A Study to Assess the Analgesic Efficacy and Safety of ASP0819 in Patients With Fibromyalgia

Inclusion criteria

• Subject has a body mass index (BMI) ≤ 45 kg/m2.
• 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 28 days after the 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 28 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 on right and left sides of the body, 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 revised (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. The 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 ASP0819.
• 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 (e.g., rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and gout), autoimmune disease (e.g., 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 the time of Visit 3 (Randomization).
• Subject has clinically significant abnormalities in clinical chemistry, hematology, or urinalysis, or a serum creatinine > 1.5 times the Upper limit of normal (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 (SBP) > 180 mmHg or < 90 mmHg, and/or a sitting diastolic blood pressure (DBP) > 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 time from electrocardiogram Q wave to the end of the T wave (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 (CPAP) 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.
• Subject has filed or is awaiting judgment on a disability claim or has any pending worker's compensation litigation or related monetary settlements.
• 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 their immediate families (spouse, parent, child, or sibling, whether biological or legally adopted).