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Safety and Efficacy of AVP-923 in the Treatment of Central Neuropathic Pain in Multiple Sclerosis (PRIME)

Primary Purpose

Central Neuropathic Pain, Multiple Sclerosis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
AVP-923-45
AVP-923-30
AVP-923-20
Placebo
Sponsored by
Avanir Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Central Neuropathic Pain

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Main Inclusion Criteria:

Multiple Sclerosis (relapsing-remitting multiple sclerosis [RRMS] or secondary progressive multiple sclerosis [SPMS]), Clinical history and symptoms of central neuropathic pain (dysesthetic pain) for at least 3 months prior to screening, pain rating scale (PRS) baseline score = or > 4, No MS relapse within previous 30 days.

Main Exclusion Criteria:

Personal history of complete heart block, QT interval corrected for heart rate (QTc) prolongation, or torsades de pointes, family history of congenital QT interval prolongation syndrome, Myasthenia Gravis, Beck Depression Inventory Second Edition (BDI-II) score > 19

Sites / Locations

  • North Central Neurology Associates PC
  • St. Joseph's Hospital Medical Center
  • Alta Bates Summit Medical Center
  • University of California, Irvine
  • Coordinated Clinical Research
  • University of California, San Francisco
  • University of Colorado
  • Neurology Associates, PA
  • Collier Neurologic Specialists
  • Laszlo J. Mate, MD
  • Neurology Associates of Ormond Beach
  • Neurological Associates
  • Neurologique Foundation
  • Suncoast Neuroscience Associates, Inc.
  • University of South Florida
  • Geodyssey Research, LLC
  • Shepard Center
  • Rush-Presbyterian St. Luke's Medical Center
  • Consultants in Neurology
  • Josephson Wallack Munshower Neurology, P.C.
  • MidAmerica Neuroscience Institute
  • Johns Hopkins University School of Medicine
  • Beth Israel Deaconess Medical Center
  • Michigan Neurology Associates, P.C.
  • Wayne State University
  • Henry Ford Health System
  • Advanced Neurology Specialists
  • Neurology Associates PC
  • Albany Medical Center Hospital
  • NYU-Hospital for Joint Diseases
  • University of Rochester
  • SUNY at Stony Brook
  • Carolinas Medical Center
  • Cleveland Clinic Foundation
  • Oklahoma Medical Research Foundation
  • Drexel University College of Medicine
  • Geisinger Health System
  • Advanced Neurosciences Institute
  • Baylor College of Medicine
  • Rocky Mountain MS Clinic
  • Neurological Associates
  • MS Center of Greater Washington
  • Swedish Medical Center
  • MultiCare Health System
  • Instituto de Neurologia Cognitiva
  • Hospital Britanico de Buenos Aires
  • Hospital Italiano
  • Instituto Argentino de Investigacion Neurologica
  • Hospital Churruca-Visca
  • Fundación Argentina Contra las Enfermedades Neurológicas del Envejecimiento - FACENE
  • Medeos - Centro de Medicina Integral e Investigación Clínica
  • Instituto de Neurología y Neurorrehabilitación del Litoral
  • Fakultni nemocnice u sv. Anny v Brne
  • Fakultni nemocnice Hradec Kralove
  • Nemocnice Jihlava, prispevkova organizace
  • Fakultni Nemocnice Ostrava
  • Vseobecna fakultni nemocnice v Praze
  • Szpital Powiatowy w Czeladzi
  • Pomorskie Centrum Traumatologii im. M. Kopernika w Gdansku
  • Diagnomed Clinical Research Sp. z.o.o.
  • Niepubliczny Zaklad Opieki Zdrowotnej NEURO-MEDIC
  • Niepubliczny Zaklad Opieki Zdrowotnej PROFILAKTYKA
  • Zespol Opieki Zdrowotnej w Konskich
  • Specjalistyczny Gabinet Neurologiczny
  • Niepubliczny Zaklad Opieki Zdrowotnej NEURO-KARD Ilkowski i Partnerzy Spolka Partnerska Lekarzy
  • Osrodek Badan Klinicznych Indywidualnej Specjalistycznej Praktyki Lekarskiej
  • Hospital del Mar
  • Hospital Vall D´Hebron
  • Hospital Universitari de Girona Dr. Josep Trueta
  • Hospital Universitario Virgen de la Arrixaca
  • Hospital Univ. Nuestra Sra. De La Candelaria
  • Hospital Universitario Vírgen Macarena

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Placebo Comparator

Experimental

Experimental

Experimental

Arm Label

Placebo

AVP-923-45

AVP-923-30

AVP-923-20

Arm Description

Outcomes

Primary Outcome Measures

Association Between the Dextromethorphan Plasma Concentration and the Change From Baseline Pain Rating Scale (PRS) Score to the Average Pain Rating Scale Score During Days 57 Through 84
PRS required participants to rate their pain over the past 12 hours (hrs) on a scale of 0 to 10 (0=no pain; 10=worst possible pain). Baseline (B) PRS was defined as the average of the PRS scores in the last 7 days collected prior to the B visit. If participants did not have at least 4 PRS scores during the last 7 days prior to the B visit, then the average of up to 7 of the most recent PRS scores available prior to the B visit was used. Post-B PRS was the average of Days 57 through 84 values. For participants who did not have any PRS scores during Days 57 through 84, the average of the last 7 available post-B PRS scores was used. Change from B was calculated as the post-B score minus B score. The average logarithms of dextromethorphan plasma concentrations (Cmax) on Days 22 and 50 are reported in primary outcome measure #2 below. Pearson correlation was calculated between Cmax as one group of data across the reporting groups and Change from Baseline in PRS score.
Average Logarithms of Dextromethorphan (DM) Plasma Concentrations (Cmax) on Days 22 and 50
The average of the logarithms of the DM plasma concentrations on Days 22 and 50 were presented.

Secondary Outcome Measures

Comparison of the Adjusted Mean Change From Baseline PRS Score to the Average PRS Score During Days 57 Through 84
The PRS required participants to rate their pain over the past 12 hours on a scale of 0 to 10 (0=no pain; 10=worst possible pain) by circling the number that best described their pain on average over the past 12 hours. Baseline PRS was defined as the average of the PRS scores in the last 7 days collected prior to the Baseline visit. If participants did not have at least 4 PRS scores during the last 7 days prior to the Baseline visit, then the average of up to 7 of the most recent PRS scores available prior to the Baseline visit was used. Post-Baseline PRS was the average of the Day 57 through 84 values. For participants who did not have any PRS scores during Days 57 through 84, the average of the last 7 available post-Baseline PRS scores was used. Change from Baseline was calculated as the post-Baseline score minus the Baseline score.
Mean Change From Baseline in Fatigue Severity Scale (FSS) Scores at Days 57 Through 84
The FSS questionnaire consisted of 9 statements that attempted to explore the severity of fatigue symptoms in participants with MS and other conditions, including chronic fatigue immune dysfunction syndrome and systemic lupus erythematosus, and was designed to differentiate fatigue from clinical depression because both share some of the same symptoms. Participants were asked to respond to each statement on a scale of 1 to 7, with 1 indicating "Strongly Disagree" and 7 indicating "Strongly Agree." Total score ranging from 9 to 63, was computed as the sum of the sub-scores for all 9 statements; a higher score indicated increasing fatigue. Baseline was defined as last non-missing measurement prior to dosing. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Post-Baseline FSS score was the average of Day 57 through 84 values. The analysis was carried out using an ANCOVA model, with the FSS change from Baseline to Days 85 as the dependent variable,
Mean Change From Baseline in Expanded Disability Status Scale (EDSS) Scores at Days 22 and 85
The EDSS, a method of quantifying disability in participants with MS was based on neurological examination of 8 functional systems (FS) (pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, cerebral, and other) that allowed neurologists to assign a FS score to each of these systems. Neurological findings in each FS were scored on a scale of 0 (low level of problems) to 5 (high level of problems). The "other" category was not rated numerically but measured disability related to a particular issue, like motor loss. A total averaged EDSS score was then calculated on a scale of 0 (normal) to 10 (death from MS). The total EDSS score was determined by 2 factors: gait and FS scores. A higher score indicated greater disability. Baseline was defined as last non-missing measurement prior to dosing. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Mean Change From Baseline in Multiple Sclerosis Impact Scale-29 (MSIS-29) Scores at Day 85
MSIS-29, an instrument measuring the physical (20 items) and psychological (9 items) impact of MS from the participants' perspective was used to evaluate therapeutic effectiveness from the participants' perspective. Participants were asked to circle the response that best described the impact of MS on daily life on a scale of 0 (not at all) to 5 (extremely). The total MSIS-29 score ranged from 0 to 145, was calculated as the sum of the sub-scores for all 29 questions, with lower scores indicating better quality of life. Baseline was defined as last non-missing measurement prior to dosing. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The analysis was carried out using an ANCOVA model, with the MSIS-29 score change from Baseline to Day 85 as the dependent variable, treatment group as a fixed effect, and the Baseline MSIS-29 as a covariate.
Mean Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) Scores at Day 85
PSQI, a self-rated questionnaire was used to assess sleep quality and disturbances over a 1-month time interval. A total of 19 individual items generated 7 component scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. Each component was scored from 0 (no difficulty) to 3 (severe difficulty). The sum of the scores for the 7 components yielded 1 global score (ranging from 0 to 21). Higher PSQI score indicated worse quality of sleep. Baseline was defined as last non-missing measurement prior to dosing. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The analysis was carried out using an ANCOVA model, with the PSQI change from Baseline to Day 85 as the dependent variable, treatment group as a fixed effect, and the Baseline PQIS as a covariate.
Mean Change From Baseline in MS Neuropsychological Screening Questionnaire (MSNQ) Scores at Day 85
MSNQ, a self-reporting, 15-item questionnaire was used to screen for cognitive impairment in participants with MS. Participants (or their informants) scored each item on a scale from 0 (not at all) to 4 (often and greatly interferes with life). The total MSNQ score was calculated as the sum of the sub-scores for all 15 questions and thus ranged from 0 to 60. A higher score indicated greater impairment. Baseline was defined as last non-missing measurement prior to dosing. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The analysis was carried out using an ANCOVA model, with the MSNQ score change from Baseline to Day 85 as the dependent variable, treatment group as a fixed effect, and the Baseline MSNQ as a covariate.
Mean Change From Baseline in Beck Depression Inventory (BDI-II) Scores at Day 85
BDI-II, a 21-item, self-reported instrument was used to assess the existence and severity of symptoms of depression. Each item corresponded to a symptom of depression and as scored on a 4-point scale, ranging from 0 to 3. Participants were asked to consider each statement as it related to the way they have felt for the past 2 weeks. Each of the 21 items were summed to give a single score for the BDI-II (ranging from 0 to 63). A total score of 0 to 13 indicated minimal depression, a score of 14 to 19 indicated mild depression, a score of 20 to 28 indicated moderate depression, and a score of 29 to 63 indicated severe depression. Baseline was defined as last non-missing measurement prior to dosing. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The analysis was carried out using an ANCOVA model, with the BDI-II change from Baseline to Day 85 as the dependent variable, treatment group as a fixed effect, and the Baseline BDI-II as a covariate.
Mean Change From Baseline in Symbol Digit Modalities Test (SDMT) Scores at Day 85
The SDMT assessed organic cerebral dysfunction in both children (8 years and older) and adults. The SDMT involved a simple substitution task that normal participants could easily perform. Using a reference key, the examinee had 90 seconds to pair specific numbers with given geometric figures. The SDMT score was the total correct response (not counting errors) in 90 seconds and ranged from 0 to 110. Lower scores indicated increased dysfunction. Baseline was defined as last non-missing measurement prior to dosing. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The analysis was carried out using an ANCOVA model, with the SDMT change from Baseline to Day 85 as the dependent variable, treatment group as a fixed effect, and the Baseline SDMT as a covariate.
Mean Numerical Rating Scale (NRS) Scores at Days 22, 50, and 85
The NRS was an 11-point scale for participant self-reporting of pain. The overall scores ranged from 0 (no spasticity) to 10 (worst possible spasticity). Higher scores indicated increased aggression.
Mean Overall Patient Global Impression of Change (PGIC) Scores at Day 85
The PGIC was a standard, validated 7-point categorical scale. The participant was asked to assess the overall change in his or her central neuropathic pain symptoms since entry into the study on a scale of 0 to 7 (0=much better; 7=much worse). Higher scores indicated worsening.

Full Information

First Posted
March 23, 2011
Last Updated
October 22, 2021
Sponsor
Avanir Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT01324232
Brief Title
Safety and Efficacy of AVP-923 in the Treatment of Central Neuropathic Pain in Multiple Sclerosis
Acronym
PRIME
Official Title
A Phase 2, Double-blind, Randomized, Placebo-controlled, Four-arm, Multicenter, Dose-finding Study to Assess the Safety and Efficacy of Three Dose Levels of AVP-923 (Dextromethorphan/Quinidine) in the Treatment of Central Neuropathic Pain in Patients With Multiple Sclerosis
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
September 8, 2011 (Actual)
Primary Completion Date
September 26, 2013 (Actual)
Study Completion Date
September 26, 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Avanir Pharmaceuticals

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The objectives of the study are to evaluate the safety, tolerability, and efficacy of 3 doses of AVP-923 capsules in the treatment of central neuropathic pain in participants with multiple sclerosis.
Detailed Description
The objectives of the study are to evaluate the safety, tolerability, and efficacy of 3 doses of AVP-923 (dextromethorphan [DM]/quinidine [Q]) capsules containing either 45 mg DM and 10 mg Q (AVP-923-45) or 30 mg DM and 10 mg Q (AVP-923-30) or 20 mg DM and 10 mg Q (AVP-923-20) compared to placebo, for the treatment of central neuropathic pain in a population of participants with multiple sclerosis (MS) over a 12-week period. The MS participant population enrolled includes participants with relapsing-remitting multiple sclerosis (RRMS) and participants with secondary progressive multiple sclerosis (SPMS).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Central Neuropathic Pain, Multiple Sclerosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
209 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Title
AVP-923-45
Arm Type
Experimental
Arm Title
AVP-923-30
Arm Type
Experimental
Arm Title
AVP-923-20
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
AVP-923-45
Intervention Description
AVP-923-45 (dextromethorphan 45 mg/quinidine 10 mg) capsules administered once daily for first 7 days followed by twice daily for 11 weeks of the study to complete 12 weeks of treatment.
Intervention Type
Drug
Intervention Name(s)
AVP-923-30
Intervention Description
AVP-923-30 (dextromethorphan 30 mg/quinidine 10 mg) capsules administered once daily for first 7 days followed by twice daily for 11 weeks of the study to complete 12 weeks of treatment.
Intervention Type
Drug
Intervention Name(s)
AVP-923-20
Other Intervention Name(s)
Nuedexta
Intervention Description
AVP-923-20 (dextromethorphan 20 mg/quinidine 10 mg) capsules administered once daily for first 7 days followed by twice daily for 11 weeks of the study to complete 12 weeks of treatment.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo capsules administered once daily for first 7 days followed by twice daily for 11 weeks of the study to complete 12 weeks of treatment.
Primary Outcome Measure Information:
Title
Association Between the Dextromethorphan Plasma Concentration and the Change From Baseline Pain Rating Scale (PRS) Score to the Average Pain Rating Scale Score During Days 57 Through 84
Description
PRS required participants to rate their pain over the past 12 hours (hrs) on a scale of 0 to 10 (0=no pain; 10=worst possible pain). Baseline (B) PRS was defined as the average of the PRS scores in the last 7 days collected prior to the B visit. If participants did not have at least 4 PRS scores during the last 7 days prior to the B visit, then the average of up to 7 of the most recent PRS scores available prior to the B visit was used. Post-B PRS was the average of Days 57 through 84 values. For participants who did not have any PRS scores during Days 57 through 84, the average of the last 7 available post-B PRS scores was used. Change from B was calculated as the post-B score minus B score. The average logarithms of dextromethorphan plasma concentrations (Cmax) on Days 22 and 50 are reported in primary outcome measure #2 below. Pearson correlation was calculated between Cmax as one group of data across the reporting groups and Change from Baseline in PRS score.
Time Frame
Baseline; Days 57 through 84 (PRS score); Days 22 and 50 (dextromethorphan plasma concentrations)
Title
Average Logarithms of Dextromethorphan (DM) Plasma Concentrations (Cmax) on Days 22 and 50
Description
The average of the logarithms of the DM plasma concentrations on Days 22 and 50 were presented.
Time Frame
0 to 3 hours post-dose on Day 22 and 50
Secondary Outcome Measure Information:
Title
Comparison of the Adjusted Mean Change From Baseline PRS Score to the Average PRS Score During Days 57 Through 84
Description
The PRS required participants to rate their pain over the past 12 hours on a scale of 0 to 10 (0=no pain; 10=worst possible pain) by circling the number that best described their pain on average over the past 12 hours. Baseline PRS was defined as the average of the PRS scores in the last 7 days collected prior to the Baseline visit. If participants did not have at least 4 PRS scores during the last 7 days prior to the Baseline visit, then the average of up to 7 of the most recent PRS scores available prior to the Baseline visit was used. Post-Baseline PRS was the average of the Day 57 through 84 values. For participants who did not have any PRS scores during Days 57 through 84, the average of the last 7 available post-Baseline PRS scores was used. Change from Baseline was calculated as the post-Baseline score minus the Baseline score.
Time Frame
Baseline; Days 57 through 84
Title
Mean Change From Baseline in Fatigue Severity Scale (FSS) Scores at Days 57 Through 84
Description
The FSS questionnaire consisted of 9 statements that attempted to explore the severity of fatigue symptoms in participants with MS and other conditions, including chronic fatigue immune dysfunction syndrome and systemic lupus erythematosus, and was designed to differentiate fatigue from clinical depression because both share some of the same symptoms. Participants were asked to respond to each statement on a scale of 1 to 7, with 1 indicating "Strongly Disagree" and 7 indicating "Strongly Agree." Total score ranging from 9 to 63, was computed as the sum of the sub-scores for all 9 statements; a higher score indicated increasing fatigue. Baseline was defined as last non-missing measurement prior to dosing. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Post-Baseline FSS score was the average of Day 57 through 84 values. The analysis was carried out using an ANCOVA model, with the FSS change from Baseline to Days 85 as the dependent variable,
Time Frame
Baseline; Days 57 through 84
Title
Mean Change From Baseline in Expanded Disability Status Scale (EDSS) Scores at Days 22 and 85
Description
The EDSS, a method of quantifying disability in participants with MS was based on neurological examination of 8 functional systems (FS) (pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, cerebral, and other) that allowed neurologists to assign a FS score to each of these systems. Neurological findings in each FS were scored on a scale of 0 (low level of problems) to 5 (high level of problems). The "other" category was not rated numerically but measured disability related to a particular issue, like motor loss. A total averaged EDSS score was then calculated on a scale of 0 (normal) to 10 (death from MS). The total EDSS score was determined by 2 factors: gait and FS scores. A higher score indicated greater disability. Baseline was defined as last non-missing measurement prior to dosing. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame
Baseline; Days 22 and 85
Title
Mean Change From Baseline in Multiple Sclerosis Impact Scale-29 (MSIS-29) Scores at Day 85
Description
MSIS-29, an instrument measuring the physical (20 items) and psychological (9 items) impact of MS from the participants' perspective was used to evaluate therapeutic effectiveness from the participants' perspective. Participants were asked to circle the response that best described the impact of MS on daily life on a scale of 0 (not at all) to 5 (extremely). The total MSIS-29 score ranged from 0 to 145, was calculated as the sum of the sub-scores for all 29 questions, with lower scores indicating better quality of life. Baseline was defined as last non-missing measurement prior to dosing. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The analysis was carried out using an ANCOVA model, with the MSIS-29 score change from Baseline to Day 85 as the dependent variable, treatment group as a fixed effect, and the Baseline MSIS-29 as a covariate.
Time Frame
Baseline; Day 85
Title
Mean Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) Scores at Day 85
Description
PSQI, a self-rated questionnaire was used to assess sleep quality and disturbances over a 1-month time interval. A total of 19 individual items generated 7 component scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. Each component was scored from 0 (no difficulty) to 3 (severe difficulty). The sum of the scores for the 7 components yielded 1 global score (ranging from 0 to 21). Higher PSQI score indicated worse quality of sleep. Baseline was defined as last non-missing measurement prior to dosing. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The analysis was carried out using an ANCOVA model, with the PSQI change from Baseline to Day 85 as the dependent variable, treatment group as a fixed effect, and the Baseline PQIS as a covariate.
Time Frame
Baseline; Day 85
Title
Mean Change From Baseline in MS Neuropsychological Screening Questionnaire (MSNQ) Scores at Day 85
Description
MSNQ, a self-reporting, 15-item questionnaire was used to screen for cognitive impairment in participants with MS. Participants (or their informants) scored each item on a scale from 0 (not at all) to 4 (often and greatly interferes with life). The total MSNQ score was calculated as the sum of the sub-scores for all 15 questions and thus ranged from 0 to 60. A higher score indicated greater impairment. Baseline was defined as last non-missing measurement prior to dosing. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The analysis was carried out using an ANCOVA model, with the MSNQ score change from Baseline to Day 85 as the dependent variable, treatment group as a fixed effect, and the Baseline MSNQ as a covariate.
Time Frame
Baseline; Day 85
Title
Mean Change From Baseline in Beck Depression Inventory (BDI-II) Scores at Day 85
Description
BDI-II, a 21-item, self-reported instrument was used to assess the existence and severity of symptoms of depression. Each item corresponded to a symptom of depression and as scored on a 4-point scale, ranging from 0 to 3. Participants were asked to consider each statement as it related to the way they have felt for the past 2 weeks. Each of the 21 items were summed to give a single score for the BDI-II (ranging from 0 to 63). A total score of 0 to 13 indicated minimal depression, a score of 14 to 19 indicated mild depression, a score of 20 to 28 indicated moderate depression, and a score of 29 to 63 indicated severe depression. Baseline was defined as last non-missing measurement prior to dosing. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The analysis was carried out using an ANCOVA model, with the BDI-II change from Baseline to Day 85 as the dependent variable, treatment group as a fixed effect, and the Baseline BDI-II as a covariate.
Time Frame
Baseline; Day 85
Title
Mean Change From Baseline in Symbol Digit Modalities Test (SDMT) Scores at Day 85
Description
The SDMT assessed organic cerebral dysfunction in both children (8 years and older) and adults. The SDMT involved a simple substitution task that normal participants could easily perform. Using a reference key, the examinee had 90 seconds to pair specific numbers with given geometric figures. The SDMT score was the total correct response (not counting errors) in 90 seconds and ranged from 0 to 110. Lower scores indicated increased dysfunction. Baseline was defined as last non-missing measurement prior to dosing. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The analysis was carried out using an ANCOVA model, with the SDMT change from Baseline to Day 85 as the dependent variable, treatment group as a fixed effect, and the Baseline SDMT as a covariate.
Time Frame
Baseline; Day 85
Title
Mean Numerical Rating Scale (NRS) Scores at Days 22, 50, and 85
Description
The NRS was an 11-point scale for participant self-reporting of pain. The overall scores ranged from 0 (no spasticity) to 10 (worst possible spasticity). Higher scores indicated increased aggression.
Time Frame
Days 22, 50, and 85
Title
Mean Overall Patient Global Impression of Change (PGIC) Scores at Day 85
Description
The PGIC was a standard, validated 7-point categorical scale. The participant was asked to assess the overall change in his or her central neuropathic pain symptoms since entry into the study on a scale of 0 to 7 (0=much better; 7=much worse). Higher scores indicated worsening.
Time Frame
Day 85
Other Pre-specified Outcome Measures:
Title
Change From Baseline in Modified Ashworth Scale (MAS) Scores
Description
MAS is not considered as a true endpoint. MAS scores were assessed at Baseline only. Change from Baseline could not be calculated because data for the later timepoints was not collected.
Time Frame
Baseline; Day 85

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Main Inclusion Criteria: Multiple Sclerosis (relapsing-remitting multiple sclerosis [RRMS] or secondary progressive multiple sclerosis [SPMS]), Clinical history and symptoms of central neuropathic pain (dysesthetic pain) for at least 3 months prior to screening, pain rating scale (PRS) baseline score = or > 4, No MS relapse within previous 30 days. Main Exclusion Criteria: Personal history of complete heart block, QT interval corrected for heart rate (QTc) prolongation, or torsades de pointes, family history of congenital QT interval prolongation syndrome, Myasthenia Gravis, Beck Depression Inventory Second Edition (BDI-II) score > 19
Facility Information:
Facility Name
North Central Neurology Associates PC
City
Cullman
State/Province
Alabama
ZIP/Postal Code
35058
Country
United States
Facility Name
St. Joseph's Hospital Medical Center
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85013
Country
United States
Facility Name
Alta Bates Summit Medical Center
City
Berkeley
State/Province
California
ZIP/Postal Code
94705
Country
United States
Facility Name
University of California, Irvine
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Coordinated Clinical Research
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Facility Name
University of Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Neurology Associates, PA
City
Maitland
State/Province
Florida
ZIP/Postal Code
32751
Country
United States
Facility Name
Collier Neurologic Specialists
City
Naples
State/Province
Florida
ZIP/Postal Code
34102
Country
United States
Facility Name
Laszlo J. Mate, MD
City
North Palm Beach
State/Province
Florida
ZIP/Postal Code
33408
Country
United States
Facility Name
Neurology Associates of Ormond Beach
City
Ormond Beach
State/Province
Florida
ZIP/Postal Code
32174
Country
United States
Facility Name
Neurological Associates
City
Pompano Beach
State/Province
Florida
ZIP/Postal Code
33060
Country
United States
Facility Name
Neurologique Foundation
City
Ponte Vedra Beach
State/Province
Florida
ZIP/Postal Code
32082-4040
Country
United States
Facility Name
Suncoast Neuroscience Associates, Inc.
City
Saint Petersburg
State/Province
Florida
ZIP/Postal Code
33713
Country
United States
Facility Name
University of South Florida
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Geodyssey Research, LLC
City
Vero Beach
State/Province
Florida
ZIP/Postal Code
32960
Country
United States
Facility Name
Shepard Center
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30309
Country
United States
Facility Name
Rush-Presbyterian St. Luke's Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Consultants in Neurology
City
Northbrook
State/Province
Illinois
ZIP/Postal Code
60062
Country
United States
Facility Name
Josephson Wallack Munshower Neurology, P.C.
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46256
Country
United States
Facility Name
MidAmerica Neuroscience Institute
City
Lenexa
State/Province
Kansas
ZIP/Postal Code
66214
Country
United States
Facility Name
Johns Hopkins University School of Medicine
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Michigan Neurology Associates, P.C.
City
Clinton Township
State/Province
Michigan
ZIP/Postal Code
48035
Country
United States
Facility Name
Wayne State University
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Henry Ford Health System
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Advanced Neurology Specialists
City
Great Falls
State/Province
Montana
ZIP/Postal Code
59405
Country
United States
Facility Name
Neurology Associates PC
City
Lincoln
State/Province
Nebraska
ZIP/Postal Code
68506
Country
United States
Facility Name
Albany Medical Center Hospital
City
Albany
State/Province
New York
ZIP/Postal Code
12208
Country
United States
Facility Name
NYU-Hospital for Joint Diseases
City
New York
State/Province
New York
ZIP/Postal Code
10003
Country
United States
Facility Name
University of Rochester
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
SUNY at Stony Brook
City
Stony Brook
State/Province
New York
ZIP/Postal Code
11794
Country
United States
Facility Name
Carolinas Medical Center
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28207
Country
United States
Facility Name
Cleveland Clinic Foundation
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Oklahoma Medical Research Foundation
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Drexel University College of Medicine
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Geisinger Health System
City
Wilkes-Barre
State/Province
Pennsylvania
ZIP/Postal Code
18711
Country
United States
Facility Name
Advanced Neurosciences Institute
City
Franklin
State/Province
Tennessee
ZIP/Postal Code
37064
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Rocky Mountain MS Clinic
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84103
Country
United States
Facility Name
Neurological Associates
City
Henrico
State/Province
Virginia
ZIP/Postal Code
23226
Country
United States
Facility Name
MS Center of Greater Washington
City
Vienna
State/Province
Virginia
ZIP/Postal Code
22182
Country
United States
Facility Name
Swedish Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98122
Country
United States
Facility Name
MultiCare Health System
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98405
Country
United States
Facility Name
Instituto de Neurologia Cognitiva
City
Ciudad Autonoma de Buenos Aires
State/Province
Buenos Aires
ZIP/Postal Code
C1126AAB
Country
Argentina
Facility Name
Hospital Britanico de Buenos Aires
City
Ciudad Autonoma de Buenos Aires
State/Province
Buenos Aires
ZIP/Postal Code
C1280AEB
Country
Argentina
Facility Name
Hospital Italiano
City
Ciudad Autónoma de Buenos Aires
State/Province
Buenos Aires
ZIP/Postal Code
C1181ACH
Country
Argentina
Facility Name
Instituto Argentino de Investigacion Neurologica
City
Ciudad de Buenos Aires
State/Province
Buenos Aires
ZIP/Postal Code
C1015ABR
Country
Argentina
Facility Name
Hospital Churruca-Visca
City
Buenos Aires
ZIP/Postal Code
C1437JCH
Country
Argentina
Facility Name
Fundación Argentina Contra las Enfermedades Neurológicas del Envejecimiento - FACENE
City
Buenos Aires
ZIP/Postal Code
CP1117ABD
Country
Argentina
Facility Name
Medeos - Centro de Medicina Integral e Investigación Clínica
City
Ciudad Autonoma de Buenos Aires
Country
Argentina
Facility Name
Instituto de Neurología y Neurorrehabilitación del Litoral
City
Santa Fe
Country
Argentina
Facility Name
Fakultni nemocnice u sv. Anny v Brne
City
Brno
Country
Czechia
Facility Name
Fakultni nemocnice Hradec Kralove
City
Hradec Kralove
ZIP/Postal Code
500 0
Country
Czechia
Facility Name
Nemocnice Jihlava, prispevkova organizace
City
Jihlava
ZIP/Postal Code
586 33
Country
Czechia
Facility Name
Fakultni Nemocnice Ostrava
City
Ostrava
ZIP/Postal Code
708 52
Country
Czechia
Facility Name
Vseobecna fakultni nemocnice v Praze
City
Praha 2
ZIP/Postal Code
128 21
Country
Czechia
Facility Name
Szpital Powiatowy w Czeladzi
City
Czeladz
ZIP/Postal Code
41-250
Country
Poland
Facility Name
Pomorskie Centrum Traumatologii im. M. Kopernika w Gdansku
City
Gdansk
ZIP/Postal Code
80-803
Country
Poland
Facility Name
Diagnomed Clinical Research Sp. z.o.o.
City
Katowice
ZIP/Postal Code
40-594
Country
Poland
Facility Name
Niepubliczny Zaklad Opieki Zdrowotnej NEURO-MEDIC
City
Katowice
ZIP/Postal Code
40-752
Country
Poland
Facility Name
Niepubliczny Zaklad Opieki Zdrowotnej PROFILAKTYKA
City
Katowice
Country
Poland
Facility Name
Zespol Opieki Zdrowotnej w Konskich
City
Konskie
ZIP/Postal Code
26-200
Country
Poland
Facility Name
Specjalistyczny Gabinet Neurologiczny
City
Plewiska
ZIP/Postal Code
62-064
Country
Poland
Facility Name
Niepubliczny Zaklad Opieki Zdrowotnej NEURO-KARD Ilkowski i Partnerzy Spolka Partnerska Lekarzy
City
Poznan
ZIP/Postal Code
61-289
Country
Poland
Facility Name
Osrodek Badan Klinicznych Indywidualnej Specjalistycznej Praktyki Lekarskiej
City
Szczecin
ZIP/Postal Code
70-215
Country
Poland
Facility Name
Hospital del Mar
City
Barcelona
State/Province
Cataluña
ZIP/Postal Code
08003
Country
Spain
Facility Name
Hospital Vall D´Hebron
City
Barcelona
State/Province
Cataluña
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Universitari de Girona Dr. Josep Trueta
City
Girona
State/Province
Cataluña
ZIP/Postal Code
17007
Country
Spain
Facility Name
Hospital Universitario Virgen de la Arrixaca
City
El Palmar
State/Province
Murcia
ZIP/Postal Code
30120
Country
Spain
Facility Name
Hospital Univ. Nuestra Sra. De La Candelaria
City
Santa Cruz De Tenerife
ZIP/Postal Code
38010
Country
Spain
Facility Name
Hospital Universitario Vírgen Macarena
City
Sevilla
ZIP/Postal Code
41009
Country
Spain

12. IPD Sharing Statement

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Safety and Efficacy of AVP-923 in the Treatment of Central Neuropathic Pain in Multiple Sclerosis

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