Pain Associated With Fibromyalgia
Conditions
Keywords
pain, fibromyalgia
Brief summary
This is an open-label study of DS-5565 in subjects who either completed participation in a preceding Phase 3 study of DS-5565 in fibromyalgia (FM); i.e. DS5565-A-E309 (NCT02146430), DS5565-A-E310 (NCT02187471), or DS5565-A-E311 (NCT02187159) or are de novo subjects. Eligible subjects will be assigned to receive open-label DS-5565 for 52 weeks. All subjects will receive DS-5565 15 mg once daily (QD) for the first three weeks of the treatment period. After three weeks, subjects may be titrated to 15 mg twice daily (BID) based on protocol-specified criteria.
Interventions
DRUGDS-5565
DS-5565 15 mg tablet for oral administration
Sponsors
Daiichi Sankyo
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Able to give written informed consent * Completed participation (i.e. completed the End-of-Tapering visit) in a preceding study of DS 5565 in FM (DS5565-A-E309, DS5565-A-E310, or DS5565-A-E311) * 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 * Able to complete subject-reported questionaires per the investigator's judgement * The subject must not have experienced any significant safety issues during the preceding study that, in the investigator's judgment, would adversely impact the subject's well-being in the long-term extension De Novo Subjects * 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 first dose (based on completion of at least 4 daily pain diaries during the 7-day baseline period) * 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 during the preceding study (for rollover subjects) or within 12 months prior to screening (for de novo subjects) that in the opinion of the investigator would interfere with study participation or assessment of safety and tolerability * Subjects who are at risk of suicide as defined by their responses to the C-SSRS or in the opinion of the investigator. * Subjects with severe or uncontrolled depression that, in the judgment of the investigator, makes the subject inappropriate for entry into the study * Subjects with pain due to other conditions (e.g. DPNP 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 * A diagnosis of untreated sleep apnea or initiation of treatment for sleep apnea within the past 3 months * Known hypersensitivity to α2δ ligands or other components of the study medications * Pregnancy or breast-feeding, or intent to become pregnant during the study period * Abnormal investigative tests (i.e. ECGs) and laboratory values judged by the investigator to be clinically significant at the End-of-Treatment visit (Visit - Week 13) in the preceding study (for rollover subjects) or at screening (for de novo subjects), with particular focus on: For De Novo Subjects Only * Unable to undergo pre-study washout of prohibited concomitant medications (as listed in Section 5.2.1 of the protocol) * Current severe or uncontrolled major depressive disorder or anxiety disorders as assessed by the Mini-international Neuropsychiatric Interview (MINI) interview (Version 6.0) at screening are excluded, but 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 * 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 * Subject is an employee of the study center, an immediate family member\* of an employee of the study center, or an employee of Daiichi Sankyo, INC Research, or any of the study vendors supporting this study. \*(spouse, parent, child, or sibling, whether biological or legally adopted)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Daily Pain Score (ADPS) for DS-5565 | Day 0 (baseline) up to to Week 52 postdose | Average of daily pain scores are reported by the participant and best describes his or her worst pain over the previous 24 hours. A daily pain score has a scale of 0 = no pain to 10 = worst possible pain. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Much Improved or Better (≤2) Status in Status at Week 52 As Assessed by the Patient-Rated Global Impression of Change | Week 52 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 status are reported. |
| Hospital Anxiety Depression Scale (HADS) Depression and Anxiety Scores for DS-5565 | Day 0 (baseline) up to Week 52 postdose | The HADS questionnaire is a 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 from 0 to 3, where higher scores indicate greater anxiety or depression. 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. |
| EuroQol Five Dimensions Questionnaire (EQ-5D) Measure for DS-5565 | Day 0 (baseline) up to Week 52 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) that are combined into an overall health utilities index, and an NRS (100 mm VAS) that measures perception of overall health, with 0 indicating worst health and 100 representing best imaginable health. |
| Short Form-36 (SF-36) Measure for DS-5565 | Day 0 (baseline) to Week 52 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 physical component summary and mental component summary scales range 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) total scores at baseline and Week 52 are reported. |
| Pain-Associated Sleep Interference as Assessed by Average Daily Sleep Interference Score (ADSIS) for DS-5565 | Day 0 (baseline) up to Week 52 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. For rollover participants, the baseline scores from the End-of-Tapering period in the preceding study are reported. For de novo participants, the baseline scores are derived from the 7 days prior to the start of treatment. |
Countries
Australia, Austria, Bulgaria, Canada, Chile, Czechia, Denmark, Estonia, Finland, France, Germany, Hungary, Latvia, Lithuania, New Zealand, Norway, Poland, Portugal, Puerto Rico, Romania, Russia, Serbia, Slovakia, Slovenia, South Africa, Spain, Ukraine, United Kingdom, United States
Participant flow
Recruitment details
A total of 2485 participants who met all inclusion and no exclusion criteria enrolled from 04 Feb 2015 to 19 Apr 2017 at 406 clinic sites. Of the 2485 enrolled, 397 discontinued prior to randomization. A total of 2088 participants received study treatment.
Pre-assignment details
Participants who completed the double-blind studies of DS-5565 in fibromyalgia were eligible to Rollover to this open-label extension study (referred to as Rollover participants). Participants who did not participate in a preceding double-blind study (referred to as De Novo participants) could be enrolled at the discretion of the Sponsor.
Participants by arm
| Arm | Count |
|---|---|
| DS-5565 15 mg QD Modal Participants received DS-5565 in a preceding Phase 3 study of DS-5565 in fibromyalgia (DS5565-A-E309 \[NCT02146430\], DS5565-A-E310 \[NCT02187471\], or DS5565-A-E311 \[NCT02187159\]) and received 15 mg DS-5565 administered once daily (QD) for the first 3 weeks. After 3 weeks, participants could be titrated to BID. This group includes both rollover and De Novo QD modal. | 847 |
| DS-5565 15 mg BID Modal Participants received DS-5565 in a preceding Phase 3 study of DS-5565 in fibromyalgia (DS5565-A-E309 \[NCT02146430\], DS5565-A-E310 \[NCT02187471\], or DS5565-A-E311 \[NCT02187159\]) and received 15 mg DS-5565 administered once daily (QD) for the first 3 weeks. After 3 weeks, participants could be titrated to twice daily (BID). This group includes both rollover and De Novo BID modal. | 1,241 |
| Total | 2,088 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 172 | 156 |
| Overall Study | Lack of Efficacy | 58 | 103 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Other | 39 | 97 |
| Overall Study | Protocol Violation | 35 | 42 |
| Overall Study | Withdrawal by Subject | 109 | 157 |
Baseline characteristics
| Characteristic | DS-5565 15 mg QD Modal | DS-5565 15 mg BID Modal | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 97 Participants | 113 Participants | 210 Participants |
| Age, Categorical Between 18 and 65 years | 750 Participants | 1128 Participants | 1878 Participants |
| Age, Continuous | 51.4 years STANDARD_DEVIATION 11.18 | 49.3 years STANDARD_DEVIATION 11.94 | 50.2 years STANDARD_DEVIATION 11.68 |
| Race (NIH/OMB) American Indian or Alaska Native | 4 Participants | 4 Participants | 8 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 5 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 82 Participants | 113 Participants | 195 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 19 Participants | 18 Participants | 37 Participants |
| Race (NIH/OMB) White | 740 Participants | 1101 Participants | 1841 Participants |
| Region of Enrollment Australia | 5 participants | 8 participants | 13 participants |
| Region of Enrollment Austria | 5 participants | 10 participants | 15 participants |
| Region of Enrollment Bulgaria | 14 participants | 6 participants | 20 participants |
| Region of Enrollment Canada | 17 participants | 35 participants | 52 participants |
| Region of Enrollment Chile | 1 participants | 4 participants | 5 participants |
| Region of Enrollment Czechia | 11 participants | 27 participants | 38 participants |
| Region of Enrollment Denmark | 7 participants | 5 participants | 12 participants |
| Region of Enrollment Estonia | 2 participants | 8 participants | 10 participants |
| Region of Enrollment Finland | 0 participants | 1 participants | 1 participants |
| Region of Enrollment France | 4 participants | 2 participants | 6 participants |
| Region of Enrollment Germany | 22 participants | 16 participants | 38 participants |
| Region of Enrollment Hungary | 6 participants | 1 participants | 7 participants |
| Region of Enrollment Latvia | 11 participants | 8 participants | 19 participants |
| Region of Enrollment Lithuania | 3 participants | 1 participants | 4 participants |
| Region of Enrollment New Zealand | 7 participants | 11 participants | 18 participants |
| Region of Enrollment Norway | 12 participants | 30 participants | 42 participants |
| Region of Enrollment Poland | 16 participants | 24 participants | 40 participants |
| Region of Enrollment Portugal | 0 participants | 4 participants | 4 participants |
| Region of Enrollment Romania | 3 participants | 1 participants | 4 participants |
| Region of Enrollment Russia | 10 participants | 1 participants | 11 participants |
| Region of Enrollment Serbia | 0 participants | 3 participants | 3 participants |
| Region of Enrollment Slovakia | 14 participants | 4 participants | 18 participants |
| Region of Enrollment Slovenia | 4 participants | 3 participants | 7 participants |
| Region of Enrollment South Africa | 9 participants | 10 participants | 38 participants |
| Region of Enrollment Spain | 8 participants | 19 participants | 27 participants |
| Region of Enrollment Ukraine | 73 participants | 59 participants | 264 participants |
| Region of Enrollment United Kingdom | 14 participants | 27 participants | 41 participants |
| Region of Enrollment United States | 569 participants | 913 participants | 1879 participants |
| Sex: Female, Male Female | 770 Participants | 1130 Participants | 1900 Participants |
| Sex: Female, Male Male | 77 Participants | 111 Participants | 188 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 847 | 2 / 1,241 |
| other Total, other adverse events | 669 / 847 | 1,056 / 1,241 |
| serious Total, serious adverse events | 41 / 847 | 94 / 1,241 |
Outcome results
Primary
Average Daily Pain Score (ADPS) for DS-5565
Average of daily pain scores are reported by the participant and best describes his or her worst pain over the previous 24 hours. A daily pain score has a scale of 0 = no pain to 10 = worst possible pain.
Time frame: Day 0 (baseline) up to to Week 52 postdose
Population: Average daily pain score was assessed in the Safety Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rollover DS-5565 15 mg QD Modal | Average Daily Pain Score (ADPS) for DS-5565 | Week 13 | 3.47 score on a scale | Standard Deviation 2.11 |
| Rollover DS-5565 15 mg QD Modal | Average Daily Pain Score (ADPS) for DS-5565 | Week 48 | 3.22 score on a scale | Standard Deviation 2.16 |
| Rollover DS-5565 15 mg QD Modal | Average Daily Pain Score (ADPS) for DS-5565 | Baseline | 4.77 score on a scale | Standard Deviation 2.23 |
| Rollover DS-5565 15 mg QD Modal | Average Daily Pain Score (ADPS) for DS-5565 | Week 36 | 3.20 score on a scale | Standard Deviation 2.06 |
| Rollover DS-5565 15 mg QD Modal | Average Daily Pain Score (ADPS) for DS-5565 | Week 24 | 3.28 score on a scale | Standard Deviation 2.08 |
| Rollover DS-5565 15 mg QD Modal | Average Daily Pain Score (ADPS) for DS-5565 | Week 52 | 3.20 score on a scale | Standard Deviation 2.18 |
| Rollover DS-5565 15 mg BID Modal | Average Daily Pain Score (ADPS) for DS-5565 | Week 24 | 4.24 score on a scale | Standard Deviation 2.35 |
| Rollover DS-5565 15 mg BID Modal | Average Daily Pain Score (ADPS) for DS-5565 | Week 36 | 4.25 score on a scale | Standard Deviation 2.34 |
| Rollover DS-5565 15 mg BID Modal | Average Daily Pain Score (ADPS) for DS-5565 | Week 52 | 4.26 score on a scale | Standard Deviation 2.42 |
| Rollover DS-5565 15 mg BID Modal | Average Daily Pain Score (ADPS) for DS-5565 | Week 13 | 4.36 score on a scale | Standard Deviation 2.32 |
| Rollover DS-5565 15 mg BID Modal | Average Daily Pain Score (ADPS) for DS-5565 | Week 48 | 4.25 score on a scale | Standard Deviation 2.37 |
| Rollover DS-5565 15 mg BID Modal | Average Daily Pain Score (ADPS) for DS-5565 | Baseline | 5.58 score on a scale | Standard Deviation 2.22 |
| De Novo DS-5565 15 mg QD Modal | Average Daily Pain Score (ADPS) for DS-5565 | Week 24 | 3.0 score on a scale | Standard Deviation 2.14 |
| De Novo DS-5565 15 mg QD Modal | Average Daily Pain Score (ADPS) for DS-5565 | Baseline | 7.08 score on a scale | Standard Deviation 1.4 |
| De Novo DS-5565 15 mg QD Modal | Average Daily Pain Score (ADPS) for DS-5565 | Week 13 | 3.21 score on a scale | Standard Deviation 2.2 |
| De Novo DS-5565 15 mg QD Modal | Average Daily Pain Score (ADPS) for DS-5565 | Week 52 | 2.31 score on a scale | Standard Deviation 1.94 |
| De Novo DS-5565 15 mg QD Modal | Average Daily Pain Score (ADPS) for DS-5565 | Week 36 | 2.74 score on a scale | Standard Deviation 2.23 |
| De Novo DS-5565 15 mg QD Modal | Average Daily Pain Score (ADPS) for DS-5565 | Week 48 | 2.46 score on a scale | Standard Deviation 2.15 |
| De Novo DS-5565 15 mg BID Modal | Average Daily Pain Score (ADPS) for DS-5565 | Week 24 | 4.0 score on a scale | Standard Deviation 2.38 |
| De Novo DS-5565 15 mg BID Modal | Average Daily Pain Score (ADPS) for DS-5565 | Week 13 | 4.06 score on a scale | Standard Deviation 2.37 |
| De Novo DS-5565 15 mg BID Modal | Average Daily Pain Score (ADPS) for DS-5565 | Week 52 | 3.80 score on a scale | Standard Deviation 2.7 |
| De Novo DS-5565 15 mg BID Modal | Average Daily Pain Score (ADPS) for DS-5565 | Week 48 | 3.80 score on a scale | Standard Deviation 2.61 |
| De Novo DS-5565 15 mg BID Modal | Average Daily Pain Score (ADPS) for DS-5565 | Baseline | 7.38 score on a scale | Standard Deviation 1.37 |
| De Novo DS-5565 15 mg BID Modal | Average Daily Pain Score (ADPS) for DS-5565 | Week 36 | 3.95 score on a scale | Standard Deviation 2.59 |
Secondary
EuroQol Five Dimensions Questionnaire (EQ-5D) Measure for DS-5565
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) that are combined into an overall health utilities index, and an NRS (100 mm VAS) that measures perception of overall health, with 0 indicating worst health and 100 representing best imaginable health.
Time frame: Day 0 (baseline) up to Week 52 postdose
Population: EQ-5D was assessed in the Safety Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rollover DS-5565 15 mg QD Modal | EuroQol Five Dimensions Questionnaire (EQ-5D) Measure for DS-5565 | Total Score Week 52 | 0.76 units on a scale | Standard Deviation 0.16 |
| Rollover DS-5565 15 mg QD Modal | EuroQol Five Dimensions Questionnaire (EQ-5D) Measure for DS-5565 | Total Score Baseline | 0.70 units on a scale | Standard Deviation 0.17 |
| Rollover DS-5565 15 mg BID Modal | EuroQol Five Dimensions Questionnaire (EQ-5D) Measure for DS-5565 | Total Score Baseline | 0.64 units on a scale | Standard Deviation 0.19 |
| Rollover DS-5565 15 mg BID Modal | EuroQol Five Dimensions Questionnaire (EQ-5D) Measure for DS-5565 | Total Score Week 52 | 0.70 units on a scale | Standard Deviation 0.2 |
| De Novo DS-5565 15 mg QD Modal | EuroQol Five Dimensions Questionnaire (EQ-5D) Measure for DS-5565 | Total Score Baseline | 0.62 units on a scale | Standard Deviation 0.16 |
| De Novo DS-5565 15 mg QD Modal | EuroQol Five Dimensions Questionnaire (EQ-5D) Measure for DS-5565 | Total Score Week 52 | 0.81 units on a scale | Standard Deviation 0.15 |
| De Novo DS-5565 15 mg BID Modal | EuroQol Five Dimensions Questionnaire (EQ-5D) Measure for DS-5565 | Total Score Week 52 | 0.77 units on a scale | Standard Deviation 0.17 |
| De Novo DS-5565 15 mg BID Modal | EuroQol Five Dimensions Questionnaire (EQ-5D) Measure for DS-5565 | Total Score Baseline | 0.61 units on a scale | Standard Deviation 0.18 |
Secondary
Hospital Anxiety Depression Scale (HADS) Depression and Anxiety Scores for DS-5565
The HADS questionnaire is a 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 from 0 to 3, where higher scores indicate greater anxiety or depression. 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: Day 0 (baseline) up to Week 52 postdose
Population: HADS-Depression and Anxiety was assessed in the Safety Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rollover DS-5565 15 mg QD Modal | Hospital Anxiety Depression Scale (HADS) Depression and Anxiety Scores for DS-5565 | Depression Subscale Baseline | 5.1 score on a scale | Standard Deviation 4.18 |
| Rollover DS-5565 15 mg QD Modal | Hospital Anxiety Depression Scale (HADS) Depression and Anxiety Scores for DS-5565 | Anxiety Subscale Week 52 | 4.8 score on a scale | Standard Deviation 3.71 |
| Rollover DS-5565 15 mg QD Modal | Hospital Anxiety Depression Scale (HADS) Depression and Anxiety Scores for DS-5565 | Depression Subscale Week 52 | 3.5 score on a scale | Standard Deviation 3.47 |
| Rollover DS-5565 15 mg QD Modal | Hospital Anxiety Depression Scale (HADS) Depression and Anxiety Scores for DS-5565 | Anxiety Subscale Baseline | 5.7 score on a scale | Standard Deviation 3.86 |
| Rollover DS-5565 15 mg BID Modal | Hospital Anxiety Depression Scale (HADS) Depression and Anxiety Scores for DS-5565 | Anxiety Subscale Week 52 | 7.0 score on a scale | Standard Deviation 4.03 |
| Rollover DS-5565 15 mg BID Modal | Hospital Anxiety Depression Scale (HADS) Depression and Anxiety Scores for DS-5565 | Depression Subscale Week 52 | 4.8 score on a scale | Standard Deviation 4.01 |
| Rollover DS-5565 15 mg BID Modal | Hospital Anxiety Depression Scale (HADS) Depression and Anxiety Scores for DS-5565 | Anxiety Subscale Baseline | 7.2 score on a scale | Standard Deviation 4.05 |
| Rollover DS-5565 15 mg BID Modal | Hospital Anxiety Depression Scale (HADS) Depression and Anxiety Scores for DS-5565 | Depression Subscale Baseline | 6.3 score on a scale | Standard Deviation 4.34 |
| De Novo DS-5565 15 mg QD Modal | Hospital Anxiety Depression Scale (HADS) Depression and Anxiety Scores for DS-5565 | Depression Subscale Week 52 | 2.8 score on a scale | Standard Deviation 3.11 |
| De Novo DS-5565 15 mg QD Modal | Hospital Anxiety Depression Scale (HADS) Depression and Anxiety Scores for DS-5565 | Anxiety Subscale Baseline | 6.9 score on a scale | Standard Deviation 3.97 |
| De Novo DS-5565 15 mg QD Modal | Hospital Anxiety Depression Scale (HADS) Depression and Anxiety Scores for DS-5565 | Depression Subscale Baseline | 5.6 score on a scale | Standard Deviation 4.06 |
| De Novo DS-5565 15 mg QD Modal | Hospital Anxiety Depression Scale (HADS) Depression and Anxiety Scores for DS-5565 | Anxiety Subscale Week 52 | 4.4 score on a scale | Standard Deviation 3.29 |
| De Novo DS-5565 15 mg BID Modal | Hospital Anxiety Depression Scale (HADS) Depression and Anxiety Scores for DS-5565 | Depression Subscale Week 52 | 3.9 score on a scale | Standard Deviation 4 |
| De Novo DS-5565 15 mg BID Modal | Hospital Anxiety Depression Scale (HADS) Depression and Anxiety Scores for DS-5565 | Anxiety Subscale Baseline | 7.4 score on a scale | Standard Deviation 4.21 |
| De Novo DS-5565 15 mg BID Modal | Hospital Anxiety Depression Scale (HADS) Depression and Anxiety Scores for DS-5565 | Anxiety Subscale Week 52 | 5.7 score on a scale | Standard Deviation 3.88 |
| De Novo DS-5565 15 mg BID Modal | Hospital Anxiety Depression Scale (HADS) Depression and Anxiety Scores for DS-5565 | Depression Subscale Baseline | 5.7 score on a scale | Standard Deviation 4.1 |
Secondary
Number of Participants With Much Improved or Better (≤2) Status in Status at Week 52 As Assessed by the Patient-Rated Global Impression of Change
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 status are reported.
Time frame: Week 52 postdose
Population: Patient Global Impression of Change was assessed in the Safety Analysis Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Rollover DS-5565 15 mg QD Modal | Number of Participants With Much Improved or Better (≤2) Status in Status at Week 52 As Assessed by the Patient-Rated Global Impression of Change | 208 Participants |
| Rollover DS-5565 15 mg BID Modal | Number of Participants With Much Improved or Better (≤2) Status in Status at Week 52 As Assessed by the Patient-Rated Global Impression of Change | 333 Participants |
| De Novo DS-5565 15 mg QD Modal | Number of Participants With Much Improved or Better (≤2) Status in Status at Week 52 As Assessed by the Patient-Rated Global Impression of Change | 96 Participants |
| De Novo DS-5565 15 mg BID Modal | Number of Participants With Much Improved or Better (≤2) Status in Status at Week 52 As Assessed by the Patient-Rated Global Impression of Change | 92 Participants |
Secondary
Pain-Associated Sleep Interference as Assessed by Average Daily Sleep Interference Score (ADSIS) for DS-5565
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. For rollover participants, the baseline scores from the End-of-Tapering period in the preceding study are reported. For de novo participants, the baseline scores are derived from the 7 days prior to the start of treatment.
Time frame: Day 0 (baseline) up to Week 52 postdose
Population: Average Daily Sleep Interference Score was assessed in the Safety Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rollover DS-5565 15 mg QD Modal | Pain-Associated Sleep Interference as Assessed by Average Daily Sleep Interference Score (ADSIS) for DS-5565 | Week 52 | 2.22 score on a scale | Standard Deviation 2.06 |
| Rollover DS-5565 15 mg QD Modal | Pain-Associated Sleep Interference as Assessed by Average Daily Sleep Interference Score (ADSIS) for DS-5565 | Week 36 | 2.25 score on a scale | Standard Deviation 1.98 |
| Rollover DS-5565 15 mg QD Modal | Pain-Associated Sleep Interference as Assessed by Average Daily Sleep Interference Score (ADSIS) for DS-5565 | Week 13 | 2.56 score on a scale | Standard Deviation 2.16 |
| Rollover DS-5565 15 mg QD Modal | Pain-Associated Sleep Interference as Assessed by Average Daily Sleep Interference Score (ADSIS) for DS-5565 | Week 24 | 2.34 score on a scale | Standard Deviation 1.96 |
| Rollover DS-5565 15 mg QD Modal | Pain-Associated Sleep Interference as Assessed by Average Daily Sleep Interference Score (ADSIS) for DS-5565 | Week 48 | 2.32 score on a scale | Standard Deviation 2.07 |
| Rollover DS-5565 15 mg QD Modal | Pain-Associated Sleep Interference as Assessed by Average Daily Sleep Interference Score (ADSIS) for DS-5565 | Baseline | 3.84 score on a scale | Standard Deviation 2.41 |
| Rollover DS-5565 15 mg BID Modal | Pain-Associated Sleep Interference as Assessed by Average Daily Sleep Interference Score (ADSIS) for DS-5565 | Week 48 | 3.22 score on a scale | Standard Deviation 2.56 |
| Rollover DS-5565 15 mg BID Modal | Pain-Associated Sleep Interference as Assessed by Average Daily Sleep Interference Score (ADSIS) for DS-5565 | Week 52 | 3.19 score on a scale | Standard Deviation 2.63 |
| Rollover DS-5565 15 mg BID Modal | Pain-Associated Sleep Interference as Assessed by Average Daily Sleep Interference Score (ADSIS) for DS-5565 | Week 13 | 3.18 score on a scale | Standard Deviation 2.5 |
| Rollover DS-5565 15 mg BID Modal | Pain-Associated Sleep Interference as Assessed by Average Daily Sleep Interference Score (ADSIS) for DS-5565 | Baseline | 4.74 score on a scale | Standard Deviation 2.52 |
| Rollover DS-5565 15 mg BID Modal | Pain-Associated Sleep Interference as Assessed by Average Daily Sleep Interference Score (ADSIS) for DS-5565 | Week 24 | 3.09 score on a scale | Standard Deviation 2.5 |
| Rollover DS-5565 15 mg BID Modal | Pain-Associated Sleep Interference as Assessed by Average Daily Sleep Interference Score (ADSIS) for DS-5565 | Week 36 | 3.09 score on a scale | Standard Deviation 2.5 |
| De Novo DS-5565 15 mg QD Modal | Pain-Associated Sleep Interference as Assessed by Average Daily Sleep Interference Score (ADSIS) for DS-5565 | Baseline | 6.71 score on a scale | Standard Deviation 1.7 |
| De Novo DS-5565 15 mg QD Modal | Pain-Associated Sleep Interference as Assessed by Average Daily Sleep Interference Score (ADSIS) for DS-5565 | Week 13 | 2.50 score on a scale | Standard Deviation 2.15 |
| De Novo DS-5565 15 mg QD Modal | Pain-Associated Sleep Interference as Assessed by Average Daily Sleep Interference Score (ADSIS) for DS-5565 | Week 48 | 1.87 score on a scale | Standard Deviation 2.05 |
| De Novo DS-5565 15 mg QD Modal | Pain-Associated Sleep Interference as Assessed by Average Daily Sleep Interference Score (ADSIS) for DS-5565 | Week 36 | 2.19 score on a scale | Standard Deviation 2.2 |
| De Novo DS-5565 15 mg QD Modal | Pain-Associated Sleep Interference as Assessed by Average Daily Sleep Interference Score (ADSIS) for DS-5565 | Week 52 | 1.79 score on a scale | Standard Deviation 1.86 |
| De Novo DS-5565 15 mg QD Modal | Pain-Associated Sleep Interference as Assessed by Average Daily Sleep Interference Score (ADSIS) for DS-5565 | Week 24 | 2.36 score on a scale | Standard Deviation 2.18 |
| De Novo DS-5565 15 mg BID Modal | Pain-Associated Sleep Interference as Assessed by Average Daily Sleep Interference Score (ADSIS) for DS-5565 | Week 52 | 3.09 score on a scale | Standard Deviation 2.71 |
| De Novo DS-5565 15 mg BID Modal | Pain-Associated Sleep Interference as Assessed by Average Daily Sleep Interference Score (ADSIS) for DS-5565 | Baseline | 6.82 score on a scale | Standard Deviation 1.82 |
| De Novo DS-5565 15 mg BID Modal | Pain-Associated Sleep Interference as Assessed by Average Daily Sleep Interference Score (ADSIS) for DS-5565 | Week 13 | 3.13 score on a scale | Standard Deviation 2.51 |
| De Novo DS-5565 15 mg BID Modal | Pain-Associated Sleep Interference as Assessed by Average Daily Sleep Interference Score (ADSIS) for DS-5565 | Week 24 | 3.19 score on a scale | Standard Deviation 2.48 |
| De Novo DS-5565 15 mg BID Modal | Pain-Associated Sleep Interference as Assessed by Average Daily Sleep Interference Score (ADSIS) for DS-5565 | Week 36 | 3.11 score on a scale | Standard Deviation 2.63 |
| De Novo DS-5565 15 mg BID Modal | Pain-Associated Sleep Interference as Assessed by Average Daily Sleep Interference Score (ADSIS) for DS-5565 | Week 48 | 3.02 score on a scale | Standard Deviation 2.64 |
Secondary
Short Form-36 (SF-36) Measure for DS-5565
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 physical component summary and mental component summary scales range 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) total scores at baseline and Week 52 are reported.
Time frame: Day 0 (baseline) to Week 52 postdose
Population: SF-36 was assessed in the Safety Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rollover DS-5565 15 mg QD Modal | Short Form-36 (SF-36) Measure for DS-5565 | Physical Component Summary Baseline | 37.91 score on a scale | Standard Deviation 8.86 |
| Rollover DS-5565 15 mg QD Modal | Short Form-36 (SF-36) Measure for DS-5565 | Physical Component Summary Week 52 | 42.96 score on a scale | Standard Deviation 8.52 |
| Rollover DS-5565 15 mg QD Modal | Short Form-36 (SF-36) Measure for DS-5565 | Mental Component Summary Baseline | 50.12 score on a scale | Standard Deviation 10.19 |
| Rollover DS-5565 15 mg QD Modal | Short Form-36 (SF-36) Measure for DS-5565 | Mental Component Summary Week 52 | 52.63 score on a scale | Standard Deviation 9.61 |
| Rollover DS-5565 15 mg BID Modal | Short Form-36 (SF-36) Measure for DS-5565 | Physical Component Summary Week 52 | 39.09 score on a scale | Standard Deviation 9.38 |
| Rollover DS-5565 15 mg BID Modal | Short Form-36 (SF-36) Measure for DS-5565 | Mental Component Summary Baseline | 47.76 score on a scale | Standard Deviation 11.15 |
| Rollover DS-5565 15 mg BID Modal | Short Form-36 (SF-36) Measure for DS-5565 | Mental Component Summary Week 52 | 49.15 score on a scale | Standard Deviation 11.24 |
| Rollover DS-5565 15 mg BID Modal | Short Form-36 (SF-36) Measure for DS-5565 | Physical Component Summary Baseline | 35.13 score on a scale | Standard Deviation 8.55 |
| De Novo DS-5565 15 mg QD Modal | Short Form-36 (SF-36) Measure for DS-5565 | Mental Component Summary Baseline | 47.54 score on a scale | Standard Deviation 10.98 |
| De Novo DS-5565 15 mg QD Modal | Short Form-36 (SF-36) Measure for DS-5565 | Physical Component Summary Week 52 | 45.61 score on a scale | Standard Deviation 9.63 |
| De Novo DS-5565 15 mg QD Modal | Short Form-36 (SF-36) Measure for DS-5565 | Mental Component Summary Week 52 | 52.75 score on a scale | Standard Deviation 8.02 |
| De Novo DS-5565 15 mg QD Modal | Short Form-36 (SF-36) Measure for DS-5565 | Physical Component Summary Baseline | 34.41 score on a scale | Standard Deviation 8.58 |
| De Novo DS-5565 15 mg BID Modal | Short Form-36 (SF-36) Measure for DS-5565 | Mental Component Summary Week 52 | 50.49 score on a scale | Standard Deviation 10.54 |
| De Novo DS-5565 15 mg BID Modal | Short Form-36 (SF-36) Measure for DS-5565 | Physical Component Summary Week 52 | 42.31 score on a scale | Standard Deviation 10.47 |
| De Novo DS-5565 15 mg BID Modal | Short Form-36 (SF-36) Measure for DS-5565 | Physical Component Summary Baseline | 32.12 score on a scale | Standard Deviation 7.85 |
| De Novo DS-5565 15 mg BID Modal | Short Form-36 (SF-36) Measure for DS-5565 | Mental Component Summary Baseline | 47.92 score on a scale | Standard Deviation 11.46 |