Clinical trial NCT02146430: Treatment of Pain Associated With Fibromyalgia
Official title: A Randomized, Double-Blind, Placebo- and Active-Controlled Study of DS-5565 for Treatment of Pain Associated With Fibromyalgia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pain Associated With Fibromyalgia
Keywords: pain
fibromyalgia
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
Collaborators: name: Syneos Health
First posted: 2014-05-23
Enrollment: 1293
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years
* Able to give written informed consent
* Able to complete participant-reported questionnaires per the investigator's judgment
* At screening, participants must meet the 1990 American College of Rheumatology (ACR) criteria for fibromyalgia (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 questions about active suicidal ideation/intent/behaviors occurring within the past 12 months must be excluded (C-SSRS Suicide Ideation section - Questions 3, 4, or 5; C-SSRS Suicidal Behavior section, any of the suicide behaviors questions). 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
* Participants 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.
* Participants 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
* Participant 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.
* Participants 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 participants documented to have Gilbert's syndrome may be enrolled.

Primary outcomes:
measure: Change From Baseline in Weekly Average Daily Pain Score (ADPS) at Week 13 in Participants Receiving DS-5565, Pregabalin, Placebo
timeFrame: Baseline up to Week 13 postdose
Secondary outcomes:
measure: Number of Participants Who Answered "Much Improved or Better" in Patient Global Impression of Change (PGIC) at Week 13 in Participants Receiving DS-5565, Pregabalin, or Placebo
timeFrame: Baseline up Week 13 postdose
measure: Change in Fibromyalgia Index Questionnaire (FIQ) Total Score From Baseline to Week 13 in Participants Receiving DS-5565, Pregabalin, or Placebo
timeFrame: Baseline up to Week 13 postdose
measure: Number of Responders at Week 13 Among Participants Receiving DS-5565, Pregabalin, or Placebo
timeFrame: Week 13 postdose
measure: Change From Baseline to Week 13 in Multidimensional Fatigue Inventory (MFI-20) General Fatigue Score in Participants Receiving DS-5565, Pregabalin, or Placebo
timeFrame: Baseline up to Week 13 postdose
measure: Change From Baseline to Week 13 in Hospital Anxiety and Depression Scale (HADS) in Participants Receiving DS-5565, Pregabalin, or Placebo
timeFrame: Baseline up to Week 13 postdose
measure: Change From Baseline to Week 13 in Short Form 36 (SF-36) in Participants Receiving DS-5565, Pregabalin, or Placebo
timeFrame: Baseline up to Week 13 postdose
measure: Change From Baseline to Week 13 in EuroQol Five Dimensions Questionnaire (EQ-5D) in Participants Receiving DS-5565, Pregabalin, or Placebo
timeFrame: Baseline up to Week 13 postdose
measure: Change From Baseline to Week 13 in Average Daily Sleep Interference in Participants Receiving DS-5565, Pregabalin, or Placebo
timeFrame: Baseline up Week 13 postdose
measure: Number of Participants Reporting Optimal Sleep at Week 13 on the Medical Outcomes Study (MOS) Sleep Scale In Participants Receiving DS-5565, Pregabalin, or Placebo
timeFrame: Week 13 postdose
measure: Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo
timeFrame: Baseline up to Week 13 postdose
measure: Proportion of Days a Rescue Medication Was Used Among Participants Receiving DS-5565, Pregabalin, or Placebo
timeFrame: Week 1 to Week 13 postdose
Other outcomes:
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city: Choceň
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city: Prague
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city: Rychnov nad Kneznou
country: Czechia
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country: Czechia
city: Aalborg
country: Denmark
city: Odense
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country: Finland
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country: Finland
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city: Saint-Étienne
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city: Toulouse
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city: Bad Doberan
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city: Berlin
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country: Netherlands
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country: Serbia
city: Borås
country: Sweden
city: Mölndal
country: Sweden
city: Stockholm
country: Sweden
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References:
citation: Arnold LM, Whitaker S, Hsu C, Jacobs D, Merante D. Efficacy and safety of mirogabalin for the treatment of fibromyalgia: results from three 13-week randomized, double-blind, placebo- and active-controlled, parallel-group studies and a 52-week open-label extension study. Curr Med Res Opin. 2019 Oct;35(10):1825-1835. doi: 10.1080/03007995.2019.1629757. Epub 2019 Jul 9.