An Open-Label Extension Study of DS-5565 for 52 Weeks in Pain Associated With Fibromyalgia

An Open-label Extension Study of DS-5565 for 52 Weeks in Pain Associated With Fibromyalgia

This is an open-label study of DS-5565 in subjects who either completed participation in a preceding Phase 3 study of DS-5565 in fibromyalgia (FM); i.e. DS5565-A-E309 (NCT02146430), DS5565-A-E310 (NCT02187471), or DS5565-A-E311 (NCT02187159) or are de novo subjects. Eligible subjects will be assigned to receive open-label DS-5565 for 52 weeks. All subjects will receive DS-5565 15 mg once daily (QD) for the first three weeks of the treatment period. After three weeks, subjects may be titrated to 15 mg twice daily (BID) based on protocol-specified criteria.

Study Overview

• Status: Completed
• Conditions: Pain Associated With Fibromyalgia
• Intervention / Treatment: Drug: DS-5565

• Study Type: Interventional
• Enrollment (Actual): 2485
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia
    • Campsie, New South Wales, Australia
    • Coffs Harbour, New South Wales, Australia
    • St. Leonards, New South Wales, Australia
  • Queensland
    • Maroochydore, Queensland, Australia
    • Sherwood, Queensland, Australia, 4075
    • Sherwood, Queensland, Australia
    • Southport, Queensland, Australia
  • South Australia
    • Woodville, South Australia, Australia
  • Tasmania
    • Hobart, Tasmania, Australia
  • Victoria
    • Clayton, Victoria, Australia
    • Malvern East, Victoria, Australia
• Austria
  • Klagenfurt, Austria
  • Senftenberg, Austria
  • Vienna, Austria, 1090
• Bulgaria
  • Burgas, Bulgaria
  • Pleven, Bulgaria
  • Plovdiv, Bulgaria
  • Ruse, Bulgaria
  • Sevlievo, Bulgaria
  • Sofia, Bulgaria
  • Targovishte, Bulgaria
  • Varna, Bulgaria
• Canada
  • British Columbia
    • Penticton, British Columbia, Canada
    • Vancouver, British Columbia, Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada
  • Ontario
    • Burlington, Ontario, Canada
    • Kitchener, Ontario, Canada
    • London, Ontario, Canada
    • Markham, Ontario, Canada
    • Markham, Ontario, Canada, L3R 9W9
    • Mississauga, Ontario, Canada
    • Newmarket, Ontario, Canada
    • Oshawa, Ontario, Canada
    • Sarnia, Ontario, Canada
    • Sarnia, Ontario, Canada, N7T 4X3
    • Toronto, Ontario, Canada
    • Toronto, Ontario, Canada, M3J 2C5
  • Quebec
    • Pointe-claire, Quebec, Canada, H9R 3J1
    • Quebec City, Quebec, Canada
    • Sherbrooke, Quebec, Canada
• Chile
  • Region 11
    • Antofagasta, Region 11, Chile
  • Region X
    • Puerto Varas, Region X, Chile
• Czechia
  • Chocen, Czechia
  • Pilsen, Czechia
  • Prague, Czechia
  • Ricany, Czechia
  • Rychnov nad Kneznou, Czechia
• Denmark
  • Aalborg, Denmark
  • Odense, Denmark
• Estonia
  • Tallinn, Estonia
  • Tartu, Estonia
• Finland
  • Hyvinkaa, Finland
  • Kuopio, Finland
• France
  • Elancourt, France
  • Cedex
    • Saint Etienne, Cedex, France
  • Nord
    • Douai, Nord, France
• Germany
  • Berlin, Germany
  • Bohlen, Germany
  • Dresden, Germany
  • Hannover, Germany
  • Leipzig, Germany
  • Magdeburg, Germany
  • Mainz, Germany
  • Stadtroda, Germany
• Hungary
  • Balassagyarmat, Hungary
  • Budapest, Hungary
  • Debrecen, Hungary
  • Nyiregyhaza, Hungary
• Latvia
  • Baldone, Latvia
  • Balvi, Latvia
  • Jekabpils, Latvia
  • Liepaja, Latvia
  • Ogre, Latvia
  • Riga, Latvia
  • Ventspils, Latvia
• Lithuania
  • Kaunas, Lithuania
  • Klaipeda, Lithuania
  • Vilnius, Lithuania
• New Zealand
  • Auckland, New Zealand
  • Hamilton, New Zealand
  • Nelson, New Zealand
  • Tauranga, New Zealand
  • Wellington, New Zealand
• Norway
  • Alesund, Norway
  • Hamar, Norway
  • Hønefoss, Norway
  • Klofta, Norway
  • Lillehammer, Norway
  • Stavanger, Norway
• Poland
  • Elblag, Poland
  • Gdansk, Poland
  • Katowice, Poland
  • Kraków, Poland
  • Lublin, Poland
  • Nadarzyn, Poland
  • Nowa Sol, Poland
  • Torun, Poland
  • Tychy, Poland
  • Warsaw, Poland
  • Wroclaw, Poland
• Portugal
  • Aveiro, Portugal
  • Guimaraes, Portugal
  • Porto, Portugal
  • Vila Nova de Gaia, Portugal
• Puerto Rico
  • Ponce, Puerto Rico, 00716
  • San Juan, Puerto Rico, 00909
• Romania
  • Bacau, Romania
  • Bucharest, Romania
  • Targu Mures, Romania
• Russian Federation
  • Krasnoyarsk, Russian Federation
  • Moscow, Russian Federation
  • Nizhniy Novgarad, Russian Federation
  • Stavropol, Russian Federation
• Serbia
  • Belgrade, Serbia
• Slovakia
  • Banska Bystrica, Slovakia
  • Bratislava, Slovakia
  • Dubnica nad Vahom, Slovakia
  • Galanta, Slovakia
  • Krompachy, Slovakia, 05342
  • Piešťany, Slovakia
  • Presov, Slovakia
• Slovenia
  • Ljubljana, Slovenia
  • Slovenj Gradec, Slovenia
• South Africa
  • Stellenbosch, South Africa
  • Chatsworth
    • Bayview, Chatsworth, South Africa
  • Gautang
    • Johannesburg, Gautang, South Africa
    • Pretoria, Gautang, South Africa
  • Kwazulu Natal
    • Durban, Kwazulu Natal, South Africa
  • Western Cape
    • Cape Town, Western Cape, South Africa
    • Somerset West, Western Cape, South Africa
• Spain
  • Barcelona, Spain
  • Granada, Spain
  • Madrid, Spain
  • A Coruna
    • Santiago de Compostela, A Coruna, Spain
• Ukraine
  • Dnipropetrovsk, Ukraine
  • Ivano-Frankivsk, Ukraine
  • Kharkiv, Ukraine
  • Kherson, Ukraine
  • Kyiv, Ukraine
  • Lviv, Ukraine
  • Vinnytsia, Ukraine
  • Zaporizhzhia, Ukraine
• United Kingdom
  • Torpoint, United Kingdom
  • Cornwall
    • Penzance, Cornwall, United Kingdom
  • Derbyshire
    • Chesterfield, Derbyshire, United Kingdom
  • Essex
    • Romford, Essex, United Kingdom
  • Greater Manchester
    • Manchester, Greater Manchester, United Kingdom
  • Lancashire
    • Blackpool, Lancashire, United Kingdom
    • Thornton-Cleveleys, Lancashire, United Kingdom
    • Wigan, Lancashire, United Kingdom
  • Leeds
    • Stourton, Leeds, United Kingdom
  • Manchester
    • Salford, Manchester, United Kingdom
  • Merseyside
    • Southport, Merseyside, United Kingdom
  • Northamptonshire
    • Wellingborough, Northamptonshire, United Kingdom
  • Northern Ireland
    • Belfast, Northern Ireland, United Kingdom
  • Staffordshire
    • Cannock, Staffordshire, United Kingdom
  • Tyne And Wear
    • North Shields, Tyne And Wear, United Kingdom
  • Warwickshire
    • Atherstone, Warwickshire, United Kingdom, CV9 1EU
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35242
    • Mobile, Alabama, United States, 36608
  • Arizona
    • Phoenix, Arizona, United States, 85018
  • California
    • Anaheim, California, United States, 92801
    • Fresno, California, United States, 93720
    • Fresno, California, United States, 93710
    • Los Alamitos, California, United States, 90720
    • Los Angeles, California, United States, 90036
    • Newport Beach, California, United States, 92660
    • Rancho Mirage, California, United States, 92270
    • Roseville, California, United States, 95661
    • San Diego, California, United States, 92103
    • Santa Ana, California, United States, 92705
    • Santa Barbara, California, United States, 93108
    • Santa Monica, California, United States, 90404
    • Spring Valley, California, United States, 91978
    • Thousand Oaks, California, United States, 91360
    • Tustin, California, United States, 92780
    • Walnut Creek, California, United States, 94598
  • Connecticut
    • Cromwell, Connecticut, United States, 06416
  • Florida
    • Bradenton, Florida, United States, 34201
    • Brandon, Florida, United States, 33511
    • Brooksville, Florida, United States, 34601
    • Clearwater, Florida, United States, 33761
    • Clearwater, Florida, United States, 33765
    • Coral Springs, Florida, United States, 33067
    • Fort Lauderdale, Florida, United States, 33308
    • Fort Myers, Florida, United States, 33912
    • Hialeah, Florida, United States, 33013
    • Jacksonville, Florida, United States, 32256
    • Kissimmee, Florida, United States, 34744
    • Lakeland, Florida, United States, 33805
    • Leesburg, Florida, United States, 34748
    • Miami, Florida, United States, 33140
    • New Port Richey, Florida, United States, 34652
    • Ocala, Florida, United States, 34471
    • Orlando, Florida, United States, 32801
    • Ormond Beach, Florida, United States, 32174
    • Royal Palm Beach, Florida, United States, 33411
    • Saint Petersburg, Florida, United States, 33709
    • Sunrise, Florida, United States, 33351
    • Tampa, Florida, United States, 33606
  • Georgia
    • Alpharetta, Georgia, United States, 30005
    • Atlanta, Georgia, United States, 30342
    • Columbus, Georgia, United States, 31909
    • Savannah, Georgia, United States, 31405
    • Smyrna, Georgia, United States, 30080
  • Illinois
    • Bolingbrook, Illinois, United States, 60490
    • Chicago, Illinois, United States, 60634
    • Gurnee, Illinois, United States, 60031
    • Melrose Park, Illinois, United States, 60160
    • Oak Brook, Illinois, United States, 60523
  • Indiana
    • Evansville, Indiana, United States, 47714
    • Indianapolis, Indiana, United States, 46260
  • Iowa
    • West Des Moines, Iowa, United States, 50265
  • Kansas
    • Newton, Kansas, United States, 67114
    • Shawnee Mission, Kansas, United States, 66218
    • Wichita, Kansas, United States, 67207
    • Wichita, Kansas, United States, 67205
  • Kentucky
    • Lexington, Kentucky, United States, 40509
    • Paducah, Kentucky, United States, 42003
  • Louisiana
    • Lake Charles, Louisiana, United States, 70601
  • Massachusetts
    • Boston, Massachusetts, United States, 02131
    • Fall River, Massachusetts, United States, 02720
    • New Bedford, Massachusetts, United States, 02740
    • Watertown, Massachusetts, United States, 02472
  • Mississippi
    • Biloxi, Mississippi, United States, 39531
  • Missouri
    • Hazelwood, Missouri, United States, 63042
    • Kansas City, Missouri, United States, 64114
    • Saint Louis, Missouri, United States, 63141
    • Springfield, Missouri, United States, 65807
  • Montana
    • Billings, Montana, United States, 59102
  • Nebraska
    • Omaha, Nebraska, United States, 68114
  • Nevada
    • Las Vegas, Nevada, United States, 89123
  • New Jersey
    • Berlin, New Jersey, United States, 08009
    • Blackwood, New Jersey, United States, 08012
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
  • New York
    • Brooklyn, New York, United States, 11230
    • Manhasset, New York, United States, 11030
    • New York, New York, United States, 10168
    • North Massapequa, New York, United States, 11758
  • North Carolina
    • Charlotte, North Carolina, United States, 28210
    • Greensboro, North Carolina, United States, 27408
    • High Point, North Carolina, United States, 27262
    • Raleigh, North Carolina, United States, 27612
    • Winston-Salem, North Carolina, United States, 27103
  • North Dakota
    • Fargo, North Dakota, United States, 58103
  • Ohio
    • Cincinnati, Ohio, United States, 45242
    • Dayton, Ohio, United States, 45417
    • Kettering, Ohio, United States, 45429
    • Tiffin, Ohio, United States, 44863
    • Willoughby, Ohio, United States, 44094
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
    • Tulsa, Oklahoma, United States, 74104
  • Oregon
    • Eugene, Oregon, United States, 97404
    • Medford, Oregon, United States, 97504
    • Portland, Oregon, United States, 97210
    • Salem, Oregon, United States, 97301
  • Pennsylvania
    • Tipton, Pennsylvania, United States, 16684
    • Wyomissing, Pennsylvania, United States, 19610
  • South Carolina
    • Anderson, South Carolina, United States, 29621
    • Fountain Inn, South Carolina, United States, 29644
    • Greer, South Carolina, United States, 29651
  • South Dakota
    • Dakota Dunes, South Dakota, United States, 57049
    • Rapid City, South Dakota, United States, 57702
  • Tennessee
    • Knoxville, Tennessee, United States, 37919
    • New Tazewell, Tennessee, United States, 37836
    • Tullahoma, Tennessee, United States, 37388
  • Texas
    • Dallas, Texas, United States, 75230
    • Lubbock, Texas, United States, 79424
    • Plano, Texas, United States, 75093
    • San Antonio, Texas, United States, 78232
  • Utah
    • Salt Lake City, Utah, United States, 84102
  • Virginia
    • Virginia Beach, Virginia, United States, 23454
  • Washington
    • Bellevue, Washington, United States, 98007
    • Seattle, Washington, United States, 98104
    • Wenatchee, Washington, United States, 98801

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Able to give written informed consent
• Completed participation (i.e. completed the End-of-Tapering visit) in a preceding study of DS 5565 in FM (DS5565-A-E309, DS5565-A-E310, or DS5565-A-E311)
• 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
• Able to complete subject-reported questionaires per the investigator's judgement
• The subject must not have experienced any significant safety issues during the preceding study that, in the investigator's judgment, would adversely impact the subject's well-being in the long-term extension

De Novo Subjects

• 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 first dose (based on completion of at least 4 daily pain diaries during the 7-day baseline period)
• 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 during the preceding study (for rollover subjects) or within 12 months prior to screening (for de novo subjects) that in the opinion of the investigator would interfere with study participation or assessment of safety and tolerability
• Subjects who are at risk of suicide as defined by their responses to the C-SSRS or in the opinion of the investigator.
• Subjects with severe or uncontrolled depression that, in the judgment of the investigator, makes the subject inappropriate for entry into the study
• Subjects with pain due to other conditions (e.g. DPNP 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
• A diagnosis of untreated sleep apnea or initiation of treatment for sleep apnea within the past 3 months
• Known hypersensitivity to α2δ ligands or other components of the study medications
• Pregnancy or breast-feeding, or intent to become pregnant during the study period
• Abnormal investigative tests (i.e. ECGs) and laboratory values judged by the investigator to be clinically significant at the End-of-Treatment visit (Visit - Week 13) in the preceding study (for rollover subjects) or at screening (for de novo subjects), with particular focus on:

For De Novo Subjects Only

• Unable to undergo pre-study washout of prohibited concomitant medications (as listed in Section 5.2.1 of the protocol)
• Current severe or uncontrolled major depressive disorder or anxiety disorders as assessed by the Mini-international Neuropsychiatric Interview (MINI) interview (Version 6.0) at screening are excluded, but 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
• 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
• Subject is an employee of the study center, an immediate family member* of an employee of the study center, or an employee of Daiichi Sankyo, INC Research, or any of the study vendors supporting this study. *(spouse, parent, child, or sibling, whether biological or legally adopted)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DS-5565; Participants receive 15 mg DS-5565 administered once or twice daily. Each participant's dose can be titrated up or down based on the investigator's decision. Analysis will be based on the dose modality at the time of data collection.	Drug: DS-5565; DS-5565 15 mg tablet for oral administration; Other Names: Investigational product

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average Daily Pain Score (ADPS) for DS-5565	Average of daily pain scores are reported by the participant and 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.	Day 0 (baseline) up to to Week 52 postdose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Much Improved or Better (≤2) Status in Status at Week 52 As Assessed by the Patient-Rated Global Impression of Change	Patient-rated global impression of change (PGIC) on a categorical scale from 1 = very much improved to 7 = very much worse. The number of participants with "much improved or better" status are reported.	Week 52 postdose
Hospital Anxiety Depression Scale (HADS) Depression and Anxiety Scores for DS-5565	The HADS questionnaire is a 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 from 0 to 3, where higher scores indicate greater anxiety or depression. 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.	Day 0 (baseline) up to Week 52 postdose
EuroQol Five Dimensions Questionnaire (EQ-5D) Measure for DS-5565	The EQ-5D is an instrument that shows high construct validity and responsiveness in patients with chronic pain and has been used specifically in fibromyalgia. 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 0 indicating worst health and 100 representing best imaginable health.	Day 0 (baseline) up to Week 52 postdose
Short Form-36 (SF-36) Measure for DS-5565	The SF-36 is a 36-question health survey that measures functional health and well-being from the participant's point of view. It is a measure of physical and mental health used across various disease areas, including fibromyalgia. The SF-36 physical component summary and mental component summary scales range from 0 to 100 where lower scores indicate more disability (worse health) and higher scores represent less disability (better health). The physical component summary (PCS) and mental component summary (MCS) total scores at baseline and Week 52 are reported.	Day 0 (baseline) to Week 52 postdose
Pain-Associated Sleep Interference as Assessed by Average Daily Sleep Interference Score (ADSIS) for DS-5565	Pain-associated sleep interference was 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). ADSIS is the mean value of all available recordings of the respective week. For rollover participants, the baseline scores from the End-of-Tapering period in the preceding study are reported. For de novo participants, the baseline scores are derived from the 7 days prior to the start of treatment.	Day 0 (baseline) up to Week 52 postdose

Collaborators and Investigators

• Sponsor: Daiichi Sankyo, Inc.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2015
• Primary Completion (Actual): April 19, 2017
• Study Completion (Actual): April 19, 2017

Study Registration Dates

• First Submitted: September 4, 2014
• First Submitted That Met QC Criteria: September 8, 2014
• First Posted (Estimate): September 9, 2014

Study Record Updates

• Last Update Posted (Actual): July 23, 2020
• Last Update Submitted That Met QC Criteria: July 22, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: pain; fibromyalgia
• Additional Relevant MeSH Terms: Nervous System Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Muscular Diseases; Neuromuscular Diseases; Fibromyalgia; Myofascial Pain Syndromes
• Other Study ID Numbers: DS5565-A-E312; 2013-005164-26 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
• IPD Sharing Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• IPD Sharing Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)