Pain Associated With Fibromyalgia
Conditions
Keywords
pain, fibromyalgia
Brief summary
The main objective of this trial is to compare change in weekly average daily pain score (ADPS) from baseline to Week 13 in participants receiving either dose of DS-5565 versus placebo. Weekly ADPS is based on daily pain scores reported by the participant that best describes his or her worst pain over the previous 24 hours.
Interventions
DRUGDS-5565
DS-5565 15 mg tablet for oral administration
DRUGPregabalin
Pregabalin 150 mg capsule for oral administration
DRUGPlacebo tablet
Placebo tablet (matching DS5565) for oral administration
DRUGPlacebo capsule
Placebo capsule (matching pregabalin) for oral administration
Sponsors
Syneos Health
Daiichi Sankyo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Able to give written informed consent * Able to complete subject-reported questionnaires per the investigator's judgment * At screening, subjects must meet the 1990 American College of Rheumatology (ACR) criteria for FM, i.e. widespread pain present for at least 3 months and pain in at least 11 of 18 specific tender point sites. In addition, the 2010 ACR criteria must be met: * Widespread pain index (WPI) ≥ 7 and symptom severity (SS) scale score ≥ 5, or WPI 3 to 6 and SS scale score ≥ 9 * Symptoms have been present at a similar level for at least 3 months * The subject does not have a disorder that would otherwise explain the pain * ADPS of ≥ 4 on the 11-point numeric rating scale (NRS) over the past 7 days prior to randomization (based on completion of at least 4 daily pain diaries during the 7-day baseline period prior to randomization) * Subject must have documented evidence of a fundoscopic examination (with pupil dilation) within 12 months prior to screening or at screening. * Women of child-bearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy during the study and for 4 weeks after study completion.
Exclusion criteria
* Clinically significant unstable neurologic, psychiatric, ophthalmologic, hepatobiliary, respiratory, or hematologic illness or unstable cardiovascular disease (e.g. severe hypotension, uncontrolled cardiac arrhythmia, or myocardial infarction) or any other concurrent disease within 12 months prior to screening that in the opinion of the investigator would interfere with study participation or assessment of safety and tolerability * Anticipation of initiation or significant change to normal daily exercise routines or need for ongoing use of concomitant medications or non-pharmacological pain management techniques that may confound assessments of efficacy and/or safety * Unable to undergo pre-study washout of prohibited concomitant medications * Subjects who are at risk of suicide as defined by their responses to the Columbia-Suicide Severity Rating Scale (C-SSRS) or in the opinion of the investigator. Note: Patients answering yes to any of the questions about active suicidal ideation/intent/behaviors occurring within the past 12 months must be excluded (C-SSRS Suicide Ideation section - Questions 3, 4, or 5; C-SSRS Suicidal Behavior section, any of the suicide behaviors questions). Such patients should be referred immediately to a mental health professional for appropriate evaluation. * Current severe or uncontrolled major depressive disorder or anxiety disorders as assessed by the Mini-international Neuropsychiatric Interview (MINI) mild to moderate major depression or anxiety disorders are permitted provided that the investigator assesses the patient as clinically stable and appropriate for entry into the study. * Any diagnosis of lifetime bipolar disorder or psychotic disorder * Subjects with pain due to other conditions (e.g. diabetic peripheral neuropathic pain or post-herpetic neuralgia) that in the opinion of the investigator, would confound assessment or self-evaluation of the pain associated with FM. * Subjects with pain due to any widespread inflammatory musculoskeletal disorder (e.g. rheumatoid arthritis, lupus) or widespread rheumatic disease other than FM. * Abuse or dependence of prescription medications, street drugs, or alcohol within the last 1 year * Any history of a malignancy other than basal cell carcinoma within the past 5 years * A diagnosis of untreated sleep apnea or initiation of treatment for sleep apnea within the past 3 months * Pregnancy or breast-feeding, or intent to become pregnant during the study period * Subject is currently enrolled in or has not yet completed at least 30 days since ending another investigational device or drug study or is receiving other investigational agents. * Known hypersensitivity to alpha2-delta (α2δ) ligands or other components of the study medications. Note: Prior exposure to DS-5565 is allowed, as long as hypersensitivity to DS-5565 was not observed. * Subjects who are unlikely to comply with the protocol (e.g. uncooperative attitude, inability to return for subsequent visits) and/or otherwise considered by the investigator to be unlikely to complete the study. * Abnormal investigative tests (i.e. electrocardiograms \[ECGs\]) and laboratory values judged by the investigator to be clinically significant at screening, with particular focus on: a. Abnormal renal function defined as calculated creatinine clearance (CrCl) \< 60 mL/min determined by the central laboratory using the modified Cockcroft-Gault equation; blood urea nitrogen\> 1.5 × upper limit of normal (ULN); creatine kinase \> 3.0 × ULN; serum creatinine \> 1.6 mg/dL (\> 141.4 μmol/L); b. Abnormal liver function defined as aspartate aminotransferase (AST) \> 2.0 × ULN, alanine aminotransferase (ALT) \> 2.0 × ULN; alkaline phosphatase \> 1.5 × ULN; total bilirubin\> 1.2 × ULN. If a subject has total bilirubin \> 1.2 ULN, unconjugated and conjugated bilirubin fractions should be analyzed and only subjects documented to have Gilbert's syndrome may be enrolled.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 13 in Average Daily Pain Score (ADPS) in Participants Receiving DS-5565, Pregabalin, or Placebo | Baseline up to Week 13 postdose | The patient reported pain intensity daily (over the past 24 hours) on a scale of 0 = no pain to 10 = worst possible pain. The daily pain scores were averaged over 7 days to calculate the weekly ADPS. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 13 in Fibromyalgia Index Questionnaire (FIQ) Total Score in Participants Receiving DS-5565, Pregabalin, or Placebo | Baseline up to Week 13 postdose | The total FIQ score is composed of 10 items, with a maximum possible score of 100. The first item contains 11 questions related to physical functioning and are rated on a 4-point Likert-type scale, where 0 indicates 'always' and 3 indicates 'never'. The overall impact items are rated on a 0-7 scale for the number of days that the patient felt well and the number of days they were unable to work (including housework) because of fibromyalgia symptoms. The symptoms items are rated on visual analog scales (0-10 cm), with higher numbers indicated greater symptomatology. Final scores range from 0 (no impairment) to 10 (maximum impairment), where higher scores indicate worse outcome. For this outcome, the change in total FIQ score from baseline is being reported. Negative values indicate improvement from baseline in impairment. |
| Number of Responders at Week 13 Among Participants Receiving DS-5565, Pregabalin, or Placebo | Week 13 postdose | The number of participants with at least a 30% or 50% reduction in average daily pain score (ADPS) at Week 13 is reported. |
| Change From Baseline to Week 13 in Multidimensional Fatigue Inventory (MFI-20) General Fatigue Score in Participants Receiving DS-5565, Pregabalin, or Placebo | Baseline up to Week 13 postdose | MFI is a validated 20-item, self-reported instrument designed to measure fatigue in the following dimensions: general fatigue, physical fatigue, mental fatigue, reduced motivation, and reduced activity. The respondent is asked to mark an 'X' in 1 of 5 boxes arranged linearly where 1 is 'Yes, that is true' and 5 is 'No, that is not true.' Each subscale consists of 4 items, 2 indicative for fatigue and 2 contraindicative. For the indicative questions, a high score indicates a high fatigue level and low scores indicate a low fatigue levels. Conversely, for the contraindicative questions a high score indicates a low fatigue level and a low score indicates a high fatigue level. Overall, respondents are rated on a scale of 0 (no fatigue) to 7 (high fatigue). For this outcome, the change from baseline in MFI-20 general fatigue subscale score is being reported. Negative values indicate an improvement in fatigue. |
| Change From Baseline to Week 13 in Hospital Anxiety and Depression Scale (HADS) in Participants Receiving DS-5565, Pregabalin, or Placebo | Baseline up to Week 13 postdose | The HADS questionnaire is a reliable, widely-used self-assessment scale to assess symptoms of anxiety and depression. The instrument consists of 7 questions related to anxiety and 7 related to depression, each rated on a 4-point scale (score of 0 to 3). Scores for anxiety and depression are independently summed to compute HADS-Anxiety and HADS-Depression subscale scores, with ranges from 0 (no anxiety/depression) to 21 (most severe anxiety/depression). |
| Change From Baseline to Week 13 in Short Form 36 (SF-36) in Participants Receiving DS-5565, Pregabalin, or Placebo | Baseline up to Week 13 postdose | The SF-36 is a 36-question health survey that measures functional health and well-being from the participant's point of view. It is a measure of physical and mental health used across various disease areas, including fibromyalgia. The SF-36 scale ranges from 0 to 100 where lower scores indicate more disability (worse health) and higher scores represent less disability (better health). The physical component summary (PCS) and mental component summary (MCS) scores are reported. |
| Number of Participants Who Answered Much Improved or Better on the Patient Global Impression of Change (PGIC) Scale at Week 13 in Participants Receiving DS-5565, Pregabalin, or Placebo | Week 13 postdose | Patient-rated global impression of change (PGIC) on a categorical scale from 1 = very much improved to 7 = very much worse. The number of participants with much improved or better (≤2 scores) are reported. |
| Change From Baseline to Week 13 in Average Daily Sleep Interference Score (ADSIS) in Participants Receiving DS-5565, Pregabalin, or Placebo | Baseline up to Week 13 postdose | Pain-associated sleep interference was assessed using electronic daily diaries using an 11-point numeric rating scale (NRS) for pain, ranging from 0 (pain does not interfere with sleep) to 10 (pain completely interferes with sleep, unable to sleep). ADSIS is the mean value of all available recordings of the respective week. |
| The Number of Participants Reporting Optimal Sleep at Week 13 on the Medical Outcomes Study (MOS) Sleep Scale in Participants Receiving DS-5565, Pregabalin, or Placebo | Week 13 postdose | The MOS sleep scale is a 12-item questionnaire from which the following subscales were derived: sleep disturbance (4 items), quantity of sleep/optimal sleep (1 item), snoring (1 item), awakening due to shortness of breath or due to headache (1 item), sleep adequacy (2 items), and somnolence (3 items). In addition, values for sleep disturbances index (9 items), optimal sleep scale (1 item), sleep quantity scale (1 item) were determine. Most subscales range from 0 to 100, where higher scores indicate more of the concept being measured (eg., higher sleep disturbance scores indicate greater sleep disturbances). |
| Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Baseline up to Week 13 postdose | The BPI-SF measures pain severity and interference within the past 24 hours. Items are rated on an 11-point NRS from 0 to 10, where 0 indicates does not interfere and 10 indicates completely interferes. Severity score is the average of the responses to the 4 pain intensity items that assess the Worst/Least/Average pain in the last 24 hours and the Pain Right Now. The individual items being reported (using the same scale as noted above) are Severity, General Activity, Mood, Walking Ability, Normal Work, Relations With Other People, Sleep, and Enjoyment of Life. Percentage relief of treatment pain scale ranges from 100% (complete pain relief) to 0% (no pain relief) and higher percentages indicate better outcome. Interference % is the average of responses for General activity, Mood, Walking ability, Normal work, Relations with other people, Sleep, Enjoyment of life where 0% (no interference) to 100% (completely interferes) and negative (ie. lower) percentages indicate better outcomes. |
| Proportion of Days a Rescue Medication Was Used in Participants Receiving DS-5565, Pregabalin, or Placebo | Week 1 to Week 13 postdose | Proportion of days with rescue medication intake during the double-blind treatment period equals number of days with rescue medication intake/(date of last study drug administration in the double-blind treatment period) - date of first study drug administration + 1). |
| Change From Baseline to Week 13 in EuroQol Five Dimensions Questionnaire (EQ-5D) in Participants Receiving DS-5565, Pregabalin, or Placebo | Baseline up to Week 13 postdose | The EQ-5D is an instrument that shows high construct validity and responsiveness in patients with chronic pain and has been used specifically in fibromyalgia. The EQ-5D includes a descriptive section with 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) each with a scale that ranges from 0 (no problems) to 5 (extreme problems). These 5 dimensions are combined into an overall health utilities index, and a numeric rating scale (100 mm visual analog scale) that measures perception of overall health, with 0 indicating worst health and 100 representing best imaginable health. A summary index with a maximum total score of 1 can be derived from these five dimensions by conversion with a table of scores. The maximum total score of 1 indicates the best health outcome. For this outcome, the change from baseline in total EQ-5D score is being reported. Positive values indicate an improvement in health. |
Countries
Australia, Bulgaria, Estonia, Hungary, India, Latvia, New Zealand, Romania, Russia, Slovakia, United Kingdom, United States
Participant flow
Recruitment details
A total of 2280 participants who met all inclusion criteria and no exclusion criteria were enrolled from 19 Nov 2014 to 07 July 2016 at 178 sites. Of the 2280 participants enrolled, 1270 participants were randomized.
Pre-assignment details
Eligible participants were randomized in a 1:1:1:1 ratio to either DS5565 15 mg QD, DS5565 15 mg BID, placebo, or pregabalin 150 mg BID.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants take one each of placebo tablet and capsule BID) | 318 |
| Pregabalin Participants take one pregabalin capsule and one placebo tablet BID | 317 |
| DS-5565 QD Participants take one each of placebo tablet and capsule in the morning, and one DS-5565 tablet once daily (QD) with a placebo capsule in the evening | 318 |
| DS-5565 BID Participants take one DS-5565 tablet and one placebo capsule, twice daily (BID) | 317 |
| Total | 1,270 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 28 | 33 | 42 | 50 |
| Overall Study | Lack of Efficacy | 10 | 5 | 4 | 7 |
| Overall Study | Other | 3 | 7 | 3 | 9 |
| Overall Study | Protocol Violation | 4 | 6 | 3 | 4 |
| Overall Study | Withdrawal by Subject | 24 | 28 | 25 | 26 |
Baseline characteristics
| Characteristic | Placebo | Pregabalin | DS-5565 QD | DS-5565 BID | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 29 Participants | 30 Participants | 32 Participants | 33 Participants | 124 Participants |
| Age, Categorical Between 18 and 65 years | 289 Participants | 287 Participants | 286 Participants | 284 Participants | 1146 Participants |
| Age, Continuous | 50.2 years STANDARD_DEVIATION 11.43 | 50.9 years STANDARD_DEVIATION 11.58 | 50.2 years STANDARD_DEVIATION 11.85 | 50.6 years STANDARD_DEVIATION 11.46 | 50.5 years STANDARD_DEVIATION 11.57 |
| Region of Enrollment Australia | 5 Participants | 5 Participants | 5 Participants | 5 Participants | 20 Participants |
| Region of Enrollment Bulgaria | 16 Participants | 19 Participants | 22 Participants | 17 Participants | 74 Participants |
| Region of Enrollment Estonia | 6 Participants | 5 Participants | 6 Participants | 4 Participants | 21 Participants |
| Region of Enrollment Hungary | 5 Participants | 7 Participants | 6 Participants | 7 Participants | 25 Participants |
| Region of Enrollment India | 12 Participants | 11 Participants | 12 Participants | 9 Participants | 44 Participants |
| Region of Enrollment Latvia | 7 Participants | 9 Participants | 6 Participants | 10 Participants | 32 Participants |
| Region of Enrollment Lithuania | 3 Participants | 1 Participants | 0 Participants | 1 Participants | 5 Participants |
| Region of Enrollment New Zealand | 7 Participants | 8 Participants | 8 Participants | 10 Participants | 33 Participants |
| Region of Enrollment Romania | 9 Participants | 11 Participants | 6 Participants | 5 Participants | 31 Participants |
| Region of Enrollment Russia | 7 Participants | 8 Participants | 12 Participants | 12 Participants | 39 Participants |
| Region of Enrollment Slovakia | 14 Participants | 7 Participants | 9 Participants | 11 Participants | 41 Participants |
| Region of Enrollment United Kingdom | 39 Participants | 38 Participants | 38 Participants | 38 Participants | 153 Participants |
| Region of Enrollment United States | 188 Participants | 188 Participants | 188 Participants | 188 Participants | 752 Participants |
| Sex: Female, Male Female | 290 Participants | 288 Participants | 295 Participants | 287 Participants | 1160 Participants |
| Sex: Female, Male Male | 28 Participants | 29 Participants | 23 Participants | 30 Participants | 110 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 | 0 / 315 | 0 / 312 | 1 / 315 | 0 / 313 |
| other Total, other adverse events | 206 / 315 | 299 / 312 | 290 / 315 | 242 / 313 |
| serious Total, serious adverse events | 6 / 315 | 5 / 312 | 7 / 315 | 11 / 313 |
Outcome results
Primary
Change From Baseline to Week 13 in Average Daily Pain Score (ADPS) in Participants Receiving DS-5565, Pregabalin, or Placebo
The patient reported pain intensity daily (over the past 24 hours) on a scale of 0 = no pain to 10 = worst possible pain. The daily pain scores were averaged over 7 days to calculate the weekly ADPS.
Time frame: Baseline up to Week 13 postdose
Population: ADPS was assessed using the modified intent-to-treat (mITT) analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 13 in Average Daily Pain Score (ADPS) in Participants Receiving DS-5565, Pregabalin, or Placebo | -1.86 units on a scale | Standard Error 0.13 |
| Pregabalin 150 mg BID | Change From Baseline to Week 13 in Average Daily Pain Score (ADPS) in Participants Receiving DS-5565, Pregabalin, or Placebo | -2.47 units on a scale | Standard Error 0.133 |
| DS-5565 15 mg QD | Change From Baseline to Week 13 in Average Daily Pain Score (ADPS) in Participants Receiving DS-5565, Pregabalin, or Placebo | -2.24 units on a scale | Standard Error 0.133 |
| DS-5565 15 mg BID | Change From Baseline to Week 13 in Average Daily Pain Score (ADPS) in Participants Receiving DS-5565, Pregabalin, or Placebo | -2.09 units on a scale | Standard Error 0.134 |
Comparison: Analysis was based on multiple imputation and pattern mixture model with delta shifting.p-value: 0.000895% CI: [-0.97, -0.25]Difference of means
Comparison: Analysis was based on multiple imputation and pattern mixture model with delta shifting.p-value: 0.039295% CI: [-0.74, -0.02]Difference of means
Comparison: Analysis was based on multiple imputation and pattern mixture model with delta shifting.p-value: 0.219295% CI: [-0.58, 0.13]Difference of means
Comparison: Analysis was based on multiple imputation and pattern mixture model with delta shifting.p-value: 0.209595% CI: [-0.13, 0.59]Difference of means
Comparison: Analysis was based on multiple imputation and pattern mixture model with delta shifting.p-value: 0.038195% CI: [0.02, 0.75]Difference of means
Secondary
Change From Baseline to Week 13 in Average Daily Sleep Interference Score (ADSIS) in Participants Receiving DS-5565, Pregabalin, or Placebo
Pain-associated sleep interference was assessed using electronic daily diaries using an 11-point numeric rating scale (NRS) for pain, ranging from 0 (pain does not interfere with sleep) to 10 (pain completely interferes with sleep, unable to sleep). ADSIS is the mean value of all available recordings of the respective week.
Time frame: Baseline up to Week 13 postdose
Population: Pain-associated sleep interference was assessed using the modified intent-to-treat (mITT) analysis set.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 13 in Average Daily Sleep Interference Score (ADSIS) in Participants Receiving DS-5565, Pregabalin, or Placebo | -1.92 units on a scale | Standard Error 0.11 |
| Pregabalin 150 mg BID | Change From Baseline to Week 13 in Average Daily Sleep Interference Score (ADSIS) in Participants Receiving DS-5565, Pregabalin, or Placebo | -2.41 units on a scale | Standard Error 0.11 |
| DS-5565 15 mg QD | Change From Baseline to Week 13 in Average Daily Sleep Interference Score (ADSIS) in Participants Receiving DS-5565, Pregabalin, or Placebo | -2.48 units on a scale | Standard Error 0.11 |
| DS-5565 15 mg BID | Change From Baseline to Week 13 in Average Daily Sleep Interference Score (ADSIS) in Participants Receiving DS-5565, Pregabalin, or Placebo | -2.44 units on a scale | Standard Error 0.11 |
p-value: 0.001595% CI: [-0.79, -0.19]Mixed Models Analysis
p-value: 0.000395% CI: [-0.86, -0.26]Mixed Models Analysis
p-value: 0.000895% CI: [-0.81, -0.21]Mixed Models Analysis
p-value: 0.646495% CI: [-0.37, 0.23]Mixed Models Analysis
p-value: 0.854395% CI: [-0.33, 0.27]Mixed Models Analysis
Secondary
Change From Baseline to Week 13 in EuroQol Five Dimensions Questionnaire (EQ-5D) in Participants Receiving DS-5565, Pregabalin, or Placebo
The EQ-5D is an instrument that shows high construct validity and responsiveness in patients with chronic pain and has been used specifically in fibromyalgia. The EQ-5D includes a descriptive section with 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) each with a scale that ranges from 0 (no problems) to 5 (extreme problems). These 5 dimensions are combined into an overall health utilities index, and a numeric rating scale (100 mm visual analog scale) that measures perception of overall health, with 0 indicating worst health and 100 representing best imaginable health. A summary index with a maximum total score of 1 can be derived from these five dimensions by conversion with a table of scores. The maximum total score of 1 indicates the best health outcome. For this outcome, the change from baseline in total EQ-5D score is being reported. Positive values indicate an improvement in health.
Time frame: Baseline up to Week 13 postdose
Population: The EQ-5D was assessed using the modified intent-to-treat (mITT) analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 13 in EuroQol Five Dimensions Questionnaire (EQ-5D) in Participants Receiving DS-5565, Pregabalin, or Placebo | 0.060 units on a scale | Standard Deviation 0.18 |
| Pregabalin 150 mg BID | Change From Baseline to Week 13 in EuroQol Five Dimensions Questionnaire (EQ-5D) in Participants Receiving DS-5565, Pregabalin, or Placebo | 0.10 units on a scale | Standard Deviation 0.19 |
| DS-5565 15 mg QD | Change From Baseline to Week 13 in EuroQol Five Dimensions Questionnaire (EQ-5D) in Participants Receiving DS-5565, Pregabalin, or Placebo | 0.08 units on a scale | Standard Deviation 0.17 |
| DS-5565 15 mg BID | Change From Baseline to Week 13 in EuroQol Five Dimensions Questionnaire (EQ-5D) in Participants Receiving DS-5565, Pregabalin, or Placebo | 0.07 units on a scale | Standard Deviation 0.19 |
p-value: 0.020195% CI: [0.0048, 0.057]ANCOVA
p-value: 0.179895% CI: [-0.0082, 0.0438]ANCOVA
p-value: 0.592295% CI: [-0.0189, 0.0332]ANCOVA
p-value: 0.322195% CI: [-0.0392, 0.0129]ANCOVA
p-value: 0.073995% CI: [-0.0499, 0.0023]ANCOVA
Secondary
Change From Baseline to Week 13 in Fibromyalgia Index Questionnaire (FIQ) Total Score in Participants Receiving DS-5565, Pregabalin, or Placebo
The total FIQ score is composed of 10 items, with a maximum possible score of 100. The first item contains 11 questions related to physical functioning and are rated on a 4-point Likert-type scale, where 0 indicates 'always' and 3 indicates 'never'. The overall impact items are rated on a 0-7 scale for the number of days that the patient felt well and the number of days they were unable to work (including housework) because of fibromyalgia symptoms. The symptoms items are rated on visual analog scales (0-10 cm), with higher numbers indicated greater symptomatology. Final scores range from 0 (no impairment) to 10 (maximum impairment), where higher scores indicate worse outcome. For this outcome, the change in total FIQ score from baseline is being reported. Negative values indicate improvement from baseline in impairment.
Time frame: Baseline up to Week 13 postdose
Population: FIQ was assessed using the modified intent-to-treat (mITT) analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 13 in Fibromyalgia Index Questionnaire (FIQ) Total Score in Participants Receiving DS-5565, Pregabalin, or Placebo | -13.88 units on a scale | Standard Deviation 1.2 |
| Pregabalin 150 mg BID | Change From Baseline to Week 13 in Fibromyalgia Index Questionnaire (FIQ) Total Score in Participants Receiving DS-5565, Pregabalin, or Placebo | -21.46 units on a scale | Standard Deviation 1.22 |
| DS-5565 15 mg QD | Change From Baseline to Week 13 in Fibromyalgia Index Questionnaire (FIQ) Total Score in Participants Receiving DS-5565, Pregabalin, or Placebo | -17.41 units on a scale | Standard Deviation 1.22 |
| DS-5565 15 mg BID | Change From Baseline to Week 13 in Fibromyalgia Index Questionnaire (FIQ) Total Score in Participants Receiving DS-5565, Pregabalin, or Placebo | -16.45 units on a scale | Standard Deviation 1.24 |
Comparison: Analysis was based on multiple imputation and pattern mixture model with delta shifting.p-value: <0.000195% CI: [-10.71, -4.44]Difference of means
Comparison: Analysis was based on multiple imputation and pattern mixture model with delta shifting.p-value: 0.028995% CI: [-6.68, -0.36]Difference of means
Comparison: Analysis was based on multiple imputation and pattern mixture model with delta shifting.p-value: 0.114895% CI: [-5.75, 0.62]Difference of means
Comparison: Analysis was based on multiple imputation and pattern mixture model with delta shifting.p-value: 0.012595% CI: [0.87, 7.23]Difference of means
Comparison: Analysis was based on multiple imputation and pattern mixture model with delta shifting.p-value: 0.002395% CI: [1.78, 8.24]Difference of means
Secondary
Change From Baseline to Week 13 in Hospital Anxiety and Depression Scale (HADS) in Participants Receiving DS-5565, Pregabalin, or Placebo
The HADS questionnaire is a reliable, widely-used self-assessment scale to assess symptoms of anxiety and depression. The instrument consists of 7 questions related to anxiety and 7 related to depression, each rated on a 4-point scale (score of 0 to 3). Scores for anxiety and depression are independently summed to compute HADS-Anxiety and HADS-Depression subscale scores, with ranges from 0 (no anxiety/depression) to 21 (most severe anxiety/depression).
Time frame: Baseline up to Week 13 postdose
Population: HADS was assessed using the modified intent-to-treat (mITT) analysis set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Week 13 in Hospital Anxiety and Depression Scale (HADS) in Participants Receiving DS-5565, Pregabalin, or Placebo | Change from baseline to Week 13: Anxiety | -0.5 units on a scale | Standard Deviation 3.43 |
| Placebo | Change From Baseline to Week 13 in Hospital Anxiety and Depression Scale (HADS) in Participants Receiving DS-5565, Pregabalin, or Placebo | Change from baseline to Week 13: Depression | -0.8 units on a scale | Standard Deviation 3.66 |
| Pregabalin 150 mg BID | Change From Baseline to Week 13 in Hospital Anxiety and Depression Scale (HADS) in Participants Receiving DS-5565, Pregabalin, or Placebo | Change from baseline to Week 13: Depression | -1.6 units on a scale | Standard Deviation 3.86 |
| Pregabalin 150 mg BID | Change From Baseline to Week 13 in Hospital Anxiety and Depression Scale (HADS) in Participants Receiving DS-5565, Pregabalin, or Placebo | Change from baseline to Week 13: Anxiety | -1.4 units on a scale | Standard Deviation 3.47 |
| DS-5565 15 mg QD | Change From Baseline to Week 13 in Hospital Anxiety and Depression Scale (HADS) in Participants Receiving DS-5565, Pregabalin, or Placebo | Change from baseline to Week 13: Anxiety | -0.7 units on a scale | Standard Deviation 3.3 |
| DS-5565 15 mg QD | Change From Baseline to Week 13 in Hospital Anxiety and Depression Scale (HADS) in Participants Receiving DS-5565, Pregabalin, or Placebo | Change from baseline to Week 13: Depression | -1.1 units on a scale | Standard Deviation 3.78 |
| DS-5565 15 mg BID | Change From Baseline to Week 13 in Hospital Anxiety and Depression Scale (HADS) in Participants Receiving DS-5565, Pregabalin, or Placebo | Change from baseline to Week 13: Anxiety | -0.8 units on a scale | Standard Deviation 3.31 |
| DS-5565 15 mg BID | Change From Baseline to Week 13 in Hospital Anxiety and Depression Scale (HADS) in Participants Receiving DS-5565, Pregabalin, or Placebo | Change from baseline to Week 13: Depression | -0.8 units on a scale | Standard Deviation 3.83 |
Comparison: Anxiety: Placebo vs Pregabalin 150 mg BIDp-value: 0.000395% CI: [-1.5, -0.4]ANCOVA
Comparison: Anxiety: Placebo vs DS-5565 15 mg QDp-value: 0.506695% CI: [-0.7, 0.3]ANCOVA
Comparison: Anxiety: Placebo vs DS-5565 15 mg BIDp-value: 0.146295% CI: [-0.9, 0.1]ANCOVA
Comparison: Anxiety: Pregabalin 150 mg BID vs DS-5565 15 mg QDp-value: 0.003595% CI: [0.3, 1.3]ANCOVA
Comparison: Anxiety: Pregabalin 150 mg BID vs DS-5565 15 mg BIDp-value: 0.033895% CI: [0, 1.1]ANCOVA
Comparison: Depression: Placebo vs Pregabalin 150 mg BIDp-value: 0.011695% CI: [-1.3, -0.2]ANCOVA
Comparison: Depression: Placebo vs DS-5565 15 mg QDp-value: 0.708595% CI: [-0.7, 0.4]ANCOVA
Comparison: Depression: Placebo vs DS-5565 15 mg BIDp-value: 0.939295% CI: [-0.5, 0.6]ANCOVA
Comparison: Depression: Pregabalin 150 mg BID vs DS-5565 15 mg QDp-value: 0.031195% CI: [0.1, 1.2]ANCOVA
Comparison: Depression: Pregabalin 150 mg BID vs DS-5565 15 mg BIDp-value: 0.009495% CI: [0.2, 1.3]ANCOVA
Secondary
Change From Baseline to Week 13 in Multidimensional Fatigue Inventory (MFI-20) General Fatigue Score in Participants Receiving DS-5565, Pregabalin, or Placebo
MFI is a validated 20-item, self-reported instrument designed to measure fatigue in the following dimensions: general fatigue, physical fatigue, mental fatigue, reduced motivation, and reduced activity. The respondent is asked to mark an 'X' in 1 of 5 boxes arranged linearly where 1 is 'Yes, that is true' and 5 is 'No, that is not true.' Each subscale consists of 4 items, 2 indicative for fatigue and 2 contraindicative. For the indicative questions, a high score indicates a high fatigue level and low scores indicate a low fatigue levels. Conversely, for the contraindicative questions a high score indicates a low fatigue level and a low score indicates a high fatigue level. Overall, respondents are rated on a scale of 0 (no fatigue) to 7 (high fatigue). For this outcome, the change from baseline in MFI-20 general fatigue subscale score is being reported. Negative values indicate an improvement in fatigue.
Time frame: Baseline up to Week 13 postdose
Population: Multidimensional Fatigue Inventory (MFI-20) was assessed in the modified intent-to-treat (mITT) population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 13 in Multidimensional Fatigue Inventory (MFI-20) General Fatigue Score in Participants Receiving DS-5565, Pregabalin, or Placebo | -1.4 units on a scale | Standard Deviation 3.45 |
| Pregabalin 150 mg BID | Change From Baseline to Week 13 in Multidimensional Fatigue Inventory (MFI-20) General Fatigue Score in Participants Receiving DS-5565, Pregabalin, or Placebo | -2.8 units on a scale | Standard Deviation 3.99 |
| DS-5565 15 mg QD | Change From Baseline to Week 13 in Multidimensional Fatigue Inventory (MFI-20) General Fatigue Score in Participants Receiving DS-5565, Pregabalin, or Placebo | -2.3 units on a scale | Standard Deviation 3.57 |
| DS-5565 15 mg BID | Change From Baseline to Week 13 in Multidimensional Fatigue Inventory (MFI-20) General Fatigue Score in Participants Receiving DS-5565, Pregabalin, or Placebo | -2.1 units on a scale | Standard Deviation 3.45 |
p-value: <0.000195% CI: [-1.8, -0.7]ANCOVA
p-value: 0.024795% CI: [-1.2, -0.1]ANCOVA
p-value: 0.041195% CI: [-1.1, 0]ANCOVA
p-value: 0.035295% CI: [0, 1.2]ANCOVA
p-value: 0.021495% CI: [0.1, 1.2]ANCOVA
Secondary
Change From Baseline to Week 13 in Short Form 36 (SF-36) in Participants Receiving DS-5565, Pregabalin, or Placebo
The SF-36 is a 36-question health survey that measures functional health and well-being from the participant's point of view. It is a measure of physical and mental health used across various disease areas, including fibromyalgia. The SF-36 scale ranges from 0 to 100 where lower scores indicate more disability (worse health) and higher scores represent less disability (better health). The physical component summary (PCS) and mental component summary (MCS) scores are reported.
Time frame: Baseline up to Week 13 postdose
Population: This outcome was assessed using the modified intent-to-treat analysis set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Week 13 in Short Form 36 (SF-36) in Participants Receiving DS-5565, Pregabalin, or Placebo | Change from baseline to Week 13:Physical Component | 4.395 units on a scale | Standard Deviation 6.81 |
| Placebo | Change From Baseline to Week 13 in Short Form 36 (SF-36) in Participants Receiving DS-5565, Pregabalin, or Placebo | Change from baseline to Week 13: Mental Component | 1.371 units on a scale | Standard Deviation 9.43 |
| Pregabalin 150 mg BID | Change From Baseline to Week 13 in Short Form 36 (SF-36) in Participants Receiving DS-5565, Pregabalin, or Placebo | Change from baseline to Week 13: Mental Component | 3.093 units on a scale | Standard Deviation 8.93 |
| Pregabalin 150 mg BID | Change From Baseline to Week 13 in Short Form 36 (SF-36) in Participants Receiving DS-5565, Pregabalin, or Placebo | Change from baseline to Week 13:Physical Component | 5.815 units on a scale | Standard Deviation 8.03 |
| DS-5565 15 mg QD | Change From Baseline to Week 13 in Short Form 36 (SF-36) in Participants Receiving DS-5565, Pregabalin, or Placebo | Change from baseline to Week 13:Physical Component | 5.000 units on a scale | Standard Deviation 7.76 |
| DS-5565 15 mg QD | Change From Baseline to Week 13 in Short Form 36 (SF-36) in Participants Receiving DS-5565, Pregabalin, or Placebo | Change from baseline to Week 13: Mental Component | 1.675 units on a scale | Standard Deviation 9.94 |
| DS-5565 15 mg BID | Change From Baseline to Week 13 in Short Form 36 (SF-36) in Participants Receiving DS-5565, Pregabalin, or Placebo | Change from baseline to Week 13:Physical Component | 4.833 units on a scale | Standard Deviation 7.18 |
| DS-5565 15 mg BID | Change From Baseline to Week 13 in Short Form 36 (SF-36) in Participants Receiving DS-5565, Pregabalin, or Placebo | Change from baseline to Week 13: Mental Component | 1.198 units on a scale | Standard Deviation 8.37 |
Comparison: Physical Component: Placebo vs Pregabalinp-value: 0.037395% CI: [0.074, 2.439]ANCOVA
Comparison: Physical Component: Placebo vs DS-5565 15 mg QDp-value: 0.545895% CI: [-0.817, 1.545]ANCOVA
Comparison: Physical Component: Placebo vs DS-5565 15 mg BIDp-value: 0.696895% CI: [-0.949, 1.42]ANCOVA
Comparison: Physical Component: Pregabalin vs DS-5565 15 mg QDp-value: 0.137995% CI: [-2.073, 0.287]ANCOVA
Comparison: Physical Component: Pregabalin vs DS-5565 15 mg BIDp-value: 0.090895% CI: [-2.205, 0.163]ANCOVA
Comparison: Mental Component: Placebo vs Pregabalinp-value: 0.006895% CI: [0.523, 3.256]ANCOVA
Comparison: Mental Component: Placebo vs DS-5565 15 mg QDp-value: 0.559495% CI: [-0.959, 1.771]ANCOVA
Comparison: Mental Component: Placebo vs DS-5565 15 mg BIDp-value: 0.973695% CI: [-1.346, 1.392]ANCOVA
Comparison: Mental Component: Pregabalin vs DS-5565 15 mg QDp-value: 0.033195% CI: [-2.848, -0.119]ANCOVA
Comparison: Mental Component: Pregabalin vs DS-5565 15 mg BIDp-value: 0.007695% CI: [-3.235, -0.498]ANCOVA
Secondary
Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo
The BPI-SF measures pain severity and interference within the past 24 hours. Items are rated on an 11-point NRS from 0 to 10, where 0 indicates does not interfere and 10 indicates completely interferes. Severity score is the average of the responses to the 4 pain intensity items that assess the Worst/Least/Average pain in the last 24 hours and the Pain Right Now. The individual items being reported (using the same scale as noted above) are Severity, General Activity, Mood, Walking Ability, Normal Work, Relations With Other People, Sleep, and Enjoyment of Life. Percentage relief of treatment pain scale ranges from 100% (complete pain relief) to 0% (no pain relief) and higher percentages indicate better outcome. Interference % is the average of responses for General activity, Mood, Walking ability, Normal work, Relations with other people, Sleep, Enjoyment of life where 0% (no interference) to 100% (completely interferes) and negative (ie. lower) percentages indicate better outcomes.
Time frame: Baseline up to Week 13 postdose
Population: BFI-SF was assessed using the modified intent-to-treat (mITT) analysis set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Mood | -1.3 units on a scale | Standard Deviation 2.84 |
| Placebo | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | General activity | -1.6 units on a scale | Standard Deviation 2.77 |
| Placebo | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Severity score | -1.59 units on a scale | Standard Deviation 2.17 |
| Placebo | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Enjoyment of life | -1.3 units on a scale | Standard Deviation 3 |
| Placebo | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Interference (%) | -14.79 units on a scale | Standard Deviation 22.33 |
| Placebo | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Relief (%) by treatment of pain | 20.1 units on a scale | Standard Deviation 33.69 |
| Placebo | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Relations with other people | -1.2 units on a scale | Standard Deviation 2.92 |
| Placebo | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Worst pain | -1.7 units on a scale | Standard Deviation 2.36 |
| Placebo | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Average pain | -1.5 units on a scale | Standard Deviation 2.13 |
| Placebo | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Sleep | -1.9 units on a scale | Standard Deviation 2.99 |
| Placebo | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Normal work | -1.6 units on a scale | Standard Deviation 2.65 |
| Placebo | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Walking ability | -1.5 units on a scale | Standard Deviation 2.6 |
| Placebo | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Pain right now | -1.8 units on a scale | Standard Deviation 2.76 |
| Placebo | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Least pain | -1.4 units on a scale | Standard Deviation 2.53 |
| Pregabalin 150 mg BID | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Normal work | -2.3 units on a scale | Standard Deviation 2.7 |
| Pregabalin 150 mg BID | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Worst pain | -2.6 units on a scale | Standard Deviation 2.37 |
| Pregabalin 150 mg BID | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Least pain | -1.9 units on a scale | Standard Deviation 2.37 |
| Pregabalin 150 mg BID | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Average pain | -2.1 units on a scale | Standard Deviation 2.15 |
| Pregabalin 150 mg BID | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Pain right now | -2.8 units on a scale | Standard Deviation 2.48 |
| Pregabalin 150 mg BID | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Severity score | -2.33 units on a scale | Standard Deviation 2.08 |
| Pregabalin 150 mg BID | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Relief (%) by treatment of pain | 31.1 units on a scale | Standard Deviation 33.15 |
| Pregabalin 150 mg BID | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Interference (%) | -23.76 units on a scale | Standard Deviation 21.81 |
| Pregabalin 150 mg BID | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | General activity | -2.5 units on a scale | Standard Deviation 2.63 |
| Pregabalin 150 mg BID | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Mood | -2.2 units on a scale | Standard Deviation 2.65 |
| Pregabalin 150 mg BID | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Walking ability | -2.1 units on a scale | Standard Deviation 2.79 |
| Pregabalin 150 mg BID | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Relations with other people | -1.8 units on a scale | Standard Deviation 2.92 |
| Pregabalin 150 mg BID | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Sleep | -3.3 units on a scale | Standard Deviation 2.83 |
| Pregabalin 150 mg BID | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Enjoyment of life | -2.4 units on a scale | Standard Deviation 2.85 |
| DS-5565 15 mg QD | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Normal work | -1.9 units on a scale | Standard Deviation 2.77 |
| DS-5565 15 mg QD | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Sleep | -3.1 units on a scale | Standard Deviation 3.14 |
| DS-5565 15 mg QD | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Least pain | -1.5 units on a scale | Standard Deviation 2.53 |
| DS-5565 15 mg QD | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Pain right now | -2.3 units on a scale | Standard Deviation 2.54 |
| DS-5565 15 mg QD | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Relations with other people | -1.6 units on a scale | Standard Deviation 3.12 |
| DS-5565 15 mg QD | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Worst pain | -2.2 units on a scale | Standard Deviation 2.55 |
| DS-5565 15 mg QD | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Walking ability | -1.8 units on a scale | Standard Deviation 2.88 |
| DS-5565 15 mg QD | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | General activity | -2.1 units on a scale | Standard Deviation 2.66 |
| DS-5565 15 mg QD | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Relief (%) by treatment of pain | 24.2 units on a scale | Standard Deviation 33.26 |
| DS-5565 15 mg QD | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Average pain | -1.8 units on a scale | Standard Deviation 2.15 |
| DS-5565 15 mg QD | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Severity score | -1.96 units on a scale | Standard Deviation 2.17 |
| DS-5565 15 mg QD | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Enjoyment of life | -1.9 units on a scale | Standard Deviation 3.22 |
| DS-5565 15 mg QD | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Interference (%) | -19.97 units on a scale | Standard Deviation 23.37 |
| DS-5565 15 mg QD | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Mood | -1.6 units on a scale | Standard Deviation 2.94 |
| DS-5565 15 mg BID | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Interference (%) | -18.35 units on a scale | Standard Deviation 20.68 |
| DS-5565 15 mg BID | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | General activity | -2.1 units on a scale | Standard Deviation 2.53 |
| DS-5565 15 mg BID | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Sleep | -3.0 units on a scale | Standard Deviation 2.8 |
| DS-5565 15 mg BID | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Mood | -1.6 units on a scale | Standard Deviation 2.65 |
| DS-5565 15 mg BID | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Average pain | -1.8 units on a scale | Standard Deviation 1.96 |
| DS-5565 15 mg BID | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Walking ability | -1.4 units on a scale | Standard Deviation 2.6 |
| DS-5565 15 mg BID | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Least pain | -1.6 units on a scale | Standard Deviation 2.25 |
| DS-5565 15 mg BID | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Normal work | -1.9 units on a scale | Standard Deviation 2.6 |
| DS-5565 15 mg BID | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Enjoyment of life | -1.7 units on a scale | Standard Deviation 2.98 |
| DS-5565 15 mg BID | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Relations with other people | -1.2 units on a scale | Standard Deviation 2.85 |
| DS-5565 15 mg BID | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Severity score | -1.91 units on a scale | Standard Deviation 1.95 |
| DS-5565 15 mg BID | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Worst pain | -2.1 units on a scale | Standard Deviation 2.3 |
| DS-5565 15 mg BID | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Relief (%) by treatment of pain | 25.9 units on a scale | Standard Deviation 35.09 |
| DS-5565 15 mg BID | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo | Pain right now | -2.2 units on a scale | Standard Deviation 2.4 |
Comparison: Severity score: Placebo vs DS-5565 15 mg BIDp-value: 0.38795% CI: [-0.465, 0.18]ANCOVA
Comparison: Severity score: Pregabalin 150 mg BID vs DS-5565 15 mg QDp-value: 0.063395% CI: [-0.02, 0.624]ANCOVA
Comparison: Worst pain: Placebo vs Pregabalin 150 mg BIDp-value: 0.001495% CI: [-1, 0.2]ANCOVA
Comparison: Severity score: Pregabalin 150 mg BID vs DS-5565 15 mg BIDp-value: 0.010895% CI: [0.097, 0.744]ANCOVA
Comparison: Relief by treatment of pain: Placebo vs Pregabalin 150 mg BIDp-value: 0.00295% CI: [2.7, 12.2]ANCOVA
Comparison: Worst pain: Placebo vs DS-5565 15 mg QDp-value: 0.128595% CI: [-0.7, 0.1]ANCOVA
Comparison: Worst pain: Placebo vs DS-5565 15 mg BIDp-value: 0.659595% CI: [-0.5, 0.3]ANCOVA
Comparison: Worst pain: Pregabalin 150 mg BID vs DS-5565 15 mg QDp-value: 0.093895% CI: [-0.1, 0.7]ANCOVA
Comparison: Worst pain: Pregabalin 150 mg BID vs DS-5565 15 mg BIDp-value: 0.006195% CI: [0.1, 0.9]ANCOVA
Comparison: Least pain: Placebo vs Pregabalin 150 mg BIDp-value: 0.023595% CI: [-0.8, -0.1]ANCOVA
Comparison: Least pain: Placebo vs DS-5565 15 mg QDp-value: 0.365295% CI: [-0.5, 0.2]ANCOVA
Comparison: Least pain: Placebo vs DS-5565 15 mg BIDp-value: 0.688595% CI: [-0.4, 0.3]ANCOVA
Comparison: Least pain: Pregabalin 150 mg BID vs DS-5565 15 mg QDp-value: 0.172695% CI: [-0.1, 0.6]ANCOVA
Comparison: Least pain: Pregabalin 150 mg BID vs DS-5565 15 mg BIDp-value: 0.062795% CI: [0, 0.7]ANCOVA
Comparison: Average pain: Placebo vs Pregabalin 150 mg BIDp-value: 0.002695% CI: [-0.8, -0.2]ANCOVA
Comparison: Average pain: Placebo vs DS-5565 15 mg QDp-value: 0.136295% CI: [-0.6, 0.1]ANCOVA
Comparison: Average pain: Placebo vs DS-5565 15 mg BIDp-value: 0.434495% CI: [-0.4, 0.2]ANCOVA
Comparison: Average pain: Pregabalin 150 mg BID vs DS-5565 15 mg QDp-value: 0.126495% CI: [-0.1, 0.6]ANCOVA
Comparison: Average pain: Pregabalin 150 mg BID vs DS-5565 15 mg BIDp-value: 0.02695% CI: [0, 0.7]ANCOVA
Comparison: Pain right now: Placebo vs Pregabalin 150 mg BIDp-value: 0.000295% CI: [-1.1, -0.4]ANCOVA
Comparison: Pain right now: Placebo vs DS-5565 15 mg QDp-value: 0.059795% CI: [-0.8, 0]ANCOVA
Comparison: Pain right now: Placebo vs DS-5565 15 mg BIDp-value: 0.119895% CI: [-0.7, 0.1]ANCOVA
Comparison: Severity score: Placebo vs Pregabalin 150 mg BIDp-value: 0.000695% CI: [-0.885, -0.24]ANCOVA
Comparison: Severity score: Placebo vs DS-5565 15 mg QDp-value: 0.111895% CI: [-0.583, 0.061]ANCOVA
Comparison: Relief by treatment of pain: Placebo vs DS-5565 15 mg QDp-value: 0.218895% CI: [-1.8, 7.7]ANCOVA
Comparison: Relief by treatment of pain: Placebo vs DS-5565 15 mg BIDp-value: 0.099195% CI: [-0.8, 8.7]ANCOVA
Comparison: Relief by treatment of pain: Pregabalin 150 mg BID vs DS-5565 15 mg QDp-value: 0.061195% CI: [-9.2, 0.2]ANCOVA
Comparison: Relief by treatment of pain: Pregabalin 150 mg BID vs DS-5565 15 mg BIDp-value: 0.148995% CI: [-8.2, 1.2]ANCOVA
Comparison: Interference: Placebo vs Pregabalin 150 mg BIDp-value: 0.000695% CI: [-9.47, -2.6]ANCOVA
Comparison: Interference: Placebo vs DS-5565 15 mg QDp-value: 0.019395% CI: [-7.52, -0.67]ANCOVA
Comparison: Interference: Placebo vs DS-5565 15 mg BIDp-value: 0.350695% CI: [-5.07, 1.8]ANCOVA
Comparison: Interference: Pregabalin 150 mg BID vs DS-5565 15 mg QDp-value: 0.26695% CI: [-1.48, 5.37]ANCOVA
Comparison: Interference: Pregabalin 150 mg BID vs DS-5565 15 mg BIDp-value: 0.012295% CI: [0.96, 7.84]ANCOVA
Comparison: General activity: Placebo vs Pregabalin 150 mg BIDp-value: 0.011995% CI: [-0.9, -0.1]ANCOVA
Comparison: General activity: Placebo vs DS-5565 15 mg QDp-value: 0.065995% CI: [-0.8, 0]ANCOVA
Comparison: General activity: Placebo vs DS-5565 15 mg BIDp-value: 0.510495% CI: [-0.5, 0.3]ANCOVA
Comparison: General activity: Pregabalin 150 mg BID vs DS-5565 15 mg QDp-value: 0.493495% CI: [-0.3, 0.5]ANCOVA
Comparison: General activity: Pregabalin 150 mg BID vs DS-5565 15 mg BIDp-value: 0.063495% CI: [0, 0.8]ANCOVA
Comparison: Mood: Placebo vs Pregabalin 150 mg BIDp-value: 0.000795% CI: [-1.1, -0.3]ANCOVA
Comparison: Mood: Placebo vs DS-5565 15 mg QDp-value: 0.083795% CI: [-0.8, 0]ANCOVA
Comparison: Mood: Placebo vs DS-5565 15 mg BIDp-value: 0.237995% CI: [-0.7, 0.2]ANCOVA
Comparison: Mood: Pregabalin 150 mg BID vs DS-5565 15 mg QDp-value: 0.09895% CI: [-0.1, 0.8]ANCOVA
Comparison: Mood: Pregabalin 150 mg BID vs DS-5565 15 mg BIDp-value: 0.028395% CI: [0, 0.9]ANCOVA
Comparison: Walking ability: Placebo vs Pregabalin 150 mg BIDp-value: 0.217995% CI: [-0.7, 0.2]ANCOVA
Comparison: Walking ability: Placebo vs DS-5565 15 mg QDp-value: 0.668395% CI: [-0.5, 0.3]ANCOVA
Comparison: Walking ability: Placebo vs DS-5565 15 mg BIDp-value: 0.224795% CI: [-0.2, 0.7]ANCOVA
Comparison: Walking ability: Pregabalin 150 mg BID vs DS-5565 15 mg QDp-value: 0.419895% CI: [-0.2, 0.6]ANCOVA
Comparison: Walking ability: Pregabalin 150 mg BID vs DS-5565 15 mg BIDp-value: 0.014695% CI: [0.1, 0.9]ANCOVA
Comparison: Normal work: Placebo vs Pregabalin 150 mg BIDp-value: 0.066295% CI: [-0.8, 0]ANCOVA
Comparison: Normal work: Placebo vs DS-5565 15 mg QDp-value: 0.228295% CI: [-0.7, 0.2]ANCOVA
Comparison: Normal work: Placebo vs DS-5565 15 mg BIDp-value: 0.733695% CI: [-0.5, 0.3]ANCOVA
Comparison: Normal work: Pregabalin 150 mg BID vs DS-5565 15 mg QDp-value: 0.52495% CI: [-0.3, 0.5]ANCOVA
Comparison: Normal work: Pregabalin 150 mg BID vs DS-5565 15 mg BIDp-value: 0.134995% CI: [-0.1, 0.7]ANCOVA
Comparison: Relations with other people: Placebo vs Pregabalin 150 mg BIDp-value: 0.046495% CI: [-0.8, 0]ANCOVA
Comparison: Relations with other people: Placebo vs DS-5565 15 mg QDp-value: 0.097595% CI: [-0.7, 0.1]ANCOVA
Comparison: Relations with other people: Placebo vs DS-5565 15 mg BIDp-value: 0.608895% CI: [-0.3, 0.5]ANCOVA
Comparison: Relations with other people: Pregabalin 150 mg BID vs DS-5565 15 mg QDp-value: 0.734195% CI: [-0.3, 0.5]ANCOVA
Comparison: Relations with other people: Pregabalin 150 mg BID vs DS-5565 15 mg BIDp-value: 0.012595% CI: [0.1, 0.9]ANCOVA
Comparison: Sleep: Placebo vs Pregabalin 150 mg BIDp-value: <0.000195% CI: [-1.4, -0.5]ANCOVA
Comparison: Sleep: Placebo vs DS-5565 15 mg QDp-value: 0.000395% CI: [-1.3, -0.4]ANCOVA
Comparison: Sleep: Placebo vs DS-5565 15 mg BIDp-value: 0.00495% CI: [-1.1, -0.2]ANCOVA
Comparison: Sleep: Pregabalin 150 mg BID vs DS-5565 15 mg QDp-value: 0.580195% CI: [-0.3, 0.6]ANCOVA
Comparison: Sleep: Pregabalin 150 mg BID vs DS-5565 15 mg BIDp-value: 0.186995% CI: [-0.1, 0.7]ANCOVA
Comparison: Enjoyment of life: Placebo vs Pregabalin 150 mg BIDp-value: 0.000295% CI: [-1.3, -0.4]ANCOVA
Comparison: Enjoyment of life: Placebo vs DS-5565 15 mg QDp-value: 0.027195% CI: [-0.9, -0.1]ANCOVA
Comparison: Enjoyment of life: Placebo vs DS-5565 15 mg BIDp-value: 0.112395% CI: [-0.8, 0.1]ANCOVA
Comparison: Enjoyment of life: Pregabalin 150 mg BID vs DS-5565 15 mg QDp-value: 0.118395% CI: [-0.1, 0.8]ANCOVA
Comparison: Enjoyment of life: Pregabalin 150 mg BID vs DS-5565 15 mg BIDp-value: 0.029995% CI: [0, 0.9]ANCOVA
Secondary
Number of Participants Who Answered Much Improved or Better on the Patient Global Impression of Change (PGIC) Scale at Week 13 in Participants Receiving DS-5565, Pregabalin, or Placebo
Patient-rated global impression of change (PGIC) on a categorical scale from 1 = very much improved to 7 = very much worse. The number of participants with much improved or better (≤2 scores) are reported.
Time frame: Week 13 postdose
Population: PGIC was assessed using the modified intent-to-treat (mITT) analysis set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Who Answered Much Improved or Better on the Patient Global Impression of Change (PGIC) Scale at Week 13 in Participants Receiving DS-5565, Pregabalin, or Placebo | 91 Participants |
| Pregabalin 150 mg BID | Number of Participants Who Answered Much Improved or Better on the Patient Global Impression of Change (PGIC) Scale at Week 13 in Participants Receiving DS-5565, Pregabalin, or Placebo | 141 Participants |
| DS-5565 15 mg QD | Number of Participants Who Answered Much Improved or Better on the Patient Global Impression of Change (PGIC) Scale at Week 13 in Participants Receiving DS-5565, Pregabalin, or Placebo | 116 Participants |
| DS-5565 15 mg BID | Number of Participants Who Answered Much Improved or Better on the Patient Global Impression of Change (PGIC) Scale at Week 13 in Participants Receiving DS-5565, Pregabalin, or Placebo | 117 Participants |
Secondary
Number of Responders at Week 13 Among Participants Receiving DS-5565, Pregabalin, or Placebo
The number of participants with at least a 30% or 50% reduction in average daily pain score (ADPS) at Week 13 is reported.
Time frame: Week 13 postdose
Population: Responder rates were assessed using the modified intent-to-treat (mITT) analysis set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Responders at Week 13 Among Participants Receiving DS-5565, Pregabalin, or Placebo | 50% Responders | 61 Participants |
| Placebo | Number of Responders at Week 13 Among Participants Receiving DS-5565, Pregabalin, or Placebo | 30% Responders | 113 Participants |
| Pregabalin 150 mg BID | Number of Responders at Week 13 Among Participants Receiving DS-5565, Pregabalin, or Placebo | 30% Responders | 139 Participants |
| Pregabalin 150 mg BID | Number of Responders at Week 13 Among Participants Receiving DS-5565, Pregabalin, or Placebo | 50% Responders | 90 Participants |
| DS-5565 15 mg QD | Number of Responders at Week 13 Among Participants Receiving DS-5565, Pregabalin, or Placebo | 30% Responders | 123 Participants |
| DS-5565 15 mg QD | Number of Responders at Week 13 Among Participants Receiving DS-5565, Pregabalin, or Placebo | 50% Responders | 79 Participants |
| DS-5565 15 mg BID | Number of Responders at Week 13 Among Participants Receiving DS-5565, Pregabalin, or Placebo | 50% Responders | 68 Participants |
| DS-5565 15 mg BID | Number of Responders at Week 13 Among Participants Receiving DS-5565, Pregabalin, or Placebo | 30% Responders | 118 Participants |
Secondary
Proportion of Days a Rescue Medication Was Used in Participants Receiving DS-5565, Pregabalin, or Placebo
Proportion of days with rescue medication intake during the double-blind treatment period equals number of days with rescue medication intake/(date of last study drug administration in the double-blind treatment period) - date of first study drug administration + 1).
Time frame: Week 1 to Week 13 postdose
Population: Rescue medication usage was assessed using the modified intent-to-treat (mITT) analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Proportion of Days a Rescue Medication Was Used in Participants Receiving DS-5565, Pregabalin, or Placebo | 0.23 proportion of days | Standard Deviation 0.32 |
| Pregabalin 150 mg BID | Proportion of Days a Rescue Medication Was Used in Participants Receiving DS-5565, Pregabalin, or Placebo | 0.21 proportion of days | Standard Deviation 0.31 |
| DS-5565 15 mg QD | Proportion of Days a Rescue Medication Was Used in Participants Receiving DS-5565, Pregabalin, or Placebo | 0.22 proportion of days | Standard Deviation 0.32 |
| DS-5565 15 mg BID | Proportion of Days a Rescue Medication Was Used in Participants Receiving DS-5565, Pregabalin, or Placebo | 0.21 proportion of days | Standard Deviation 0.31 |
p-value: 0.557895% CI: [-0.063, 0.034]ANCOVA
p-value: 0.703495% CI: [-0.058, 0.039]ANCOVA
p-value: 0.414395% CI: [-0.069, 0.028]ANCOVA
p-value: 0.836595% CI: [-0.044, 0.054]ANCOVA
p-value: 0.818995% CI: [-0.055, 0.043]ANCOVA
Secondary
The Number of Participants Reporting Optimal Sleep at Week 13 on the Medical Outcomes Study (MOS) Sleep Scale in Participants Receiving DS-5565, Pregabalin, or Placebo
The MOS sleep scale is a 12-item questionnaire from which the following subscales were derived: sleep disturbance (4 items), quantity of sleep/optimal sleep (1 item), snoring (1 item), awakening due to shortness of breath or due to headache (1 item), sleep adequacy (2 items), and somnolence (3 items). In addition, values for sleep disturbances index (9 items), optimal sleep scale (1 item), sleep quantity scale (1 item) were determine. Most subscales range from 0 to 100, where higher scores indicate more of the concept being measured (eg., higher sleep disturbance scores indicate greater sleep disturbances).
Time frame: Week 13 postdose
Population: The MOS sleep scale outcome was assessed in the modified intent-to-treat (mITT) analysis set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | The Number of Participants Reporting Optimal Sleep at Week 13 on the Medical Outcomes Study (MOS) Sleep Scale in Participants Receiving DS-5565, Pregabalin, or Placebo | 90 Participants |
| Pregabalin 150 mg BID | The Number of Participants Reporting Optimal Sleep at Week 13 on the Medical Outcomes Study (MOS) Sleep Scale in Participants Receiving DS-5565, Pregabalin, or Placebo | 94 Participants |
| DS-5565 15 mg QD | The Number of Participants Reporting Optimal Sleep at Week 13 on the Medical Outcomes Study (MOS) Sleep Scale in Participants Receiving DS-5565, Pregabalin, or Placebo | 101 Participants |
| DS-5565 15 mg BID | The Number of Participants Reporting Optimal Sleep at Week 13 on the Medical Outcomes Study (MOS) Sleep Scale in Participants Receiving DS-5565, Pregabalin, or Placebo | 106 Participants |