Neuralgia, Postherpetic
Conditions
Keywords
Neuropathic Pain, Post-herpetic neuralgia, PHN
Brief summary
The purpose of this study is to determine whether gabapentin enacarbil (XP13512/GSK1838262), hereafter referred to as GEn is effective in the treatment of neuropathic pain associated with post-herpetic neuralgia (PHN).
Detailed description
The primary purpose of study PXN110748 was to evaluate efficacy and safety of 3 fixed doses of GEn in the treatment of PHN.
Interventions
DRUGGEn 1200mg/day
gabapentin enacarbil 1200mg/day
DRUGGEn 2400mg/day
gabapentin enacarbil 2400mg/day
DRUGGEn 3600mg/day
gabapentin enacarbil 3600mg/day
DRUGPlacebo
placebo
Sponsors
XenoPort, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years or older * Female subjects are eligible if of non-childbearing potential or not lactating, has a negative pregnancy, and agrees to use one a specified highly effective method for avoiding pregnancy * Documented medical diagnosis of PHN of with pain present for at least three months from the healing of a herpes zoster rash * Baseline 24-hour average pain intensity score ≥ 4.0 based on an 11-point PI-NRS * Provides written informed consent in accordance with all applicable regulatory requirements
Exclusion criteria
* Other chronic pain conditions not associated with PHN. However, the subject will not be excluded if: * The pain is located at a different region of the body; and * The pain intensity is not greater than the pain intensity of the PHN; and * The subject can assess PHN pain independently of other pain * Is unable to discontinue prohibited medications or non-drug therapies or procedures throughout the duration of the study * Hepatic impairment defined as ALT or AST \> 2x upper limit of normal (ULN), or alkaline phosphatase or bilirubin \> 1.5x ULN * Chronic hepatitis B or C * Impaired renal function defined as creatinine clearance \<60 mL/min or requiring hemodialysis * Corrected QT (QTc) interval ≥ 450 msec or QTc interval ≥480 msec for patients with Bundle Branch Block * Uncontrolled hypertension at screen (sitting systolic \>160 mmHg and/or sitting diastolic \>90 mmHg) * Current diagnosis of active epilepsy or any active seizure disorder requiring chronic therapy with antiepileptic drugs * Medical condition or disorder that would interfere with the action, absorption, distribution, metabolism, or excretion of GEn, or, in the investigator's judgment * Is considered to be clinically significant and may pose a safety concern, or, * Could interfere with the accurate assessment of safety or efficacy, or, * Could potentially affect a subject's safety or study outcome * Meets criteria defined by the DSM-IV-TR for a major depressive episode or for active significant psychiatric disorders within last year * Depression in remission, with or without antidepressant treatment, may participate, unless stable antidepressant regimen is a prohibited medication * Antidepressant medication may not be changed or discontinued to meet entry criteria and must be stable for at least three months prior to enrollment * History of clinically significant drug or alcohol abuse (DSM-IV-TR) or is unable to refrain from substance abuse throughout the study. Benzodiazepines or atypical benzodiazepines as hypnotic sleep agents permitted. * Currently participating in another clinical study in which the subject is, or will be exposed to an investigational or non-investigational drug or device * Has participated in a clinical study and was exposed to investigational or non-investigational drug or device: * Within preceding month for studies unrelated to PHN, or * Within preceding six months for studies related to PHN * Treated previously with GEn * History of allergic or medically significant adverse reaction to investigational products (including gabapentin) or their excipients, acetaminophen or related compounds
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Mean 24-hour Average Pain Intensity (API) Score at the End of Maintenance Treatment (EOMT) Using Last Observation Carried Forward (LOCF) Data | Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit) | Baseline and EOMT values are the calculated means of the daily 24-hour API scores for each participant during the last 7 days prior to randomization (Baseline) and the earliest date of Week 13 visit/Withdrawal visit/last dose of study drug (EOMT). Participants used a hand-held diary to rate their average pain intensity over the preceding 24 hours, using an 11-point PI-Numerical Rating Scale (0=no pain, 10=pain as bad as you can imagine). LOCF was used if less than 4 days of diary data were provided. Change from baseline was calculated as EOMT score minus Baseline score. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Mean Current Morning Pain Intensity Score at EOMT Using LOCF Data | Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit) | Current pain is defined as the participant's assessment of pain intensity right now. Participants recorded their current morning pain intensity in the morning upon wakening using an 11-point PI-NRS (0=no pain, 10=pain as bad as you can imagine). Baseline and EOMT are as defined for the primary endpoint. Change from baseline was calculated as the EOMT score minus the baseline score. An ANCOVA model with baseline value, BMI, grouped center as covariates was used. |
| Change From Baseline in the Mean Night-time Worst Pain Intensity Score at EOMT Using LOCF Data | Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit) | Night-time worst pain is defined as the participant's assessment of their worst pain between going to bed at night and rising in the morning. Participants recorded night-time worst pain in the morning upon awakening using an 11-point PI-NRS (0=no pain, 10=pain as bad as you can imagine). Baseline and EOMT are as defined for the primary endpoint. Change from baseline was calculated as the EOMT score minus the baseline score. An ANCOVA model with baseline value, BMI, grouped center as covariates was used. |
| Change From Baseline in the Mean Sleep Interference Score at EOMT Using LOCF Data | Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit) | Participants assessed sleep interference due to pain on a daily basis using the 11-point NRS (0=pain does not interfere with sleep, 10=pain completely interferes with sleep). Baseline and EOMT are as defined for the primary endpoint. Change from baseline was calculated as the EOMT score minus the baseline score. An ANCOVA model with baseline value, BMI, grouped center as covariates was used. |
| Change From Baseline in the Mean Day-time Average Pain Intensity(API) Score at EOMT Using LOCF Data | Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit) | Day-time is defined as the time between rising in the morning and going to bed at night. Participants recorded day-time API on a daily basis in the evening before bedtime using an 11-point PI-NRS (0=no pain, 10=pain as bad as you can imagine). Baseline and EOMT are as defined for the primary endpoint. Change from baseline was calculated as the EOMT score minus the baseline score. An ANCOVA model with baseline value, BMI, grouped center as covariates was used. |
| Change From Baseline in the Mean Current Evening Pain Intensity Score at EOMT Using LOCF Data | Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit) | Current pain is defined as the participant's assessment of pain intensity right now. Participants recorded their current evening pain intensity in the evening before bedtime using an 11-point PI-NRS (0=no pain, 10=pain as bad as you can imagine). Baseline and EOMT are as defined for the primary endpoint. Change from baseline was calculated as the EOMT score minus the baseline score. An ANCOVA model with baseline value, BMI, grouped center as covariates was used. |
| Change From Baseline in the Mean Day-time Worst Pain Intensity Score at EOMT Using LOCF Data | Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit) | Day-time worst pain is defined as the participant's assessment of their worst pain between rising in the morning and going to bed at night. Participants recorded day-time worst pain in the evening before bedtime using an 11-point PI-NRS (0=no pain, 10=pain as bad as you can imagine). Baseline and EOMT are as defined for the primary endpoint. Change from baseline was calculated as the EOMT score minus the baseline score. An ANCOVA model with baseline value, BMI, grouped center as covariates was used. |
| Change From Baseline in Pain Quality as Assessed by the Neuropathic Pain Scale (NPS) Summary Scores at EOMT Using LOCF Data | Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit) | The NPS assesses pain qualities and consists of 11-items, 10 assessed on an 11-point NRS (0=no impact to 10=greatest impact); and 1 open-ended question not used in score calculation. 4 summary scores are calculated: NPS 10 (items 1-7, 9-11), NPS 8 (8 pain descriptor items), NPS Non-Allodynic (NA) (8 NA items), and NPS 4 (4 pain quality items); and range from 0 to 100 (0=no impact and 100=greatest impact). The analysis is based on the change from baseline (BL) (EOMT score minus the BL score) using an ANCOVA model with BL value, BMI, grouped center as covariates. |
| Change From Baseline in Pain Characteristics and Intensity as Assessed by the Short Form-McGill Pain Questionnaire (SF-MPQ) at EOMT Using LOCF Data | Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit) | The SF-MPQ, a general pain instrument, assesses the characteristics and intensity of pain and consists of 15-items assessed on a 4-point scale (0=none, 1=mild, 2=moderate, and 3=severe). 3 summary scores are calculated: sensory score (sum of items 1-11, range 0-33), affective score (sum of items 12-15, range 0-12), total score (sum of items 1-15, range 0-45), where lower scores = lower pain/impact. Analysis is based on the change from baseline (BL) (EOMT score minus the BL score) using an ANCOVA model with BL value, BMI, grouped center as covariates. |
| Change From Baseline in the Mean Night-time Average Pain Intensity (API) Score at EOMT Using LOCF Data | Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit) | Night-time is defined as the time between going to bed at night and rising in the morning. Participants recorded night-time API on a daily basis in the morning upon awakening using an 11-point PI-NRS (0=no pain, 10=pain as bad as you can imagine). Baseline and EOMT are as defined for the primary endpoint. Change from baseline wss calculated as the EOMT score minus the baseline score. An ANCOVA model with baseline value, BMI, grouped center as covariates was used. |
| Number of Participants Who Are Responders on the Patient Global Impression of Change (PGIC) Questionnaire at EOMT Using LOCF Data | EOMT (representing the earliest date of Week 13 visit/withdrawal visit) | The PGIC is a single-item questionnaire designed to provide an overall assessment of treatment from the participant's perspective since the start of the study. It is measured on a 7-point scale, where 1=very much improved and 7=very much worse. A participant is considered a responder if they have a response of very much improved or much improved. EOMT response is defined as the score recorded at the Week13/Withdrawal visit. |
| Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit) | Baseline and EOMT scores are the calculated means of the 24-hour average pain scores for each participant during the last 7 days prior to randomization and EOMT, respectively. Percent reduction from baseline was calculated as the \[(EOMT score minus the baseline score)divided by the baseline score\], multiplied by 100. The PI-NRS is an 11-point scale (0=no pain, 10=pain as bad as you can imagine) by which a participant assesses their 24-hour average pain intensity. |
| Time to Onset of Sustained Improvement in the 24-hour Average Pain Intensity Score | Anytime post-baseline until date of last dose of study medication (up to Week 13) | Sustained improvement in the 24-hour average pain intensity score is defined as at least 2 consecutive days on which the 24-hour average pain intensity score is \>=2 points less than the mean 24-hour average pain intensity score at baseline. Time to onset is measured from baseline and was calculated as the first day of event minus the last day of baseline and is expressed in days. Baseline score is the calculated mean of the 24-hour average pain score for each participant during the last 7 days prior to randomization. |
| Change From Baseline in the Mean Daily Dose in Milligrams of Rescue Medication at EOMT Using LOCF Data | Baseline and EOMT (Week 13 or early withdrawal) | Mean daily use of rescue medication (milligrams of acetaminophen) was calculated by determining the average number of tablets taken per day of rescue medication (Commerical Tylenol) during treatment and multiplying that by 500 mg. Baseline and EOMT are as defined for the primary endpoint. Change from baseline was calculated as the EOMT score minus the baseline score. An ANCOVA model with baseline value, BMI, grouped center as covariates was used. |
| Change From Baseline in Severity of Pain and the Impact of Pain as Assessed by the Brief Pain Inventory (BPI) at EOMT Using LOCF Data | Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit) | The BPI, a general pain instrument, assesses the severity and interference of pain; and consists of 6 items assessed on an 11-point NRS (0=no impact and 10=greatest impact). 2 summary scores are calculated: BPI Severity Score (average of first 4 items) and BPI Interference Score (average of 7 responses to item 6); where each summary score ranges from 0 to 10 (0=no impact and 10=greatest impact). Analysis of this endpoint is based on the change from baseline (BL) (EOMT score minus the BL score) using an ANCOVA model with BL value, BMI, grouped center as covariates. |
| Change From Baseline in Quality of Life as Assessed by the SF-36 at EOMT Using LOCF Data | Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit) | The SF-36 is a general health-related quality of life instrument consisting of 36 items with various response options (Yes/No, 5- to 6-point Likert scale). Summary scores are calculated for 8 domains and 2 components (physical and mental); where scores range from 0 to 100 (higher scores = better quality of life). Analysis of this endpoint is based on the change from baseline (BL) (EOMT score minus the BL score) using an ANCOVA model with BL value, BMI, grouped center as covariates. |
| Change From Baseline in Emotional Functioning as Assessed by the POMS-B at EOMT Using LOCF Data | Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit) | The POMS-B, an emotional functioning instrument, assesses mood, tension, and other psychological symptoms and consists of 30-items assessed on a 5-point scale (0=not at all to 4=extremely). 6 summary scores are calculated: Tension/Anxiety, Depression/Rejection, Anger/Hostility, Vigor/Activity, Fatigue/Inertia, and Confusion/Bewilderment; and range from 0-20 (higher scores = more negative mood state). Analysis of this endpoint is based on the change from baseline (BL) (EOMT score minus the BL score) using an ANCOVA model with BL value, BMI, grouped center as covariates. |
| Number of Participants Who Are Responders on the Clinician Global Impression of Change (CGIC) Questionnaire at EOMT Using LOCF Data | EOMT (representing the earliest date of Week 13 visit/withdrawal visit) | The CGIC is a single-item questionnaire designed to provide an overall assessment of treatment from the clinician's perspective since the start of the study. It is measured on a 7-point scale, where 1=very much improved and 7=very much worse. A participant is considered a responder if they have a response of very much improved or much improved. EOMT response is defined as the score recorded at the Week13/Withdrawal visit. |
| Change From Baseline in Dynamic Allodynia at EOMT Using LOCF Data | Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit) | Dynamic allodynia (pain in response to a standardized light touch stimulus, a foam brush applied with light pressure to the site of maximum pain) was assessed by an 11-point PI-NRS (0=no pain, 10=pain as bad as you can imagine). Baseline and EOMT are as defined for the primary endpoint. Change from baseline was calculated as the EOMT score minus the baseline score. An ANCOVA model with baseline value, BMI, grouped center as covariates was used. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Three 600 milligram (mg) gabapentin enacarbil (XP13512/GSK1838262), hereafter referred to as GEn, placebo tablets taken orally twice daily (morning and evening) | 95 |
| GEn 1200 mg/Day One 600 mg GEn tablet and two GEn placebo tablets taken orally twice daily (morning and evening) | 107 |
| GEn 2400 mg/Day Two 600 mg GEn tablets and one GEN placebo tablet taken orally twice daily (morning and evening) | 82 |
| GEn 3600 mg/Day Three 600 mg GEn tablets taken orally twice daily (morning and evening) | 87 |
| Total | 371 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 12 | 6 | 12 | 16 |
| Overall Study | Investigator Discretion | 2 | 2 | 2 | 0 |
| Overall Study | Lack of Efficacy | 6 | 1 | 1 | 4 |
| Overall Study | Lost to Follow-up | 1 | 2 | 0 | 1 |
| Overall Study | Protocol Violation | 5 | 4 | 4 | 9 |
| Overall Study | Withdrawal by Subject | 5 | 7 | 5 | 4 |
Baseline characteristics
| Characteristic | Placebo | GEn 1200 mg/Day | GEn 2400 mg/Day | GEn 3600 mg/Day | Total |
|---|---|---|---|---|---|
| Age Continuous | 61.7 Years STANDARD_DEVIATION 12.77 | 61.7 Years STANDARD_DEVIATION 12.58 | 64.1 Years STANDARD_DEVIATION 8.94 | 61.3 Years STANDARD_DEVIATION 15.41 | 62.1 Years STANDARD_DEVIATION 12.67 |
| Race/Ethnicity, Customized African American/African Heritage | 14 participants | 11 participants | 8 participants | 11 participants | 44 participants |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 0 participants | 0 participants | 2 participants | 1 participants | 3 participants |
| Race/Ethnicity, Customized Asian - Central/South Asian Heritage | 1 participants | 0 participants | 1 participants | 0 participants | 2 participants |
| Race/Ethnicity, Customized Asian - Japanese/ East Asian Heritage | 0 participants | 1 participants | 1 participants | 1 participants | 3 participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 0 participants | 0 participants | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Not Provided | 1 participants | 1 participants | 1 participants | 0 participants | 3 participants |
| Race/Ethnicity, Customized White | 79 participants | 94 participants | 69 participants | 73 participants | 315 participants |
| Sex: Female, Male Female | 45 Participants | 54 Participants | 35 Participants | 48 Participants | 182 Participants |
| Sex: Female, Male Male | 50 Participants | 53 Participants | 47 Participants | 39 Participants | 189 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 63 / 120 | 75 / 107 | 64 / 82 | 71 / 87 |
| serious Total, serious adverse events | 2 / 95 | 0 / 107 | 6 / 82 | 2 / 87 |
Outcome results
Primary
Change From Baseline in the Mean 24-hour Average Pain Intensity (API) Score at the End of Maintenance Treatment (EOMT) Using Last Observation Carried Forward (LOCF) Data
Baseline and EOMT values are the calculated means of the daily 24-hour API scores for each participant during the last 7 days prior to randomization (Baseline) and the earliest date of Week 13 visit/Withdrawal visit/last dose of study drug (EOMT). Participants used a hand-held diary to rate their average pain intensity over the preceding 24 hours, using an 11-point PI-Numerical Rating Scale (0=no pain, 10=pain as bad as you can imagine). LOCF was used if less than 4 days of diary data were provided. Change from baseline was calculated as EOMT score minus Baseline score.
Time frame: Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
Population: ITT Population: all randomized participants who took at least one dose of investigational product and provided at least one post-baseline efficacy measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Mean 24-hour Average Pain Intensity (API) Score at the End of Maintenance Treatment (EOMT) Using Last Observation Carried Forward (LOCF) Data | -1.66 points on a scale | Standard Error 0.216 |
| GEn 1200 mg/Day | Change From Baseline in the Mean 24-hour Average Pain Intensity (API) Score at the End of Maintenance Treatment (EOMT) Using Last Observation Carried Forward (LOCF) Data | -2.47 points on a scale | Standard Error 0.204 |
| GEn 2400 mg/Day | Change From Baseline in the Mean 24-hour Average Pain Intensity (API) Score at the End of Maintenance Treatment (EOMT) Using Last Observation Carried Forward (LOCF) Data | -2.36 points on a scale | Standard Error 0.237 |
| GEn 3600 mg/Day | Change From Baseline in the Mean 24-hour Average Pain Intensity (API) Score at the End of Maintenance Treatment (EOMT) Using Last Observation Carried Forward (LOCF) Data | -2.72 points on a scale | Standard Error 0.227 |
p-value: 0.01395% CI: [-1.4, -0.23]ANCOVA
p-value: 0.02995% CI: [-1.33, -0.07]ANCOVA
p-value: 0.00295% CI: [-1.68, -0.45]ANCOVA
Secondary
Change From Baseline in Dynamic Allodynia at EOMT Using LOCF Data
Dynamic allodynia (pain in response to a standardized light touch stimulus, a foam brush applied with light pressure to the site of maximum pain) was assessed by an 11-point PI-NRS (0=no pain, 10=pain as bad as you can imagine). Baseline and EOMT are as defined for the primary endpoint. Change from baseline was calculated as the EOMT score minus the baseline score. An ANCOVA model with baseline value, BMI, grouped center as covariates was used.
Time frame: Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
Population: ITT Population. The NRS analysis included a subset of the ITT Population who completed that NRS at both the Baseline and the Week13/Withdrawal Visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Dynamic Allodynia at EOMT Using LOCF Data | -2.29 points on a scale | Standard Error 0.15 |
| GEn 1200 mg/Day | Change From Baseline in Dynamic Allodynia at EOMT Using LOCF Data | -1.97 points on a scale | Standard Error 0.137 |
| GEn 2400 mg/Day | Change From Baseline in Dynamic Allodynia at EOMT Using LOCF Data | -2.16 points on a scale | Standard Error 0.161 |
| GEn 3600 mg/Day | Change From Baseline in Dynamic Allodynia at EOMT Using LOCF Data | -2.25 points on a scale | Standard Error 0.161 |
Secondary
Change From Baseline in Emotional Functioning as Assessed by the POMS-B at EOMT Using LOCF Data
The POMS-B, an emotional functioning instrument, assesses mood, tension, and other psychological symptoms and consists of 30-items assessed on a 5-point scale (0=not at all to 4=extremely). 6 summary scores are calculated: Tension/Anxiety, Depression/Rejection, Anger/Hostility, Vigor/Activity, Fatigue/Inertia, and Confusion/Bewilderment; and range from 0-20 (higher scores = more negative mood state). Analysis of this endpoint is based on the change from baseline (BL) (EOMT score minus the BL score) using an ANCOVA model with BL value, BMI, grouped center as covariates.
Time frame: Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
Population: ITT Population. Not all participants completed a POMS-B at both Baseline and Week 13/Withdrawal; as such, the number analyzed is different from the full ITT Population counts.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Emotional Functioning as Assessed by the POMS-B at EOMT Using LOCF Data | Tension/Anxiety Domain Score | -1.6 points on a scale | Standard Error 0.29 |
| Placebo | Change From Baseline in Emotional Functioning as Assessed by the POMS-B at EOMT Using LOCF Data | Anger/Hostility Domain Score | -1.6 points on a scale | Standard Error 0.29 |
| Placebo | Change From Baseline in Emotional Functioning as Assessed by the POMS-B at EOMT Using LOCF Data | Vigor/Activity Domain Score | 0.4 points on a scale | Standard Error 0.38 |
| Placebo | Change From Baseline in Emotional Functioning as Assessed by the POMS-B at EOMT Using LOCF Data | Fatigue/Inertia Domain Score | -1.4 points on a scale | Standard Error 0.4 |
| Placebo | Change From Baseline in Emotional Functioning as Assessed by the POMS-B at EOMT Using LOCF Data | Depression/Rejection Domain Score | -1.4 points on a scale | Standard Error 0.28 |
| Placebo | Change From Baseline in Emotional Functioning as Assessed by the POMS-B at EOMT Using LOCF Data | Confusion/Bewilderment Domain Score | -0.7 points on a scale | Standard Error 0.25 |
| GEn 1200 mg/Day | Change From Baseline in Emotional Functioning as Assessed by the POMS-B at EOMT Using LOCF Data | Anger/Hostility Domain Score | -2.0 points on a scale | Standard Error 0.27 |
| GEn 1200 mg/Day | Change From Baseline in Emotional Functioning as Assessed by the POMS-B at EOMT Using LOCF Data | Depression/Rejection Domain Score | -1.5 points on a scale | Standard Error 0.26 |
| GEn 1200 mg/Day | Change From Baseline in Emotional Functioning as Assessed by the POMS-B at EOMT Using LOCF Data | Fatigue/Inertia Domain Score | -1.9 points on a scale | Standard Error 0.37 |
| GEn 1200 mg/Day | Change From Baseline in Emotional Functioning as Assessed by the POMS-B at EOMT Using LOCF Data | Tension/Anxiety Domain Score | -1.8 points on a scale | Standard Error 0.26 |
| GEn 1200 mg/Day | Change From Baseline in Emotional Functioning as Assessed by the POMS-B at EOMT Using LOCF Data | Vigor/Activity Domain Score | 0.8 points on a scale | Standard Error 0.35 |
| GEn 1200 mg/Day | Change From Baseline in Emotional Functioning as Assessed by the POMS-B at EOMT Using LOCF Data | Confusion/Bewilderment Domain Score | -0.5 points on a scale | Standard Error 0.22 |
| GEn 2400 mg/Day | Change From Baseline in Emotional Functioning as Assessed by the POMS-B at EOMT Using LOCF Data | Fatigue/Inertia Domain Score | -2.4 points on a scale | Standard Error 0.43 |
| GEn 2400 mg/Day | Change From Baseline in Emotional Functioning as Assessed by the POMS-B at EOMT Using LOCF Data | Anger/Hostility Domain Score | -2.4 points on a scale | Standard Error 0.31 |
| GEn 2400 mg/Day | Change From Baseline in Emotional Functioning as Assessed by the POMS-B at EOMT Using LOCF Data | Vigor/Activity Domain Score | 0.5 points on a scale | Standard Error 0.41 |
| GEn 2400 mg/Day | Change From Baseline in Emotional Functioning as Assessed by the POMS-B at EOMT Using LOCF Data | Confusion/Bewilderment Domain Score | -1.0 points on a scale | Standard Error 0.26 |
| GEn 2400 mg/Day | Change From Baseline in Emotional Functioning as Assessed by the POMS-B at EOMT Using LOCF Data | Tension/Anxiety Domain Score | -2.0 points on a scale | Standard Error 0.3 |
| GEn 2400 mg/Day | Change From Baseline in Emotional Functioning as Assessed by the POMS-B at EOMT Using LOCF Data | Depression/Rejection Domain Score | -1.9 points on a scale | Standard Error 0.3 |
| GEn 3600 mg/Day | Change From Baseline in Emotional Functioning as Assessed by the POMS-B at EOMT Using LOCF Data | Confusion/Bewilderment Domain Score | -0.5 points on a scale | Standard Error 0.26 |
| GEn 3600 mg/Day | Change From Baseline in Emotional Functioning as Assessed by the POMS-B at EOMT Using LOCF Data | Depression/Rejection Domain Score | -1.7 points on a scale | Standard Error 0.3 |
| GEn 3600 mg/Day | Change From Baseline in Emotional Functioning as Assessed by the POMS-B at EOMT Using LOCF Data | Tension/Anxiety Domain Score | -2.0 points on a scale | Standard Error 0.3 |
| GEn 3600 mg/Day | Change From Baseline in Emotional Functioning as Assessed by the POMS-B at EOMT Using LOCF Data | Vigor/Activity Domain Score | 1.4 points on a scale | Standard Error 0.41 |
| GEn 3600 mg/Day | Change From Baseline in Emotional Functioning as Assessed by the POMS-B at EOMT Using LOCF Data | Fatigue/Inertia Domain Score | -2.5 points on a scale | Standard Error 0.43 |
| GEn 3600 mg/Day | Change From Baseline in Emotional Functioning as Assessed by the POMS-B at EOMT Using LOCF Data | Anger/Hostility Domain Score | -1.7 points on a scale | Standard Error 0.31 |
Secondary
Change From Baseline in Pain Characteristics and Intensity as Assessed by the Short Form-McGill Pain Questionnaire (SF-MPQ) at EOMT Using LOCF Data
The SF-MPQ, a general pain instrument, assesses the characteristics and intensity of pain and consists of 15-items assessed on a 4-point scale (0=none, 1=mild, 2=moderate, and 3=severe). 3 summary scores are calculated: sensory score (sum of items 1-11, range 0-33), affective score (sum of items 12-15, range 0-12), total score (sum of items 1-15, range 0-45), where lower scores = lower pain/impact. Analysis is based on the change from baseline (BL) (EOMT score minus the BL score) using an ANCOVA model with BL value, BMI, grouped center as covariates.
Time frame: Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
Population: ITT Population. The SF-MPQ analysis included a subset of the ITT Population who completed a SF-MPQ assessment at both Baseline and the Week 13/Withdrawal Visit.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Pain Characteristics and Intensity as Assessed by the Short Form-McGill Pain Questionnaire (SF-MPQ) at EOMT Using LOCF Data | SF-MPQ Sensory Score | -4.51 points on a scale | Standard Error 0.737 |
| Placebo | Change From Baseline in Pain Characteristics and Intensity as Assessed by the Short Form-McGill Pain Questionnaire (SF-MPQ) at EOMT Using LOCF Data | SF-MPQ Affective Score | -1.58 points on a scale | Standard Error 0.27 |
| Placebo | Change From Baseline in Pain Characteristics and Intensity as Assessed by the Short Form-McGill Pain Questionnaire (SF-MPQ) at EOMT Using LOCF Data | SF-MPQ Total Score | -6.08 points on a scale | Standard Error 0.949 |
| GEn 1200 mg/Day | Change From Baseline in Pain Characteristics and Intensity as Assessed by the Short Form-McGill Pain Questionnaire (SF-MPQ) at EOMT Using LOCF Data | SF-MPQ Total Score | -8.35 points on a scale | Standard Error 0.869 |
| GEn 1200 mg/Day | Change From Baseline in Pain Characteristics and Intensity as Assessed by the Short Form-McGill Pain Questionnaire (SF-MPQ) at EOMT Using LOCF Data | SF-MPQ Affective Score | -2.27 points on a scale | Standard Error 0.247 |
| GEn 1200 mg/Day | Change From Baseline in Pain Characteristics and Intensity as Assessed by the Short Form-McGill Pain Questionnaire (SF-MPQ) at EOMT Using LOCF Data | SF-MPQ Sensory Score | -6.07 points on a scale | Standard Error 0.675 |
| GEn 2400 mg/Day | Change From Baseline in Pain Characteristics and Intensity as Assessed by the Short Form-McGill Pain Questionnaire (SF-MPQ) at EOMT Using LOCF Data | SF-MPQ Sensory Score | -5.43 points on a scale | Standard Error 0.795 |
| GEn 2400 mg/Day | Change From Baseline in Pain Characteristics and Intensity as Assessed by the Short Form-McGill Pain Questionnaire (SF-MPQ) at EOMT Using LOCF Data | SF-MPQ Total Score | -7.45 points on a scale | Standard Error 1.024 |
| GEn 2400 mg/Day | Change From Baseline in Pain Characteristics and Intensity as Assessed by the Short Form-McGill Pain Questionnaire (SF-MPQ) at EOMT Using LOCF Data | SF-MPQ Affective Score | -2.08 points on a scale | Standard Error 0.291 |
| GEn 3600 mg/Day | Change From Baseline in Pain Characteristics and Intensity as Assessed by the Short Form-McGill Pain Questionnaire (SF-MPQ) at EOMT Using LOCF Data | SF-MPQ Total Score | -8.15 points on a scale | Standard Error 1.006 |
| GEn 3600 mg/Day | Change From Baseline in Pain Characteristics and Intensity as Assessed by the Short Form-McGill Pain Questionnaire (SF-MPQ) at EOMT Using LOCF Data | SF-MPQ Affective Score | -1.99 points on a scale | Standard Error 0.286 |
| GEn 3600 mg/Day | Change From Baseline in Pain Characteristics and Intensity as Assessed by the Short Form-McGill Pain Questionnaire (SF-MPQ) at EOMT Using LOCF Data | SF-MPQ Sensory Score | -6.13 points on a scale | Standard Error 0.782 |
Secondary
Change From Baseline in Pain Quality as Assessed by the Neuropathic Pain Scale (NPS) Summary Scores at EOMT Using LOCF Data
The NPS assesses pain qualities and consists of 11-items, 10 assessed on an 11-point NRS (0=no impact to 10=greatest impact); and 1 open-ended question not used in score calculation. 4 summary scores are calculated: NPS 10 (items 1-7, 9-11), NPS 8 (8 pain descriptor items), NPS Non-Allodynic (NA) (8 NA items), and NPS 4 (4 pain quality items); and range from 0 to 100 (0=no impact and 100=greatest impact). The analysis is based on the change from baseline (BL) (EOMT score minus the BL score) using an ANCOVA model with BL value, BMI, grouped center as covariates.
Time frame: Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
Population: ITT Population. The NPS summary included a subset of the ITT Population that completed an NPS assessment at both Baseline and Week 13/Withdrawal.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Pain Quality as Assessed by the Neuropathic Pain Scale (NPS) Summary Scores at EOMT Using LOCF Data | NPS 10 Score | -17.17 points on a scale | Standard Error 2.094 |
| Placebo | Change From Baseline in Pain Quality as Assessed by the Neuropathic Pain Scale (NPS) Summary Scores at EOMT Using LOCF Data | NPS 8 Score | -17.05 points on a scale | Standard Error 2.059 |
| Placebo | Change From Baseline in Pain Quality as Assessed by the Neuropathic Pain Scale (NPS) Summary Scores at EOMT Using LOCF Data | NPS Non-Allodynic Score | -16.87 points on a scale | Standard Error 2.107 |
| Placebo | Change From Baseline in Pain Quality as Assessed by the Neuropathic Pain Scale (NPS) Summary Scores at EOMT Using LOCF Data | NPS 4 Score | -18.25 points on a scale | Standard Error 2.34 |
| GEn 1200 mg/Day | Change From Baseline in Pain Quality as Assessed by the Neuropathic Pain Scale (NPS) Summary Scores at EOMT Using LOCF Data | NPS 8 Score | -22.23 points on a scale | Standard Error 1.875 |
| GEn 1200 mg/Day | Change From Baseline in Pain Quality as Assessed by the Neuropathic Pain Scale (NPS) Summary Scores at EOMT Using LOCF Data | NPS Non-Allodynic Score | -22.58 points on a scale | Standard Error 1.92 |
| GEn 1200 mg/Day | Change From Baseline in Pain Quality as Assessed by the Neuropathic Pain Scale (NPS) Summary Scores at EOMT Using LOCF Data | NPS 4 Score | -24.37 points on a scale | Standard Error 2.133 |
| GEn 1200 mg/Day | Change From Baseline in Pain Quality as Assessed by the Neuropathic Pain Scale (NPS) Summary Scores at EOMT Using LOCF Data | NPS 10 Score | -22.78 points on a scale | Standard Error 1.907 |
| GEn 2400 mg/Day | Change From Baseline in Pain Quality as Assessed by the Neuropathic Pain Scale (NPS) Summary Scores at EOMT Using LOCF Data | NPS Non-Allodynic Score | -24.18 points on a scale | Standard Error 2.269 |
| GEn 2400 mg/Day | Change From Baseline in Pain Quality as Assessed by the Neuropathic Pain Scale (NPS) Summary Scores at EOMT Using LOCF Data | NPS 8 Score | -23.77 points on a scale | Standard Error 2.217 |
| GEn 2400 mg/Day | Change From Baseline in Pain Quality as Assessed by the Neuropathic Pain Scale (NPS) Summary Scores at EOMT Using LOCF Data | NPS 4 Score | -26.08 points on a scale | Standard Error 2.519 |
| GEn 2400 mg/Day | Change From Baseline in Pain Quality as Assessed by the Neuropathic Pain Scale (NPS) Summary Scores at EOMT Using LOCF Data | NPS 10 Score | -24.02 points on a scale | Standard Error 2.256 |
| GEn 3600 mg/Day | Change From Baseline in Pain Quality as Assessed by the Neuropathic Pain Scale (NPS) Summary Scores at EOMT Using LOCF Data | NPS 4 Score | -26.55 points on a scale | Standard Error 2.464 |
| GEn 3600 mg/Day | Change From Baseline in Pain Quality as Assessed by the Neuropathic Pain Scale (NPS) Summary Scores at EOMT Using LOCF Data | NPS 8 Score | -24.49 points on a scale | Standard Error 2.165 |
| GEn 3600 mg/Day | Change From Baseline in Pain Quality as Assessed by the Neuropathic Pain Scale (NPS) Summary Scores at EOMT Using LOCF Data | NPS 10 Score | -25.2 points on a scale | Standard Error 2.202 |
| GEn 3600 mg/Day | Change From Baseline in Pain Quality as Assessed by the Neuropathic Pain Scale (NPS) Summary Scores at EOMT Using LOCF Data | NPS Non-Allodynic Score | -24.54 points on a scale | Standard Error 2.216 |
Secondary
Change From Baseline in Quality of Life as Assessed by the SF-36 at EOMT Using LOCF Data
The SF-36 is a general health-related quality of life instrument consisting of 36 items with various response options (Yes/No, 5- to 6-point Likert scale). Summary scores are calculated for 8 domains and 2 components (physical and mental); where scores range from 0 to 100 (higher scores = better quality of life). Analysis of this endpoint is based on the change from baseline (BL) (EOMT score minus the BL score) using an ANCOVA model with BL value, BMI, grouped center as covariates.
Time frame: Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
Population: ITT Population. Not all participants completed an SF-36 at both Baseline and Week 13/Withdrawal; as such, the number analyzed is different from the full ITT Population counts.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Quality of Life as Assessed by the SF-36 at EOMT Using LOCF Data | SF-36 Mental Component Summary Score | 3.2 points on a scale | Standard Error 0.92 |
| Placebo | Change From Baseline in Quality of Life as Assessed by the SF-36 at EOMT Using LOCF Data | SF-36 Physical Component Summary Score | 3.3 points on a scale | Standard Error 0.74 |
| GEn 1200 mg/Day | Change From Baseline in Quality of Life as Assessed by the SF-36 at EOMT Using LOCF Data | SF-36 Mental Component Summary Score | 5.1 points on a scale | Standard Error 0.85 |
| GEn 1200 mg/Day | Change From Baseline in Quality of Life as Assessed by the SF-36 at EOMT Using LOCF Data | SF-36 Physical Component Summary Score | 4.3 points on a scale | Standard Error 0.67 |
| GEn 2400 mg/Day | Change From Baseline in Quality of Life as Assessed by the SF-36 at EOMT Using LOCF Data | SF-36 Mental Component Summary Score | 4.5 points on a scale | Standard Error 0.99 |
| GEn 2400 mg/Day | Change From Baseline in Quality of Life as Assessed by the SF-36 at EOMT Using LOCF Data | SF-36 Physical Component Summary Score | 4.4 points on a scale | Standard Error 0.79 |
| GEn 3600 mg/Day | Change From Baseline in Quality of Life as Assessed by the SF-36 at EOMT Using LOCF Data | SF-36 Physical Component Summary Score | 4.9 points on a scale | Standard Error 0.78 |
| GEn 3600 mg/Day | Change From Baseline in Quality of Life as Assessed by the SF-36 at EOMT Using LOCF Data | SF-36 Mental Component Summary Score | 5.8 points on a scale | Standard Error 0.99 |
Secondary
Change From Baseline in Severity of Pain and the Impact of Pain as Assessed by the Brief Pain Inventory (BPI) at EOMT Using LOCF Data
The BPI, a general pain instrument, assesses the severity and interference of pain; and consists of 6 items assessed on an 11-point NRS (0=no impact and 10=greatest impact). 2 summary scores are calculated: BPI Severity Score (average of first 4 items) and BPI Interference Score (average of 7 responses to item 6); where each summary score ranges from 0 to 10 (0=no impact and 10=greatest impact). Analysis of this endpoint is based on the change from baseline (BL) (EOMT score minus the BL score) using an ANCOVA model with BL value, BMI, grouped center as covariates.
Time frame: Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
Population: ITT Population. Not all participants completed a BPI assessment at both Baseline and Week 13/Withdrawal; as such, the number analyzed is different from the full ITT Population counts.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Severity of Pain and the Impact of Pain as Assessed by the Brief Pain Inventory (BPI) at EOMT Using LOCF Data | Brief Pain Inventory Interference of Pain | -2.0 points on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline in Severity of Pain and the Impact of Pain as Assessed by the Brief Pain Inventory (BPI) at EOMT Using LOCF Data | Brief Pain Inventory Severity of Pain | -1.8 points on a scale | Standard Error 0.22 |
| GEn 1200 mg/Day | Change From Baseline in Severity of Pain and the Impact of Pain as Assessed by the Brief Pain Inventory (BPI) at EOMT Using LOCF Data | Brief Pain Inventory Severity of Pain | -2.4 points on a scale | Standard Error 0.2 |
| GEn 1200 mg/Day | Change From Baseline in Severity of Pain and the Impact of Pain as Assessed by the Brief Pain Inventory (BPI) at EOMT Using LOCF Data | Brief Pain Inventory Interference of Pain | -2.2 points on a scale | Standard Error 0.19 |
| GEn 2400 mg/Day | Change From Baseline in Severity of Pain and the Impact of Pain as Assessed by the Brief Pain Inventory (BPI) at EOMT Using LOCF Data | Brief Pain Inventory Interference of Pain | -2.2 points on a scale | Standard Error 0.22 |
| GEn 2400 mg/Day | Change From Baseline in Severity of Pain and the Impact of Pain as Assessed by the Brief Pain Inventory (BPI) at EOMT Using LOCF Data | Brief Pain Inventory Severity of Pain | -2.4 points on a scale | Standard Error 0.24 |
| GEn 3600 mg/Day | Change From Baseline in Severity of Pain and the Impact of Pain as Assessed by the Brief Pain Inventory (BPI) at EOMT Using LOCF Data | Brief Pain Inventory Severity of Pain | -2.5 points on a scale | Standard Error 0.24 |
| GEn 3600 mg/Day | Change From Baseline in Severity of Pain and the Impact of Pain as Assessed by the Brief Pain Inventory (BPI) at EOMT Using LOCF Data | Brief Pain Inventory Interference of Pain | -2.3 points on a scale | Standard Error 0.22 |
Secondary
Change From Baseline in the Mean Current Evening Pain Intensity Score at EOMT Using LOCF Data
Current pain is defined as the participant's assessment of pain intensity right now. Participants recorded their current evening pain intensity in the evening before bedtime using an 11-point PI-NRS (0=no pain, 10=pain as bad as you can imagine). Baseline and EOMT are as defined for the primary endpoint. Change from baseline was calculated as the EOMT score minus the baseline score. An ANCOVA model with baseline value, BMI, grouped center as covariates was used.
Time frame: Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
Population: ITT Population. There was one participant in the GEn 1200 mg group and two in the 2400 mg group who did not complete enough post-baseline evening diaries to calculate a score for the EMOT timepoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Mean Current Evening Pain Intensity Score at EOMT Using LOCF Data | -1.45 points on a scale | Standard Error 0.225 |
| GEn 1200 mg/Day | Change From Baseline in the Mean Current Evening Pain Intensity Score at EOMT Using LOCF Data | -2.45 points on a scale | Standard Error 0.213 |
| GEn 2400 mg/Day | Change From Baseline in the Mean Current Evening Pain Intensity Score at EOMT Using LOCF Data | -2.24 points on a scale | Standard Error 0.247 |
| GEn 3600 mg/Day | Change From Baseline in the Mean Current Evening Pain Intensity Score at EOMT Using LOCF Data | -2.69 points on a scale | Standard Error 0.236 |
Secondary
Change From Baseline in the Mean Current Morning Pain Intensity Score at EOMT Using LOCF Data
Current pain is defined as the participant's assessment of pain intensity right now. Participants recorded their current morning pain intensity in the morning upon wakening using an 11-point PI-NRS (0=no pain, 10=pain as bad as you can imagine). Baseline and EOMT are as defined for the primary endpoint. Change from baseline was calculated as the EOMT score minus the baseline score. An ANCOVA model with baseline value, BMI, grouped center as covariates was used.
Time frame: Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
Population: ITT Population. There was one participant in the GEn 2400 mg group and one in the 3600 mg group who did not complete enough post-baseline morning diaries to calculate an API for the EMOT timepoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Mean Current Morning Pain Intensity Score at EOMT Using LOCF Data | -1.34 points on a scale | Standard Error 0.223 |
| GEn 1200 mg/Day | Change From Baseline in the Mean Current Morning Pain Intensity Score at EOMT Using LOCF Data | -2.29 points on a scale | Standard Error 0.209 |
| GEn 2400 mg/Day | Change From Baseline in the Mean Current Morning Pain Intensity Score at EOMT Using LOCF Data | -2.13 points on a scale | Standard Error 0.242 |
| GEn 3600 mg/Day | Change From Baseline in the Mean Current Morning Pain Intensity Score at EOMT Using LOCF Data | -2.41 points on a scale | Standard Error 0.234 |
Secondary
Change From Baseline in the Mean Daily Dose in Milligrams of Rescue Medication at EOMT Using LOCF Data
Mean daily use of rescue medication (milligrams of acetaminophen) was calculated by determining the average number of tablets taken per day of rescue medication (Commerical Tylenol) during treatment and multiplying that by 500 mg. Baseline and EOMT are as defined for the primary endpoint. Change from baseline was calculated as the EOMT score minus the baseline score. An ANCOVA model with baseline value, BMI, grouped center as covariates was used.
Time frame: Baseline and EOMT (Week 13 or early withdrawal)
Population: ITT Population. There was one participant in the GEn 1200 mg and two in the GEn 2400 mg group who did not have enough data available to calculate the rescue mediation consumed while on treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Mean Daily Dose in Milligrams of Rescue Medication at EOMT Using LOCF Data | -41.00 milligrams | Standard Error 89.488 |
| GEn 1200 mg/Day | Change From Baseline in the Mean Daily Dose in Milligrams of Rescue Medication at EOMT Using LOCF Data | -289.94 milligrams | Standard Error 84.35 |
| GEn 2400 mg/Day | Change From Baseline in the Mean Daily Dose in Milligrams of Rescue Medication at EOMT Using LOCF Data | -260.03 milligrams | Standard Error 97.853 |
| GEn 3600 mg/Day | Change From Baseline in the Mean Daily Dose in Milligrams of Rescue Medication at EOMT Using LOCF Data | -266.21 milligrams | Standard Error 93.503 |
Secondary
Change From Baseline in the Mean Day-time Average Pain Intensity(API) Score at EOMT Using LOCF Data
Day-time is defined as the time between rising in the morning and going to bed at night. Participants recorded day-time API on a daily basis in the evening before bedtime using an 11-point PI-NRS (0=no pain, 10=pain as bad as you can imagine). Baseline and EOMT are as defined for the primary endpoint. Change from baseline was calculated as the EOMT score minus the baseline score. An ANCOVA model with baseline value, BMI, grouped center as covariates was used.
Time frame: Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
Population: ITT Population. There was one participant in the GEn 1200 mg group and two in the 2400 mg group who did not complete enough post-baseline evening diaries to calculate an API for the EOMT timepoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Mean Day-time Average Pain Intensity(API) Score at EOMT Using LOCF Data | -1.59 points on a scale | Standard Error 0.218 |
| GEn 1200 mg/Day | Change From Baseline in the Mean Day-time Average Pain Intensity(API) Score at EOMT Using LOCF Data | -2.47 points on a scale | Standard Error 0.206 |
| GEn 2400 mg/Day | Change From Baseline in the Mean Day-time Average Pain Intensity(API) Score at EOMT Using LOCF Data | -2.23 points on a scale | Standard Error 0.239 |
| GEn 3600 mg/Day | Change From Baseline in the Mean Day-time Average Pain Intensity(API) Score at EOMT Using LOCF Data | -2.67 points on a scale | Standard Error 0.229 |
Secondary
Change From Baseline in the Mean Day-time Worst Pain Intensity Score at EOMT Using LOCF Data
Day-time worst pain is defined as the participant's assessment of their worst pain between rising in the morning and going to bed at night. Participants recorded day-time worst pain in the evening before bedtime using an 11-point PI-NRS (0=no pain, 10=pain as bad as you can imagine). Baseline and EOMT are as defined for the primary endpoint. Change from baseline was calculated as the EOMT score minus the baseline score. An ANCOVA model with baseline value, BMI, grouped center as covariates was used.
Time frame: Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
Population: ITT Population. There was one participant in the GEn 1220 mg group and two in the 2400 mg group who did not complete enough post-baseline evening diaries to calculate a score for the EOMT timepoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Mean Day-time Worst Pain Intensity Score at EOMT Using LOCF Data | -1.74 points on a scale | Standard Error 0.242 |
| GEn 1200 mg/Day | Change From Baseline in the Mean Day-time Worst Pain Intensity Score at EOMT Using LOCF Data | -2.61 points on a scale | Standard Error 0.229 |
| GEn 2400 mg/Day | Change From Baseline in the Mean Day-time Worst Pain Intensity Score at EOMT Using LOCF Data | -2.41 points on a scale | Standard Error 0.265 |
| GEn 3600 mg/Day | Change From Baseline in the Mean Day-time Worst Pain Intensity Score at EOMT Using LOCF Data | -2.82 points on a scale | Standard Error 0.253 |
Secondary
Change From Baseline in the Mean Night-time Average Pain Intensity (API) Score at EOMT Using LOCF Data
Night-time is defined as the time between going to bed at night and rising in the morning. Participants recorded night-time API on a daily basis in the morning upon awakening using an 11-point PI-NRS (0=no pain, 10=pain as bad as you can imagine). Baseline and EOMT are as defined for the primary endpoint. Change from baseline wss calculated as the EOMT score minus the baseline score. An ANCOVA model with baseline value, BMI, grouped center as covariates was used.
Time frame: Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
Population: ITT Population. There was one participant in the GEn 2400 mg group and one in the 3600 mg group who did not complete enough post-baseline morning diaries to calculate an API for the EOMT timepoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Mean Night-time Average Pain Intensity (API) Score at EOMT Using LOCF Data | -1.65 points on a scale | Standard Error 0.219 |
| GEn 1200 mg/Day | Change From Baseline in the Mean Night-time Average Pain Intensity (API) Score at EOMT Using LOCF Data | -2.35 points on a scale | Standard Error 0.206 |
| GEn 2400 mg/Day | Change From Baseline in the Mean Night-time Average Pain Intensity (API) Score at EOMT Using LOCF Data | -2.44 points on a scale | Standard Error 0.238 |
| GEn 3600 mg/Day | Change From Baseline in the Mean Night-time Average Pain Intensity (API) Score at EOMT Using LOCF Data | -2.50 points on a scale | Standard Error 0.231 |
Secondary
Change From Baseline in the Mean Night-time Worst Pain Intensity Score at EOMT Using LOCF Data
Night-time worst pain is defined as the participant's assessment of their worst pain between going to bed at night and rising in the morning. Participants recorded night-time worst pain in the morning upon awakening using an 11-point PI-NRS (0=no pain, 10=pain as bad as you can imagine). Baseline and EOMT are as defined for the primary endpoint. Change from baseline was calculated as the EOMT score minus the baseline score. An ANCOVA model with baseline value, BMI, grouped center as covariates was used.
Time frame: Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
Population: ITT Population. There was one participant in the GEn 2400 mg group and one in the 3600 mg group who did not complete enough post-baseline morning diaries to calculate an API for the EMOT timepoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Mean Night-time Worst Pain Intensity Score at EOMT Using LOCF Data | -1.76 points on a scale | Standard Error 0.239 |
| GEn 1200 mg/Day | Change From Baseline in the Mean Night-time Worst Pain Intensity Score at EOMT Using LOCF Data | -2.49 points on a scale | Standard Error 0.225 |
| GEn 2400 mg/Day | Change From Baseline in the Mean Night-time Worst Pain Intensity Score at EOMT Using LOCF Data | -2.65 points on a scale | Standard Error 0.26 |
| GEn 3600 mg/Day | Change From Baseline in the Mean Night-time Worst Pain Intensity Score at EOMT Using LOCF Data | -2.71 points on a scale | Standard Error 0.252 |
Secondary
Change From Baseline in the Mean Sleep Interference Score at EOMT Using LOCF Data
Participants assessed sleep interference due to pain on a daily basis using the 11-point NRS (0=pain does not interfere with sleep, 10=pain completely interferes with sleep). Baseline and EOMT are as defined for the primary endpoint. Change from baseline was calculated as the EOMT score minus the baseline score. An ANCOVA model with baseline value, BMI, grouped center as covariates was used.
Time frame: Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
Population: ITT Population. There was one participant in the GEn 2400 mg group and one in the 3600 mg group who did not complete enough post-baseline morning diaries to calculate a score for the EMOT timepoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Mean Sleep Interference Score at EOMT Using LOCF Data | -2.04 points on a scale | Standard Error 0.225 |
| GEn 1200 mg/Day | Change From Baseline in the Mean Sleep Interference Score at EOMT Using LOCF Data | -2.72 points on a scale | Standard Error 0.212 |
| GEn 2400 mg/Day | Change From Baseline in the Mean Sleep Interference Score at EOMT Using LOCF Data | -2.58 points on a scale | Standard Error 0.245 |
| GEn 3600 mg/Day | Change From Baseline in the Mean Sleep Interference Score at EOMT Using LOCF Data | -2.78 points on a scale | Standard Error 0.237 |
Secondary
Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data
Baseline and EOMT scores are the calculated means of the 24-hour average pain scores for each participant during the last 7 days prior to randomization and EOMT, respectively. Percent reduction from baseline was calculated as the \[(EOMT score minus the baseline score)divided by the baseline score\], multiplied by 100. The PI-NRS is an 11-point scale (0=no pain, 10=pain as bad as you can imagine) by which a participant assesses their 24-hour average pain intensity.
Time frame: Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
Population: ITT Population. There was one participant in the GEn 1200 mg and one in the GEn 2400 mg group who did not have enough data available to calculate the percent reduction.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | >= 10% reduction from baseline | 62 participants |
| Placebo | Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | >=0 reducation from baseline | 79 participants |
| Placebo | Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | >= 60% reduction from baseline | 15 participants |
| Placebo | Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | 100% reduction from baseline | 1 participants |
| Placebo | Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | >= 80% reduction from baseline | 8 participants |
| Placebo | Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | >= 90% reduction from baseline | 3 participants |
| Placebo | Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | >= 50% reduction from baseline | 22 participants |
| Placebo | Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | >= 40% reduction from baseline | 32 participants |
| Placebo | Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | >= 70% reduction from baseline | 9 participants |
| Placebo | Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | >= 30% reduction from baseline | 40 participants |
| Placebo | Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | >= 20% reduction from baseline | 50 participants |
| GEn 1200 mg/Day | Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | >= 80% reduction from baseline | 17 participants |
| GEn 1200 mg/Day | Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | >= 60% reduction from baseline | 34 participants |
| GEn 1200 mg/Day | Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | >= 70% reduction from baseline | 25 participants |
| GEn 1200 mg/Day | Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | >= 90% reduction from baseline | 9 participants |
| GEn 1200 mg/Day | Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | 100% reduction from baseline | 6 participants |
| GEn 1200 mg/Day | Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | >=0 reducation from baseline | 94 participants |
| GEn 1200 mg/Day | Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | >= 10% reduction from baseline | 83 participants |
| GEn 1200 mg/Day | Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | >= 20% reduction from baseline | 71 participants |
| GEn 1200 mg/Day | Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | >= 30% reduction from baseline | 57 participants |
| GEn 1200 mg/Day | Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | >= 40% reduction from baseline | 50 participants |
| GEn 1200 mg/Day | Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | >= 50% reduction from baseline | 44 participants |
| GEn 2400 mg/Day | Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | >=0 reducation from baseline | 71 participants |
| GEn 2400 mg/Day | Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | >= 80% reduction from baseline | 12 participants |
| GEn 2400 mg/Day | Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | >= 10% reduction from baseline | 61 participants |
| GEn 2400 mg/Day | Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | >= 60% reduction from baseline | 14 participants |
| GEn 2400 mg/Day | Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | >= 20% reduction from baseline | 55 participants |
| GEn 2400 mg/Day | Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | >= 70% reduction from baseline | 18 participants |
| GEn 2400 mg/Day | Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | >= 30% reduction from baseline | 48 participants |
| GEn 2400 mg/Day | Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | >= 90% reduction from baseline | 9 participants |
| GEn 2400 mg/Day | Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | >= 50% reduction from baseline | 28 participants |
| GEn 2400 mg/Day | Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | 100% reduction from baseline | 3 participants |
| GEn 2400 mg/Day | Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | >= 40% reduction from baseline | 39 participants |
| GEn 3600 mg/Day | Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | >= 70% reduction from baseline | 24 participants |
| GEn 3600 mg/Day | Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | >=0 reducation from baseline | 84 participants |
| GEn 3600 mg/Day | Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | 100% reduction from baseline | 7 participants |
| GEn 3600 mg/Day | Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | >= 40% reduction from baseline | 46 participants |
| GEn 3600 mg/Day | Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | >= 30% reduction from baseline | 52 participants |
| GEn 3600 mg/Day | Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | >= 10% reduction from baseline | 70 participants |
| GEn 3600 mg/Day | Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | >= 50% reduction from baseline | 37 participants |
| GEn 3600 mg/Day | Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | >= 60% reduction from baseline | 31 participants |
| GEn 3600 mg/Day | Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | >= 90% reduction from baseline | 12 participants |
| GEn 3600 mg/Day | Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | >= 20% reduction from baseline | 65 participants |
| GEn 3600 mg/Day | Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data | >= 80% reduction from baseline | 19 participants |
Secondary
Number of Participants Who Are Responders on the Clinician Global Impression of Change (CGIC) Questionnaire at EOMT Using LOCF Data
The CGIC is a single-item questionnaire designed to provide an overall assessment of treatment from the clinician's perspective since the start of the study. It is measured on a 7-point scale, where 1=very much improved and 7=very much worse. A participant is considered a responder if they have a response of very much improved or much improved. EOMT response is defined as the score recorded at the Week13/Withdrawal visit.
Time frame: EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
Population: ITT Population. The CGIC analysis included a subset of the ITT Population who completed the PGIC questionnaire at the end of treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants Who Are Responders on the Clinician Global Impression of Change (CGIC) Questionnaire at EOMT Using LOCF Data | 21 participants |
| GEn 1200 mg/Day | Number of Participants Who Are Responders on the Clinician Global Impression of Change (CGIC) Questionnaire at EOMT Using LOCF Data | 38 participants |
| GEn 2400 mg/Day | Number of Participants Who Are Responders on the Clinician Global Impression of Change (CGIC) Questionnaire at EOMT Using LOCF Data | 34 participants |
| GEn 3600 mg/Day | Number of Participants Who Are Responders on the Clinician Global Impression of Change (CGIC) Questionnaire at EOMT Using LOCF Data | 33 participants |
Secondary
Number of Participants Who Are Responders on the Patient Global Impression of Change (PGIC) Questionnaire at EOMT Using LOCF Data
The PGIC is a single-item questionnaire designed to provide an overall assessment of treatment from the participant's perspective since the start of the study. It is measured on a 7-point scale, where 1=very much improved and 7=very much worse. A participant is considered a responder if they have a response of very much improved or much improved. EOMT response is defined as the score recorded at the Week13/Withdrawal visit.
Time frame: EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
Population: ITT Population. The PGIC analysis included a subset of the ITT Population who completed the PGIC questionnaire at the end of treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants Who Are Responders on the Patient Global Impression of Change (PGIC) Questionnaire at EOMT Using LOCF Data | 24 participants |
| GEn 1200 mg/Day | Number of Participants Who Are Responders on the Patient Global Impression of Change (PGIC) Questionnaire at EOMT Using LOCF Data | 45 participants |
| GEn 2400 mg/Day | Number of Participants Who Are Responders on the Patient Global Impression of Change (PGIC) Questionnaire at EOMT Using LOCF Data | 35 participants |
| GEn 3600 mg/Day | Number of Participants Who Are Responders on the Patient Global Impression of Change (PGIC) Questionnaire at EOMT Using LOCF Data | 39 participants |
Secondary
Time to Onset of Sustained Improvement in the 24-hour Average Pain Intensity Score
Sustained improvement in the 24-hour average pain intensity score is defined as at least 2 consecutive days on which the 24-hour average pain intensity score is \>=2 points less than the mean 24-hour average pain intensity score at baseline. Time to onset is measured from baseline and was calculated as the first day of event minus the last day of baseline and is expressed in days. Baseline score is the calculated mean of the 24-hour average pain score for each participant during the last 7 days prior to randomization.
Time frame: Anytime post-baseline until date of last dose of study medication (up to Week 13)
Population: ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Onset of Sustained Improvement in the 24-hour Average Pain Intensity Score | 49 days |
| GEn 1200 mg/Day | Time to Onset of Sustained Improvement in the 24-hour Average Pain Intensity Score | 27 days |
| GEn 2400 mg/Day | Time to Onset of Sustained Improvement in the 24-hour Average Pain Intensity Score | 10 days |
| GEn 3600 mg/Day | Time to Onset of Sustained Improvement in the 24-hour Average Pain Intensity Score | 10 days |