A Study to Assess the Analgesic Efficacy and Safety of ASP8062 in Subjects With Fibromyalgia

• Sponsor: Astellas Pharma Global Development, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03092726
• Collaborator: (none)
• Enrollment: 183
• Locations: 24
• Arms: 2
• Actual Duration (Months): 9.9
• Patients Per Site: 7.6
• Patients Per Site Per Month: 0.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Fibromyalgia	Drug: ASP8062; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 183 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: May 8, 2017
• Actual Primary Completion Date: Mar 6, 2018
• Actual Study Completion Date: Mar 6, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ASP8062 Participants received 30 mg of ASP8062 orally once daily for 8 weeks.	Drug: ASP8062; ASP8062 30 mg was administered orally as a single daily dose, taken preferably in the morning with or without food.
Placebo Comparator: Placebo Participants received matching placebo orally once daily for 8 weeks.	Drug: Placebo; Placebo was administered orally as a single daily dose, taken preferably in the morning with or without food.

Outcome Measures

Primary Outcome Measures

1. 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).

2. 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).

3. 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).

4. 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 Outcome Measures

1. 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.

2. 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.

3. 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).

4. 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).

5. 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).

6. 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").

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts 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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Noesis Pharma, LLC	Phoenix	Arizona	United States	85032
2	Excell Research, Inc	Oceanside	California	United States	92056
3	Collaborative Neuroscience Network, LLC.	Torrance	California	United States	90502
4	PAB Clinical Research	Brandon	Florida	United States	33511
5	Avail Clinical Research, LLC	DeLand	Florida	United States	32720
6	Clinical Neuroscience Solutions, Inc	Orlando	Florida	United States	32801
7	Chicago Research Center, Inc	Chicago	Illinois	United States	60634
8	Medisphere Medical Research Center, LLC	Evansville	Indiana	United States	47714
9	Infinity Medical Research, Inc	North Dartmouth	Massachusetts	United States	02747
10	Elite Clinical Research, LLC	Jackson	Mississippi	United States	39202
11	The Center For Pharmaceutical Research	Kansas City	Missouri	United States	64114
12	Advanced Biomedical Research of America	Las Vegas	Nevada	United States	89123
13	NY Scientific	Brooklyn	New York	United States	11235
14	Neurobehavioral Research, Inc	Cedarhurst	New York	United States	11516
15	Private Practice	Raleigh	North Carolina	United States	27609
16	PMG of Winston-Salem, LLC	Winston-Salem	North Carolina	United States	27103
17	Neuro-Behavioral Clinical Research, Inc	Canton	Ohio	United States	44718
18	University of Cincinnati	Cincinnati	Ohio	United States	45219
19	Summit Research Network	Portland	Oregon	United States	97210
20	Lehigh Center for Clinical Research	Allentown	Pennsylvania	United States	18104
21	Omega Medical Research	Warwick	Rhode Island	United States	02886
22	Meridian Clinical Research	Dakota Dunes	South Dakota	United States	57049
23	ClinSearch, LLC	Chattanooga	Tennessee	United States	37421
24	Clinical Investigation Specialists, Inc	Kenosha	Wisconsin	United States	53142

Sponsors and Collaborators

• Astellas Pharma Global Development, Inc.

Investigators

• Study Director: Executive Director, Astellas Pharma Global Development, Inc.

Study Documents (Full-Text)

• Study Protocol - Aug 14, 2017
• Statistical Analysis Plan - Apr 19, 2018

More Information

Additional Information:

• Link to results on Astellas Clinical Study Results website

Publications

None provided.

• Responsible Party: Astellas Pharma Global Development, Inc.
• ClinicalTrials.gov Identifier: NCT03092726
• Other Study ID Numbers: 8062-CL-0101
• First Posted: Mar 28, 2017
• Last Update Posted: Aug 14, 2019
• Last Verified: Aug 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Astellas Pharma Global Development, Inc.: ASP8062; Fibromyalgia
• Additional relevant MeSH terms: Fibromyalgia; Myofascial Pain Syndromes; ASP8062

Study Results

Participant Flow

Recruitment Details	Participants with fibromyalgia (FM) were enrolled in 24 sites in the United States.
Pre-assignment Detail	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).

Arm/Group Title	Placebo	ASP8062
Arm/Group Description	Participants received matching placebo orally once daily for 8 weeks.	Participants received 30 mg of ASP8062 orally once daily for 8 weeks.
Period Title: Overall Study
STARTED	88	95
Treated	88	95
COMPLETED	79	81
NOT COMPLETED	9	14

Baseline Characteristics

Arm/Group Title	Placebo	ASP8062	Total
Arm/Group Description	Participants received matching placebo orally once daily for 8 weeks.	Participants received 30 mg of ASP8062 orally once daily for 8 weeks.	Total of all reporting groups
Overall Participants	88	95	183
Age (Years) [Mean (Standard Deviation) ]
Age	51.3 (12.9)	52.5 (11.9)	51.9 (12.3)
Sex: Female, Male (Count of Participants)
Female	83 94.3%	93 97.9%	176 96.2%
Male	5 5.7%	2 2.1%	7 3.8%
Race/Ethnicity, Customized (Count of Participants)
White	69 78.4%	70 73.7%	139 76%
Black or African American	15 17%	20 21.1%	35 19.1%
Asian	3 3.4%	1 1.1%	4 2.2%
American Indian or Alaska Native	0 0%	3 3.2%	3 1.6%
Other	1 1.1%	1 1.1%	2 1.1%
Ethnicity (Count of Participants)
Not Hispanic or Latino	71 80.7%	77 81.1%	148 80.9%
Hispanic or Latino	17 19.3%	18 18.9%	35 19.1%
Baseline Mean Daily Average Pain Score Group (Count of Participants)
No pain: 0	0 0%	0 0%	0 0%
Mild: > 0 to < 4	0 0%	0 0%	0 0%
Moderate: >= 4 to < 7	59 67%	57 60%	116 63.4%
Severe: >= 7 to 10	29 33%	38 40%	67 36.6%
Baseline Mean Daily Average Pain Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	6.49 (1.03)	6.54 (0.97)	6.51 (1)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to Week 8 in Mean Daily Average Pain Score as Assessed by Numerical Rating Scale (NRS)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo	ASP8062
Arm/Group Description	Participants received matching placebo orally once daily for 8 weeks.	Participants received 30 mg of ASP8062 orally once daily for 8 weeks.
Measure Participants	88	95
Least Squares Mean (Standard Error) [Units on a scale]	-1.42 (0.19)	-1.36 (0.19)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ASP8062
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.590
	Comments	1-sided p-value is for comparison of ASP8062 30 mg with placebo from the above described MMRM model.
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	LS Mean (LSM) Difference
	Estimated Value	0.06
	Confidence Interval	(2-Sided) 90%; -0.38 to 0.50
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.26
	Estimation Comments

2. Primary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Description	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)

Outcome Measure Data

Analysis Population Description

The analysis population was the SAF.

Arm/Group Title	Placebo	ASP8062
Arm/Group Description	Participants received matching placebo orally once daily for 8 weeks.	Participants received 30 mg of ASP8062 orally once daily for 8 weeks.
Measure Participants	88	95
Any TEAE	43 48.9%	67 70.5%
Drug-related TEAE	19 21.6%	45 47.4%
Serious TEAE	0 0%	0 0%
Drug-related serious TEAE	0 0%	0 0%
TEAE leading to withdrawal of treatment	3 3.4%	10 10.5%
Death	0 0%	0 0%
TEAE in drug abuse, dependence, withdrawal SMQ	0 0%	0 0%
TEAE in drug abuse and dependence SMQ	0 0%	0 0%
TEAE in drug withdrawal SMQ	0 0%	0 0%
Drug abuse-related TEAEs	0 0%	1 1.1%
Drug withdrawal-related TEAEs	18 20.5%	26 27.4%

3. Primary Outcome

Title	Number of Participants With an Affirmative Response to Columbia Suicide Severity Rating Scale (C-SSRS): Suicidal Ideation
Description	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

Outcome Measure Data

Analysis Population Description

The analysis population was the SAF. Participants with available data were included in the analysis.

Arm/Group Title	Placebo	ASP8062
Arm/Group Description	Participants received matching placebo orally once daily for 8 weeks.	Participants received 30 mg of ASP8062 orally once daily for 8 weeks.
Measure Participants	86	90
Wish to be dead	1 1.1%	1 1.1%
Non-specific active suicidal thoughts	0 0%	0 0%
With any methods (not plan) w/o intent to act	0 0%	0 0%
With some intent to act, w/o specific plan	0 0%	0 0%
With specific plan and intent	0 0%	0 0%

4. Primary Outcome

Title	Number of Participants With an Affirmative Response to C-SSRS: Suicidal Behavior
Description	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

Outcome Measure Data

Analysis Population Description

The analysis population was the SAF. Participants with available data were included in the analysis.

Arm/Group Title	Placebo	ASP8062
Arm/Group Description	Participants received matching placebo orally once daily for 8 weeks.	Participants received 30 mg of ASP8062 orally once daily for 8 weeks.
Measure Participants	86	90
Preparatory acts or behavior	0 0%	0 0%
Aborted attempt	0 0%	0 0%
Interrupted attempt	0 0%	0 0%
Actual attempt	0 0%	0 0%
Completed suicide	0 0%	0 0%

5. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo	ASP8062
Arm/Group Description	Participants received matching placebo orally once daily for 8 weeks.	Participants received 30 mg of ASP8062 orally once daily for 8 weeks.
Measure Participants	88	95
Week 8	31.8 36.1%	25.3 26.6%
EOT	33.0 37.5%	27.4 28.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ASP8062
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.874
	Comments	1-sided p-value is for comparison of ASP8062 30 mg with placebo using Fisher's Exact method.
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference of percentages
	Estimated Value	-6.6
	Confidence Interval	(2-Sided) 90%; -18.7 to 5.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ASP8062
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.838
	Comments	1-sided p-value is for comparison of ASP8062 30 mg with placebo using Fisher's Exact method.
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Differences of percentages
	Estimated Value	-5.6
	Confidence Interval	(2-Sided) 90%; -17.7 to 6.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Percentage of Participants With ≥ 50% Reduction From Baseline to Week 8 and EOT in Mean Daily Average Pain Score as Assessed by NRS
Description	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

Outcome Measure Data

Analysis Population Description

The analysis population was the FAS. BOCF was used for week 8. LOCF was used for EOT.

Arm/Group Title	Placebo	ASP8062
Arm/Group Description	Participants received matching placebo orally once daily for 8 weeks.	Participants received 30 mg of ASP8062 orally once daily for 8 weeks.
Measure Participants	88	95
Week 8	12.5 14.2%	14.7 15.5%
EOT	12.5 14.2%	16.8 17.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ASP8062
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.412
	Comments	1-sided p-value is for comparison of ASP8062 30 mg with placebo using Fisher's Exact method.
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Differences of percentages
	Estimated Value	2.2
	Confidence Interval	(2-Sided) 90%; -10.0 to 14.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ASP8062
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.269
	Comments	1-sided p-value is for comparison of ASP8062 30 mg with placebo using Fisher's Exact method.
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Differences of percentages
	Estimated Value	4.3
	Confidence Interval	(2-Sided) 90%; -7.9 to 16.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Change From Baseline to Weeks 2, 4, 8 and EOT in the Fibromyalgia Impact Questionnaire Revised (FIQR) Function Subscale Score
Description	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

Outcome Measure Data

Analysis Population Description

The analysis population was the FAS. Participants with available data at baseline were included in the analysis. LOCF was used for EOT.

Arm/Group Title	Placebo	ASP8062
Arm/Group Description	Participants received matching placebo orally once daily for 8 weeks.	Participants received 30 mg of ASP8062 orally once daily for 8 weeks.
Measure Participants	88	95
Week 2	-8.21 (1.46)	-8.89 (1.42)
Week 4	-10.25 (1.67)	-10.89 (1.65)
Week 8	-12.88 (1.91)	-12.02 (1.89)
EOT	-12.05 (1.87)	-10.96 (1.78)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ASP8062
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.369
	Comments	1-sided p-value is for comparison of ASP8062 30 mg with placebo from the above described MMRM model.
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	-0.68
	Confidence Interval	(2-Sided) 90%; -4.05 to 2.68
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.03
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ASP8062
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.393
	Comments	1-sided p-value is for comparison of ASP8062 30 mg with placebo from the above described MMRM model.
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	-0.64
	Confidence Interval	(2-Sided) 90%; -4.51 to 3.24
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.34
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, ASP8062
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.626
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	0.86
	Confidence Interval	(2-Sided) 90%; -3.57 to 5.30
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.68
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ASP8062
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.664
	Comments	1-sided p-value is for comparison of ASP8062 30 mg with placebo from the above described ANCOVA model.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	1.09
	Confidence Interval	(2-Sided) 90%; -3.16 to 5.34
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.57
	Estimation Comments

8. Secondary Outcome

Title	Change From Baseline to Weeks 2, 4, 8, and EOT in the FIQR Symptoms Subscale Score
Description	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

Outcome Measure Data

Analysis Population Description

The analysis population was the FAS. Participants with available data at baseline were included in the analysis. LOCF was used for EOT.

Arm/Group Title	Placebo	ASP8062
Arm/Group Description	Participants received matching placebo orally once daily for 8 weeks.	Participants received 30 mg of ASP8062 orally once daily for 8 weeks.
Measure Participants	88	95
Week 2	-9.05 (1.33)	-8.89 (1.29)
Week 4	-10.91 (1.49)	-9.45 (1.46)
Week 8	-12.40 (1.83)	-10.70 (1.82)
EOT	-11.47 (1.77)	-9.79 (1.69)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ASP8062
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.534
	Comments	1-sided p-value is for comparison of ASP8062 30 mg with placebo from the above described MMRM model.
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	0.16
	Confidence Interval	(2-Sided) 90%; -2.90 to 3.22
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.85
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ASP8062
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.758
	Comments	1-sided p-value is for comparison of ASP8062 30 mg with placebo from the above described MMRM model.
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	1.46
	Confidence Interval	(2-Sided) 90%; -1.98 to 4.91
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.08
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, ASP8062
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.745
	Comments	1-sided p-value is for comparison of ASP8062 30 mg with placebo from the above described MMRM model.
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	1.70
	Confidence Interval	(2-Sided) 90%; -2.56 to 5.96
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.57
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ASP8062
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.755
	Comments	1-sided p-value is for comparison of ASP8062 30 mg with placebo from the above described ANCOVA model.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	1.68
	Confidence Interval	(2-Sided) 90%; -2.34 to 5.69
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.43
	Estimation Comments

9. Secondary Outcome

Title	Change From Baseline to Weeks 2, 4, 8, and EOT in the FIQR Overall Impact Subscale Score
Description	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

Outcome Measure Data

Analysis Population Description

The analysis population was the FAS. Participants with available data at baseline were included in the analysis. LOCF was used for EOT.

Arm/Group Title	Placebo	ASP8062
Arm/Group Description	Participants received matching placebo orally once daily for 8 weeks.	Participants received 30 mg of ASP8062 orally once daily for 8 weeks.
Measure Participants	88	95
Week 2	-2.79 (0.42)	-2.60 (0.41)
Week 4	-3.04 (0.52)	-3.20 (0.51)
Week 8	-3.50 (0.50)	-3.44 (0.50)
EOT	-3.38 (0.49)	-3.21 (0.46)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ASP8062
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.629
	Comments	1-sided p-value is for comparison of ASP8062 30 mg with placebo from the above described MMRM model.
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	0.19
	Confidence Interval	(2-Sided) 90%; -0.78 to 1.17
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.59
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ASP8062
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.410
	Comments	1-sided p-value is for comparison of ASP8062 30 mg with placebo from the above described MMRM model.
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	-0.17
	Confidence Interval	(2-Sided) 90%; -1.37 to 1.04
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.73
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, ASP8062
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.531
	Comments	1-sided p-value is for comparison of ASP8062 30 mg with placebo from the above described MMRM model.
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	0.06
	Confidence Interval	(2-Sided) 90%; -1.11 to 1.22
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.71
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ASP8062
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.603
	Comments	1-sided p-value is for comparison of ASP8062 30 mg with placebo from the above described ANCOVA model.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LSM Difference
	Estimated Value	0.17
	Confidence Interval	(2-Sided) 90%; -0.93 to 1.28
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.67
	Estimation Comments

10. Secondary Outcome

Title	Overall Participant Improvement as Assessed by Patient Global Impression of Change (PGIC)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo	ASP8062
Arm/Group Description	Participants received matching placebo orally once daily for 8 weeks.	Participants received 30 mg of ASP8062 orally once daily for 8 weeks.
Measure Participants	88	95
Very Much Improved	0 0%	4 4.2%
Much Improved	7 8%	9 9.5%
Minimally Improved	34 38.6%	28 29.5%
No Change	34 38.6%	42 44.2%
Minimally Worse	7 8%	9 9.5%
Much Worse	5 5.7%	3 3.2%
Very Much Worse	1 1.1%	0 0%
Very Much Improved	2 2.3%	6 6.3%
Much Improved	13 14.8%	13 13.7%
Minimally Improved	34 38.6%	23 24.2%
No Change	28 31.8%	39 41.1%
Minimally Worse	8 9.1%	6 6.3%
Much Worse	3 3.4%	8 8.4%
Very Much Worse	0 0%	0 0%
Very Much Improved	5 5.7%	12 12.6%
Much Improved	13 14.8%	12 12.6%
Minimally Improved	33 37.5%	17 17.9%
No Change	26 29.5%	38 40%
Minimally Worse	6 6.8%	10 10.5%
Much Worse	4 4.5%	6 6.3%
Very Much Worse	1 1.1%	0 0%
Very Much Improved	5 5.7%	12 12.6%
Much Improved	13 14.8%	12 12.6%
Minimally Improved	34 38.6%	19 20%
No Change	24 27.3%	34 35.8%
Minimally Worse	6 6.8%	11 11.6%
Much Worse	4 4.5%	7 7.4%
Very Much Worse	2 2.3%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ASP8062
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.811
	Comments	2-sided p-value is for the comparison of ASP8062 30 mg with placebo from the above described proportional odds model.
	Method	Proportional Odds model
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.07
	Confidence Interval	(2-Sided) 90%; 0.68 to 1.67
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ASP8062
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.368
	Comments	2-sided p-value is for the comparison of ASP8062 30 mg with placebo from the above described proportional odds model.
	Method	Proportional Odds model
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.79
	Confidence Interval	(2-Sided) 90%; 0.50 to 1.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, ASP8062
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.357
	Comments	2-sided p-value is for the comparison of ASP8062 30 mg with placebo from the above described proportional odds model.
	Method	Proportional Odds model
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.78
	Confidence Interval	(2-Sided) 90%; 0.50 to 1.21
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ASP8062
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.407
	Comments	2-sided p-value is for the comparison of ASP8062 30 mg with placebo from the above described proportional odds model.
	Method	Proportional Odds model
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.80
	Confidence Interval	(2-Sided) 90%; 0.52 to 1.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	From first dose of study drug up to 30 days after last dose of study drug (up to 87 days)
Arm/Group Title	Placebo		ASP8062 30 mg
Arm/Group Description	Participants received matching placebo orally once daily for 8 weeks.		Participants received 30 mg of ASP8062 orally once daily for 8 weeks.
All Cause Mortality
	Placebo		ASP8062 30 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/88 (0%)		0/95 (0%)
Serious Adverse Events
	Placebo		ASP8062 30 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/88 (0%)		0/95 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		ASP8062 30 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/88 (19.3%)		38/95 (40%)
Gastrointestinal disorders
Nausea	4/88 (4.5%)	5	6/95 (6.3%)	6
Infections and infestations
Urinary tract infection	5/88 (5.7%)	5	3/95 (3.2%)	3
Nervous system disorders
Dizziness	2/88 (2.3%)	2	28/95 (29.5%)	33
Headache	10/88 (11.4%)	11	14/95 (14.7%)	17

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Institute and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data. Sponsor must receive a site's manuscript prior to publication for review and comment as specified in the Investigator Agreement.