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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 21 August 2017
Main ID:  EUCTR2011-002178-22-ES
Date of registration: 31/10/2011
Prospective Registration: Yes
Primary sponsor: Avanir Pharmaceuticals, Inc.
Public 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
Scientific 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
Date of first enrolment: 26/12/2011
Target sample size: 400
Recruitment status: Not Recruiting
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-002178-22
Study type:  Interventional clinical trial of medicinal product
Study design:  Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 4  
Phase:  Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no
Countries of recruitment
Argentina Bulgaria Czech Republic Poland Spain United Kingdom United States
Contacts
Name: Clinical Trial Information Desk   
Address:  20 Enterprise, Suite 200 CA 92656 Aliso Viejo United States
Telephone: +1 949-268-1167
Email: study11AVR130@avanir.com
Affiliation:  Avanir Pharmaceuticals, Inc.
Name: Clinical Trial Information Desk   
Address:  20 Enterprise, Suite 200 CA 92656 Aliso Viejo United States
Telephone: +1 949-268-1167
Email: study11AVR130@avanir.com
Affiliation:  Avanir Pharmaceuticals, Inc.
Key inclusion & exclusion criteria
Inclusion criteria:
1.Males and females 18 to 85 years of age, inclusive.
2.The patient has a diagnosis of RRMS or SPMS (MS must be diagnosed according to the McDonald criteria).
3.The patient has a clinical history and clinical relevant symptoms of central neuropathic pain (dysesthetic pain) secondary to MS for at least 30 days prior to screening and expected to remain otherwise stable during the study. Patients meeting the criterion for central neuropathic pain and experiencing concomitant non-central neuropathic pain are allowed to participate in the study.
4.Mean PRS score at Baseline is more or equal to 4.
5.The patient has not experienced an MS relapse within the previous 30 days.
6.The patient has stable hematologic, hepatic, and renal function, with no clinically significant symptoms, and with clinical laboratory results (complete blood cell count [CBC], clinical chemistry, and urinalysis) up to 1-fold higher than the upper limit of the normal range.
7.The patient has a resting respiratory rate between 12 and 20 breaths per minute.
8.The patient has an ECG (obtained within 4 weeks prior to entry and evaluated by a certified cardiologist) with no evidence of clinically significant abnormality and with no evidence of: complete heart block, ventricular tachycardia, or frequent unifocal ventricular ectopic beats (>5 per minute).
9.If female, must not be pregnant, breast-feeding, or planning a pregnancy during the course of the study, and must have a negative urine pregnancy test at Screening and at baseline.
10.If female, must have been practicing a medically-acceptable method of birth control for at least 1 month prior to randomization (oral contraceptive tablets, hormonal implant device, hormone patch, intrauterine device, diaphragm and contraceptive cream or foam, condom with spermicide, tubal ligation, or abstinence) or be surgically sterile or post-menopausal.
11.Patients currently receiving an MS disease-modifying therapy ([MS DMT] eg, interferon beta, glatiramer, natalizumab, fingolimod) are eligible provided they have been on a stable dose of these medications for at least 2 months prior to randomization.
12.Patients currently receiving fampridine should be on a stable dose for at least 2 months prior to randomization.
13.Patients currently taking SSRIs (selective serotonin reuptake inhibitors) for the treatment of major depression for at least 3 months on a stable dose prior to randomization are eligible, provided the SSRI dose remains unchanged during the study.
14.Patient must not show current symptoms of a depressive disorder.
15.Patient must have a score of ?19 in the BDI-II at screening and at baseline.
16.Patient must be willing to not take any prohibited medications during the study.
17.Patient or their legal guardian signed and received a copy of an informed consent form (ICF) after the nature and risks of study participation had been fully explained to them
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 400
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 400

Exclusion criteria:
1.Patient (or caregiver) is unwilling or unable, in the opinion of the investigator, to comply with study instructions.
2.The patient has other types of non-central neuropathic pain (e.g., back pain, headache, painful tonic spasms) without having clinical symptoms of central neuropathic pain.
3.Patients with myasthenia gravis.
4.Any personal history of complete heart block, QTc prolongation, or torsades de pointes.
5.Any family history of congenital QT interval prolongation syndrome.
6.Patients with known sensitivity to DM, Q, or opiate drugs (codeine, etc.).
7.Patients with known sensitivity to acetaminophen (also known as paracetamol).
8.Patients experiencing an MS relapse within the previous 30 days.
9.Patients who have been taking disallowed concomitant medications within 2 weeks prior to Baseline (Day 1).
10.Patients currently using, or have been using marijuana or dronabinol within 2 weeks prior to Baseline (Day 1).
11.Patients with a current or prior history of major psychiatric disorder. Exclusionary psychiatric diagnoses, to be determined by chart review and patient interview, include the following Axis I disorders (according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [DSM-IV] criteria): (i) current symptoms of major depression; (ii) bipolar disorder; (iii) schizophrenia or other psychotic disorder; (iv) somatoform disorders; and the Axis II disorder of borderline personality.
12.Patients that have a score of ?20 in the BDI-II.
13.Patients with co-existent major systemic diseases that would interfere with interpretation of the results of the study (eg, malignancy [except skin basal-cell carcinoma], poorly controlled diabetes, poorly controlled hypertension, ischemic cardiac disease, dilated cardiomyopathy, or valvular heart disease).
14.Patients who are currently participating in, or who have participated in other clinical study within the past 30 days.
15.Patients with severe and/or unstable pulmonary disease.
16.Patients with resting respiratory rate <12 breaths per minute or >20 breaths per minute.
17.Patients who have received DM co-administered with Q within the previous 3 months.
18.Patients with hypotension (systolic blood pressure [BP] <100 mm Hg), history of postural syncope, or any history of unexplained syncope (evaluated on a case by case basis).
19.Patients with a history of substance and/or alcohol abuse within the past 2 years.
20.Women who are pregnant or likely to become pregnant during the course of the study.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
Central Neuropathic Pain in Multiple Sclerosis
MedDRA version: 14.0 Level: LLT Classification code 10054095 Term: Neuropathic pain System Organ Class: 10029205 - Nervous system disorders
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]
Intervention(s)

Product Name: Dextrometorfano/Quinidina
Product Code: AVP-923
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: DEXTROMETORFANO HIDROBROMURO
CAS Number: 125-69-9
Current Sponsor code: 11-AVR-130
Other descriptive name: N/A
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 45-
INN or Proposed INN: Quinidina sulfato
Current Sponsor code: 11-AVR-130
Other descriptive name: N/A
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: Dextrometorfano/Quinidina
Product Code: AVP-923
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: DEXTROMETORFANO HiDROBROMURO
CAS Number: 125-69-9
Current Sponsor code: 11-AVR-130
Other descriptive name: N/A
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 30-
INN or Proposed INN: Quinidina sulfato
Current Sponsor code: 11-AVR-130
Other descriptive name: N/A
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: Dextrometorfano/Quinidina
Product Code: AVP-923
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: DEXTROMETORFANO HIDROBROMURO
CAS Number: 125-69-9
Current Sponsor code: 11-AVR-130
Other descriptive name: N/A
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
INN or Proposed INN: Quinidina sulfato
Current Sponsor code: 11-AVR-130
Other descriptive name: N/A
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)
Main Objective: The objectives of the study are to evaluate the safety, tolerability, and efficacy of 3 doses of AVP-923 capsules containing either 45 mg DM and 10 mg Q (AVP-923-45) or 30 mg DM 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 patients with multiple sclerosis (MS) over a 12-week period.
Primary end point(s): The primary efficacy endpoint is the 11 point (0-10) PRS obtained from daily patient diaries.
Secondary Objective: Not applicable.
Timepoint(s) of evaluation of this end point: The primary analysis of the primary endpoint will be a comparison of the average PRS scores on Days 57-84 to the average PRS scores during the 7-day baseline recording period prior to randomization, using a mixed-effects regression model that accounts for within-patient correlation.
Secondary Outcome(s)
Secondary end point(s): Secondary efficacy endpoints include the FSS, MSIS-29, PSQI, MSNQ, and BDI-II.
Timepoint(s) of evaluation of this end point: A secondary analysis will be a baseline-adjusted comparison of the area under the PRS curve over the on-treatment period using a parametric mixed-effects model.
Secondary ID(s)
11-AVR-130
NCT01324232
Source(s) of Monetary Support
Avanir Pharmaceuticals, Inc.
Secondary Sponsor(s)
Ethics review
Results
Results available:
Date Posted:
Date Completed:
URL:
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