Treatment of Pain Associated With Fibromyalgia

Daiichi Sankyo1,301 enrolled

Overview

The main objective of this trial is to compare change in weekly average daily pain score (ADPS) from baseline to Week 13 in participants receiving either dose of DS-5565 versus placebo. Weekly ADPS is based on daily pain scores reported by the subject that best describes his or her worst pain over the previous 24 hours.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

1,301

Conditions

Pain Associated With Fibromyalgia

Interventions

DS-5565DRUG

DS-5565 15 mg QD or BID; tablet for oral use

PregabalinDRUG

Pregabalin capsule for oral use; 75 mg capsule for one week, then 150 mg capsule

Placebo tabletDRUG

Placebo tablet for oral use, matching DS-5565 tablet

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age ≥ 18 years * Able to give written informed consent * Able to complete subject-reported questionnaires per the investigator's judgment * At screening, subjects must meet the 1990 American College of Rheumatology (ACR) criteria for FM, i.e. widespread pain present for at least 3 months and pain in at least 11 of 18 specific tender point sites. In addition, the 2010 ACR criteria must be met: * Widespread pain index (WPI) ≥ 7 and symptom severity (SS) scale score ≥ 5, or WPI 3 to 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 * ADPS of ≥ 4 on the 11-point numeric rating scale (NRS) over the past 7 days prior to randomization (based on completion of at least 4 daily pain diaries during the 7-day baseline period prior to randomization) * Subject must have documented evidence of a fundoscopic examination (with pupil dilation) within 12 months prior to screening or at screening. * Women of child-bearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy during the study and for 4 weeks after study completion. Exclusion Criteria: * Clinically significant unstable neurologic, psychiatric, ophthalmologic, hepatobiliary, respiratory, or hematologic illness or unstable cardiovascular disease (e.g. severe hypotension, uncontrolled cardiac arrhythmia, or myocardial infarction) or any other concurrent disease within 12 months prior to screening that in the opinion of the investigator would interfere with study participation or assessment of safety and tolerability * Anticipation of initiation or significant change to normal daily exercise routines or need for ongoing use of concomitant medications or non-pharmacological pain management techniques that may confound assessments of efficacy and/or safety * Unable to undergo pre-study washout of prohibited concomitant medications * Subjects who are at risk of suicide as defined by their responses to the Columbia-Suicide Severity Rating Scale (C-SSRS) or in the opinion of the investigator. Note: Patients answering "yes" to any of the C-SSRS questions at screening must be excluded. Such patients should be referred immediately to a mental health professional for appropriate evaluation. * Current severe or uncontrolled major depressive disorder or anxiety disorders as assessed by the Mini-international Neuropsychiatric Interview (MINI) mild to moderate major depression or anxiety disorders are permitted provided that the investigator assesses the patient as clinically stable and appropriate for entry into the study. * Any diagnosis of lifetime bipolar disorder or psychotic disorder * Subjects with pain due to other conditions (e.g. diabetic peripheral neuropathic pain or post-herpetic neuralgia) that in the opinion of the investigator, would confound assessment or self-evaluation of the pain associated with FM. * Subjects with pain due to any widespread inflammatory musculoskeletal disorder (e.g. rheumatoid arthritis, lupus) or widespread rheumatic disease other than FM. * Abuse or dependence of prescription medications, street drugs, or alcohol within the last 1 year * Any history of a malignancy other than basal cell carcinoma within the past 5 years * A diagnosis of untreated sleep apnea or initiation of treatment for sleep apnea within the past 3 months * Pregnancy or breast-feeding, or intent to become pregnant during the study period * Subject is currently enrolled in or has not yet completed at least 30 days since ending another investigational device or drug study or is receiving other investigational agents. * Known hypersensitivity to alpha2-delta (α2δ) ligands or other components of the study medications. Note: Prior exposure to DS-5565 is allowed, as long as hypersensitivity to DS-5565 was not observed. * Subjects who are unlikely to comply with the protocol (e.g. uncooperative attitude, inability to return for subsequent visits) and/or otherwise considered by the investigator to be unlikely to complete the study. * Abnormal investigative tests (i.e. electrocardiograms \[ECGs\]) and laboratory values judged by the investigator to be clinically significant at screening, with particular focus on: a. Abnormal renal function defined as calculated creatinine clearance (CrCl) \< 60 mL/min determined by the central laboratory using the modified Cockcroft-Gault equation; blood urea nitrogen\> 1.5 × upper limit of normal (ULN); creatine kinase \> 3.0 × ULN; serum creatinine \> 1.6 mg/dL (\> 141.4 μmol/L); b. Abnormal liver function defined as aspartate aminotransferase (AST) \> 2.0 × ULN, alanine aminotransferase (ALT) \> 2.0 × ULN; alkaline phosphatase \> 1.5 × ULN; total bilirubin\> 1.2 × ULN. If a subject has total bilirubin \> 1.2 ULN, unconjugated and conjugated bilirubin fractions should be analyzed and only subjects documented to have Gilbert's syndrome may be enrolled.

Locations (154)

Outcomes

Primary Outcomes

Change From Baseline to Week 13 in Average Daily Pain Score (ADPS) Among Participants Receiving DS-5565, Pregabalin, or Placebo

Average daily pain scores (ADPS) reported by the participant that best describes his or her worst pain over the previous 24 hours. A daily pain score has a scale where 0 = no pain to 10 = worst possible pain. Higher scores indicate a worse outcome. For participants with no Week 13 data, the baseline observation was carried forward (BOCF). The mean (multiple imputation estimate) and standard error (multiple imputation) are reported.

Time frame: Baseline up to Week 13 postdose

Secondary Outcomes

Number of Participants Who Answered "Much Improved or Better" in Patient Global Impression of Change at Week 13 Receiving DS-5565, Pregabalin, or Placebo

Patient global impression of change (PGIC) on a 7-point categorical scale, where 1 = very much improved and 7 = very much worse. Higher scores indicate worse outcomes. The number of participants with 'much improved or better' status (≤2) is being reported.

Time frame: Baseline up to Week 13 postdose

Change From Baseline to Week 13 in Average Score on the Fibromyalgia Index Questionnaire (FIQ) in Participants Receiving DS-5565, Pregabalin, or Placebo

The total FIQ score is composed of 10 items, with a maximum possible score of 100. The first item contains 11 questions related to physical functioning and are rated on a 4-point Likert-type scale, where 0 indicates 'always' and 3 indicates 'never'. The overall impact items are rated on a 0-7 scale for the number of days that the patient felt well and the number of days they were unable to work (including housework) because of fibromyalgia symptoms. The symptoms items are rated on visual analog scales (0-10 cm), with higher numbers indicated greater symptomatology. Final scores range from 0 (no impairment) to 10 (maximum impairment), where higher scores indicate worse outcome. For this outcome, the change in total FIQ score from baseline is being reported. Negative values indicate improvement from baseline in impairment.

Time frame: Baseline up to Week 13 postdose

Data from ClinicalTrials.gov

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