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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: 27 January 2014
Main ID:  EUCTR2011-002178-22-CZ
Date of registration: 02/11/2011
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: 08/02/2012
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: 
Countries of recruitment
Argentina Bulgaria Czech Republic Germany 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
3 months 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 (e.g.,
back pain, headache, chronic visceral pain, musculoskeletal postural
pain, trigeminal neuralgia or Lhermitte's sign) are allowed to participate
in the study as long as central neuropathic pain of the extremities is the
predominant type of pain.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 no clinically significant clinical
laboratory abnormalities.
7.The patient has negative urine drug screening panel results (including
amphetamines, barbiturates, cocaine metabolite, opiates, and THC [cannabinoids]).
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.
12Patients currently receiving fampridine/dalfampridine 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 signed and received a copy of an 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.Other types of neuropathic pain unrelated to MS (e.g., DPN 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 ibuprofen8.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 symptomatic hypotension, history of postural syncope,
or any history of unexplained syncope (evaluated on a case-by-case
basis).
17.Evidence of uncontrolled diabetes based on HbA1c below 53
mmol/mol (>7.0%)
18.Patients with a history of substance and/or alcohol abuse within the
past 2 years.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
Central Neuropathic Pain in Multiple Sclerosis
MedDRA version: 14.1 Level: LLT Classification code 10054095 Term: Neuropathic pain System Organ Class: 100000004852
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]
Intervention(s)

Product Name: Dextromethorphan/Quinidine
Product Code: AVP-923
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: DEXTROMETHORPHAN HYDROBROMIDE
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: Quinidine Sulfate
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: Dextromethorphan/Quinidine
Product Code: AVP-923
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: DEXTROMETHORPHAN HYDROBROMIDE
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: Quinidine Sulfate
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: Dextromethorphan/Quinidine
Product Code: AVP-923
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: DEXTROMETHORPHAN HYDROBROMIDE
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: Quinidine Sulfate
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 will be carried out using an analysis of covariance
(ANCOVA) model with the PRS change from baseline to Days 57-84 as
the dependent variable, treatment group as a factor, and the baseline
PRS score as a covariate. The primary analysis will compare the AVP
923-45 group to the placebo group.
Secondary Outcome(s)
Secondary end point(s): Secondary efficacy endpoints include the FSS, MSIS-29, PSQI, MSNQ, SDMT, BDI-II, MAS, NRS and PGIC scores
Timepoint(s) of evaluation of this end point: The primary analysis of the secondary efficacy variables will be based on
the change from baseline to the Day 85 visit using an analysis of
covariance (ANCOVA) model with treatment group as factors and the
baseline scores as covariates.
Secondary ID(s)
11-AVR-130
2011-002178-22-ES
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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