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 subject that best describes his or her worst pain over the previous 24 hours.
Interventions
DRUGDS-5565
DS-5565 15 mg QD or BID; tablet for oral use
DRUGPregabalin
Pregabalin capsule for oral use; 75 mg capsule for one week, then 150 mg capsule
DRUGPlacebo tablet
Placebo tablet for oral use, matching DS-5565 tablet
DRUGPlacebo capsule
Placebo capsule for oral use, matching pregabalin capsule
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 C-SSRS questions at screening must be excluded. 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) Among Participants Receiving DS-5565, Pregabalin, or Placebo | Baseline up to Week 13 postdose | Average daily pain scores (ADPS) reported by the participant that best describes his or her worst pain over the previous 24 hours. A daily pain score has a scale where 0 = no pain to 10 = worst possible pain. Higher scores indicate a worse outcome. For participants with no Week 13 data, the baseline observation was carried forward (BOCF). The mean (multiple imputation estimate) and standard error (multiple imputation) are reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 13 in Average Score on the Fibromyalgia Index Questionnaire (FIQ) 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 Participants Classified As Responders at Week 13 Among Participants Receiving DS-5565, Pregabalin, or Placebo | Week 13 postdose | The ADPS responder rate was defined a priori as the proportion of participants who met the clinically relevant reductions (ie, ≥30% and ≥50%) in ADPS at Week 13 (baseline observation carried forward) compared to Baseline. |
| Change From Baseline to Week 13 in Multidimensional Fatigue Inventory (MFI-20) General Fatigue Score Among 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) Measure Among 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 to 21, where higher scores indicate greater severity. |
| Change From Baseline to Week 13 in Short Form 36 (SF-36) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Baseline up to Week 13 postdose | The SF-36 is a generic health survey that asks 36 questions to measure functional health and well-being from the patient's point of view. The SF-36 provides scores for 8 health domains (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health) as well as psychometrically-based physical component summary (PCS) and mental component summary (MCS) scores. Each scale is transformed into a 0-100 scale with each question carrying the same weight. The lower the score indicates more disability (ie, worse outcome). |
| Number of Participants Who Answered Much Improved or Better in Patient Global Impression of Change at Week 13 Receiving DS-5565, Pregabalin, or Placebo | Baseline up to Week 13 postdose | Patient global impression of change (PGIC) on a 7-point categorical scale, where 1 = very much improved and 7 = very much worse. Higher scores indicate worse outcomes. The number of participants with 'much improved or better' status (≤2) is being reported. |
| Change From Baseline to Week 13 in Average Daily Sleep Interference Score (ADSIS) Among Participants Receiving DS-5565, Pregabalin, or Placebo | Baseline up to Week 13 postdose | Pain-associated sleep interference will be assessed using the Average Daily Sleep Interference Score that utilize electronic daily diaries with 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). Higher scores indicate worse outcomes. |
| Number of Participants Reporting Optimal Sleep at Week 13 on the Medical Outcomes Study (MOS) Sleep Scale Among 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), and sleep quantity scale (1 item) were determined. Most subscales range from 0 to 100, where higher scores indicate more of the concept begin measured (eg., higher sleep disturbance scores indicate greater sleep disturbances). |
| Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among 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 Among 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) Measure Among 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 an 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
Argentina, Austria, Belarus, Belgium, Chile, Colombia, Israel, Mexico, Poland, Portugal, Slovenia, Spain, Switzerland, United States
Participant flow
Recruitment details
A total of 2526 participants who met all inclusion criteria and no exclusion criteria were enrolled from 16 Jan 2015 to 12 Jan 2017 at 182 sites. Of the 2526 participants enrolled, 1301 were randomized to treatment.
Pre-assignment details
Eligible participants were randomized 1:1:1:1 to either DS-5565 15 mg every day (QD) given orally, DS-5565 15 mg twice daily (BID) given orally, placebo given orally as pregabalin placebo and DS-5565 placebo BID, or pregabalin 150 mg BID.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and evening. | 325 |
| Pregabalin 150 mg BID Participants who received oral DS-5565 placebo and pregabalin 150 mg BID in the morning and evening. | 324 |
| DS-5565 15 mg QD Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and DS-5565 15 mg and pregabalin placebo in the evening. | 326 |
| DS-5565 15 mg BID Participants who received oral DS-5565 15 mg and pregabalin placebo in the morning and evening. | 326 |
| Total | 1,301 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 24 | 34 | 44 | 36 |
| Overall Study | Lack of Efficacy | 18 | 9 | 13 | 11 |
| Overall Study | Missing | 0 | 0 | 0 | 1 |
| Overall Study | Other | 7 | 5 | 3 | 4 |
| Overall Study | Protocol Violation | 4 | 5 | 4 | 4 |
| Overall Study | Withdrawal by Subject | 23 | 29 | 22 | 24 |
Baseline characteristics
| Characteristic | Placebo | Pregabalin 150 mg BID | DS-5565 15 mg QD | DS-5565 15 mg 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 | 36 Participants | 127 Participants |
| Age, Categorical Between 18 and 65 years | 296 Participants | 294 Participants | 294 Participants | 290 Participants | 1174 Participants |
| Age, Continuous | 48.9 years STANDARD_DEVIATION 11.16 | 49.9 years STANDARD_DEVIATION 12.02 | 50.1 years STANDARD_DEVIATION 11.22 | 49.0 years STANDARD_DEVIATION 12.03 | 49.5 years STANDARD_DEVIATION 11.62 |
| Region of Enrollment Argentina | 25 participants | 25 participants | 19 participants | 19 participants | 88 participants |
| Region of Enrollment Austria | 4 participants | 4 participants | 10 participants | 11 participants | 29 participants |
| Region of Enrollment Belarus | 5 participants | 2 participants | 2 participants | 3 participants | 12 participants |
| Region of Enrollment Belgium | 5 participants | 5 participants | 3 participants | 2 participants | 15 participants |
| Region of Enrollment Chile | 7 participants | 11 participants | 12 participants | 15 participants | 45 participants |
| Region of Enrollment Colombia | 0 participants | 0 participants | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Mexico | 9 participants | 4 participants | 9 participants | 7 participants | 29 participants |
| Region of Enrollment Poland | 20 participants | 21 participants | 23 participants | 22 participants | 86 participants |
| Region of Enrollment Portugal | 8 participants | 8 participants | 1 participants | 5 participants | 22 participants |
| Region of Enrollment Russia | 7 participants | 7 participants | 6 participants | 7 participants | 27 participants |
| Region of Enrollment Slovenia | 4 participants | 2 participants | 4 participants | 1 participants | 11 participants |
| Region of Enrollment Spain | 25 participants | 25 participants | 27 participants | 24 participants | 101 participants |
| Region of Enrollment Switzerland | 0 participants | 0 participants | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Ukraine | 16 participants | 20 participants | 18 participants | 20 participants | 74 participants |
| Region of Enrollment United States | 190 participants | 190 participants | 190 participants | 190 participants | 760 participants |
| Sex: Female, Male Female | 303 Participants | 302 Participants | 302 Participants | 296 Participants | 1203 Participants |
| Sex: Female, Male Male | 22 Participants | 22 Participants | 24 Participants | 30 Participants | 98 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 / 324 | 0 / 319 | 0 / 324 | 0 / 323 |
| other Total, other adverse events | 171 / 324 | 289 / 319 | 258 / 324 | 247 / 323 |
| serious Total, serious adverse events | 9 / 324 | 2 / 319 | 5 / 324 | 5 / 323 |
Outcome results
Primary
Change From Baseline to Week 13 in Average Daily Pain Score (ADPS) Among Participants Receiving DS-5565, Pregabalin, or Placebo
Average daily pain scores (ADPS) reported by the participant that best describes his or her worst pain over the previous 24 hours. A daily pain score has a scale where 0 = no pain to 10 = worst possible pain. Higher scores indicate a worse outcome. For participants with no Week 13 data, the baseline observation was carried forward (BOCF). The mean (multiple imputation estimate) and standard error (multiple imputation) 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 | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 13 in Average Daily Pain Score (ADPS) Among Participants Receiving DS-5565, Pregabalin, or Placebo | -1.90 units on a scale | Standard Error 0.135 |
| Pregabalin 150 mg BID | Change From Baseline to Week 13 in Average Daily Pain Score (ADPS) Among Participants Receiving DS-5565, Pregabalin, or Placebo | -2.64 units on a scale | Standard Error 0.137 |
| DS-5565 15 mg QD | Change From Baseline to Week 13 in Average Daily Pain Score (ADPS) Among Participants Receiving DS-5565, Pregabalin, or Placebo | -2.04 units on a scale | Standard Error 0.138 |
| DS-5565 15 mg BID | Change From Baseline to Week 13 in Average Daily Pain Score (ADPS) Among Participants Receiving DS-5565, Pregabalin, or Placebo | -2.30 units on a scale | Standard Error 0.136 |
p-value: 0.460195% CI: [-0.52, 0.23]Difference of means
p-value: 0.03595% CI: [-0.77, -0.03]Difference of means
p-value: 0.000195% CI: [-1.12, -0.37]Difference of means
p-value: 0.001995% CI: [0.22, 0.98]Difference of means
p-value: 0.076195% CI: [-0.04, 0.72]Difference of means
Secondary
Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among 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: This outcome was assessed using the modified intent-to-treat analysis set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Pain right now | -2.1 units on a scale | Standard Deviation 2.44 |
| Placebo | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Sleep | -2.1 units on a scale | Standard Deviation 3.13 |
| Placebo | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Mood | -1.6 units on a scale | Standard Deviation 2.83 |
| Placebo | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | General activity | -1.7 units on a scale | Standard Deviation 2.6 |
| Placebo | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Severity score | -1.75 units on a scale | Standard Deviation 2.05 |
| Placebo | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Least pain | -1.5 units on a scale | Standard Deviation 2.48 |
| Placebo | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Percentage of relief by treatment of pain | 23.1 units on a scale | Standard Deviation 31.93 |
| Placebo | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Worst pain | -1.9 units on a scale | Standard Deviation 2.26 |
| Placebo | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Relations with other people | -1.3 units on a scale | Standard Deviation 2.89 |
| Placebo | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Interference (%) | -16.19 units on a scale | Standard Deviation 21.83 |
| Placebo | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Average pain | -1.5 units on a scale | Standard Deviation 2.11 |
| Placebo | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Enjoyment of life | -1.6 units on a scale | Standard Deviation 2.94 |
| Placebo | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Normal work | -1.6 units on a scale | Standard Deviation 2.52 |
| Placebo | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Walking ability | -1.4 units on a scale | Standard Deviation 2.66 |
| Pregabalin 150 mg BID | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Normal work | -2.3 units on a scale | Standard Deviation 2.93 |
| Pregabalin 150 mg BID | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Interference (%) | -23.55 units on a scale | Standard Deviation 23.6 |
| Pregabalin 150 mg BID | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Worst pain | -2.7 units on a scale | Standard Deviation 2.78 |
| Pregabalin 150 mg BID | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Least pain | -2.3 units on a scale | Standard Deviation 2.58 |
| Pregabalin 150 mg BID | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Average pain | -2.3 units on a scale | Standard Deviation 2.27 |
| Pregabalin 150 mg BID | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Pain right now | -2.8 units on a scale | Standard Deviation 2.74 |
| Pregabalin 150 mg BID | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Severity score | -2.55 units on a scale | Standard Deviation 2.35 |
| Pregabalin 150 mg BID | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Percentage of relief by treatment of pain | 32.6 units on a scale | Standard Deviation 35.39 |
| Pregabalin 150 mg BID | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | General activity | -2.5 units on a scale | Standard Deviation 2.87 |
| Pregabalin 150 mg BID | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Mood | -2.1 units on a scale | Standard Deviation 2.92 |
| Pregabalin 150 mg BID | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Walking ability | -1.7 units on a scale | Standard Deviation 2.96 |
| Pregabalin 150 mg BID | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Relations with other people | -1.9 units on a scale | Standard Deviation 3.03 |
| Pregabalin 150 mg BID | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Sleep | -3.6 units on a scale | Standard Deviation 3.13 |
| Pregabalin 150 mg BID | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Enjoyment of life | -2.4 units on a scale | Standard Deviation 3.06 |
| DS-5565 15 mg QD | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Normal work | -2.1 units on a scale | Standard Deviation 2.63 |
| DS-5565 15 mg QD | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Sleep | -3.1 units on a scale | Standard Deviation 3.06 |
| DS-5565 15 mg QD | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Least pain | -2.0 units on a scale | Standard Deviation 2.43 |
| DS-5565 15 mg QD | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Pain right now | -2.5 units on a scale | Standard Deviation 2.5 |
| DS-5565 15 mg QD | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Relations with other people | -1.6 units on a scale | Standard Deviation 2.95 |
| DS-5565 15 mg QD | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Worst pain | -2.2 units on a scale | Standard Deviation 2.48 |
| DS-5565 15 mg QD | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Walking ability | -1.8 units on a scale | Standard Deviation 2.73 |
| DS-5565 15 mg QD | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | General activity | -2.3 units on a scale | Standard Deviation 2.69 |
| DS-5565 15 mg QD | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Severity score | -2.16 units on a scale | Standard Deviation 2.13 |
| DS-5565 15 mg QD | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Enjoyment of life | -2.3 units on a scale | Standard Deviation 2.95 |
| DS-5565 15 mg QD | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Percentage of relief by treatment of pain | 31.8 units on a scale | Standard Deviation 32.28 |
| DS-5565 15 mg QD | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Average pain | -2.0 units on a scale | Standard Deviation 2.28 |
| DS-5565 15 mg QD | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Interference (%) | -21.66 units on a scale | Standard Deviation 22.29 |
| DS-5565 15 mg QD | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Mood | -1.9 units on a scale | Standard Deviation 2.95 |
| DS-5565 15 mg BID | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Interference (%) | -25.97 units on a scale | Standard Deviation 23.38 |
| DS-5565 15 mg BID | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | General activity | -2.6 units on a scale | Standard Deviation 2.82 |
| DS-5565 15 mg BID | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Sleep | -3.9 units on a scale | Standard Deviation 3.08 |
| DS-5565 15 mg BID | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Mood | -2.4 units on a scale | Standard Deviation 2.95 |
| DS-5565 15 mg BID | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Average pain | -2.3 units on a scale | Standard Deviation 2.39 |
| DS-5565 15 mg BID | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Walking ability | -2.1 units on a scale | Standard Deviation 2.66 |
| DS-5565 15 mg BID | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Least pain | -2.1 units on a scale | Standard Deviation 2.53 |
| DS-5565 15 mg BID | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Normal work | -2.7 units on a scale | Standard Deviation 2.73 |
| DS-5565 15 mg BID | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Enjoyment of life | -2.4 units on a scale | Standard Deviation 3.27 |
| DS-5565 15 mg BID | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Relations with other people | -2.0 units on a scale | Standard Deviation 2.97 |
| DS-5565 15 mg BID | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Worst pain | -2.7 units on a scale | Standard Deviation 2.52 |
| DS-5565 15 mg BID | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Severity score | -2.51 units on a scale | Standard Deviation 2.26 |
| DS-5565 15 mg BID | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Percentage of relief by treatment of pain | 36.0 units on a scale | Standard Deviation 34.68 |
| DS-5565 15 mg BID | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Pain right now | -2.9 units on a scale | Standard Deviation 2.72 |
Comparison: Worst pain: Placebo vs Pregabalin 150 mg BIDp-value: <0.000195% CI: [-1.2, -0.4]ANCOVA
Comparison: Worst pain: Placebo vs DS-5565 15 mg QDp-value: 0.200595% CI: [-0.6, 0.1]ANCOVA
Comparison: Worst pain: Placebo vs DS-5565 15 mg BIDp-value: 0.00195% CI: [-1, -0.3]ANCOVA
Comparison: Worst pain: Pregabalin 150 mg BID vs DS-5565 15 mg QDp-value: 0.00395% CI: [0.2, 1]ANCOVA
Comparison: Worst pain: Pregabalin 150 mg BID vs DS-5565 15 mg BIDp-value: 0.335195% CI: [-0.2, 0.6]ANCOVA
Comparison: Least pain: Placebo vs Pregabalin 150 mg BIDp-value: <0.000195% CI: [-1.1, -0.4]ANCOVA
Comparison: Least pain: Placebo vs DS-5565 15 mg QDp-value: 0.078295% CI: [-0.7, 0]ANCOVA
Comparison: Least pain: Placebo vs DS-5565 15 mg BIDp-value: 0.006895% CI: [-0.9, -0.1]ANCOVA
Comparison: Least pain: Pregabalin 150 mg BID vs DS-5565 15 mg QDp-value: 0.016995% CI: [0.1, 0.8]ANCOVA
Comparison: Least pain: Pregabalin 150 mg BID vs DS-5565 15 mg BIDp-value: 0.148195% CI: [-0.1, 0.6]ANCOVA
Comparison: Average pain: Placebo vs Pregabalin 150 mg BIDp-value: <0.000195% CI: [-1.1, -0.4]ANCOVA
Comparison: Average pain: Placebo vs DS-5565 15 mg QDp-value: 0.008895% CI: [-0.8, -0.1]ANCOVA
Comparison: Average pain: Placebo vs DS-5565 15 mg BIDp-value: 0.000595% CI: [-0.9, -0.3]ANCOVA
Comparison: Average pain: Pregabalin 150 mg BID vs DS-5565 15 mg QDp-value: 0.062795% CI: [0, 0.7]ANCOVA
Comparison: Average pain: Pregabalin 150 mg BID vs DS-5565 15 mg BIDp-value: 0.306495% CI: [-0.2, 0.5]ANCOVA
Comparison: Pain right now: Placebo vs Pregabalin 150 mg BIDp-value: <0.000195% CI: [-1.2, -0.4]ANCOVA
Comparison: Pain right now: Placebo vs DS-5565 15 mg QDp-value: 0.086895% CI: [-0.7, 0]ANCOVA
Comparison: Pain right now: Placebo vs DS-5565 15 mg BIDp-value: 0.000495% CI: [-1.1, -0.3]ANCOVA
Comparison: Pain right now: Pregabalin 150 mg BID vs DS-5565 15 mg QDp-value: 0.027195% CI: [0.1, 0.8]ANCOVA
Comparison: Pain right now: Pregabalin 150 mg BID vs DS-5565 15 mg BIDp-value: 0.683895% CI: [-0.3, 0.5]ANCOVA
Comparison: Severity score: Placebo vs Pregabalin 150 mg BIDp-value: <0.000195% CI: [-1.129, -0.454]ANCOVA
Comparison: Severity score: Placebo vs DS-5565 15 mg QDp-value: 0.055295% CI: [-0.667, 0.007]ANCOVA
Comparison: Severity score: Placebo vs DS-5565 15 mg BIDp-value: 0.000495% CI: [-0.95, -0.275]ANCOVA
Comparison: Severity score: Pregabalin 150 mg BID vs DS-5565 15 mg QDp-value: 0.007795% CI: [0.122, 0.801]ANCOVA
Comparison: Severity score: Pregabalin 150 mg BID vs DS-5565 15 mg BIDp-value: 0.301495% CI: [-0.161, 0.518]ANCOVA
Comparison: Relief (%) by treatment of pain: Placebo vs Pregabalin 150 mg BIDp-value: <0.000195% CI: [4.9, 14.3]ANCOVA
Comparison: Relief (%) by treatment of pain: Placebo vs DS-5565 15 mg QDp-value: 0.000495% CI: [3.8, 13.2]ANCOVA
Comparison: Relief (%) by treatment of pain: Placebo vs DS-5565 15 mg BIDp-value: <0.000195% CI: [5.7, 15.1]ANCOVA
Comparison: Relief (%) by treatment of pain: Pregabalin 150 mg BID vs DS-5565 15 mg QDp-value: 0.644995% CI: [-5.8, 3.6]ANCOVA
Comparison: Relief (%) by treatment of pain: Pregabalin 150 mg BID vs DS-5565 15 mg BIDp-value: 0.73495% CI: [-3.9, 5.5]ANCOVA
Secondary
Change From Baseline to Week 13 in Average Daily Sleep Interference Score (ADSIS) Among Participants Receiving DS-5565, Pregabalin, or Placebo
Pain-associated sleep interference will be assessed using the Average Daily Sleep Interference Score that utilize electronic daily diaries with 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). Higher scores indicate worse outcomes.
Time frame: Baseline up to Week 13 postdose
Population: This outcome was assessed using the modified intent-to-treat analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 13 in Average Daily Sleep Interference Score (ADSIS) Among Participants Receiving DS-5565, Pregabalin, or Placebo | -1.76 units on a scale | Standard Deviation 0.116 |
| Pregabalin 150 mg BID | Change From Baseline to Week 13 in Average Daily Sleep Interference Score (ADSIS) Among Participants Receiving DS-5565, Pregabalin, or Placebo | -2.71 units on a scale | Standard Deviation 0.116 |
| DS-5565 15 mg QD | Change From Baseline to Week 13 in Average Daily Sleep Interference Score (ADSIS) Among Participants Receiving DS-5565, Pregabalin, or Placebo | -2.31 units on a scale | Standard Deviation 0.117 |
| DS-5565 15 mg BID | Change From Baseline to Week 13 in Average Daily Sleep Interference Score (ADSIS) Among Participants Receiving DS-5565, Pregabalin, or Placebo | -2.64 units on a scale | Standard Deviation 0.116 |
p-value: 0.000695% CI: [-0.87, -0.24]Mixed Models Analysis
p-value: <0.000195% CI: [-1.2, -0.57]Mixed Models Analysis
p-value: <0.000195% CI: [-1.27, -0.63]Mixed Models Analysis
p-value: 0.015895% CI: [0.07, 0.71]Mixed Models Analysis
p-value: 0.681995% CI: [-0.25, 0.38]Mixed Models Analysis
Secondary
Change From Baseline to Week 13 in Average Score on the Fibromyalgia Index Questionnaire (FIQ) 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: This outcome was assessed using the modified intent-to-treat analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 13 in Average Score on the Fibromyalgia Index Questionnaire (FIQ) in Participants Receiving DS-5565, Pregabalin, or Placebo | -15.02 units on a scale | Standard Error 1.198 |
| Pregabalin 150 mg BID | Change From Baseline to Week 13 in Average Score on the Fibromyalgia Index Questionnaire (FIQ) in Participants Receiving DS-5565, Pregabalin, or Placebo | -19.42 units on a scale | Standard Error 1.222 |
| DS-5565 15 mg QD | Change From Baseline to Week 13 in Average Score on the Fibromyalgia Index Questionnaire (FIQ) in Participants Receiving DS-5565, Pregabalin, or Placebo | -16.61 units on a scale | Standard Error 1.215 |
| DS-5565 15 mg BID | Change From Baseline to Week 13 in Average Score on the Fibromyalgia Index Questionnaire (FIQ) in Participants Receiving DS-5565, Pregabalin, or Placebo | -20.44 units on a scale | Standard Error 1.209 |
p-value: 0.340795% CI: [-4.86, 1.68]Difference of means
p-value: 0.001295% CI: [-8.69, -2.15]Difference of means
p-value: 0.008395% CI: [-7.66, -1.13]Difference of means
p-value: 0.094695% CI: [-0.48, 6.09]Difference of means
p-value: 0.538495% CI: [-4.3, 2.24]Difference of means
Secondary
Change From Baseline to Week 13 in EuroQol Five Dimensions Questionnaire (EQ-5D) Measure Among 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 an 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: This outcome was assessed in the modified intent-to-treat analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 13 in EuroQol Five Dimensions Questionnaire (EQ-5D) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | 0.09 units on a scale | Standard Deviation 0.19 |
| Pregabalin 150 mg BID | Change From Baseline to Week 13 in EuroQol Five Dimensions Questionnaire (EQ-5D) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | 0.1274 units on a scale | Standard Deviation 0.2 |
| DS-5565 15 mg QD | Change From Baseline to Week 13 in EuroQol Five Dimensions Questionnaire (EQ-5D) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | 0.10 units on a scale | Standard Deviation 0.19 |
| DS-5565 15 mg BID | Change From Baseline to Week 13 in EuroQol Five Dimensions Questionnaire (EQ-5D) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | 0.11 units on a scale | Standard Deviation 0.21 |
p-value: 0.139495% CI: [-0.0066, 0.0471]ANCOVA
p-value: 0.123795% CI: [-0.0058, 0.048]ANCOVA
p-value: 0.004995% CI: [0.0117, 0.0655]ANCOVA
p-value: 0.182495% CI: [-0.0454, 0.0086]ANCOVA
p-value: 0.203695% CI: [-0.0446, 0.0095]ANCOVA
Secondary
Change From Baseline to Week 13 in Hospital Anxiety and Depression Scale (HADS) Measure Among 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 to 21, where higher scores indicate greater severity.
Time frame: Baseline up to Week 13 postdose
Population: This outcome was assessed in the modified intent-to-treat analysis set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Week 13 in Hospital Anxiety and Depression Scale (HADS) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Change from baseline at Week 13: Anxiety | -1.0 units on a scale | Standard Deviation 3.58 |
| Placebo | Change From Baseline to Week 13 in Hospital Anxiety and Depression Scale (HADS) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Change from baseline at Week 13: Depression | -0.8 units on a scale | Standard Deviation 3.67 |
| Pregabalin 150 mg BID | Change From Baseline to Week 13 in Hospital Anxiety and Depression Scale (HADS) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Change from baseline at Week 13: Depression | -1.0 units on a scale | Standard Deviation 4.07 |
| Pregabalin 150 mg BID | Change From Baseline to Week 13 in Hospital Anxiety and Depression Scale (HADS) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Change from baseline at Week 13: Anxiety | -0.9 units on a scale | Standard Deviation 3.81 |
| DS-5565 15 mg QD | Change From Baseline to Week 13 in Hospital Anxiety and Depression Scale (HADS) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Change from baseline at Week 13: Depression | -1.0 units on a scale | Standard Deviation 3.8 |
| DS-5565 15 mg QD | Change From Baseline to Week 13 in Hospital Anxiety and Depression Scale (HADS) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Change from baseline at Week 13: Anxiety | -1.0 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) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Change from baseline at Week 13: Anxiety | -1.0 units on a scale | Standard Deviation 4.1 |
| DS-5565 15 mg BID | Change From Baseline to Week 13 in Hospital Anxiety and Depression Scale (HADS) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Change from baseline at Week 13: Depression | -1.2 units on a scale | Standard Deviation 3.69 |
Comparison: Anxiety: Placebo vs DS-5565 15 mg QDp-value: 0.518395% CI: [-0.7, 0.4]ANCOVA
Comparison: Anxiety: Placebo vs DS-5565 15 mg BIDp-value: 0.266995% CI: [-0.9, 0.2]ANCOVA
Comparison: Anxiety: Placebo vs Pregabalin 150 mg BIDp-value: 0.46395% CI: [-0.8, 0.3]ANCOVA
Comparison: Anxiety: Pregabalin 150 mg BID vs DS-5565 15 mg QDp-value: 0.92895% CI: [-0.5, 0.6]ANCOVA
Comparison: Anxiety: Pregabalin 150 mg BID vs DS-5565 15 mg BIDp-value: 0.708995% CI: [-0.7, 0.5]ANCOVA
Comparison: Depression: Placebo vs DS-5565 15 mg QDp-value: 0.066995% CI: [-1.1, 0]ANCOVA
Comparison: Depression: Placebo vs DS-5565 15 mg BIDp-value: 0.008195% CI: [-1.3, -0.2]ANCOVA
Comparison: Depression: Placebo vs Pregabalin 150 mg BIDp-value: 0.086795% CI: [-1, 0.1]ANCOVA
Comparison: Depression: Pregabalin 150 mg BID vs DS-5565 15 mg QDp-value: 0.906695% CI: [-0.6, 0.5]ANCOVA
Comparison: Depression: Pregabalin 150 mg BID vs DS-5565 15 mg BIDp-value: 0.350995% CI: [-0.8, 0.3]ANCOVA
Secondary
Change From Baseline to Week 13 in Multidimensional Fatigue Inventory (MFI-20) General Fatigue Score Among 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: MFI-20 was assessed in the modified intent-to-treat population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 13 in Multidimensional Fatigue Inventory (MFI-20) General Fatigue Score Among Participants Receiving DS-5565, Pregabalin, or Placebo | -1.6 units on a scale | Standard Deviation 3.55 |
| Pregabalin 150 mg BID | Change From Baseline to Week 13 in Multidimensional Fatigue Inventory (MFI-20) General Fatigue Score Among Participants Receiving DS-5565, Pregabalin, or Placebo | -2.6 units on a scale | Standard Deviation 4 |
| DS-5565 15 mg QD | Change From Baseline to Week 13 in Multidimensional Fatigue Inventory (MFI-20) General Fatigue Score Among Participants Receiving DS-5565, Pregabalin, or Placebo | -2.4 units on a scale | Standard Deviation 3.91 |
| DS-5565 15 mg BID | Change From Baseline to Week 13 in Multidimensional Fatigue Inventory (MFI-20) General Fatigue Score Among Participants Receiving DS-5565, Pregabalin, or Placebo | -3.4 units on a scale | Standard Deviation 4.54 |
p-value: 0.00395% CI: [-1.5, -0.3]ANCOVA
p-value: <0.000195% CI: [-2.3, -1.1]ANCOVA
p-value: 0.000195% CI: [-1.7, -0.6]ANCOVA
p-value: 0.356295% CI: [-0.3, 0.9]ANCOVA
p-value: 0.086295% CI: [-1.1, 0.1]ANCOVA
Secondary
Change From Baseline to Week 13 in Short Form 36 (SF-36) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo
The SF-36 is a generic health survey that asks 36 questions to measure functional health and well-being from the patient's point of view. The SF-36 provides scores for 8 health domains (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health) as well as psychometrically-based physical component summary (PCS) and mental component summary (MCS) scores. Each scale is transformed into a 0-100 scale with each question carrying the same weight. The lower the score indicates more disability (ie, worse outcome).
Time frame: Baseline up to Week 13 postdose
Population: This outcome was assessed in 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) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Change from baseline to Week 13:Physical Component | 3.78 units on a scale | Standard Deviation 7.22 |
| Placebo | Change From Baseline to Week 13 in Short Form 36 (SF-36) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Change from baseline to Week 13: Mental Component | 2.23 units on a scale | Standard Deviation 9.54 |
| Pregabalin 150 mg BID | Change From Baseline to Week 13 in Short Form 36 (SF-36) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Change from baseline to Week 13: Mental Component | 1.97 units on a scale | Standard Deviation 10.53 |
| Pregabalin 150 mg BID | Change From Baseline to Week 13 in Short Form 36 (SF-36) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Change from baseline to Week 13:Physical Component | 6.46 units on a scale | Standard Deviation 8.32 |
| DS-5565 15 mg QD | Change From Baseline to Week 13 in Short Form 36 (SF-36) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Change from baseline to Week 13:Physical Component | 5.94 units on a scale | Standard Deviation 8.06 |
| DS-5565 15 mg QD | Change From Baseline to Week 13 in Short Form 36 (SF-36) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Change from baseline to Week 13: Mental Component | 1.56 units on a scale | Standard Deviation 10.19 |
| DS-5565 15 mg BID | Change From Baseline to Week 13 in Short Form 36 (SF-36) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Change from baseline to Week 13:Physical Component | 6.22 units on a scale | Standard Deviation 8.46 |
| DS-5565 15 mg BID | Change From Baseline to Week 13 in Short Form 36 (SF-36) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo | Change from baseline to Week 13: Mental Component | 2.71 units on a scale | Standard Deviation 9.67 |
Comparison: Physical Component: Placebo vs DS-5565 15 mg QDp-value: 0.000495% CI: [0.97, 3.404]ANCOVA
Comparison: Physical Component: Placebo vs DS-5565 15 mg BIDp-value: <0.000195% CI: [1.265, 3.701]ANCOVA
Comparison: Physical Component: Placebo vs Pregabalin 150 mg BIDp-value: <0.000195% CI: [1.401, 3.84]ANCOVA
Comparison: Physical Component: Pregabalin 150 mg BID vs DS-5565 15 mg QDp-value: 0.487795% CI: [-1.659, 0.792]ANCOVA
Comparison: Physical Component: Pregabalin 150 mg BID vs DS-5565 15 mg BIDp-value: 0.826395% CI: [-1.364, 1.089]ANCOVA
Comparison: Mental Component: Placebo vs DS-5565 15 mg QDp-value: 0.756795% CI: [-1.213, 1.669]ANCOVA
Comparison: Mental Component: Placebo vs DS-5565 15 mg BIDp-value: 0.078795% CI: [-0.149, 2.735]ANCOVA
Comparison: Mental Component: Placebo vs Pregabalin 150 mg BIDp-value: 0.351695% CI: [-0.758, 2.129]ANCOVA
Comparison: Mental Component: Pregabalin 150 mg BID vs DS-5565 15 mg QDp-value: 0.534495% CI: [-1.905, 0.988]ANCOVA
Comparison: Mental Component: Pregabalin 150 mg BID vs DS-5565 15 mg BIDp-value: 0.410795% CI: [-0.84, 2.055]ANCOVA
Secondary
Number of Participants Classified As Responders at Week 13 Among Participants Receiving DS-5565, Pregabalin, or Placebo
The ADPS responder rate was defined a priori as the proportion of participants who met the clinically relevant reductions (ie, ≥30% and ≥50%) in ADPS at Week 13 (baseline observation carried forward) compared to Baseline.
Time frame: Week 13 postdose
Population: This outcome was assessed using the modified intent-to-treat analysis set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants Classified As Responders at Week 13 Among Participants Receiving DS-5565, Pregabalin, or Placebo | 30% Responders | 122 Participants |
| Placebo | Number of Participants Classified As Responders at Week 13 Among Participants Receiving DS-5565, Pregabalin, or Placebo | 50% Responders | 68 Participants |
| Pregabalin 150 mg BID | Number of Participants Classified As Responders at Week 13 Among Participants Receiving DS-5565, Pregabalin, or Placebo | 50% Responders | 95 Participants |
| Pregabalin 150 mg BID | Number of Participants Classified As Responders at Week 13 Among Participants Receiving DS-5565, Pregabalin, or Placebo | 30% Responders | 144 Participants |
| DS-5565 15 mg QD | Number of Participants Classified As Responders at Week 13 Among Participants Receiving DS-5565, Pregabalin, or Placebo | 30% Responders | 121 Participants |
| DS-5565 15 mg QD | Number of Participants Classified As Responders at Week 13 Among Participants Receiving DS-5565, Pregabalin, or Placebo | 50% Responders | 77 Participants |
| DS-5565 15 mg BID | Number of Participants Classified As Responders at Week 13 Among Participants Receiving DS-5565, Pregabalin, or Placebo | 30% Responders | 125 Participants |
| DS-5565 15 mg BID | Number of Participants Classified As Responders at Week 13 Among Participants Receiving DS-5565, Pregabalin, or Placebo | 50% Responders | 89 Participants |
Secondary
Number of Participants Reporting Optimal Sleep at Week 13 on the Medical Outcomes Study (MOS) Sleep Scale Among 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), and sleep quantity scale (1 item) were determined. Most subscales range from 0 to 100, where higher scores indicate more of the concept begin measured (eg., higher sleep disturbance scores indicate greater sleep disturbances).
Time frame: Week 13 postdose
Population: This outcome was assessed using the modified intent-to-treat analysis set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Reporting Optimal Sleep at Week 13 on the Medical Outcomes Study (MOS) Sleep Scale Among Participants Receiving DS-5565, Pregabalin, or Placebo | 78 Participants |
| Pregabalin 150 mg BID | Number of Participants Reporting Optimal Sleep at Week 13 on the Medical Outcomes Study (MOS) Sleep Scale Among Participants Receiving DS-5565, Pregabalin, or Placebo | 107 Participants |
| DS-5565 15 mg QD | Number of Participants Reporting Optimal Sleep at Week 13 on the Medical Outcomes Study (MOS) Sleep Scale Among Participants Receiving DS-5565, Pregabalin, or Placebo | 102 Participants |
| DS-5565 15 mg BID | Number of Participants Reporting Optimal Sleep at Week 13 on the Medical Outcomes Study (MOS) Sleep Scale Among Participants Receiving DS-5565, Pregabalin, or Placebo | 119 Participants |
Secondary
Number of Participants Who Answered Much Improved or Better in Patient Global Impression of Change at Week 13 Receiving DS-5565, Pregabalin, or Placebo
Patient global impression of change (PGIC) on a 7-point categorical scale, where 1 = very much improved and 7 = very much worse. Higher scores indicate worse outcomes. The number of participants with 'much improved or better' status (≤2) is being reported.
Time frame: Baseline up to Week 13 postdose
Population: This outcome was assessed using the modified intent-to-treat analysis set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Who Answered Much Improved or Better in Patient Global Impression of Change at Week 13 Receiving DS-5565, Pregabalin, or Placebo | 88 Participants |
| Pregabalin 150 mg BID | Number of Participants Who Answered Much Improved or Better in Patient Global Impression of Change at Week 13 Receiving DS-5565, Pregabalin, or Placebo | 145 Participants |
| DS-5565 15 mg QD | Number of Participants Who Answered Much Improved or Better in Patient Global Impression of Change at Week 13 Receiving DS-5565, Pregabalin, or Placebo | 127 Participants |
| DS-5565 15 mg BID | Number of Participants Who Answered Much Improved or Better in Patient Global Impression of Change at Week 13 Receiving DS-5565, Pregabalin, or Placebo | 134 Participants |
Secondary
Proportion of Days a Rescue Medication Was Used Among 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: This outcome was assessed using the modified intent-to-treat analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Proportion of Days a Rescue Medication Was Used Among 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 Among Participants Receiving DS-5565, Pregabalin, or Placebo | 0.15 proportion of days | Standard Deviation 0.25 |
| DS-5565 15 mg QD | Proportion of Days a Rescue Medication Was Used Among Participants Receiving DS-5565, Pregabalin, or Placebo | 0.21 proportion of days | Standard Deviation 0.31 |
| DS-5565 15 mg BID | Proportion of Days a Rescue Medication Was Used Among Participants Receiving DS-5565, Pregabalin, or Placebo | 0.16 proportion of days | Standard Deviation 0.26 |
p-value: 0.481695% CI: [-0.06, 0.028]ANCOVA
p-value: 0.004495% CI: [-0.109, -0.02]ANCOVA
p-value: 0.00195% CI: [-0.119, -0.03]ANCOVA
p-value: 0.009495% CI: [0.014, 0.103]ANCOVA
p-value: 0.652795% CI: [-0.034, 0.055]ANCOVA