 | 0 |
| Double Blind Phase | Lack of Efficacy | 2 | 11 | 0 |
| Double Blind Phase | Lost to Follow-up | 1 | 2 | 0 |
| Double Blind Phase | Protocol and GCP non-compliance | 4 | 3 | 0 |
| Double Blind Phase | Protocol Violation | 0 | 1 | 0 |
| Double Blind Phase | Reason Unspecified | 7 | 4 | 0 |
| Double Blind Phase | Withdrawal by Subject | 6 | 15 | 0 |
| Pregabalin CR SB | Enrolled but not treated | 0 | 0 | 5 |
| Pregabalin CR SB | Lack of Efficacy | 0 | 0 | 32 |
| Pregabalin CR SB | Lost to Follow-up | 0 | 0 | 10 |
| Pregabalin CR SB | Protocol Violation | 0 | 0 | 8 |
| Pregabalin CR SB | Reason Unspecified | 0 | 0 | 8 |
| Pregabalin CR SB | Related adverse event | 0 | 0 | 46 |
| Pregabalin CR SB | Unrelated AE | 0 | 0 | 8 |
| Pregabalin CR SB | Withdrawal by Subject | 0 | 0 | 29 |
Baseline characteristics
| Characteristic | Pregabalin CR DB | Placebo DB | Total |
|---|---|---|---|
| Age, Customized 18-44 years | 26 Participants | 24 Participants | 50 Participants |
| Age, Customized <18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized 45-64 years | 86 Participants | 78 Participants | 164 Participants |
| Age, Customized ≥65 years | 96 Participants | 103 Participants | 199 Participants |
| Sex: Female, Male Female | 134 Participants | 122 Participants | 256 Participants |
| Sex: Female, Male Male | 74 Participants | 83 Participants | 157 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 208 | 1 / 205 | 202 / 801 |
| serious Total, serious adverse events | 7 / 208 | 3 / 205 | 17 / 801 |
Outcome results
Primary
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.
Time frame: 13 Weeks
Population: The full analysis set (FAS) was the primary efficacy analysis set and consisted of all participants randomized to the DB phase who received at least 1 dose of study drug in the DB phase.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pregabalin CR DB | Number of Participants With Loss of Therapeutic Response. | 29 Participants |
| Placebo DB | Number of Participants With Loss of Therapeutic Response. | 63 Participants |
Comparison: Kaplan-Meier method was used for the analysis.p-value: <0.0001Log Rank
Secondary
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
Time frame: SB Baseline (Enrollment) to Week 19 and DB Baseline (Week 6) to Week 19
Population: The FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study drug in the DB phase.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin CR DB | Change From Baseline to Endpoint in Weekly Mean Pain Score. | SB Baseline to Week 19 | -4.89 Units on a scale | Standard Error 0.12 |
| Pregabalin CR DB | Change From Baseline to Endpoint in Weekly Mean Pain Score. | DB Baseline to Week 19 | -0.04 Units on a scale | Standard Error 0.11 |
| Placebo DB | Change From Baseline to Endpoint in Weekly Mean Pain Score. | SB Baseline to Week 19 | -3.95 Units on a scale | Standard Error 0.12 |
| Placebo DB | Change From Baseline to Endpoint in Weekly Mean Pain Score. | DB Baseline to Week 19 | 0.87 Units on a scale | Standard Error 0.11 |
Comparison: This ANCOVA model analysis is for DB Baseline to Week 19. Estimates and p-values are from an ANCOVA main effects model with baseline value, pooled center decided before unblinding, and treatment in the model.p-value: <0.000195% CI: [-1.21, -0.61]ANCOVA
Comparison: This ANCOVA model analysis is for SB Baseline to Week 19. Estimates and p-values are from an ANCOVA main effects model with baseline value, pooled center decided before unblinding, and treatment in the model.p-value: <0.000195% CI: [-1.26, -0.62]ANCOVA
Secondary
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
Time frame: Week 19
Population: The FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study drug in the DB phase.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin CR DB | Change in Hospital Anxiety and Depression Scales (HADS) | HADS-Anxiety-SB Baseline to Week 19 | -1.8 Units on a scale | Standard Error 0.21 |
| Pregabalin CR DB | Change in Hospital Anxiety and Depression Scales (HADS) | HADS-Anxiety-DB Baseline to Week 19 | 0.1 Units on a scale | Standard Error 0.19 |
| Pregabalin CR DB | Change in Hospital Anxiety and Depression Scales (HADS) | HADS-Depression-SB Baseline to Week 19 | -1.8 Units on a scale | Standard Error 0.2 |
| Pregabalin CR DB | Change in Hospital Anxiety and Depression Scales (HADS) | HADS-Depression-DB Baseline to Week 19 | 0.2 Units on a scale | Standard Error 0.19 |
| Placebo DB | Change in Hospital Anxiety and Depression Scales (HADS) | HADS-Depression-DB Baseline to Week 19 | 0.8 Units on a scale | Standard Error 0.19 |
| Placebo DB | Change in Hospital Anxiety and Depression Scales (HADS) | HADS-Anxiety-SB Baseline to Week 19 | -1.1 Units on a scale | Standard Error 0.21 |
| Placebo DB | Change in Hospital Anxiety and Depression Scales (HADS) | HADS-Depression-SB Baseline to Week 19 | -1.2 Units on a scale | Standard Error 0.21 |
| Placebo DB | Change in Hospital Anxiety and Depression Scales (HADS) | HADS-Anxiety-DB Baseline to Week 19 | 0.9 Units on a scale | Standard Error 0.2 |
Comparison: This ANCOVA model analysis is for HADS-Anxiety-SB Baseline to Week 19. Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: 0.015495% CI: [-1.2, -0.1]ANCOVA
Comparison: This ANCOVA model analysis is for HADS-Anxiety-DB Baseline to Week 19. Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: 0.002795% CI: [-1.3, -0.3]ANCOVA
Comparison: This ANCOVA model analysis is for HADS-Depression-SB Baseline to Week 19. Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: 0.016695% CI: [-1.2, -0.1]ANCOVA
Comparison: This ANCOVA model analysis is for HADS-Depression-DB Baseline to Week 19. Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: 0.021795% CI: [-1.1, -0.1]ANCOVA
Secondary
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.
Time frame: Week 19
Population: The FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study drug in the DB phase.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin CR DB | Change in Mean Daily Sleep Interference Scores | SB Baseline to Week 19 (N=205,203) | -4.5 Units on a scale | Standard Error 0.11 |
| Pregabalin CR DB | Change in Mean Daily Sleep Interference Scores | DB Baseline to Week 19 (N=206,204) | -0.2 Units on a scale | Standard Error 0.1 |
| Placebo DB | Change in Mean Daily Sleep Interference Scores | SB Baseline to Week 19 (N=205,203) | -3.5 Units on a scale | Standard Error 0.11 |
| Placebo DB | Change in Mean Daily Sleep Interference Scores | DB Baseline to Week 19 (N=206,204) | 0.7 Units on a scale | Standard Error 0.1 |
Comparison: This ANCOVA model analysis is for SB Baseline to Week 19.Estimates and p-values are from an analysis of covariance main effects model with baseline value, pooled center decided before unblinding, and treatment in the model.p-value: <0.000195% CI: [-1.23, -0.64]ANCOVA
Comparison: This ANCOVA model analysis is for DB Baseline to Week 19. Estimates and p-values are from an analysis of covariance main effects model with baseline value, pooled center decided before unblinding, and treatment in the model.p-value: <0.000195% CI: [-1.12, -0.58]ANCOVA
Secondary
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).
Time frame: Week 19
Population: The FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study drug in the DB phase.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin CR DB | Change in the Brief Pain Inventory (BPI-sf) | Pain Severity Index-SB Baseline to Week 19 | -18.0 Units on a scale | Standard Error 0.47 |
| Pregabalin CR DB | Change in the Brief Pain Inventory (BPI-sf) | Pain Severity Index-DB Baseline to Week 19 | -0.7 Units on a scale | Standard Error 0.43 |
| Pregabalin CR DB | Change in the Brief Pain Inventory (BPI-sf) | Pain Interference Index-SB Baseline to Week 19 | -21.9 Units on a scale | Standard Error 0.71 |
| Pregabalin CR DB | Change in the Brief Pain Inventory (BPI-sf) | Pain Interference Index-DB Baseline to Week 19 | -0.2 Units on a scale | Standard Error 0.67 |
| Placebo DB | Change in the Brief Pain Inventory (BPI-sf) | Pain Interference Index-DB Baseline to Week 19 | 4.0 Units on a scale | Standard Error 0.7 |
| Placebo DB | Change in the Brief Pain Inventory (BPI-sf) | Pain Severity Index-SB Baseline to Week 19 | -13.8 Units on a scale | Standard Error 0.49 |
| Placebo DB | Change in the Brief Pain Inventory (BPI-sf) | Pain Interference Index-SB Baseline to Week 19 | -17.2 Units on a scale | Standard Error 0.74 |
| Placebo DB | Change in the Brief Pain Inventory (BPI-sf) | Pain Severity Index-DB Baseline to Week 19 | 3.1 Units on a scale | Standard Error 0.44 |
Comparison: This ANCOVA model analysis is for Pain Severity Index-SB Baseline to Week 19. Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: <0.000195% CI: [-5.5, -3]ANCOVA
Comparison: This ANCOVA model analysis is for Pain Severity Index-DB Baseline to Week 19. Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: <0.000195% CI: [-5, -2.7]ANCOVA
Comparison: This ANCOVA model analysis is for Pain Interference Index-SB Baseline to Week 19.~Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: <0.000195% CI: [-6.5, -2.7]ANCOVA
Comparison: This ANCOVA model analysis is for Pain Interference Index-DB Baseline to Week 19.~Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: <0.000195% CI: [-6, -2.4]ANCOVA
Secondary
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.
Time frame: SB Baseline (BL) (Enrollment) to Week 19 and DB Baseline (Week 6) to Week 19
Population: The FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study drug in the DB phase. N in the below table refers to number of participants analyzed: 203 in Pregabalin DB CR group and 195 in Placebo DB group, unless otherwise specified.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin CR DB | Change in the Medical Outcomes Study-Sleep Scale (MOS-SS). | Sleep Problems Index I-SB BL to wk 19(N=202,195) | -19.9 Units on a scale | Standard Error 1.09 |
| Pregabalin CR DB | Change in the Medical Outcomes Study-Sleep Scale (MOS-SS). | Sleep Problems Index I-DB BL to wk 19(N=202,195) | 1.2 Units on a scale | Standard Error 1.05 |
| Pregabalin CR DB | Change in the Medical Outcomes Study-Sleep Scale (MOS-SS). | SleepProblems Index II-SB BL to wk 19(N=202,195) | -21.2 Units on a scale | Standard Error 1.07 |
| Pregabalin CR DB | Change in the Medical Outcomes Study-Sleep Scale (MOS-SS). | SleepProblems Index II-DB BL to wk 19(N=202,194) | 0.2 Units on a scale | Standard Error 1.01 |
| Pregabalin CR DB | Change in the Medical Outcomes Study-Sleep Scale (MOS-SS). | Sleep Disturbance-SB BL to wk 19 | -28.3 Units on a scale | Standard Error 1.42 |
| Pregabalin CR DB | Change in the Medical Outcomes Study-Sleep Scale (MOS-SS). | Sleep Disturbance-DB BL to wk 19 | -1.1 Units on a scale | Standard Error 1.31 |
| Pregabalin CR DB | Change in the Medical Outcomes Study-Sleep Scale (MOS-SS). | Snoring-SB BL to wk 19(N=202,194) | -3.3 Units on a scale | Standard Error 1.57 |
| Pregabalin CR DB | Change in the Medical Outcomes Study-Sleep Scale (MOS-SS). | Snoring-DB BL to wk 19(N=201,194) | -0.6 Units on a scale | Standard Error 1.41 |
| Pregabalin CR DB | Change in the Medical Outcomes Study-Sleep Scale (MOS-SS). | Awaken short of breath/headache-SB BL to wk 19 | -11.9 Units on a scale | Standard Error 1.21 |
| Pregabalin CR DB | Change in the Medical Outcomes Study-Sleep Scale (MOS-SS). | Awaken short of breath/headache-DB BL to wk 19 | -1.2 Units on a scale | Standard Error 1.23 |
| Pregabalin CR DB | Change in the Medical Outcomes Study-Sleep Scale (MOS-SS). | Sleep adequacy-SB BL to wk 19 | 19.9 Units on a scale | Standard Error 1.83 |
| Pregabalin CR DB | Change in the Medical Outcomes Study-Sleep Scale (MOS-SS). | Sleep adequacy-DB BL to wk 19(N=202,195) | -3.3 Units on a scale | Standard Error 1.82 |
| Pregabalin CR DB | Change in the Medical Outcomes Study-Sleep Scale (MOS-SS). | Somnolence-SB BL to wk 19(N=202,195) | -12.0 Units on a scale | Standard Error 1.19 |
| Pregabalin CR DB | Change in the Medical Outcomes Study-Sleep Scale (MOS-SS). | Somnolence-DB BL to wk 19(N=203,194) | -0.7 Units on a scale | Standard Error 1.15 |
| Placebo DB | Change in the Medical Outcomes Study-Sleep Scale (MOS-SS). | Sleep adequacy-SB BL to wk 19 | 17.5 Units on a scale | Standard Error 1.9 |
| Placebo DB | Change in the Medical Outcomes Study-Sleep Scale (MOS-SS). | Sleep Problems Index I-SB BL to wk 19(N=202,195) | -16.7 Units on a scale | Standard Error 1.13 |
| Placebo DB | Change in the Medical Outcomes Study-Sleep Scale (MOS-SS). | Snoring-DB BL to wk 19(N=201,194) | 0.8 Units on a scale | Standard Error 1.46 |
| Placebo DB | Change in the Medical Outcomes Study-Sleep Scale (MOS-SS). | Sleep Problems Index I-DB BL to wk 19(N=202,195) | 4.4 Units on a scale | Standard Error 1.09 |
| Placebo DB | Change in the Medical Outcomes Study-Sleep Scale (MOS-SS). | Somnolence-SB BL to wk 19(N=202,195) | -12.0 Units on a scale | Standard Error 1.23 |
| Placebo DB | Change in the Medical Outcomes Study-Sleep Scale (MOS-SS). | SleepProblems Index II-SB BL to wk 19(N=202,195) | -17.4 Units on a scale | Standard Error 1.11 |
| Placebo DB | Change in the Medical Outcomes Study-Sleep Scale (MOS-SS). | Awaken short of breath/headache-SB BL to wk 19 | -10.4 Units on a scale | Standard Error 1.26 |
| Placebo DB | Change in the Medical Outcomes Study-Sleep Scale (MOS-SS). | SleepProblems Index II-DB BL to wk 19(N=202,194) | 4.3 Units on a scale | Standard Error 1.05 |
| Placebo DB | Change in the Medical Outcomes Study-Sleep Scale (MOS-SS). | Sleep adequacy-DB BL to wk 19(N=202,195) | -6.0 Units on a scale | Standard Error 1.89 |
| Placebo DB | Change in the Medical Outcomes Study-Sleep Scale (MOS-SS). | Sleep Disturbance-SB BL to wk 19 | -21.1 Units on a scale | Standard Error 1.48 |
| Placebo DB | Change in the Medical Outcomes Study-Sleep Scale (MOS-SS). | Awaken short of breath/headache-DB BL to wk 19 | -0.2 Units on a scale | Standard Error 1.27 |
| Placebo DB | Change in the Medical Outcomes Study-Sleep Scale (MOS-SS). | Sleep Disturbance-DB BL to wk 19 | 7.6 Units on a scale | Standard Error 1.36 |
| Placebo DB | Change in the Medical Outcomes Study-Sleep Scale (MOS-SS). | Somnolence-DB BL to wk 19(N=203,194) | -0.9 Units on a scale | Standard Error 1.19 |
| Placebo DB | Change in the Medical Outcomes Study-Sleep Scale (MOS-SS). | Snoring-SB BL to wk 19(N=202,194) | -4.7 Units on a scale | Standard Error 1.64 |
Comparison: This ANCOVA model analysis is for Sleep Problem Index I-SB Baseline to Week 19. Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: 0.032495% CI: [-6.1, -0.3]ANCOVA
Comparison: This ANCOVA model analysis is for Sleep Problem Index I-DB Baseline to Week 19. Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: 0.022395% CI: [-6.1, -0.5]ANCOVA
Comparison: This ANCOVA model analysis is for Sleep Problem Index II-SB Baseline to Week 19.~Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: 0.009895% CI: [-6.6, -0.9]ANCOVA
Comparison: This ANCOVA model analysis is for Sleep Problem Index II-DB Baseline to Week 19.~Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: 0.003395% CI: [-6.7, -1.4]ANCOVA
Comparison: This ANCOVA model analysis is for Sleep Disturbance-SB Baseline to Week 19. Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: 0.000295% CI: [-11.1, -3.5]ANCOVA
Comparison: This ANCOVA model analysis is for Sleep Disturbance-DB Baseline to Week 19. Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: <0.000195% CI: [-12.2, -5.2]ANCOVA
Comparison: This ANCOVA model analysis is for Snoring-SB Baseline to Week 19. Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: 0.526495% CI: [-2.8, 5.6]ANCOVA
Comparison: This ANCOVA model analysis is for Snoring-DB Baseline to Week 19. Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: 0.45295% CI: [-5.2, 2.3]ANCOVA
Comparison: This ANCOVA model analysis is for Awaken Short of Breath or with a Headache-SB Baseline to Week 19.~Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: 0.371495% CI: [-4.7, 1.8]ANCOVA
Comparison: This ANCOVA model analysis is for Awaken Short of Breath or with a Headache-DB Baseline to Week 19.~Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: 0.563995% CI: [-4.2, 2.3]ANCOVA
Comparison: This ANCOVA model analysis is for Sleep adequacy-SB Baseline to Week 19. Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: 0.322395% CI: [-2.4, 7.3]ANCOVA
Comparison: This ANCOVA model analysis is for Sleep adequacy-DB Baseline to Week 19. Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: 0.274295% CI: [-2.2, 7.6]ANCOVA
Comparison: This ANCOVA model analysis is for Somnolence-SB Baseline to Week 19. Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: 0.981695% CI: [-3.2, 3.1]ANCOVA
Comparison: This ANCOVA model analysis is for Somnolence-DB Baseline to Week 19. Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: 0.928295% CI: [-2.9, 3.2]ANCOVA
Secondary
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.
Time frame: SB Baseline (BL) (Enrollment) to Week 19 and DB Baseline (Week 6) to Week 19
Population: The FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study drug in the DB phase.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin CR DB | Change in the MOS-SS-Quantity of Sleep. | Quantity of sleep-SB BL to wk 19(N=203,192) | 0.9 Hours | Standard Error 0.09 |
| Pregabalin CR DB | Change in the MOS-SS-Quantity of Sleep. | Quantity of sleep-DB BL to wk 19(N=202,192) | -0.1 Hours | Standard Error 0.08 |
| Placebo DB | Change in the MOS-SS-Quantity of Sleep. | Quantity of sleep-SB BL to wk 19(N=203,192) | 0.7 Hours | Standard Error 0.1 |
| Placebo DB | Change in the MOS-SS-Quantity of Sleep. | Quantity of sleep-DB BL to wk 19(N=202,192) | -0.4 Hours | Standard Error 0.09 |
Comparison: This ANCOVA model analysis is for SB Baseline to Week 19. Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: 0.163595% CI: [-0.1, 0.4]ANCOVA
Comparison: This ANCOVA model analysis is for DB Baseline to Week 19. Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: 0.036395% CI: [0, 0.5]ANCOVA
Secondary
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.
Time frame: Week 19
Population: The FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study drug in the DB phase. N in the below table refers to number of participants analyzed: 203 in Pregabalin DB CR group and 195 in Placebo DB group, unless otherwise specified.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin CR DB | Change in the Short Form 36 Health Survey (SF-36) | Physical Component-SB BL to wk 19(N=202,195) | 7.5 Units on a scale | Standard Error 0.54 |
| Pregabalin CR DB | Change in the Short Form 36 Health Survey (SF-36) | Physical Component-DB BL to wk 19(N=202,195) | 0.1 Units on a scale | Standard Error 0.51 |
| Pregabalin CR DB | Change in the Short Form 36 Health Survey (SF-36) | Mental Component-SB BL to wk 19(N=202,195) | 6.4 Units on a scale | Standard Error 0.62 |
| Pregabalin CR DB | Change in the Short Form 36 Health Survey (SF-36) | Mental Component-DB BL to wk 19(N=202,195) | -1.1 Units on a scale | Standard Error 0.62 |
| Pregabalin CR DB | Change in the Short Form 36 Health Survey (SF-36) | Physical functioning-SB BL to wk 19 | 11.7 Units on a scale | Standard Error 1.44 |
| Pregabalin CR DB | Change in the Short Form 36 Health Survey (SF-36) | Physical functioning-DB BL to wk 19 | -1.4 Units on a scale | Standard Error 1.25 |
| Pregabalin CR DB | Change in the Short Form 36 Health Survey (SF-36) | Role-Physical-SB BL to wk 19 | 18.9 Units on a scale | Standard Error 1.62 |
| Pregabalin CR DB | Change in the Short Form 36 Health Survey (SF-36) | Role-Physical-DB BL to wk 19 | -2.4 Units on a scale | Standard Error 1.54 |
| Pregabalin CR DB | Change in the Short Form 36 Health Survey (SF-36) | Bodily pain-SB BL to wk 19 | 31.0 Units on a scale | Standard Error 1.51 |
| Pregabalin CR DB | Change in the Short Form 36 Health Survey (SF-36) | Bodily pain-DB BL to wk 19 | 1.4 Units on a scale | Standard Error 1.38 |
| Pregabalin CR DB | Change in the Short Form 36 Health Survey (SF-36) | General Health Perception-SB BL to wk19(N=202,195) | 11.3 Units on a scale | Standard Error 1.05 |
| Pregabalin CR DB | Change in the Short Form 36 Health Survey (SF-36) | General Health Perception-DB BL to wk19(N=202,195) | 1.4 Units on a scale | Standard Error 0.96 |
| Pregabalin CR DB | Change in the Short Form 36 Health Survey (SF-36) | Vitality-SB BL to wk 19(N=202,195) | 13.7 Units on a scale | Standard Error 1.25 |
| Pregabalin CR DB | Change in the Short Form 36 Health Survey (SF-36) | Vitality-DB BL to wk 19(N=202,195) | -3.5 Units on a scale | Standard Error 1.21 |
| Pregabalin CR DB | Change in the Short Form 36 Health Survey (SF-36) | Social Functioning-SB BL to wk 19 | 18.5 Units on a scale | Standard Error 1.35 |
| Pregabalin CR DB | Change in the Short Form 36 Health Survey (SF-36) | Social Functioning-DB BL to wk 19 | -2.1 Units on a scale | Standard Error 1.28 |
| Pregabalin CR DB | Change in the Short Form 36 Health Survey (SF-36) | Role-Emotional-SB BL to wk 19 | 15.0 Units on a scale | Standard Error 1.43 |
| Pregabalin CR DB | Change in the Short Form 36 Health Survey (SF-36) | Role-Emotional-DB BL to wk 19 | -1.4 Units on a scale | Standard Error 1.42 |
| Pregabalin CR DB | Change in the Short Form 36 Health Survey (SF-36) | Mental Health-SB BL to wk 19(N=202,195) | 11.1 Units on a scale | Standard Error 1.05 |
| Pregabalin CR DB | Change in the Short Form 36 Health Survey (SF-36) | Mental Health-DB BL to wk 19(N=202,195) | -1.3 Units on a scale | Standard Error 1.04 |
| Placebo DB | Change in the Short Form 36 Health Survey (SF-36) | Role-Emotional-DB BL to wk 19 | -5.4 Units on a scale | Standard Error 1.47 |
| Placebo DB | Change in the Short Form 36 Health Survey (SF-36) | Physical Component-SB BL to wk 19(N=202,195) | 5.6 Units on a scale | Standard Error 0.56 |
| Placebo DB | Change in the Short Form 36 Health Survey (SF-36) | General Health Perception-SB BL to wk19(N=202,195) | 8.2 Units on a scale | Standard Error 1.08 |
| Placebo DB | Change in the Short Form 36 Health Survey (SF-36) | Physical Component-DB BL to wk 19(N=202,195) | -2.3 Units on a scale | Standard Error 0.53 |
| Placebo DB | Change in the Short Form 36 Health Survey (SF-36) | Social Functioning-DB BL to wk 19 | -4.3 Units on a scale | Standard Error 1.32 |
| Placebo DB | Change in the Short Form 36 Health Survey (SF-36) | Mental Component-SB BL to wk 19(N=202,195) | 5.5 Units on a scale | Standard Error 0.64 |
| Placebo DB | Change in the Short Form 36 Health Survey (SF-36) | General Health Perception-DB BL to wk19(N=202,195) | -4.0 Units on a scale | Standard Error 1 |
| Placebo DB | Change in the Short Form 36 Health Survey (SF-36) | Mental Component-DB BL to wk 19(N=202,195) | -2.2 Units on a scale | Standard Error 0.64 |
| Placebo DB | Change in the Short Form 36 Health Survey (SF-36) | Mental Health-DB BL to wk 19(N=202,195) | -3.7 Units on a scale | Standard Error 1.08 |
| Placebo DB | Change in the Short Form 36 Health Survey (SF-36) | Physical functioning-SB BL to wk 19 | 8.9 Units on a scale | Standard Error 1.49 |
| Placebo DB | Change in the Short Form 36 Health Survey (SF-36) | Vitality-SB BL to wk 19(N=202,195) | 10.7 Units on a scale | Standard Error 1.3 |
| Placebo DB | Change in the Short Form 36 Health Survey (SF-36) | Physical functioning-DB BL to wk 19 | -4.9 Units on a scale | Standard Error 1.29 |
| Placebo DB | Change in the Short Form 36 Health Survey (SF-36) | Role-Emotional-SB BL to wk 19 | 11.6 Units on a scale | Standard Error 1.47 |
| Placebo DB | Change in the Short Form 36 Health Survey (SF-36) | Role-Physical-SB BL to wk 19 | 13.9 Units on a scale | Standard Error 1.67 |
| Placebo DB | Change in the Short Form 36 Health Survey (SF-36) | Vitality-DB BL to wk 19(N=202,195) | -6.5 Units on a scale | Standard Error 1.25 |
| Placebo DB | Change in the Short Form 36 Health Survey (SF-36) | Role-Physical-DB BL to wk 19 | -7.7 Units on a scale | Standard Error 1.6 |
| Placebo DB | Change in the Short Form 36 Health Survey (SF-36) | Mental Health-SB BL to wk 19(N=202,195) | 9.5 Units on a scale | Standard Error 1.08 |
| Placebo DB | Change in the Short Form 36 Health Survey (SF-36) | Bodily pain-SB BL to wk 19 | 23.6 Units on a scale | Standard Error 1.56 |
| Placebo DB | Change in the Short Form 36 Health Survey (SF-36) | Social Functioning-SB BL to wk 19 | 15.7 Units on a scale | Standard Error 1.39 |
| Placebo DB | Change in the Short Form 36 Health Survey (SF-36) | Bodily pain-DB BL to wk 19 | -6.2 Units on a scale | Standard Error 1.43 |
Comparison: This ANCOVA model analysis is for Vitality-SB Baseline to Week 19. Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: 0.073595% CI: [-0.3, 6.4]ANCOVA
Comparison: This ANCOVA model analysis is for Vitality-DB Baseline to Week 19. Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: 0.068495% CI: [-0.2, 6.2]ANCOVA
Comparison: This ANCOVA model analysis is for Bodily pain-SB Baseline to Week 19. Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: 0.000395% CI: [3.4, 11.5]ANCOVA
Comparison: This ANCOVA model analysis is for Bodily pain-DB Baseline to Week 19. Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: <0.000195% CI: [4, 11.3]ANCOVA
Comparison: This ANCOVA model analysis is for General Health Perceptions-SB Baseline to Week 19.~Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: 0.027595% CI: [0.4, 6]ANCOVA
Comparison: This ANCOVA model analysis is for General Health Perceptions-DB Baseline to Week 19.~Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: <0.000195% CI: [2.8, 8]ANCOVA
Comparison: This ANCOVA model analysis is for Social Functioning-SB Baseline to Week 19. Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: 0.119795% CI: [-0.7, 6.4]ANCOVA
Comparison: This ANCOVA model analysis is for Social Functioning-DB Baseline to Week 19. Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: 0.22195% CI: [-1.3, 5.5]ANCOVA
Comparison: This ANCOVA model analysis is for Role-Emotional-SB Baseline to Week 19. Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: 0.084795% CI: [-0.5, 7.1]ANCOVA
Comparison: This ANCOVA model analysis is for Role-Emotional-DB Baseline to Week 19. Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: 0.036595% CI: [0.3, 7.8]ANCOVA
Comparison: This ANCOVA model analysis is for Mental Health-SB Baseline to Week 19. Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: 0.274995% CI: [-1.2, 4.3]ANCOVA
Comparison: This ANCOVA model analysis is for Mental Health-SB Baseline to Week 19. Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: 0.080695% CI: [-0.3, 5.2]ANCOVA
Comparison: This ANCOVA model analysis is for Physical component-SB Baseline to Week 19. Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: 0.008295% CI: [0.5, 3.4]ANCOVA
Comparison: This ANCOVA model analysis is for Physical component-DB Baseline to Week 19. Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: 0.000895% CI: [1, 3.7]ANCOVA
Comparison: This ANCOVA model analysis is for Mental component-SB Baseline to Week 19. Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: 0.209795% CI: [-0.8, 2.5]ANCOVA
Comparison: This ANCOVA model analysis is for Mental component-DB Baseline to Week 19. Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: 0.166995% CI: [-0.5, 2.8]ANCOVA
Comparison: This ANCOVA model analysis is for Physical functioning-SB Baseline to Week 19. Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: 0.146695% CI: [-1, 6.7]ANCOVA
Comparison: This ANCOVA model analysis is for Physical functioning-DB Baseline to Week 19. Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: 0.043995% CI: [0.1, 6.7]ANCOVA
Comparison: This ANCOVA model analysis is for Role Physical-SB Baseline to Week 19. Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: 0.02595% CI: [0.6, 9.3]ANCOVA
Comparison: This ANCOVA model analysis is for Role Physical-DB Baseline to Week 19. Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: 0.010795% CI: [1.3, 9.5]ANCOVA
Secondary
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.
Time frame: SB Baseline (Enrollment) to Week 19 and DB Baseline (Week 6) to Week 19
Population: The FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study drug in the DB phase.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin CR DB | Change in the Weekly NRS-Pain (1-Week Recall). | SB Baseline to Week 19 | -5.0 Units on a scale | Standard Error 0.13 |
| Pregabalin CR DB | Change in the Weekly NRS-Pain (1-Week Recall). | DB Baseline to Week 19 | -0.1 Units on a scale | Standard Error 0.13 |
| Placebo DB | Change in the Weekly NRS-Pain (1-Week Recall). | SB Baseline to Week 19 | -3.9 Units on a scale | Standard Error 0.14 |
| Placebo DB | Change in the Weekly NRS-Pain (1-Week Recall). | DB Baseline to Week 19 | 0.9 Units on a scale | Standard Error 0.13 |
Comparison: This ANCOVA model analysis is for SB Baseline to Week 19. Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: <0.000195% CI: [-1.47, -0.75]ANCOVA
Comparison: This ANCOVA model analysis is for DB Baseline to Week 19. Estimates and p-values are from an analysis of covariance main effects model with SB baseline value, center, and treatment in the model.p-value: <0.000195% CI: [-1.34, -0.65]ANCOVA
Secondary
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.
Time frame: Baseline to Week 20
Population: The SB Analysis Set (SBAS) consisted of all participants who were enrolled into the SB phase of the study and received at least 1 dose of study medication; The FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study medication in the DB phase.~Both SBAS and FAS were included in this analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pregabalin CR DB | Number of Participants With Adverse Events | Participants with Serious AEs | 7 Participants |
| Pregabalin CR DB | Number of Participants With Adverse Events | Participants with AEs | 80 Participants |
| Pregabalin CR DB | Number of Participants With Adverse Events | Participants with Severe AEs | 9 Participants |
| Placebo DB | Number of Participants With Adverse Events | Participants with Serious AEs | 3 Participants |
| Placebo DB | Number of Participants With Adverse Events | Participants with AEs | 63 Participants |
| Placebo DB | Number of Participants With Adverse Events | Participants with Severe AEs | 3 Participants |
| Pregabalin CR SB | Number of Participants With Adverse Events | Participants with AEs | 441 Participants |
| Pregabalin CR SB | Number of Participants With Adverse Events | Participants with Severe AEs | 35 Participants |
| Pregabalin CR SB | Number of Participants With Adverse Events | Participants with Serious AEs | 17 Participants |
Secondary
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: 1. At least a 30% increase in the 5 days rolling average pain score during DB relative to the 5 Day randomization baseline pain score 2. 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.
Time frame: 13 Weeks
Population: The FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study drug in the DB phase
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pregabalin CR DB | Participants With Secondary LTR Based on 5 Day Rolling Average Diary Results | 49 Participants |
| Placebo DB | Participants With Secondary LTR Based on 5 Day Rolling Average Diary Results | 87 Participants |
Comparison: Kaplan-Meier method was used for the analysis.p-value: <0.0001Log Rank
Secondary
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.
Time frame: 13 Weeks
Population: The FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study drug in the DB phase.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pregabalin CR DB | Percentage of Participants With 30% Reduction in the Mean Pain Score. | 95.6 Percentage of participants |
| Placebo DB | Percentage of Participants With 30% Reduction in the Mean Pain Score. | 83.8 Percentage of participants |
Comparison: Chi-square test was used for analysis.p-value: <0.0001Chi-squared
Secondary
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.
Time frame: 13 Weeks
Population: The FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study drug in the DB phase.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pregabalin CR DB | Percentage of Participants With 50% Reduction in the Mean Pain Score. | 88.3 Percentage of participants |
| Placebo DB | Percentage of Participants With 50% Reduction in the Mean Pain Score. | 68.6 Percentage of participants |
Comparison: Chi-square test was used for analysis.p-value: <0.0001Chi-squared
Secondary
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.
Time frame: Week 19
Population: The FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study drug in the DB phase.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pregabalin CR DB | Percentage of Participants With Benefit From Treatment, Satisfaction With Treatment and Willingness to Continue Treatement (BSW) | Benefit from treatment | 98.5 Percentage of participants |
| Pregabalin CR DB | Percentage of Participants With Benefit From Treatment, Satisfaction With Treatment and Willingness to Continue Treatement (BSW) | Satisfaction with treatment | 96.0 Percentage of participants |
| Pregabalin CR DB | Percentage of Participants With Benefit From Treatment, Satisfaction With Treatment and Willingness to Continue Treatement (BSW) | Willingness to continue treatment | 87.6 Percentage of participants |
| Placebo DB | Percentage of Participants With Benefit From Treatment, Satisfaction With Treatment and Willingness to Continue Treatement (BSW) | Benefit from treatment | 93.3 Percentage of participants |
| Placebo DB | Percentage of Participants With Benefit From Treatment, Satisfaction With Treatment and Willingness to Continue Treatement (BSW) | Satisfaction with treatment | 90.7 Percentage of participants |
| Placebo DB | Percentage of Participants With Benefit From Treatment, Satisfaction With Treatment and Willingness to Continue Treatement (BSW) | Willingness to continue treatment | 81.3 Percentage of participants |
Comparison: This analysis is for 'Benefit from treatment'. Proportional odds logistic regression was used with a term for treatment in the model.p-value: 0.016195% CI: [1.34, 17]Regression, Logistic
Comparison: This analysis is for 'Satisfaction with treatment'. Proportional odds logistic regression was used with a term for treatment in the model.p-value: 0.037895% CI: [1.05, 5.85]Regression, Logistic
Comparison: This analysis is for 'Willingness to continue treatment'. Proportional odds logistic regression was used with a term for treatment in the model.p-value: 0.090195% CI: [0.93, 2.81]Regression, Logistic
Secondary
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.
Time frame: Week 19
Population: The FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study drug in the DB phase.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pregabalin CR DB | Percentage of Participants With Change in the Patient Global Impression of Change (PGIC) Score | Minimally improved | 16.7 Percentage of participants |
| Pregabalin CR DB | Percentage of Participants With Change in the Patient Global Impression of Change (PGIC) Score | Minimally worse | 2.5 Percentage of participants |
| Pregabalin CR DB | Percentage of Participants With Change in the Patient Global Impression of Change (PGIC) Score | Much improved | 36.9 Percentage of participants |
| Pregabalin CR DB | Percentage of Participants With Change in the Patient Global Impression of Change (PGIC) Score | Much worse | 1.5 Percentage of participants |
| Pregabalin CR DB | Percentage of Participants With Change in the Patient Global Impression of Change (PGIC) Score | No change | 10.3 Percentage of participants |
| Pregabalin CR DB | Percentage of Participants With Change in the Patient Global Impression of Change (PGIC) Score | Very much worse | 0.5 Percentage of participants |
| Pregabalin CR DB | Percentage of Participants With Change in the Patient Global Impression of Change (PGIC) Score | Very much improved | 31.5 Percentage of participants |
| Placebo DB | Percentage of Participants With Change in the Patient Global Impression of Change (PGIC) Score | Very much worse | 0.5 Percentage of participants |
| Placebo DB | Percentage of Participants With Change in the Patient Global Impression of Change (PGIC) Score | Very much improved | 23.1 Percentage of participants |
| Placebo DB | Percentage of Participants With Change in the Patient Global Impression of Change (PGIC) Score | Much improved | 30.3 Percentage of participants |
| Placebo DB | Percentage of Participants With Change in the Patient Global Impression of Change (PGIC) Score | Minimally improved | 19.0 Percentage of participants |
| Placebo DB | Percentage of Participants With Change in the Patient Global Impression of Change (PGIC) Score | No change | 12.8 Percentage of participants |
| Placebo DB | Percentage of Participants With Change in the Patient Global Impression of Change (PGIC) Score | Minimally worse | 7.2 Percentage of participants |
| Placebo DB | Percentage of Participants With Change in the Patient Global Impression of Change (PGIC) Score | Much worse | 7.2 Percentage of participants |
Comparison: This analysis is for the original score. Proportional odds Logistic regression with a term for treatment in the model.p-value: 0.000795% CI: [1.3, 2.65]Regression, Logistic
Comparison: This analysis is for the categorized score. Proportional odds Logistic regression with a term for treatment in the model.p-value: 0.000995% CI: [1.41, 3.81]Regression, Logistic
Secondary
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.
Time frame: Baseline, Weeks 6, 11, 15, 19 and 20
Population: The FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study drug in the DB phase.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pregabalin CR DB | Percentage of Participants With Suicidal Behaviour/Ideation | SB BL(N=208,205) | 0 Percentage of participants |
| Pregabalin CR DB | Percentage of Participants With Suicidal Behaviour/Ideation | Week 6 (N=208,205) | 0 Percentage of participants |
| Pregabalin CR DB | Percentage of Participants With Suicidal Behaviour/Ideation | Week 11 (N=194,178) | 0 Percentage of participants |
| Pregabalin CR DB | Percentage of Participants With Suicidal Behaviour/Ideation | Week 15 (N=183,167) | 0 Percentage of participants |
| Pregabalin CR DB | Percentage of Participants With Suicidal Behaviour/Ideation | Week 19 (N=204,197) | 0 Percentage of participants |
| Pregabalin CR DB | Percentage of Participants With Suicidal Behaviour/Ideation | Week 20 (N=199,194) | 0 Percentage of participants |
| Placebo DB | Percentage of Participants With Suicidal Behaviour/Ideation | Week 19 (N=204,197) | 0 Percentage of participants |
| Placebo DB | Percentage of Participants With Suicidal Behaviour/Ideation | SB BL(N=208,205) | 0.5 Percentage of participants |
| Placebo DB | Percentage of Participants With Suicidal Behaviour/Ideation | Week 15 (N=183,167) | 0 Percentage of participants |
| Placebo DB | Percentage of Participants With Suicidal Behaviour/Ideation | Week 6 (N=208,205) | 0 Percentage of participants |
| Placebo DB | Percentage of Participants With Suicidal Behaviour/Ideation | Week 20 (N=199,194) | 0 Percentage of participants |
| Placebo DB | Percentage of Participants With Suicidal Behaviour/Ideation | Week 11 (N=194,178) | 0 Percentage of participants |
Secondary
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.
Time frame: Week 6 and Week 19
Population: The FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study drug in the DB phase.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Pregabalin CR DB | The MOS-SS-Optimal Sleep. | Week 6 (N=208,205) | 58.7 Percentage of participants | 0.09 |
| Pregabalin CR DB | The MOS-SS-Optimal Sleep. | Week 19 (N=204,197) | 54.9 Percentage of participants | 0.08 |
| Placebo DB | The MOS-SS-Optimal Sleep. | Week 6 (N=208,205) | 62.4 Percentage of participants | 0.1 |
| Placebo DB | The MOS-SS-Optimal Sleep. | Week 19 (N=204,197) | 54.8 Percentage of participants | 0.09 |
Comparison: This analysis is for Week 6p-value: 0.432Chi-squared
Comparison: This analysis is for Week 19p-value: 0.987Chi-squared