Duloxetine for Multiple Sclerosis Pain

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00755807
First received: September 17, 2008
Last updated: November 4, 2011
Last verified: November 2011
  Purpose

This study is designed to primarily assess the efficacy and safety of duloxetine 60-120 mg once daily (QD) compared with placebo on the reduction of pain severity in participants with central neuropathic pain due to Multiple Sclerosis.


Condition Intervention Phase
Multiple Sclerosis
Drug: Duloxetine Hydrochloride (HCI)
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Duloxetine in Patients With Central Neuropathic Pain Due to Multiple Sclerosis.

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Change From Baseline in the Weekly 24-Hour Average Pain Scores at Week 6 (Acute Phase) [ Time Frame: Baseline, 6 weeks ] [ Designated as safety issue: No ]
    24-hour average pain severity scores recorded daily on an 11-point Likert scale, evaluated as a weekly mean, with scores ranging from 0 (no pain) to 10 (worst possible pain). Participants should complete electronic diary each day upon awakening. The 11-point Likert scale was used for assessment of 24-hour average pain and evaluated as weekly means. Scores range from 0 (no pain) to 10 (worst possible pain). The Least Squares Mean (LS Mean) Value was adjusted for investigative site and baseline severity.


Secondary Outcome Measures:
  • Change From Baseline in the Weekly 24-Hour Average Pain Scores up to Week 6 (Acute Phase) [ Time Frame: Baseline, 6 weeks ] [ Designated as safety issue: No ]
    This is a nominal outcome reflecting whether or not a clinically-important efficacy outcome (≥30% or ≥50% pain reduction from baseline) was achieved at endpoint. It is based on a comparison between baseline and endpoint scores on an ordinal scale with scores from 0 (no pain) to 10 (worst possible pain). Used were the weekly mean of the scores of the average pain severity over the last 24 hours. The weekly averages were based on daily assessments recorded by participants in their diaries.

  • Patient Global Impressions of Improvement Scale (PGI-I) at 6 Weeks [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    A scale that measures the participant's perception of improvement at the time of assessment compared with the start of treatment. The score ranges from 1 (very much better) to 7 (very much worse). The Least Squares (LS) Mean Value was adjusted for investigative site and baseline severity.

  • Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 6 (Acute Phase) [ Time Frame: Baseline, 6 weeks ] [ Designated as safety issue: No ]
    Measures pain severity and interference on function. Severity scores: 0 (no pain) to 10 (severe pain) on each question assessing worst, least, and average pain in past 24 hours, and pain right now. Interference scores: 0 (does not interfere) to 10 (completely interferes) on each question assessing pain interference in past 24 hours, such as general activity, mood, normal work, relations with other people, and sleep. Average interference=average of non-missing scores of individual interference items. Least Squares (LS) Mean Value was adjusted for investigative site and baseline severity.

  • Change From Baseline in the Clinical Global Impression of Severity Scale (CGI-S) at 6 Weeks (Acute Phase) [ Time Frame: Baseline, 6 weeks ] [ Designated as safety issue: No ]
    Measures severity of illness at the time of assessment compared with start of treatment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). The Least Squares (LS) Mean Value was adjusted for investigative site and baseline severity.

  • Change From Baseline in the Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at 6 Weeks (Acute Phase) [ Time Frame: Baseline, 6 weeks ] [ Designated as safety issue: No ]
    A 54 question measure covers 12 domains; assesses mental and physical health. Each domain score is converted into a 0-100 score based on individual item responses; higher scores=better health status. The physical health composite score is a weighted average of the physical health scales, such as physical function, health perceptions, and energy. The mental health composite score is a weighted average of the mental health scales, such as overall quality of life, cognitive function, and health distress. The Least Squares (LS) Mean Value was adjusted for investigative site and baseline severity.

  • Number of Participants With Suicidal Behaviors, Ideations, and Acts Based on The Columbia Suicide Severity Rating Scale (C-SSRS) at Week 6 [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
    C-SSRS scale captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Number of participants with suicidal behaviors, ideations, and acts are provided. Suicidal behavior: a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation: a "yes" answer to any one of 5 suicidal ideation questions, which includes wish to be dead, and 4 different categories of active suicidal ideation. Suicidal act: a "yes" answer to actual attempt or completed suicide.

  • Change From Baseline in the Weekly Mean of Night Pain Scores at Week 6 (Acute Phase) [ Time Frame: Baseline, 6 weeks ] [ Designated as safety issue: No ]
    Weekly mean of the night pain severity scores recorded daily on an 11-point Likert scale, an ordinal scale ranging from 0 (no pain) to 10 (worst possible pain). Participants should complete the electronic diary each day upon awakening. The Least Squares (LS) Mean Value was adjusted for investigative site and baseline severity.

  • Change From Baseline in the Beck Depression Inventory II (BDI-II) Question #9 at Week 6 (Acute Phase) [ Time Frame: Baseline, 6 weeks ] [ Designated as safety issue: Yes ]
    The BDI-II is completed by the participant to rate the severity of depressive symptoms and any improvement during the course of the trial. The total score ranges from 0 to 63 with higher the score indicating more severe depressive symptoms. Question #9 is suicidal thoughts and wishes with a score ranging from 0 to 3.

  • Number of Participants Who Discontinued During the Acute Phase (by Week 6) [ Time Frame: Baseline through 6 weeks ] [ Designated as safety issue: Yes ]
  • Number of Participants With Treatment Emergent Adverse Events (TEAEs) During the Acute Phase [ Time Frame: Baseline through 6 weeks ] [ Designated as safety issue: Yes ]
    Summary tables of serious adverse events (SAEs) and all other non-serious adverse events are located in the Reported Adverse Event Module.

  • Number of Participants With Adverse Events (AEs) Resulting in Discontinuation From Baseline During the Acute Phase [ Time Frame: Baseline through 6 weeks ] [ Designated as safety issue: Yes ]
  • Change From Baseline in Blood Pressure at Week 6 (Acute Phase) [ Time Frame: Baseline, 6 weeks ] [ Designated as safety issue: Yes ]
  • Change From Baseline in Pulse Rate at Week 6 (Acute Phase) [ Time Frame: Baseline, 6 weeks ] [ Designated as safety issue: Yes ]
  • Change From Baseline in Weight at Week 6 (Acute Phase) [ Time Frame: Baseline, 6 weeks ] [ Designated as safety issue: Yes ]
  • Patient Global Impressions of Improvement Scale (PGI-I) Score at 18 Weeks [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]
    A scale that measures the participant's perception of improvement at the time of assessment compared with the start of treatment. The scores range from 1 (very much better) to 7 (very much worse).

  • Change From Baseline in Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 18 [ Time Frame: Baseline (end of acute phase/Week 6), Endpoint (Week 18) ] [ Designated as safety issue: No ]
    BPI-S and BPI-I are self-reported scales measuring severity of pain and interference on function. Severity scores: 0 (no pain) to 10 (severe pain) on each question assessing worst pain, least pain, and average pain in past 24 hours, and pain right now. Interference scores: 0 (does not interfere) to 10 (completely interferes) on each question assessing interference of pain in past 24 hours for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. Average interference = average of non-missing scores of individual interference items.

  • Change From Baseline in the Clinical Global Impression of Severity Scale (CGI-S) Score at Week 18 (Open-label Extension Phase) [ Time Frame: Baseline (6 weeks), Endpoint (18 weeks) ] [ Designated as safety issue: No ]
    Measures severity of illness at the time of assessment compared with start of treatment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill participants).

  • Change From Baseline in Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at Week 18 (Open-label Extension Phase) [ Time Frame: Baseline (6 weeks), Endpoint (18 weeks) ] [ Designated as safety issue: No ]
    A 54 question measure covers 12 domains; assesses mental and physical health. Each domain score is converted into a 0-100 score based on individual item responses; higher scores=better health status. The physical health composite score is a weighted average of the physical health scales, such as physical function, health perceptions, and energy. The mental health composite score is a weighted average of the mental health scales, such as overall quality of life, cognitive function, and health distress.

  • Number of Participants With Suicidal Behaviors, Ideations, and Acts Based on The Columbia Suicide Severity Rating Scale (C-SSRS) at Week 18 [ Time Frame: 18 weeks ] [ Designated as safety issue: Yes ]
    C-SSRS scale captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Number of participants with suicidal behaviors, ideations, and acts are provided. Suicidal behavior: a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation: a "yes" answer to any one of 5 suicidal ideation questions, which includes wish to be dead, and 4 different categories of active suicidal ideation. Suicidal act: a "yes" answer to actual attempt or completed suicide.

  • Change in the Weekly Mean of the Night Pain Scores From Week 6 Through Week 18 (Open-label Extension Phase) [ Time Frame: Baseline (6 weeks) through Endpoint (18 weeks) ] [ Designated as safety issue: No ]
    Weekly mean of the night pain severity scores recorded daily on an 11-point Likert scale, an ordinal scale ranging from 0 (no pain) to 10 (worst possible pain). Participants should complete the electronic diary each day upon awakening. Each weekly mean change represents change relative to week 6, the baseline of the extension phase.

  • Change From Baseline in Beck Depression Inventory II (BDI-II), Question #9 at Week 18 (Open-label Extension Phase) [ Time Frame: Baseline (6 weeks), Endpoint (18 weeks) ] [ Designated as safety issue: Yes ]
    The BDI-II is completed by the participant to rate the severity of depressive symptoms and any improvement during the course of the trial. The total score ranges from 0 to 63 with higher the score indicating more severe depressive symptoms. Question #9 is suicidal thoughts and wishes with the score ranging from 0 to 3.

  • Number of Participants Who Discontinued During the Open-label Extension Phase (by Week 18) [ Time Frame: Baseline (6 weeks) through Endpoint (18 weeks) ] [ Designated as safety issue: Yes ]
  • Number of Participants With Treatment Emergent Adverse Events (TEAEs) During the Open-label Extension Phase [ Time Frame: Baseline (6 weeks) through Endpoint (18 weeks) ] [ Designated as safety issue: Yes ]
    Summary tables of serious adverse events (SAEs) and all other non-serious adverse events are located in the Reported Adverse Event Module.

  • Number of Participants With Adverse Events (AEs) Resulting in Discontinuation During the Open-label Extension Phase [ Time Frame: Baseline (6 weeks) through Endpoint (18 weeks) ] [ Designated as safety issue: Yes ]
  • Change From Baseline in Blood Pressure at Week 18 (Open-label Extension Phase) [ Time Frame: Baseline (6 weeks), Endpoint (18 weeks) ] [ Designated as safety issue: Yes ]
  • Change From Baseline in Pulse Rate at Week 18 (Open-label Extension Phase) [ Time Frame: Baseline (6 weeks), endpoint (18 weeks) ] [ Designated as safety issue: Yes ]
  • Change From Baseline in Weight at Week 18 (Open-label Extension Phase) [ Time Frame: Baseline (6 weeks), Endpoint (18 weeks) ] [ Designated as safety issue: Yes ]

Enrollment: 239
Study Start Date: October 2008
Study Completion Date: November 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Drug: Placebo
Participants received placebo oral (po), once daily (QD) for 6 weeks (acute phase). If the participant completes the 6-week double-blind portion of the trial, the participant will be offered the option to participate in the open-label extension period (given 60, 90, or 120 milligrams [mg] QD for 12 weeks).
Experimental: Duloxetine Drug: Duloxetine Hydrochloride (HCI)
Participants received 30 mg duloxetine (po, QD) for 1 week followed by 5 weeks at 60 mg in the acute placebo-controlled period. If the participant completes the double-blind portion of the trial, the participant will be offered the option to participate in the open-label extension period (given 60, 90, or 120 mg QD for 12 weeks).
Other Names:
  • LY248686
  • Cymbalta

Detailed Description:

Study is a multicenter, randomized, double-blind, parallel, placebo-controlled, 20-week trial with 4 study periods. Participants who screen successfully (Study Period I) will be randomized in a 1:1 fashion to duloxetine 60 mg QD or placebo. Starting with Study Period II, participants will be treated in a double-blind manner for 6 weeks. Participants who complete the 6-week, double-blind period will have the opportunity to participate in a 12-week, open-label, flexible-dose portion of the study (Study Period III). Study Period IV is a taper phase designed to reduce the occurrence of discontinuation adverse events. Participants may enter Study Period IV at any time after Visit 3.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Have central neuropathic pain due to multiple sclerosis (MS) based on the disease diagnostic criteria
  • Adult males or females
  • Have a score of 4 or greater on the daily 24-hour average pain score
  • Females must test negative for pregnancy at study entry
  • Complete the daily diaries for at least 70% of the days of the study
  • Participants may continue other prescription and nonprescription analgesic pain medications as long as the dose has been stable for 1 month prior to study entry, and they agree to maintain that stable dose throughout the study Disease Diagnostic Criteria:

    • Diagnosis of MS at least 1 year prior to study entry
    • No MS flares or change in disease treatment for the 3 months prior to study entry
    • Daily pain due to MS for a minimum of 3 months prior to study entry

Exclusion Criteria:

  • Are currently in a clinical trial of MS disease-modifying therapy
  • Have pain that cannot be clearly differentiated from causes other than MS
  • Any current or historical diagnosis of mania, bipolar disorder, psychosis, or schizoaffective disorder
  • History of substance abuse or dependence
  • Are pregnant or breast-feeding
  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: NCT00755807

  Show 22 Study Locations
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 Hours, EST) Eli Lilly and Company
  More Information

Additional Information:
No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00755807     History of Changes
Other Study ID Numbers: 11666, F1J-US-HMFR
Study First Received: September 17, 2008
Results First Received: June 13, 2011
Last Updated: November 4, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Eli Lilly and Company:
Central Neuropathic Pain
Multiple Sclerosis

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Neuralgia
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pain
Neurologic Manifestations
Peripheral Nervous System Diseases
Neuromuscular Diseases
Signs and Symptoms
Pathologic Processes
Duloxetine
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Antidepressive Agents
Psychotropic Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin Agents

ClinicalTrials.gov processed this record on August 27, 2014