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PRIME

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
CompletedPhase 2Relapsing and progressiveNCT013242322011-002178-22

What it found

Missed its main goal

The main measure did not show a significant benefit.

MeasureEstimate95% CIp
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 84Pearson correlation 0.0019= 0.9827

Statistical analysis as posted on ClinicalTrials.gov.

What was tested

Treatment tested

  • AVP-923-45
  • AVP-923-30
  • AVP-923-20
  • Dextromethorphan

Placebo or sham

  • Placebo

Results by group

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

Baseline; Days 57 through 84 (PRS score); Days 22 and 50 (dextromethorphan plasma concentrations)

GroupValueIntervalNumber analysed
Placebo-1.821 units on a scale-7.86–2.0649
AVP-923-20-2.143 units on a scale-7.6–5.7153
AVP-923-30-2.650 units on a scale-6.54–354
AVP-923-45-1.679 units on a scale-6.79–253
Total-2.000 units on a scale-7.86–5.71209

p = = 0.9827; Pearson correlation 0.0019

Average Logarithms of Dextromethorphan (DM) Plasma Concentrations (Cmax) on Days 22 and 50

0 to 3 hours post-dose on Day 22 and 50

GroupValueIntervalNumber analysed
AVP-923-204.019 Log Micrograms per Liter2.38–4.8443
AVP-923-304.493 Log Micrograms per Liter3.27–5.5545
AVP-923-454.758 Log Micrograms per Liter-1.61–5.8145
Total4.394 Log Micrograms per Liter-1.61–5.81133

AVP-923-20

4.019

AVP-923-30

4.493

AVP-923-45

4.758

Total

4.394

Values as posted on ClinicalTrials.gov. Outcomes measured differently across trials are not directly comparable.

Safety

GroupParticipants at riskSerious adverse eventsDeaths
Placebo491 (2.0%)0
AVP-923-20541 (1.9%)0
AVP-923-30531 (1.9%)0
AVP-923-45532 (3.8%)0

As posted on ClinicalTrials.gov. Serious adverse events include any serious health event during the trial, whether or not the treatment caused it.

What it measured

Main 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

    Baseline; Days 57 through 84 (PRS score); Days 22 and 50 (dextromethorphan plasma concentrations)

    PainHow the body handles the medicine

  • Average Logarithms of Dextromethorphan (DM) Plasma Concentrations (Cmax) on Days 22 and 50

    0 to 3 hours post-dose on Day 22 and 50

    How the body handles the medicine

  • The primary efficacy endpoint is the 11 point (0-10) PRS obtained from daily patient diaries.

Other measures (11)

  • Comparison of the Adjusted Mean Change From Baseline PRS Score to the Average PRS Score During Days 57 Through 84

    Baseline; Days 57 through 84

    Pain

  • Mean Change From Baseline in Fatigue Severity Scale (FSS) Scores at Days 57 Through 84

    Baseline; Days 57 through 84

    FatigueMood and sleep

  • Mean Change From Baseline in Expanded Disability Status Scale (EDSS) Scores at Days 22 and 85

    Baseline; Days 22 and 85

    Disability progressionWalking and mobilityBladder, bowel and sexual function

  • Mean Change From Baseline in Multiple Sclerosis Impact Scale-29 (MSIS-29) Scores at Day 85

    Baseline; Day 85

    Quality of life (reported by participants)

  • Mean Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) Scores at Day 85

    Baseline; Day 85

    Myelin repairMood and sleep

  • Mean Change From Baseline in MS Neuropsychological Screening Questionnaire (MSNQ) Scores at Day 85

    Baseline; Day 85

    Thinking and memory

  • Mean Change From Baseline in Beck Depression Inventory (BDI-II) Scores at Day 85

    Baseline; Day 85

    Mood and sleep

  • Mean Change From Baseline in Symbol Digit Modalities Test (SDMT) Scores at Day 85

    Baseline; Day 85

    Thinking and memory

  • Mean Numerical Rating Scale (NRS) Scores at Days 22, 50, and 85

    Days 22, 50, and 85

    SpasticityPain

  • Mean Overall Patient Global Impression of Change (PGIC) Scores at Day 85

    Day 85

    Pain

Who could take part

Relapsing and progressive · 18 to 85

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

As registered. Criteria can change, so ask the trial team or your neurologist.

About this trial

In the sponsor's words

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.

Papers

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    History

      1. Started

        Sept 2011

      2. Main results due

        Sept 2013

      3. Finished

        Sept 2013

      4. Results posted

        Nov 2021

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