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Treatment of Pain Associated With Fibromyalgia

This study has been completed.
Sponsor:
Collaborator:
INC Research
Information provided by (Responsible Party):
Daiichi Sankyo Inc.
ClinicalTrials.gov Identifier:
NCT02146430
First received: May 21, 2014
Last updated: June 30, 2017
Last verified: June 2017
  Purpose
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 subject that best describes his or her worst pain over the previous 24 hours.

Condition Intervention Phase
Pain Associated With Fibromyalgia Drug: DS-5565 Drug: Pregabalin Drug: Placebo tablet and/or capsule Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Investigator
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo- and Active-Controlled Study of DS-5565 for Treatment of Pain Associated With Fibromyalgia

Resource links provided by NLM:


Further study details as provided by Daiichi Sankyo Inc.:

Primary Outcome Measures:
  • Change from baseline in weekly average daily pain score (ADPS) at Week 13 for either dose of DS-5565 versus placebo [ Time Frame: Baseline, Week 13 ]
    Weekly ADPS is based on daily pain scores reported by the patient that best describes his or her worst pain over the previous 24 hours. A daily pain score has a scale of 0 = no pain to 10 = worst possible pain.


Secondary Outcome Measures:
  • Number of participants who answered "much improved or better" in PGIC at Week 13 receiving either dose of DS-5565 versus placebo [ Time Frame: Baseline, Week 13 ]
    Participants rate global impression of change (PGIC) on a categorical scale from 1 = very much improved to 7 = very much worse

  • Change in fibromyalgia index questionnaire (FIQ) total score from baseline to Week 13 in subjects receiving either dose of DS-5565 or placebo [ Time Frame: Baseline, Week 13 ]
    The FIQ is composed of 10 items. The first item contains 11 questions related to physical functioning - each question is rated on a 4-point Likert-type scale. Items 2 and 3 ask the patient to mark the number of days that they feel well and the number of days they were unable to work (including housework) because of fibromyalgia (FM) symptoms. Items 4 through 10 are horizontal linear scales marked in 10 increments on which the patient rates work difficulty, pain, fatigue, morning tiredness, stiffness, anxiety, and depression. A higher score indicates a greater impact of the syndrome on the participant.

  • Number of 50% Responders at Week 13 among participants receiving either dose of DS-5565 or placebo [ Time Frame: Baseline, Week 13 ]
    Number of patients with at least a 50% reduction in ADPS in Week 13 compared to baseline period (50% Responders). Baseline period is the week prior to randomization.

  • Change from baseline in weekly ADPS at Week 13 for either dose of DS-5565 versus pregabalin [ Time Frame: Baseline, Week 13 ]
    Weekly ADPS is based on daily pain scores reported by the patient that best describes his or her worst pain over the previous 24 hours. A daily pain score has a scale of 0 = no pain to 10 = worst possible pain. Note that the data presented are actually Estimated mean (standard error) based on multiple imputation (MI).

  • Number of 30% Responders at Week 13 among participants receiving either dose of DS-5565 or placebo [ Time Frame: Baseline, Week 13 ]
    Number of participants with at least a 30% reduction in ADPS in Week 13 compared to baseline period (30% Responders). Baseline period is the week prior to randomization.

  • Change from Baseline in Hospital Anxiety and Depression Scale (HADS) measure, DS-5565 versus placebo [ Time Frame: Baseline, Week 13 ]
    The HADS questionnaire is a reliable, widely-used self-assessment scale to assess symptoms of anxiety and depression. The instrument consists of 7 questions related to anxiety and 7 related to depression, each rated on a 4-point scale (score of 0 to 3). Scores for anxiety and depression are independently summed to compute HADS-Anxiety and HADS-Depression subscale scores, with ranges from 0 to 21, where higher scores indicate greater severity.

  • Change from Baseline in Short Form 36 (SF-36) measure, DS-5565 versus placebo [ Time Frame: Baseline, Week 13 ]
    The SF-36 is a generic health survey that asks 36 questions to measure functional health and well-being from the patient's point of view. It is a practical, reliable, and valid measure of physical and mental health widely used across various disease areas, including FM. The SF-36 provides scores for 8 health domains (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health) as well as psychometrically-based physical component summary (PCS) and mental component summary (MCS) scores.

  • Change from Baseline in EuroQol five dimensions questionnaire (EQ-5D) measure, DS-5565 versus placebo [ Time Frame: Baseline, Week 13 ]
    The EQ-5D is a well-standardized instrument that shows high construct validity and responsiveness in patients with chronic pain and has been used specifically in FM. The EQ-5D includes a descriptive section with 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) that are combined into an overall health utilities index, and an NRS (100 mm VAS) that measures perception of overall health, with zero indicating worst health and 100 representing best imaginable health.

  • Change from Baseline in Pain-associated Sleep Interference, DS-5565 versus placebo [ Time Frame: Baseline, Week 13 ]
    Pain-associated sleep interference will be assessed using electronic daily diaries using an 11-point numeric rating scale (NRS) for pain, ranging from 0 (pain does not interfere with sleep) to 10 (pain completely interferes with sleep, unable to sleep). The diary is to be filled out every day, along with the pain diary question, from the start of the Baseline Period through the last day on blinded study drug (including the morning following the last dose of blinded study medication).

  • Change from Baseline in the Brief Pain Inventory Short Form (BPI-SF) measure, DS-5565 versus placebo [ Time Frame: Baseline, Week 13 ]
    The BPI-SF has been used in many clinical studies across a wide variety of chronic pain conditions, including FM. This instrument measures pain severity and interference within the past 24 hours. Each item is rated on an 11-point NRS from 0 to 10.

  • Percentage of days a rescue medication was used [ Time Frame: Baseline, Week 13 ]
    Number of days rescue medication used divided by total number of study days


Enrollment: 1293
Study Start Date: October 2014
Study Completion Date: July 2016
Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: DS-5565 QD
Participants take one each of placebo tablet and capsule in the morning, and one DS-5565 tablet once daily (QD) with a placebo capsule in the evening
Drug: DS-5565
DS-5565 15 mg tablet for oral administration
Other Name: mirogabalin
Drug: Placebo tablet and/or capsule
Placebo tablet (matching DS5565) and/or capsule (matching pregabalin) for oral administration
Other Name: Matching Placebo
Experimental: DS-5565 BID
Participants take one DS-5565 tablet and one placebo capsule, twice daily (BID)
Drug: DS-5565
DS-5565 15 mg tablet for oral administration
Other Name: mirogabalin
Drug: Placebo tablet and/or capsule
Placebo tablet (matching DS5565) and/or capsule (matching pregabalin) for oral administration
Other Name: Matching Placebo
Active Comparator: Pregabalin
Participants take one pregabalin capsule and one placebo tablet BID
Drug: Pregabalin
Pregabalin 150 mg capsule for oral administration
Other Name: Lyrica
Drug: Placebo tablet and/or capsule
Placebo tablet (matching DS5565) and/or capsule (matching pregabalin) for oral administration
Other Name: Matching Placebo
Placebo Comparator: Placebo
Participants take one each of placebo tablet and capsule BID
Drug: Placebo tablet and/or capsule
Placebo tablet (matching DS5565) and/or capsule (matching pregabalin) for oral administration
Other Name: Matching Placebo

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 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
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02146430

  Show 165 Study Locations
Sponsors and Collaborators
Daiichi Sankyo Inc.
INC Research
Investigators
Study Director: Global Clinical Leader, MD Daiichi Sankyo Inc.
  More Information

Responsible Party: Daiichi Sankyo Inc.
ClinicalTrials.gov Identifier: NCT02146430     History of Changes
Other Study ID Numbers: DS5565-A-E309
2013-005161-40 ( EudraCT Number )
Study First Received: May 21, 2014
Last Updated: June 30, 2017

Keywords provided by Daiichi Sankyo Inc.:
pain
fibromyalgia

Additional relevant MeSH terms:
Fibromyalgia
Myofascial Pain Syndromes
Muscular Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Neuromuscular Diseases
Nervous System Diseases
Pregabalin
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anticonvulsants
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs

ClinicalTrials.gov processed this record on July 21, 2017