Clinical trial NCT03092726: A Study to Assess the Analgesic Efficacy and Safety of ASP8062 in Subjects With Fibromyalgia
Official title: A Phase 2a, Randomized, Double-Blind Placebo-controlled, Parallel-group Study to Assess the Analgesic Efficacy and Safety of ASP8062 in Subjects With Fibromyalgia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Fibromyalgia
Keywords: ASP8062
Fibromyalgia
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2017-03-28
Enrollment: 183
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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).

Primary outcomes:
measure: Change From Baseline to Week 8 in Mean Daily Average Pain Score as Assessed by Numerical Rating Scale (NRS)
timeFrame: Baseline and week 8
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From first dose of study drug up to 30 days after last dose of study drug (up to 87 days)
measure: Number of Participants With an Affirmative Response to Columbia Suicide Severity Rating Scale (C-SSRS): Suicidal Ideation
timeFrame: Weeks 1 to 8
measure: Number of Participants With an Affirmative Response to C-SSRS: Suicidal Behavior
timeFrame: Weeks 1 to 8
Secondary outcomes:
measure: 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
timeFrame: Baseline to week 8
measure: Percentage of Participants With ≥ 50% Reduction From Baseline to Week 8 and EOT in Mean Daily Average Pain Score as Assessed by NRS
timeFrame: Baseline to week 8
measure: Change From Baseline to Weeks 2, 4, 8 and EOT in the Fibromyalgia Impact Questionnaire Revised (FIQR) Function Subscale Score
timeFrame: Baseline and weeks 2, 4, 8
measure: Change From Baseline to Weeks 2, 4, 8, and EOT in the FIQR Symptoms Subscale Score
timeFrame: Baseline and weeks 2, 4, 8
measure: Change From Baseline to Weeks 2, 4, 8, and EOT in the FIQR Overall Impact Subscale Score
timeFrame: Baseline and weeks 2, 4, 8
measure: Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC)
timeFrame: Weeks 2, 4, 8
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Noesis Pharma, LLC
state: Arizona
city: Oceanside
country: United States
facility: Excell Research, Inc
state: California
city: Torrance
country: United States
facility: Collaborative Neuroscience Network, LLC.
state: California
city: Brandon
country: United States
facility: PAB Clinical Research
state: Florida
city: DeLand
country: United States
facility: Avail Clinical Research, LLC
state: Florida
city: Orlando
country: United States
facility: Clinical Neuroscience Solutions, Inc
state: Florida
city: Chicago
country: United States
facility: Chicago Research Center, Inc
state: Illinois
city: Evansville
country: United States
facility: Medisphere Medical Research Center, LLC
state: Indiana
city: North Dartmouth
country: United States
facility: Infinity Medical Research, Inc
state: Massachusetts
city: Jackson
country: United States
facility: Elite Clinical Research, LLC
state: Mississippi
city: Kansas City
country: United States
facility: The Center For Pharmaceutical Research
state: Missouri
city: Las Vegas
country: United States
facility: Advanced Biomedical Research of America
state: Nevada
city: Brooklyn
country: United States
facility: NY Scientific
state: New York
city: Cedarhurst
country: United States
facility: Neurobehavioral Research, Inc
state: New York
city: Raleigh
country: United States
facility: Private Practice
state: North Carolina
city: Winston-Salem
country: United States
facility: PMG of Winston-Salem, LLC
state: North Carolina
city: Canton
country: United States
facility: Neuro-Behavioral Clinical Research, Inc
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Portland
country: United States
facility: Summit Research Network
state: Oregon
city: Allentown
country: United States
facility: Lehigh Center for Clinical Research
state: Pennsylvania
city: Warwick
country: United States
facility: Omega Medical Research
state: Rhode Island
city: Dakota Dunes
country: United States
facility: Meridian Clinical Research
state: South Dakota
city: Chattanooga
country: United States
facility: ClinSearch, LLC
state: Tennessee
city: Kenosha
country: United States
facility: Clinical Investigation Specialists, Inc
state: Wisconsin
Study officials:
affiliation: Astellas Pharma Global Development, Inc.
name: Executive Director
role: STUDY_DIRECTOR
References: