Clinical trial NCT02496884: Safety Study of DS-5565 for Treatment of Fibromyalgia Pain in Subjects With Chronic Kidney Disease
Official title: A Randomized, Double-blind, Placebo-controlled Safety Study of DS-5565 for Treatment of Pain Due to Fibromyalgia in Subjects With Chronic Kidney Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Fibromyalgia
Keywords: chronic kidney disease
. α2δ ligands
mirogabalin
pain relief
kidney metabolism
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
Collaborators: name: Syneos Health
First posted: 2015-07-14
Enrollment: 56
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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants Experiencing a Treatment Emergent Adverse Event (TEAE)
timeFrame: Baseline up to 30 days after last dose, up to 25 months
measure: Patients Answering Yes to Any Question on the Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: Screening up to Week 13 postdose
Secondary outcomes:
measure: Mean Weekly Average of Individual Daily Pain Scores (ADPS)
timeFrame: 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
measure: Number of Participants With Different Scale Ranges of the Patient Global Impression of Change (PGIC) Scale at Week 13
timeFrame: Week 13 postdose
Other outcomes:
Locations:
city: Phoenix
country: United States
state: Arizona
city: Colton
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Santa Ana
country: United States
state: California
city: Colorado Springs
country: United States
state: Colorado
city: Brooksville
country: United States
state: Florida
city: DeBary
country: United States
state: Florida
city: Hialeah
country: United States
state: Florida
city: Kissimmee
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Grand Blanc
country: United States
state: Michigan
city: High Point
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Wyomissing
country: United States
state: Pennsylvania
city: Greer
country: United States
state: South Carolina
city: Rapid City
country: United States
state: South Dakota
city: Knoxville
country: United States
state: Tennessee
city: Houston
country: United States
state: Texas
city: Plano
country: United States
state: Texas
city: Bellevue
country: United States
state: Washington
city: Charleston
country: United States
state: West Virginia
city: Morgantown
country: United States
state: West Virginia
city: Plovdiv
country: Bulgaria
city: Sevlievo
country: Bulgaria
city: Sofia
country: Bulgaria
city: Stara Zagora
country: Bulgaria
city: Varna
country: Bulgaria
city: Prague
country: Czechia
city: Ricany
country: Czechia
city: Budapest
country: Hungary
city: Nyiregyhaza
country: Hungary
city: Elblag
country: Poland
city: Kraków
country: Poland
city: Cluj-napoca
country: Romania
city: Johannesburg
country: South Africa
city: Pretoria
country: South Africa
city: Barcelona
country: Spain
city: Santiago de Compostela
country: Spain
city: Valencia
country: Spain
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References: