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

NCT02496884 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: DS5565-A-U3072014-003972-21
• Study Type: interventional
• Target: 56
• Locations: 8 countries
• Sites: 39

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.

Conditions

Fibromyalgia

Keywords

chronic kidney disease; . α2δ ligands; mirogabalin; pain relief; kidney metabolism

Outcome Measures

Primary Outcomes (2)

• Number of Participants Experiencing a Treatment Emergent Adverse Event (TEAE)

  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.

  Baseline up to 30 days after last dose, up to 25 months

• Patients Answering Yes to Any Question on the Columbia-Suicide Severity Rating Scale (C-SSRS)

  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).

  Screening up to Week 13 postdose

Secondary Outcomes (2)

• Mean Weekly Average of Individual Daily Pain Scores (ADPS)

  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

• Number of Participants With Different Scale Ranges of the Patient Global Impression of Change (PGIC) Scale at Week 13

  Week 13 postdose

Study Arms (4)

M-CKD DS-5565 7.5 mg BID

EXPERIMENTAL

Patients with moderate chronic kidney disease (M-CKD) randomized to receive DS-5565 BID during the treatment period.

Drug: DS-5565

S-CKD DS-5565 7.5 mg QD

EXPERIMENTAL

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

Drug: DS-5565; Drug: Placebo

M-CKD Placebo

PLACEBO COMPARATOR

Patients with M-CKD randomized to receive placebo twice daily (BID) during the treatment period.

Drug: Placebo

S-CKD Placebo

PLACEBO COMPARATOR

Patients with S-CKD randomized to receive placebo once daily (QD) during the treatment period.

Drug: Placebo

Interventions

DS-5565 DRUG

DS-5565 7.5 mg tablet for oral use

Also known as: Experimental drug, Mirogabalin, SUB60040

M-CKD DS-5565 7.5 mg BID; S-CKD DS-5565 7.5 mg QD

Placebo DRUG

Placebo tablet for oral use to match DS-5565 7.5 mg tablet

Also known as: No drug, Placebo comparator

M-CKD Placebo; S-CKD DS-5565 7.5 mg QD; S-CKD Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Daiichi Sankyo: lead
• Syneos Health: collaborator

Study Sites (39)

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Phoenix, Arizona, 85018, United States

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Colton, California, 92324, United States

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Los Angeles, California, 90033, United States

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Santa Ana, California, 92705, United States

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Colorado Springs, Colorado, 80918, United States

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Brooksville, Florida, 34601, United States

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DeBary, Florida, 32713, United States

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Hialeah, Florida, 33013, United States

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Kissimmee, Florida, 34744, United States

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Miami, Florida, 33144, United States

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Grand Blanc, Michigan, 48439, United States

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High Point, North Carolina, 27262, United States

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Cincinnati, Ohio, 45224, United States

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Wyomissing, Pennsylvania, 19610, United States

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Greer, South Carolina, 29651, United States

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Rapid City, South Dakota, 57702, United States

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Knoxville, Tennessee, 37919, United States

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Houston, Texas, 77098, United States

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Plano, Texas, 75093, United States

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Bellevue, Washington, 98007, United States

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Charleston, West Virginia, 25304, United States

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Morgantown, West Virginia, 26505, United States

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Plovdiv, Bulgaria

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Sevlievo, Bulgaria

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Sofia, Bulgaria

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Stara Zagora, Bulgaria

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Varna, Bulgaria

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Prague, Czechia

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Říčany, Czechia

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Budapest, Hungary

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Nyíregyháza, Hungary

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Elblag, Poland

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Krakow, Poland

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Cluj-Napoca, Romania

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Johannesburg, South Africa

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Pretoria, South Africa

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Barcelona, Spain

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Santiago de Compostela, Spain

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Valencia, Spain

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MeSH Terms

Conditions

Fibromyalgia; Renal Insufficiency, Chronic

Interventions

mirogabalin; Drugs, Investigational

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Neuromuscular Diseases; Nervous System Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations

Results Point of Contact

• Title: Contact for Clinical Trial Information
• Organization: Daiichi Sankyo

CTRinfo@dsi.com

908-992-6400

Study Officials

• Global Clinical Leader

  Daiichi Sankyo

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2015
• First Posted: July 14, 2015
• Study Start: June 26, 2015
• Primary Completion: July 6, 2017
• Study Completion: July 6, 2017
• Last Updated: November 24, 2020
• Results First Posted: October 12, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, 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.

Locations

PL (2); RO (1); US (22); CZ (2); ES (3); ZA (2); HU (2); BU (5)