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Safety Study of DS-5565 for Treatment of Fibromyalgia Pain in Subjects With Chronic Kidney Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02496884
Recruitment Status : Completed
First Posted : July 14, 2015
Results First Posted : October 12, 2020
Last Update Posted : November 24, 2020
Sponsor:
Collaborator:
Syneos Health
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

Tracking Information
First Submitted Date  ICMJE July 8, 2015
First Posted Date  ICMJE July 14, 2015
Results First Submitted Date  ICMJE September 16, 2020
Results First Posted Date  ICMJE October 12, 2020
Last Update Posted Date November 24, 2020
Actual Study Start Date  ICMJE June 26, 2015
Actual Primary Completion Date July 6, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 16, 2020)
  • Number of Participants Experiencing a Treatment Emergent Adverse Event (TEAE) [ Time Frame: Baseline up to 30 days after last dose, up to 25 months ]
    A TEAE is any adverse event that emerges on or after the first dosing of double blind study medication and during study treatment up to 4 weeks after the last dose of double blind study medication (having been absent prior to treatment) or worsens relative to the pre-double blind treatment state. Relationship of TEAEs to study drug is assessed by the investigator. Clinically significant changes from baseline in clinical laboratory evaluations, neurological examinations, and electrocardiograms are reported as TEAEs.
  • Patients Answering Yes to Any Question on the Columbia-Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Screening up to Week 13 postdose ]
    The C-SSRS is described as a scale developed at Columbia University that has 2-6 questions each in categories of Suicidal Ideation, Intensity of Ideation, Suicidal Behavior, and Actual Attempts. Four constructs were measured. Severity of Suicidal ideation is rated on a 5-point ordinal scale. Intensity of ideation is comprised of 5 items (frequency, duration, controllability, deterrents, and reason for ideation), each rated on a 5-point ordinal scale. Suicidal behavior is rated on a nominal scale that includes actual, aborted, and interrupted attempts; preparatory behavior; and non-suicidal self-injurious behavior. Lethality, assesses actual attempts; actual lethality is rated on a 6-point ordinal scale, and if actual lethality is 0, potential lethality of attempts is rated on a 3-point ordinal scale.The higher the C-SSRS score, the higher the suicide risk (ie. worse outcome).
Original Primary Outcome Measures  ICMJE
 (submitted: July 13, 2015)
measure the frequency of Adverse Events [ Time Frame: baseline through end of week 13 ]
To determine the safety and tolerability of subjects with FM and moderate to severe renal dysfunction during 13 weeks of renally adjusted dosing of DS-5565 compared to placebo by measuring the frequency of Treatment Emergent Adverse Events (TEAE).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 6, 2020)
  • Mean Weekly Average of Individual Daily Pain Scores (ADPS) [ Time Frame: Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 9, Week 10, Week 11, Week 12, and Week 13 postdose ]
    Each day participants will rate their worst pain over the last 24 hours on a scale from 0-10, where 0=no pain and 10=worst pain imaginable. Each week individual pain scores will be averaged, and the mean weekly score for the treatment group will be calculated. Higher ADPS scores indicate worse outcome.
  • Number of Participants With Different Scale Ranges of the Patient Global Impression of Change (PGIC) Scale at Week 13 [ Time Frame: Week 13 postdose ]
    The PGIC is a validated outcome measure for treatment of pain in the acute pain setting. At the end of treatment, participants will rate their overall status on a scale of 1-7, where 1=very much improved and 7=very much worse using the standard PGIC questionnaire. Higher scores indicate worse outcome.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 13, 2015)
  • change in Average Daily Pain Score (ADPS) for each dose DS-5565 versus placebo [ Time Frame: baseline to week 13 ]
    To compare change in weekly average pain as assessed by average daily pain score (ADPS) from baseline measured at randomization 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 the worst pain over the previous 24 hours
  • percent change in patient global impression of change (PGIC) scores [ Time Frame: up to week 13 ]
    To measure the change in patient global impression of change (PGIC) up to Week 13
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety Study of DS-5565 for Treatment of Fibromyalgia Pain in Subjects With Chronic Kidney Disease
Official Title  ICMJE A Randomized, Double-blind, Placebo-controlled Safety Study of DS-5565 for Treatment of Pain Due to Fibromyalgia in Subjects With Chronic Kidney Disease
Brief Summary DS-5565 (mirogabalin) is being studied as treatment for fibromyalgia (FM) pain. Because it is excreted through the kidneys, people who have reduced kidney function will not process the drug as well as with those with normal kidney function, so the dose must be reduced. This study will test two reduced dose levels for both moderately reduced and severely reduced kidney function. The study will test the hypothesis that the drug will be safe and well-tolerated in people who have both fibromyalgia and chronic kidney disease.
Detailed Description

The main objective of the trial is to determine the safety and tolerability of subjects with FM and moderate to severe renal dysfunction during 13 weeks of renally-adjusted dosing of DS-5565 compared to placebo, followed by a short-term (4-week) safety follow-up.

This trial is conducted in accordance with the ethical principles of Good Clinical Practice, according to the International Council for Harmonisation (ICH) Harmonised Tripartite Guidelines. An independent Data Safety Monitoring Board (DSMB) is created to further protect the rights, safety, and well-being of subjects who participate in this study by monitoring their progress and results. The independent DSMB is composed of qualified scientists who are not investigators in the study and not otherwise directly associated with the sponsor.

Additional protection is provided by special monitoring of liver enzyme elevations and liver dysfunction performed by a Hepatic Adjudication Committee (HAC), comprised of three qualified hepatologists who are not investigators in the study and not otherwise directly associated with the sponsor. The HAC completes assessments on an ongoing basis. Adjudication of hepatic events is based on evaluation of electronic case report forms (eCRFs) and source documents, as available, including but not limited to hospital discharge summaries, diagnostic imaging, histopathology, consultation, and laboratory reports.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Fibromyalgia
Intervention  ICMJE
  • Drug: DS-5565
    DS-5565 7.5 mg tablet for oral use
    Other Names:
    • Experimental drug
    • Mirogabalin
    • SUB60040
  • Drug: Placebo
    Placebo tablet for oral use to match DS-5565 7.5 mg tablet
    Other Names:
    • No drug
    • Placebo comparator
Study Arms  ICMJE
  • Experimental: M-CKD DS-5565 7.5 mg BID
    Patients with moderate chronic kidney disease (M-CKD) randomized to receive DS-5565 BID during the treatment period.
    Intervention: Drug: DS-5565
  • Experimental: S-CKD DS-5565 7.5 mg QD
    Fibromyalgia patients with severe chronic kidney disease (S-CKD) randomized to receive a DS-5565 7.5 mg tablet once per day (QD), and a placebo tablet (no drug) QD, for a total of 7.5 mg DS-5565
    Interventions:
    • Drug: DS-5565
    • Drug: Placebo
  • Placebo Comparator: M-CKD Placebo
    Patients with M-CKD randomized to receive placebo twice daily (BID) during the treatment period.
    Intervention: Drug: Placebo
  • Placebo Comparator: S-CKD Placebo
    Patients with S-CKD randomized to receive placebo once daily (QD) during the treatment period.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 12, 2017)
56
Original Estimated Enrollment  ICMJE
 (submitted: July 13, 2015)
60
Actual Study Completion Date  ICMJE July 6, 2017
Actual Primary Completion Date July 6, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Abbreviations: alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine clearance [(CrCL) determined by the central laboratory using the Cockcroft-Gault equation], upper limit of normal (ULN), Columbia-Suicide Severity Rating Scale (C-SSRS)

Inclusion Criteria:

  • Age ≥ 18 years
  • Able to give written informed consent
  • Able to complete patient-reported questionnaires per the Investigator's judgment
  • Estimated CrCl between 15-59 mL/min from serum creatinine by the central laboratory using the Cockcroft-Gault equation
  • Fibromyalgia meeting American College of Rheumatology criteria for FM:

    • Widespread pain index (WPI) ≥ 7 and symptom severity (SS) scale score ≥ 5 or WPI 3 to 6 and SS scale score ≥ 9,
    • Pain in at least 11 of 18 specific tender point sites,
    • Symptoms have been present at a similar level for at least 3 months, and
    • The subject does not have a disorder that would otherwise explain the pain
  • Average Daily Pain Score of ≥ 4 on the 11-point numeric rating scale (NRS) over the 7 days prior to randomization (based on completion of at least 4 daily pain assessments during the 7-day baseline period prior to randomization)
  • Women of child bearing potential (WOCBP) must be using adequate methods of contraception to avoid pregnancy during the study and for 4 weeks after study completion.

Exclusion Criteria:

  • Need for ongoing use of concomitant chronic pain medications or any new non-pharmacological pain management techniques that may confound assessments of efficacy and/or safety, including neurolytic treatments (destruction of nerves by chemicals, heat, cold) or surgery, intrathecal pumps, spinal cord stimulators or psychological support within the previous year. Also excluded: topical capsaicin within 6 months; or systemic corticosteroids within 3 months of baseline period.
  • Unable to undergo pre-study washout of prohibited concomitant medications
  • Subjects with recent history (i.e., within 1 year prior to screening) of alcohol abuse or illicit drug use (cocaine, heroin, marijuana [including medical, prescribed], etc.)
  • Use of any selective serotonin reuptake inhibitor (SSRI), unless the subject has been on a stable dose for ≥ 90 days prior to screening and is not anticipated to need any dose adjustment during the course of the study
  • Subjects with severe or uncontrolled depression that, in the judgment of the Investigator, makes the subject inappropriate for entry into the study
  • Significant neurological or psychiatric disorder unrelated to neuropathic pain
  • Other severe pain (eg, sciatica, rheumatoid arthritis) that might impair the assessment of neuropathic pain
  • CrCl ≥ 60 mL/min estimated from serum creatinine by the central laboratory using the Cockcroft-Gault equation.
  • Subjects who are on hemodialysis or who require hemodialysis before the follow-up assessment; acute renal failure; history of kidney transplant
  • Any history of a malignancy other than basal cell carcinoma within the past 5 years
  • Clinically significant unstable neurologic, ophthalmologic, hepatobiliary, respiratory, or hematologic illness or unstable cardiovascular disease (eg, severe hypotension, uncontrolled cardiac arrhythmia, or myocardial infarction) within 12 months prior to screening
  • Pregnancy or breast feeding or intent to become pregnant during the study period
  • Known hypersensitivity to 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.
  • Clinically significant ECG abnormalities at the Screening Visit
  • Subjects who are at risk of suicide, as defined by their responses to the C-SSRS or in the opinion of the Investigator. Note: Subjects answering "yes" to any of the questions about active suicidal ideation/intent/behaviors that occurred 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 subjects should be referred immediately to a mental health professional for appropriate evaluation.
  • Subjects who are unlikely to comply with the protocol (eg, uncooperative attitude, inability to return for subsequent visits, and/or otherwise considered by the Investigator to be unlikely to complete the study)
  • Subject is currently enrolled in, or it has been fewer than 30 days since ending, another investigational device or drug study or is receiving another investigational agent.
  • Subjects who are employees or immediate family of employees of the study site, Sponsor, or contract research organization (CRO)
  • Screening laboratory values outside the limits listed in the table below:

    • Hematology
    • Hemoglobin < 8 g/dL
    • Platelet count < 100,000/mm3
    • Absolute neutrophil count < 1,500/mm3
    • Blood chemistry
    • AST > 2.0 × ULN
    • ALT > 2.0 × ULN
    • Alkaline phosphatase > 1.5 × ULN
    • Total bilirubin > 1.2 × ULN (If a subject has total bilirubin >ULN: unconjugated and conjugated bilirubin fractions should be analyzed and only subject documented to have Gilbert's syndrome may be enrolled)
    • Creatine kinase > 3.0 × ULN
    • Calculated CrCl ≥ 60 mL/min
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Bulgaria,   Czechia,   Hungary,   Poland,   Romania,   South Africa,   Spain,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT02496884
Other Study ID Numbers  ICMJE DS5565-A-U307
2014-003972-21 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
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/
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Clinical Study Report (CSR)
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.
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.
URL: https://vivli.org/ourmember/daiichi-sankyo/
Responsible Party Daiichi Sankyo, Inc.
Study Sponsor  ICMJE Daiichi Sankyo, Inc.
Collaborators  ICMJE Syneos Health
Investigators  ICMJE
Study Director: Global Clinical Leader Daiichi Sankyo, Inc.
PRS Account Daiichi Sankyo, Inc.
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP