Fibromyalgia
Conditions
Keywords
ASP8062, Fibromyalgia
Brief summary
The purpose of this study was to assess analgesic efficacy of ASP8062 relative to placebo as well as the safety and tolerability. This study also assessed the treatment differences in physical function as well the improvements in overall subject status (e.g., fibromyalgia symptoms, global functioning) of ASP8062 relative to placebo.
Interventions
DRUGASP8062
ASP8062 30 mg was administered orally as a single daily dose, taken preferably in the morning with or without food.
DRUGPlacebo
Placebo was administered orally as a single daily dose, taken preferably in the morning with or without food.
Sponsors
Astellas Pharma Global Development, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Subject has a body mass index (BMI) ≤ 45 kg/m\^2. * Female subject must either: * Be of nonchildbearing potential: * Postmenopausal (defined as at least 1 year without any menses) prior to Screening, or, * Documented surgically sterile (e.g., hysterectomy, bilateral salpingectomy, bilateral oophorectomy). * Or, if of childbearing potential, agree not to try to become pregnant during the study and for 28 days after the final study drug administration, have a negative blood pregnancy test at Screening and negative urine test on Day 1, and if heterosexually active, agree to consistently use 1 form of highly effective birth control starting at Screening and throughout the study period and for 28 days after the final study drug administration. * Female subject must agree not to breastfeed at Screening and throughout the study period, and for 28 days after the final study drug administration. * Female subject must not donate ova starting at Screening, throughout the study period, and for 28 days after the final study drug administration. * Male subject must not donate sperm starting at Screening and throughout the study period, and for 90 days after the final study drug administration. * A sexually active male subject with female partner(s) who are of childbearing potential is eligible if: * Agree to use a male condom starting at screening and continue throughout study treatment and for 90 days after the final study drug administration. If the male subject has not had a vasectomy or is not sterile the male subjects female partner(s) is utilizing 1 form of highly effective birth control starting at screening and continue throughout study treatment, and for 90 days after the male subject receives final study drug administration. * Male subject with a partner of child-bearing potential, or a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom throughout the study period and for 90 days after the final study drug administration. * Subject meets the American College of Rheumatology (ACR) 1990 fibromyalgia diagnostic criteria at Screening: * Widespread pain for at least 3 months, defined as the presence of all of the following: Pain above and below the waist and pain in the axial skeleton (cervical spine or anterior chest or thoracic spine or low back) must be present. * Pain in at least 11 of 18 tender point sites on digital palpation. Digital palpation should be performed with an approximate force of 4 kg. * Subject meets the ACR 2010 fibromyalgia diagnostic criteria at Screening: * Widespread pain index (WPI) ≥ 7 and symptom severity (SS) scale score ≥ 5 or WPI 3-6 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. * Subject has a pain score ≥ 4 on the revised fibromyalgia impact questionnaire (FIQR) pain item at Screening. * Subject is compliant with daily pain recordings during the Baseline Diary Run-In period, as defined by the completion of a minimum of 5 of 7 daily average pain ratings and agrees to complete daily diaries throughout the duration of the study. * Subject has a mean daily average pain score ≥ 4 and ≤ 9 on an 11-point 0 to 10 NRS as recorded in the subject e-diary during the Baseline Diary Run-In period, and meeting pre-specified criteria for daily average pain scores. * Subject agrees to use only acetaminophen as rescue medication for fibromyalgia pain throughout the course of the trial (up to 1000 mg per dose and not to exceed 3000 mg/day). * Subject agrees not to initiate or change any non-pharmacologic interventions (including normal daily exercise routines, chiropractic care, physical therapy, psychotherapy, and massage therapy) during the course of the study. Non-pharmacologic interventions must be stable for a minimum of 30 days prior to Screening. And subject agrees to maintain usual level of activity for the duration of the study. * Subject is capable of completing study assessments and procedures. * Subject agrees not to participate in another interventional study from Screening through the End of Study (EOS) visit.
Exclusion criteria
* Subject has received an investigational therapy within 28 days or 5 half-lives, whichever is longer, prior to Screening. * Subject has had no meaningful improvement from 2 or more prior treatments (commercially available) for fibromyalgia (in at least 2 pharmacologic classes). * Subject has had known hypersensitivity or intolerance to the use of acetaminophen or associated formulation components; known hypersensitivity to the formulation components of ASP8062. * Subject has pain due to diabetic peripheral neuropathy, post-herpetic neuralgia, traumatic injury, prior surgery, complex regional pain syndrome, or other source of pain that would confound or interfere with the assessment of the subject's fibromyalgia pain or require excluded therapies during the subject's study participation. * Subject has infectious or inflammatory arthritis (for example, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, gout), autoimmune disease (for example, systemic lupus erythematosus), or other widespread rheumatic disease other than fibromyalgia. * Subject has a current, untreated moderate or severe major depressive disorder as assessed by the Mini-International Neuropsychiatric Interview (M.I.N.I.). Subject with current, treated major depressive disorder can be included provided that it is without clinically significant changes in symptoms while on the same dose of a protocol allowed antidepressant for greater than 60 days prior to Screening. * Subject has initiated any non-pharmacologic interventions for the treatment of fibromyalgia or depression within 30 days prior to Screening or during the Screening period. * Subject has a history of any psychotic and/or bipolar disorder as assessed by the M.I.N.I. * Subject has a Hospital Anxiety and Depression Scale (HADS) score \> 14 on the Depression subscale at Screening or at the time of Visit 3 (Randomization). * Subject has a history of suicide attempt or suicidal behavior within the last 12 months, or has suicidal ideation within the last 12 months (a response of yes to questions 4 or 5 on the suicidal ideation portion of the Columbia-Suicide Severity Rating Scale C-SSRS\]), or who is at significant risk to commit suicide at Screening and at the time of Visit 3 (Randomization). * Subject has clinically significant abnormalities in clinical chemistry, hematology, or urinalysis, or a serum creatinine \> 1.5 x the ULN at Screening. These assessments may be repeated once, after a reasonable time period (but within the Screening period). * Subject has aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 1.5 times the upper limit of the reference range at Screening. These assessments may be repeated once, after a reasonable time period (but within the Screening period). * Subject has a positive test for hepatitis B surface antigen (HBsAg), hepatitis A virus antibodies (immunoglobulin M) (anti-HAV \[IgM\]) or hepatitis C virus antibodies (anti-HCV) at Screening or has history of a positive test for human immunodeficiency virus type 1(HIV-1) and/or type 2 (HIV-2). * Subject has a resting systolic blood pressure \> 180 mmHg or \< 90 mmHg, and/or a sitting diastolic blood pressure \> 100 mmHg at Screening. These assessments may be repeated once, after a reasonable time period (but within the Screening period). * Subject has a clinically significant abnormality on 12-lead electrocardiogram (ECG) at Screening or Visit 3 (Randomization). If the ECG is abnormal an additional ECG can be carried out. If this also gives an abnormal result, the subject must be excluded. * Subject has a history of myocardial infarction (within 6 months of Screening), unexplained syncope, cardiac arrest, unexplained cardiac arrhythmias or torsade de pointes, structural heart disease or a family history of Long QT Syndrome. * Subject has evidence of any clinically significant, uncontrolled cardiovascular, gastrointestinal, endocrinologic (low thyroid stimulating hormone \[TSH\], but euthyroid is allowed), hematologic, hepatic, immunologic, infectious, metabolic, urologic, pulmonary (including obstructive sleep apnea not controlled by a continuous positive airway pressure device) neurologic, dermatologic, psychiatric, renal and/or other major disease (exclusive of fibromyalgia). * Subject has planned surgery during the study participation. * Subject has an active malignancy or a history of malignancy (except for treated nonmelanoma skin cancer) within 5 years of Screening. * Subject has a positive drug or alcohol test at Screening, Baseline Diary Run-In or prior to Randomization. However, a positive test for tetrahydrocannabinol (THC) and/or opioids is allowed at the Screening visit, but must be confirmed negative prior to Baseline Diary Run-In and Randomization. * Subject has a current or recent (within 12 months of Screening) history of a substance use disorder including cannabinoid and/or alcohol abuse disorder. Subject has used opioids for pain for more than 4 days during the week preceding the Screening visit. * Subject is currently using protocol specified prohibited medications and is unable to wash-out including over-the-counter (OTC) products and grapefruit and/or grapefruit juice. * Subject has filed or is awaiting judgment on a disability claim or has any pending worker's compensation litigation or related monetary settlements. * Subject has any condition which makes the subject unsuitable for study participation. * Subject is an employee of the Astellas Group, the Contract Research Organization (CRO) involved, or the investigator site personnel directly affiliated with this study and/or immediate families (spouse, parent, child, or sibling, whether biological or legally adopted).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 8 in Mean Daily Average Pain Score as Assessed by Numerical Rating Scale (NRS) | Baseline and week 8 | The mean daily average pain score was assessed thorugh the Daily Average Pain NRS, which is a generic instrument for the assessment of pain that consists of a single question that asks participants to record their daily average pain on an 11-point scale, where 0 anchors no pain and 10 pain as bad as you can imagine. The mean daily average pain score was calculated from data recorded by participants daily in the electronic diary, and the recall period was the last 24 hours. A negative change indicated a reduction/improvement from baseline (i.e., a favorable outcome). |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | From first dose of study drug up to 30 days after last dose of study drug (up to 87 days) | Safety was assessed by adverse events (AEs), which included abnormalities identified during a medical test (e.g. laboratory tests, vital signs, electrocardiogram, etc.) if the abnormality induced clinical signs or symptoms, needed active intervention, interruption or discontinuation of study drug or was clinically significant. A TEAE was defined as any AE that started or worsened after the first dose of study drug up to 30 days after the last dose of study drug. AEs were considered serious (SAEs) if the AE resulted in death, was life-threatening, resulted in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, resulted in congenital anomaly, or birth defect or required inpatient hospitalization or led to prolongation of hospitalization. TEAEs in drug abuse, dependence and withdrawal standardized MedDRA query (SMQ) are special AEs of interest grouped together using the SMQ tool (MedDRA v20.0). |
| Number of Participants With an Affirmative Response to Columbia Suicide Severity Rating Scale (C-SSRS): Suicidal Ideation | Weeks 1 to 8 | The Columbia Suicide Severity Rating Scale (C-SSRS) is a questionnaire used for suicide risk assessment. Affirmative or negative responses were provided to 5 items to suicidal ideation (1. Wish to be dead, 2. Non-specific active suicidal thoughts, 3. Active suicidal ideation with any methods (not plan) without intent to act, 4. Active suicidal ideation with some intent to act, without specific plan, 5. Active suicidal ideation with specific plan and intent). |
| Number of Participants With an Affirmative Response to C-SSRS: Suicidal Behavior | Weeks 1 to 8 | The C-SSRS is a questionnaire used for suicide risk assessment. Affirmative or negative responses were provided to 5 items to suicidal behavior (1. Preparatory acts or behavior, 2. Aborted attempt, 3. Interrupted attempt, 4. Actual attempt, 5. Completed suicide). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Weeks 2, 4, 8, and EOT in the FIQR Overall Impact Subscale Score | Baseline and weeks 2, 4, 8 | The FIQR was developed to capture the total spectrum of problems related to fibromyalgia and the responses to therapy. The 21-item FIQR contains 3 subscales: function (9 questions), overall impact (2 questions), and symptoms (10 questions). Participants answer each question on an 11-point NRS, with anchors appropriate to each question on a tablet device during a visit. The recall period was the last 7 days. The Overall Impact subscale has a range of scores from 0 to 20, with a lower score indicating better (lower) impact. A negative change indicated a reduction/improvement from baseline (i.e., a favorable outcome). |
| Percentage of Participants With ≥ 30% Reduction From Baseline to Week 8 and End of Treatment (EOT) in Mean Daily Average Pain Score as Assessed by NRS | Baseline to week 8 | The mean daily average pain score was assessed through the Daily Average Pain NRS, which is a generic instrument for the assessment of pain that consists of a single question that asks participants to record their daily average pain on an 11-point scale, where 0 anchors no pain and 10 pain as bad as you can imagine. The mean daily average pain score was calculated from data recorded by participants daily in the electronic diary, and the recall period was the last 24 hours. For the week 8 analysis, participants with missing baseline or week 8 data were classified as nonresponders. For EOT analysis, participants with missing baseline or EOT data were classified as nonresponders. |
| Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | Weeks 2, 4, 8 | The PGIC is a self-administered 7-point Likert scale that asks participants to evaluate their fibromyalgia relative to baseline. This is a single question and the grade ranges from 1 (Very Much Improved) to 7 (Very Much Worse). |
| Percentage of Participants With ≥ 50% Reduction From Baseline to Week 8 and EOT in Mean Daily Average Pain Score as Assessed by NRS | Baseline to week 8 | The mean daily average pain score was assessed thorugh the Daily Average Pain NRS, which is a generic instrument for the assessment of pain that consists of a single question that asks participants to record their daily average pain on an 11-point scale, where 0 anchors no pain and 10 pain as bad as you can imagine. The mean daily average pain score was calculated from data recorded by participants daily in the electronic diary, and the recall period was the last 24 hours. For the week 8 analysis, participants with missing baseline or week 8 data were classified as nonresponders. For EOT analysis, participants with missing baseline or EOT data were classified as nonresponders. |
| Change From Baseline to Weeks 2, 4, 8 and EOT in the Fibromyalgia Impact Questionnaire Revised (FIQR) Function Subscale Score | Baseline and weeks 2, 4, 8 | The FIQR was developed to capture total spectrum of problems related to fibromyalgia and the responses to therapy. The 21-item FIQR contains 3 subscales: function (9 questions), overall impact (2 questions), and symptoms (10 questions). Participants answer each question on an 11-point NRS, with anchors appropriate to each question on a tablet device during a visit. The recall period was the last 7 days or the last time the activity was performed if not within the 7-day recall period. The Function subscale has a range of scores of 0 to 90, with a lower score indicating better (higher) function. A negative change indicated a reduction/improvement from baseline (i.e., a favorable outcome). |
| Change From Baseline to Weeks 2, 4, 8, and EOT in the FIQR Symptoms Subscale Score | Baseline and weeks 2, 4, 8 | The FIQR was developed to capture the total spectrum of problems related to fibromyalgia and the responses to therapy. The 21-item FIQR contains 3 subscales: function (9 questions), overall impact (2 questions), and symptoms (10 questions). Participants answer each question on an 11-point NRS, with anchors appropriate to each question on a tablet device during a visit. The recall period was the last 7 days. The Symptoms subscale range of scores is 0 to 100, with a lower score indicating a better (lower) level of symptoms. A negative change indicates a reduction/improvement from baseline (i.e., a favorable outcome). |
Countries
United States
Participant flow
Recruitment details
Participants with fibromyalgia (FM) were enrolled in 24 sites in the United States.
Pre-assignment details
Participants underwent a screening period (up to 42 days), where washout of medications and a 7-day baseline diary run-in were completed. Participants were randomized (1:1 ratio) after confirmation of eligibility (which also required a mean daily average pain score of ≥ 4 and ≤ 9 \[per Daily Average Pain Numerical Rating Scale\] to enter the study).
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received matching placebo orally once daily for 8 weeks. | 88 |
| ASP8062 Participants received 30 mg of ASP8062 orally once daily for 8 weeks. | 95 |
| Total | 183 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 10 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Withdrawal by Subject | 5 | 3 |
Baseline characteristics
| Characteristic | ASP8062 | Placebo | Total |
|---|---|---|---|
| Age, Continuous Age | 52.5 Years STANDARD_DEVIATION 11.9 | 51.3 Years STANDARD_DEVIATION 12.9 | 51.9 Years STANDARD_DEVIATION 12.3 |
| Baseline Mean Daily Average Pain Score | 6.54 units on a scale STANDARD_DEVIATION 0.97 | 6.49 units on a scale STANDARD_DEVIATION 1.03 | 6.51 units on a scale STANDARD_DEVIATION 1 |
| Baseline Mean Daily Average Pain Score Group Mild: > 0 to < 4 | 0 Participants | 0 Participants | 0 Participants |
| Baseline Mean Daily Average Pain Score Group Moderate: >= 4 to < 7 | 57 Participants | 59 Participants | 116 Participants |
| Baseline Mean Daily Average Pain Score Group No pain: 0 | 0 Participants | 0 Participants | 0 Participants |
| Baseline Mean Daily Average Pain Score Group Severe: >= 7 to 10 | 38 Participants | 29 Participants | 67 Participants |
| Ethnicity Hispanic or Latino | 18 Participants | 17 Participants | 35 Participants |
| Ethnicity Not Hispanic or Latino | 77 Participants | 71 Participants | 148 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 3 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Race Asian | 1 Participants | 3 Participants | 4 Participants |
| Race/Ethnicity, Customized Race Black or African American | 20 Participants | 15 Participants | 35 Participants |
| Race/Ethnicity, Customized Race Other | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Race White | 70 Participants | 69 Participants | 139 Participants |
| Sex: Female, Male Female | 93 Participants | 83 Participants | 176 Participants |
| Sex: Female, Male Male | 2 Participants | 5 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 88 | 0 / 95 |
| other Total, other adverse events | 17 / 88 | 38 / 95 |
| serious Total, serious adverse events | 0 / 88 | 0 / 95 |
Outcome results
Primary
Change From Baseline to Week 8 in Mean Daily Average Pain Score as Assessed by Numerical Rating Scale (NRS)
The mean daily average pain score was assessed thorugh the Daily Average Pain NRS, which is a generic instrument for the assessment of pain that consists of a single question that asks participants to record their daily average pain on an 11-point scale, where 0 anchors no pain and 10 pain as bad as you can imagine. The mean daily average pain score was calculated from data recorded by participants daily in the electronic diary, and the recall period was the last 24 hours. A negative change indicated a reduction/improvement from baseline (i.e., a favorable outcome).
Time frame: Baseline and week 8
Population: The analysis population was the full analysis set (FAS), which consisted of all randomized participants who took at least 1 dose of study drug. Participants with available data at baseline were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 8 in Mean Daily Average Pain Score as Assessed by Numerical Rating Scale (NRS) | -1.42 Units on a scale | Standard Error 0.19 |
| ASP8062 | Change From Baseline to Week 8 in Mean Daily Average Pain Score as Assessed by Numerical Rating Scale (NRS) | -1.36 Units on a scale | Standard Error 0.19 |
Comparison: Differences of least squares (LS) means were calculated by subtracting the LS mean of placebo group from the LS mean of ASP8062 30 mg group using a mixed-effect, repeated measures (MMRM) model with change from baseline to each week from weeks 1 to 8 as response, treatment, center (pooled where necessary), time (study weeks 1 to 8) and treatment-by-time interaction as fixed effects, baseline and baseline-by-time interaction as covariates.p-value: 0.5990% CI: [-0.38, 0.5]MMRM
Primary
Number of Participants With an Affirmative Response to Columbia Suicide Severity Rating Scale (C-SSRS): Suicidal Ideation
The Columbia Suicide Severity Rating Scale (C-SSRS) is a questionnaire used for suicide risk assessment. Affirmative or negative responses were provided to 5 items to suicidal ideation (1. Wish to be dead, 2. Non-specific active suicidal thoughts, 3. Active suicidal ideation with any methods (not plan) without intent to act, 4. Active suicidal ideation with some intent to act, without specific plan, 5. Active suicidal ideation with specific plan and intent).
Time frame: Weeks 1 to 8
Population: The analysis population was the SAF. Participants with available data were included in the analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With an Affirmative Response to Columbia Suicide Severity Rating Scale (C-SSRS): Suicidal Ideation | Non-specific active suicidal thoughts | 0 Participants |
| Placebo | Number of Participants With an Affirmative Response to Columbia Suicide Severity Rating Scale (C-SSRS): Suicidal Ideation | With some intent to act, w/o specific plan | 0 Participants |
| Placebo | Number of Participants With an Affirmative Response to Columbia Suicide Severity Rating Scale (C-SSRS): Suicidal Ideation | With any methods (not plan) w/o intent to act | 0 Participants |
| Placebo | Number of Participants With an Affirmative Response to Columbia Suicide Severity Rating Scale (C-SSRS): Suicidal Ideation | With specific plan and intent | 0 Participants |
| Placebo | Number of Participants With an Affirmative Response to Columbia Suicide Severity Rating Scale (C-SSRS): Suicidal Ideation | Wish to be dead | 1 Participants |
| ASP8062 | Number of Participants With an Affirmative Response to Columbia Suicide Severity Rating Scale (C-SSRS): Suicidal Ideation | With specific plan and intent | 0 Participants |
| ASP8062 | Number of Participants With an Affirmative Response to Columbia Suicide Severity Rating Scale (C-SSRS): Suicidal Ideation | Wish to be dead | 1 Participants |
| ASP8062 | Number of Participants With an Affirmative Response to Columbia Suicide Severity Rating Scale (C-SSRS): Suicidal Ideation | Non-specific active suicidal thoughts | 0 Participants |
| ASP8062 | Number of Participants With an Affirmative Response to Columbia Suicide Severity Rating Scale (C-SSRS): Suicidal Ideation | With any methods (not plan) w/o intent to act | 0 Participants |
| ASP8062 | Number of Participants With an Affirmative Response to Columbia Suicide Severity Rating Scale (C-SSRS): Suicidal Ideation | With some intent to act, w/o specific plan | 0 Participants |
Primary
Number of Participants With an Affirmative Response to C-SSRS: Suicidal Behavior
The C-SSRS is a questionnaire used for suicide risk assessment. Affirmative or negative responses were provided to 5 items to suicidal behavior (1. Preparatory acts or behavior, 2. Aborted attempt, 3. Interrupted attempt, 4. Actual attempt, 5. Completed suicide).
Time frame: Weeks 1 to 8
Population: The analysis population was the SAF. Participants with available data were included in the analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With an Affirmative Response to C-SSRS: Suicidal Behavior | Aborted attempt | 0 Participants |
| Placebo | Number of Participants With an Affirmative Response to C-SSRS: Suicidal Behavior | Actual attempt | 0 Participants |
| Placebo | Number of Participants With an Affirmative Response to C-SSRS: Suicidal Behavior | Interrupted attempt | 0 Participants |
| Placebo | Number of Participants With an Affirmative Response to C-SSRS: Suicidal Behavior | Completed suicide | 0 Participants |
| Placebo | Number of Participants With an Affirmative Response to C-SSRS: Suicidal Behavior | Preparatory acts or behavior | 0 Participants |
| ASP8062 | Number of Participants With an Affirmative Response to C-SSRS: Suicidal Behavior | Completed suicide | 0 Participants |
| ASP8062 | Number of Participants With an Affirmative Response to C-SSRS: Suicidal Behavior | Preparatory acts or behavior | 0 Participants |
| ASP8062 | Number of Participants With an Affirmative Response to C-SSRS: Suicidal Behavior | Aborted attempt | 0 Participants |
| ASP8062 | Number of Participants With an Affirmative Response to C-SSRS: Suicidal Behavior | Interrupted attempt | 0 Participants |
| ASP8062 | Number of Participants With an Affirmative Response to C-SSRS: Suicidal Behavior | Actual attempt | 0 Participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Safety was assessed by adverse events (AEs), which included abnormalities identified during a medical test (e.g. laboratory tests, vital signs, electrocardiogram, etc.) if the abnormality induced clinical signs or symptoms, needed active intervention, interruption or discontinuation of study drug or was clinically significant. A TEAE was defined as any AE that started or worsened after the first dose of study drug up to 30 days after the last dose of study drug. AEs were considered serious (SAEs) if the AE resulted in death, was life-threatening, resulted in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, resulted in congenital anomaly, or birth defect or required inpatient hospitalization or led to prolongation of hospitalization. TEAEs in drug abuse, dependence and withdrawal standardized MedDRA query (SMQ) are special AEs of interest grouped together using the SMQ tool (MedDRA v20.0).
Time frame: From first dose of study drug up to 30 days after last dose of study drug (up to 87 days)
Population: The analysis population was the SAF.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Drug-related serious TEAE | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE in drug abuse, dependence, withdrawal SMQ | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Serious TEAE | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE in drug abuse and dependence SMQ | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE leading to withdrawal of treatment | 3 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE in drug withdrawal SMQ | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Drug-related TEAE | 19 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Drug abuse-related TEAEs | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Death | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Drug withdrawal-related TEAEs | 18 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE | 43 Participants |
| ASP8062 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Drug withdrawal-related TEAEs | 26 Participants |
| ASP8062 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE | 67 Participants |
| ASP8062 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Drug-related TEAE | 45 Participants |
| ASP8062 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Serious TEAE | 0 Participants |
| ASP8062 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Drug-related serious TEAE | 0 Participants |
| ASP8062 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE leading to withdrawal of treatment | 10 Participants |
| ASP8062 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Death | 0 Participants |
| ASP8062 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE in drug abuse, dependence, withdrawal SMQ | 0 Participants |
| ASP8062 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE in drug abuse and dependence SMQ | 0 Participants |
| ASP8062 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE in drug withdrawal SMQ | 0 Participants |
| ASP8062 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Drug abuse-related TEAEs | 1 Participants |
Secondary
Change From Baseline to Weeks 2, 4, 8 and EOT in the Fibromyalgia Impact Questionnaire Revised (FIQR) Function Subscale Score
The FIQR was developed to capture total spectrum of problems related to fibromyalgia and the responses to therapy. The 21-item FIQR contains 3 subscales: function (9 questions), overall impact (2 questions), and symptoms (10 questions). Participants answer each question on an 11-point NRS, with anchors appropriate to each question on a tablet device during a visit. The recall period was the last 7 days or the last time the activity was performed if not within the 7-day recall period. The Function subscale has a range of scores of 0 to 90, with a lower score indicating better (higher) function. A negative change indicated a reduction/improvement from baseline (i.e., a favorable outcome).
Time frame: Baseline and weeks 2, 4, 8
Population: The analysis population was the FAS. Participants with available data at baseline were included in the analysis. LOCF was used for EOT.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Weeks 2, 4, 8 and EOT in the Fibromyalgia Impact Questionnaire Revised (FIQR) Function Subscale Score | Week 2 | -8.21 Units on a scale | Standard Error 1.46 |
| Placebo | Change From Baseline to Weeks 2, 4, 8 and EOT in the Fibromyalgia Impact Questionnaire Revised (FIQR) Function Subscale Score | Week 4 | -10.25 Units on a scale | Standard Error 1.67 |
| Placebo | Change From Baseline to Weeks 2, 4, 8 and EOT in the Fibromyalgia Impact Questionnaire Revised (FIQR) Function Subscale Score | Week 8 | -12.88 Units on a scale | Standard Error 1.91 |
| Placebo | Change From Baseline to Weeks 2, 4, 8 and EOT in the Fibromyalgia Impact Questionnaire Revised (FIQR) Function Subscale Score | EOT | -12.05 Units on a scale | Standard Error 1.87 |
| ASP8062 | Change From Baseline to Weeks 2, 4, 8 and EOT in the Fibromyalgia Impact Questionnaire Revised (FIQR) Function Subscale Score | EOT | -10.96 Units on a scale | Standard Error 1.78 |
| ASP8062 | Change From Baseline to Weeks 2, 4, 8 and EOT in the Fibromyalgia Impact Questionnaire Revised (FIQR) Function Subscale Score | Week 2 | -8.89 Units on a scale | Standard Error 1.42 |
| ASP8062 | Change From Baseline to Weeks 2, 4, 8 and EOT in the Fibromyalgia Impact Questionnaire Revised (FIQR) Function Subscale Score | Week 8 | -12.02 Units on a scale | Standard Error 1.89 |
| ASP8062 | Change From Baseline to Weeks 2, 4, 8 and EOT in the Fibromyalgia Impact Questionnaire Revised (FIQR) Function Subscale Score | Week 4 | -10.89 Units on a scale | Standard Error 1.65 |
Comparison: Week 2: Differences of LS means were calculated by subtracting the LS mean of placebo group from the LS mean of ASP8062 30 mg group using a MMRM model with change from baseline to weeks 2, 4 and 8 as response, treatment, center (pooled where necessary), time (study weeks 2, 4 and 8) and treatment-by-time interaction as fixed effects, baseline and baseline-by-time interaction as covariates.p-value: 0.36990% CI: [-4.05, 2.68]MMRM
Comparison: Week 4: Differences of LS means were calculated by subtracting the LS mean of placebo group from the LS mean of ASP8062 30 mg group using a MMRM model with change from baseline to weeks 2, 4 and 8 as response, treatment, center (pooled where necessary), time (study weeks 2, 4 and 8) and treatment-by-time interaction as fixed effects, baseline and baseline-by-time interaction as covariates.p-value: 0.39390% CI: [-4.51, 3.24]MMRM
Comparison: Week 8: Differences of LS means were calculated by subtracting the LS mean of placebo group from the LS mean of ASP8062 30 mg group using a MMRM model with change from baseline to weeks 2, 4 and 8 as response, treatment, center (pooled where necessary), time (study weeks 2, 4 and 8) and treatment-by-time interaction as fixed effects, baseline and baseline-by-time interaction as covariates.p-value: 0.62690% CI: [-3.57, 5.3]MMRM
Comparison: EOT: Differences of LS means were calculated by subtracting the LS mean of placebo group from the LS mean of ASP8062 30 mg group using an ANCOVA model that was performed with change from baseline at the EOT timepoint as response, treatment and center (pooled where necessary) as fixed effects and baseline as a covariate.p-value: 0.66490% CI: [-3.16, 5.34]ANCOVA
Secondary
Change From Baseline to Weeks 2, 4, 8, and EOT in the FIQR Overall Impact Subscale Score
The FIQR was developed to capture the total spectrum of problems related to fibromyalgia and the responses to therapy. The 21-item FIQR contains 3 subscales: function (9 questions), overall impact (2 questions), and symptoms (10 questions). Participants answer each question on an 11-point NRS, with anchors appropriate to each question on a tablet device during a visit. The recall period was the last 7 days. The Overall Impact subscale has a range of scores from 0 to 20, with a lower score indicating better (lower) impact. A negative change indicated a reduction/improvement from baseline (i.e., a favorable outcome).
Time frame: Baseline and weeks 2, 4, 8
Population: The analysis population was the FAS. Participants with available data at baseline were included in the analysis. LOCF was used for EOT.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Weeks 2, 4, 8, and EOT in the FIQR Overall Impact Subscale Score | Week 2 | -2.79 Units on a scale | Standard Error 0.42 |
| Placebo | Change From Baseline to Weeks 2, 4, 8, and EOT in the FIQR Overall Impact Subscale Score | Week 4 | -3.04 Units on a scale | Standard Error 0.52 |
| Placebo | Change From Baseline to Weeks 2, 4, 8, and EOT in the FIQR Overall Impact Subscale Score | Week 8 | -3.50 Units on a scale | Standard Error 0.5 |
| Placebo | Change From Baseline to Weeks 2, 4, 8, and EOT in the FIQR Overall Impact Subscale Score | EOT | -3.38 Units on a scale | Standard Error 0.49 |
| ASP8062 | Change From Baseline to Weeks 2, 4, 8, and EOT in the FIQR Overall Impact Subscale Score | EOT | -3.21 Units on a scale | Standard Error 0.46 |
| ASP8062 | Change From Baseline to Weeks 2, 4, 8, and EOT in the FIQR Overall Impact Subscale Score | Week 2 | -2.60 Units on a scale | Standard Error 0.41 |
| ASP8062 | Change From Baseline to Weeks 2, 4, 8, and EOT in the FIQR Overall Impact Subscale Score | Week 8 | -3.44 Units on a scale | Standard Error 0.5 |
| ASP8062 | Change From Baseline to Weeks 2, 4, 8, and EOT in the FIQR Overall Impact Subscale Score | Week 4 | -3.20 Units on a scale | Standard Error 0.51 |
Comparison: Week 2: Differences of LS means were calculated by subtracting the LS mean of placebo group from the LS mean of ASP8062 30 mg group using a MMRM model with change from baseline to weeks 2, 4 and 8 as response, treatment, center (pooled where necessary), time (study weeks 2, 4 and 8) and treatment-by-time interaction as fixed effects, baseline and baseline-by-time interaction as covariates.p-value: 0.62990% CI: [-0.78, 1.17]MMRM
Comparison: Week 4: Differences of LS means were calculated by subtracting the LS mean of placebo group from the LS mean of ASP8062 30 mg group using a MMRM model with change from baseline to weeks 2, 4 and 8 as response, treatment, center (pooled where necessary), time (study weeks 2, 4 and 8) and treatment-by-time interaction as fixed effects, baseline and baseline-by-time interaction as covariates.p-value: 0.4190% CI: [-1.37, 1.04]MMRM
Comparison: Week 8: Differences of LS means were calculated by subtracting the LS mean of placebo group from the LS mean of ASP8062 30 mg group using a MMRM model with change from baseline to weeks 2, 4 and 8 as response, treatment, center (pooled where necessary), time (study weeks 2, 4 and 8) and treatment-by-time interaction as fixed effects, baseline and baseline-by-time interaction as covariates.p-value: 0.53190% CI: [-1.11, 1.22]MMRM
Comparison: EOT: Differences of LS means were calculated by subtracting the LS mean of placebo group from the LS mean of ASP8062 30 mg group using an ANCOVA model that was performed with change from baseline at the EOT timepoint as response, treatment and center (pooled where necessary) as fixed effects and baseline as a covariate.p-value: 0.60390% CI: [-0.93, 1.28]ANCOVA
Secondary
Change From Baseline to Weeks 2, 4, 8, and EOT in the FIQR Symptoms Subscale Score
The FIQR was developed to capture the total spectrum of problems related to fibromyalgia and the responses to therapy. The 21-item FIQR contains 3 subscales: function (9 questions), overall impact (2 questions), and symptoms (10 questions). Participants answer each question on an 11-point NRS, with anchors appropriate to each question on a tablet device during a visit. The recall period was the last 7 days. The Symptoms subscale range of scores is 0 to 100, with a lower score indicating a better (lower) level of symptoms. A negative change indicates a reduction/improvement from baseline (i.e., a favorable outcome).
Time frame: Baseline and weeks 2, 4, 8
Population: The analysis population was the FAS. Participants with available data at baseline were included in the analysis. LOCF was used for EOT.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Weeks 2, 4, 8, and EOT in the FIQR Symptoms Subscale Score | Week 4 | -10.91 Units on a scale | Standard Error 1.49 |
| Placebo | Change From Baseline to Weeks 2, 4, 8, and EOT in the FIQR Symptoms Subscale Score | Week 2 | -9.05 Units on a scale | Standard Error 1.33 |
| Placebo | Change From Baseline to Weeks 2, 4, 8, and EOT in the FIQR Symptoms Subscale Score | Week 8 | -12.40 Units on a scale | Standard Error 1.83 |
| Placebo | Change From Baseline to Weeks 2, 4, 8, and EOT in the FIQR Symptoms Subscale Score | EOT | -11.47 Units on a scale | Standard Error 1.77 |
| ASP8062 | Change From Baseline to Weeks 2, 4, 8, and EOT in the FIQR Symptoms Subscale Score | EOT | -9.79 Units on a scale | Standard Error 1.69 |
| ASP8062 | Change From Baseline to Weeks 2, 4, 8, and EOT in the FIQR Symptoms Subscale Score | Week 8 | -10.70 Units on a scale | Standard Error 1.82 |
| ASP8062 | Change From Baseline to Weeks 2, 4, 8, and EOT in the FIQR Symptoms Subscale Score | Week 2 | -8.89 Units on a scale | Standard Error 1.29 |
| ASP8062 | Change From Baseline to Weeks 2, 4, 8, and EOT in the FIQR Symptoms Subscale Score | Week 4 | -9.45 Units on a scale | Standard Error 1.46 |
Comparison: Week 2: Differences of LS means were calculated by subtracting the LS mean of placebo group from the LS mean of ASP8062 30 mg group using a MMRM model with change from baseline to weeks 2, 4 and 8 as response, treatment, center (pooled where necessary), time (study weeks 2, 4 and 8) and treatment-by-time interaction as fixed effects, baseline and baseline-by-time interaction as covariates.p-value: 0.53490% CI: [-2.9, 3.22]MMRM
Comparison: Week 4: Differences of LS means were calculated by subtracting the LS mean of placebo group from the LS mean of ASP8062 30 mg group using a MMRM model with change from baseline to weeks 2, 4 and 8 as response, treatment, center (pooled where necessary), time (study weeks 2, 4 and 8) and treatment-by-time interaction as fixed effects, baseline and baseline-by-time interaction as covariates.p-value: 0.75890% CI: [-1.98, 4.91]MMRM
Comparison: Week 8: Differences of LS means were calculated by subtracting the LS mean of placebo group from the LS mean of ASP8062 30 mg group using a MMRM model with change from baseline to weeks 2, 4 and 8 as response, treatment, center (pooled where necessary), time (study weeks 2, 4 and 8) and treatment-by-time interaction as fixed effects, baseline and baseline-by-time interaction as covariates.p-value: 0.74590% CI: [-2.56, 5.96]MMRM
Comparison: EOT: Differences of LS means were calculated by subtracting the LS mean of placebo group from the LS mean of ASP8062 30 mg group using an ANCOVA model that was performed with change from baseline at the EOT timepoint as response, treatment and center (pooled where necessary) as fixed effects and baseline as a covariate.p-value: 0.75590% CI: [-2.34, 5.69]ANCOVA
Secondary
Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC)
The PGIC is a self-administered 7-point Likert scale that asks participants to evaluate their fibromyalgia relative to baseline. This is a single question and the grade ranges from 1 (Very Much Improved) to 7 (Very Much Worse).
Time frame: Weeks 2, 4, 8
Population: The analysis population was the FAS. Modified LOCF (mLOCF) was used for weeks 2, 4, and 8, where No Change was imputed for participants who discontinued due to lack of efficacy or AEs, and LOCF was used for participants who discontinued due to other reasons. LOCF was used for EOT.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Placebo | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | Week 8 | Very Much Improved | 5 Participants |
| Placebo | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | Week 2 | Minimally Worse | 7 Participants |
| Placebo | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | Week 8 | Much Improved | 13 Participants |
| Placebo | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | Week 4 | Much Improved | 13 Participants |
| Placebo | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | Week 8 | Minimally Improved | 33 Participants |
| Placebo | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | Week 2 | Much Improved | 7 Participants |
| Placebo | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | Week 8 | No Change | 26 Participants |
| Placebo | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | Week 4 | Minimally Improved | 34 Participants |
| Placebo | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | Week 8 | Minimally Worse | 6 Participants |
| Placebo | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | Week 2 | Much Worse | 5 Participants |
| Placebo | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | Week 8 | Much Worse | 4 Participants |
| Placebo | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | Week 4 | No Change | 28 Participants |
| Placebo | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | Week 8 | Very Much Worse | 1 Participants |
| Placebo | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | Week 2 | No Change | 34 Participants |
| Placebo | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | EOT | Very Much Improved | 5 Participants |
| Placebo | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | Week 4 | Minimally Worse | 8 Participants |
| Placebo | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | EOT | Much Improved | 13 Participants |
| Placebo | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | Week 2 | Very Much Worse | 1 Participants |
| Placebo | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | EOT | Minimally Improved | 34 Participants |
| Placebo | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | Week 4 | Much Worse | 3 Participants |
| Placebo | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | EOT | No Change | 24 Participants |
| Placebo | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | Week 2 | Minimally Improved | 34 Participants |
| Placebo | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | EOT | Minimally Worse | 6 Participants |
| Placebo | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | Week 4 | Very Much Worse | 0 Participants |
| Placebo | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | EOT | Much Worse | 4 Participants |
| Placebo | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | Week 4 | Very Much Improved | 2 Participants |
| Placebo | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | EOT | Very Much Worse | 2 Participants |
| Placebo | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | Week 2 | Very Much Improved | 0 Participants |
| ASP8062 | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | EOT | Very Much Worse | 0 Participants |
| ASP8062 | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | Week 2 | Very Much Improved | 4 Participants |
| ASP8062 | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | Week 2 | Much Improved | 9 Participants |
| ASP8062 | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | Week 2 | Minimally Improved | 28 Participants |
| ASP8062 | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | Week 2 | No Change | 42 Participants |
| ASP8062 | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | Week 2 | Minimally Worse | 9 Participants |
| ASP8062 | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | Week 2 | Much Worse | 3 Participants |
| ASP8062 | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | Week 2 | Very Much Worse | 0 Participants |
| ASP8062 | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | Week 4 | Very Much Improved | 6 Participants |
| ASP8062 | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | Week 4 | Much Improved | 13 Participants |
| ASP8062 | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | Week 4 | Minimally Improved | 23 Participants |
| ASP8062 | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | Week 4 | No Change | 39 Participants |
| ASP8062 | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | Week 4 | Minimally Worse | 6 Participants |
| ASP8062 | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | Week 4 | Much Worse | 8 Participants |
| ASP8062 | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | Week 4 | Very Much Worse | 0 Participants |
| ASP8062 | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | Week 8 | Very Much Improved | 12 Participants |
| ASP8062 | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | Week 8 | Much Improved | 12 Participants |
| ASP8062 | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | Week 8 | Minimally Improved | 17 Participants |
| ASP8062 | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | Week 8 | No Change | 38 Participants |
| ASP8062 | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | Week 8 | Minimally Worse | 10 Participants |
| ASP8062 | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | Week 8 | Much Worse | 6 Participants |
| ASP8062 | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | Week 8 | Very Much Worse | 0 Participants |
| ASP8062 | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | EOT | Very Much Improved | 12 Participants |
| ASP8062 | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | EOT | Much Improved | 12 Participants |
| ASP8062 | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | EOT | Minimally Improved | 19 Participants |
| ASP8062 | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | EOT | No Change | 34 Participants |
| ASP8062 | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | EOT | Minimally Worse | 11 Participants |
| ASP8062 | Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC) | EOT | Much Worse | 7 Participants |
Comparison: Week 2: Odds ratio of ASP8062 30 mg versus placebo, associated 90% 2-sided CI and p-value was estimated using a proportional odds model including treatment group as a factor.p-value: 0.81190% CI: [0.68, 1.67]Proportional Odds model
Comparison: Week 4: Odds ratio of ASP8062 30 mg versus placebo, associated 90% 2-sided CI and p-value was estimated using a proportional odds model including treatment group as a factor.p-value: 0.36890% CI: [0.5, 1.22]Proportional Odds model
Comparison: Week 8: Odds ratio of ASP8062 30 mg versus placebo, associated 90% 2-sided CI and p-value was estimated using a proportional odds model including treatment group as a factor.p-value: 0.35790% CI: [0.5, 1.21]Proportional Odds model
Comparison: EOT: Odds ratio of ASP8062 30 mg versus placebo, associated 90% 2-sided CI and p-value was estimated using a proportional odds model including treatment group as a factor.p-value: 0.40790% CI: [0.52, 1.24]Proportional Odds model
Secondary
Percentage of Participants With ≥ 30% Reduction From Baseline to Week 8 and End of Treatment (EOT) in Mean Daily Average Pain Score as Assessed by NRS
The mean daily average pain score was assessed through the Daily Average Pain NRS, which is a generic instrument for the assessment of pain that consists of a single question that asks participants to record their daily average pain on an 11-point scale, where 0 anchors no pain and 10 pain as bad as you can imagine. The mean daily average pain score was calculated from data recorded by participants daily in the electronic diary, and the recall period was the last 24 hours. For the week 8 analysis, participants with missing baseline or week 8 data were classified as nonresponders. For EOT analysis, participants with missing baseline or EOT data were classified as nonresponders.
Time frame: Baseline to week 8
Population: The analysis population was the FAS. Baseline Observation Carried Forward (BOCF) was used for week 8. Last Observation Carried Forward (LOCF) was used for EOT.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With ≥ 30% Reduction From Baseline to Week 8 and End of Treatment (EOT) in Mean Daily Average Pain Score as Assessed by NRS | Week 8 | 31.8 Percentage of participants |
| Placebo | Percentage of Participants With ≥ 30% Reduction From Baseline to Week 8 and End of Treatment (EOT) in Mean Daily Average Pain Score as Assessed by NRS | EOT | 33.0 Percentage of participants |
| ASP8062 | Percentage of Participants With ≥ 30% Reduction From Baseline to Week 8 and End of Treatment (EOT) in Mean Daily Average Pain Score as Assessed by NRS | Week 8 | 25.3 Percentage of participants |
| ASP8062 | Percentage of Participants With ≥ 30% Reduction From Baseline to Week 8 and End of Treatment (EOT) in Mean Daily Average Pain Score as Assessed by NRS | EOT | 27.4 Percentage of participants |
Comparison: Week 8: Differences of the percentages were calculated by subtracting the percentage of placebo group from the percentage of ASP8062 30 mg group. Confidence Interval (CI) for each treatment group and the difference of the percentages was an exact unconditional confidence interval based on Santner-Snell approach.p-value: 0.87490% CI: [-18.7, 5.7]Fisher Exact
Comparison: EOT: Differences of the percentages were calculated by subtracting the percentage of placebo group from the percentage of ASP8062 30 mg group. Confidence Interval (CI) for each treatment group and the difference of the percentages was an exact unconditional confidence interval based on Santner-Snell approach.p-value: 0.83890% CI: [-17.7, 6.7]Fisher Exact
Secondary
Percentage of Participants With ≥ 50% Reduction From Baseline to Week 8 and EOT in Mean Daily Average Pain Score as Assessed by NRS
The mean daily average pain score was assessed thorugh the Daily Average Pain NRS, which is a generic instrument for the assessment of pain that consists of a single question that asks participants to record their daily average pain on an 11-point scale, where 0 anchors no pain and 10 pain as bad as you can imagine. The mean daily average pain score was calculated from data recorded by participants daily in the electronic diary, and the recall period was the last 24 hours. For the week 8 analysis, participants with missing baseline or week 8 data were classified as nonresponders. For EOT analysis, participants with missing baseline or EOT data were classified as nonresponders.
Time frame: Baseline to week 8
Population: The analysis population was the FAS. BOCF was used for week 8. LOCF was used for EOT.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With ≥ 50% Reduction From Baseline to Week 8 and EOT in Mean Daily Average Pain Score as Assessed by NRS | Week 8 | 12.5 Percentage of participants |
| Placebo | Percentage of Participants With ≥ 50% Reduction From Baseline to Week 8 and EOT in Mean Daily Average Pain Score as Assessed by NRS | EOT | 12.5 Percentage of participants |
| ASP8062 | Percentage of Participants With ≥ 50% Reduction From Baseline to Week 8 and EOT in Mean Daily Average Pain Score as Assessed by NRS | Week 8 | 14.7 Percentage of participants |
| ASP8062 | Percentage of Participants With ≥ 50% Reduction From Baseline to Week 8 and EOT in Mean Daily Average Pain Score as Assessed by NRS | EOT | 16.8 Percentage of participants |
Comparison: Week 8: Differences of the percentages were calculated by subtracting the percentage of placebo group from the percentage of ASP8062 30 mg group. Confidence Interval (CI) for each treatment group and the difference of the percentages was an exact unconditional confidence interval based on Santner-Snell approach.p-value: 0.41290% CI: [-10, 14.4]Fisher Exact
Comparison: EOT: Differences of the percentages were calculated by subtracting the percentage of placebo group from the percentage of ASP8062 30 mg group. Confidence Interval (CI) for each treatment group and the difference of the percentages was an exact unconditional confidence interval based on Santner-Snell approach.p-value: 0.26990% CI: [-7.9, 16.4]Fisher Exact