A Study to Assess the Analgesic Efficacy and Safety of ASP0819 in Patients With Fibromyalgia
Condition: Fibromyalgia
MeSH terms: Fibromyalgia; Myofascial Pain Syndromes
Intervention: ASP0819; Placebo
Intervention description: Oral capsule; Oral capsule
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 186.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: ASP0819; Fibromyalgia

Summary:

      This study assessed analgesic efficacy of ASP0819 relative to placebo as well as the safety
      and tolerability.

      This study assessed treatment differences in physical function as well as the improvements in
      overall subject status (e.g., fibromyalgia symptoms and global functioning) of ASP0819
      relative to placebo.
    

Eligibility criteria:

        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).