A RANDOMIZED, DOUBLE-BLIND PLACEBO CONTROLLED TRIAL OF [S,S]-REBOXETINE IN PATIENTS WITH CHRONIC PAINFUL DIABETIC PERIPHERAL NEUROPATHY

• Register: EUCTR
• Last refreshed on: 12 June 2012
• Main ID: EUCTR2007-004733-41-NL
• Date of registration: 07/11/2007
• Prospective Registration: Yes
• Primary sponsor: Pfizer Ltd
• Public title: A RANDOMIZED, DOUBLE-BLIND PLACEBO CONTROLLED TRIAL OF [S,S]-REBOXETINE IN PATIENTS WITH CHRONIC PAINFUL DIABETIC PERIPHERAL NEUROPATHY
• Scientific title: A RANDOMIZED, DOUBLE-BLIND PLACEBO CONTROLLED TRIAL OF [S,S]-REBOXETINE IN PATIENTS WITH CHRONIC PAINFUL DIABETIC PERIPHERAL NEUROPATHY
• Date of first enrolment: 14/03/2008
• Target sample size: 450
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-004733-41
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Finland, Netherlands, Spain

Key inclusion & exclusion criteria

Inclusion criteria:
• Male or female of any race at least 18 years of age
• Female patients must be postmenopausal, or surgically sterilized, or (if they are of
childbearing potential) they must be non-pregnant and non-lactating and must be using appropriate methods of contraception. Prior to starting the trial, it is strongly
recommended that women of childbearing potential use two of the following methods of birth control for at least one month or for whatever amount of time the prescribing doctor determines it will take for the methods of birth control to be fully effective: oral birth control pills, diaphragms, progesterone implanted rods, medroxyprogesterone acetate or condoms. Women of childbearing potential must have a confirmed negative urine pregnancy test at the Screening visit (Visit 1) and Visit 2
• Diagnosis of type 1 or 2 diabetes mellitus (by American Diabetic Association Clinical
Practice Recommendations diagnostic criteria www.diabetes.org) for at least 1 year.
• Hemoglobin A1c levels of =11% at Visit 1 (with fluctuations of =1% in the 6 to 12 weeks prior to Visit 1)
• Diagnosis of painful, distal, symmetrical, sensori-motor polyneuropathy, which is due to diabetes, for at least 1 year.
•Patients at Visit 1 must have a score =40 mm on the Pain Visual Analogue Scale (VAS)
• Patients must be able to understand and cooperate with trial procedures, and have signed a written informed consent prior to entering the trial.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
• Malignancy within the past 2 years with the exception of basal cell carcinoma
• Patients with significant hepatic impairment (i.e. AST/ALT > 3 x ULN, Total bilirubin >2 x ULN)
• Clinically significant abnormal 12-lead ECG (in the opinion of the investigator)
• Neurological disorders unrelated to diabetic neuropathy that may confuse the assessment of neuropathic pain
• Any pain or other condition that may confound assessment or self-evaluation of the pain due to diabetic neuropathy
• History of chronic hepatitis B or C, acute hepatitis A, B or C within the past 3 months, or HIV infection
• Skin conditions in the area affected by the neuropathy that (in the opinion of the investigator) could alter sensation
• Amputations other than toes
• Administration of any investigational drug and/or agent within 30 days prior to the screening visit
• Use of prohibited medications, in the absence of appropriate washout period
• Abuse of drugs or alcohol within the last 2 years
• Depression sub-scale score >10 on the Hospital and Anxiety Depression Scale
• A current or recent diagnosis (past 6 months) or episode of major depressive disorder (as diagnosed by the MINI) and/or uncontrolled depression (dysthymia as diagnosed by the MINI)
• History of mania, hypomania, psychotic disorder, or current mood disorder with psychotic features
• Any patient judged clinically to be at serious risk of suicide based on Beck’s Scale for Suicide Ideation
• History of recurrent syncope or evidence of low blood pressure (systolic <90mmHg, diastolic <40mmHg)
• Postural hypotension (a fall of 20mmHg in systolic blood pressure or 10mmHg in diastolic blood pressure on standing)
• History of transient ischemic attack or stroke
• Myocardial infarction or unstable angina within the past three months
• Carotid bruit, unless significant carotid stenosis (e.g. >70%) has been excluded by appropriate investigation
• History of urinary retention
• History of uncontrolled narrow angle glaucoma
• Patients who have a history of a seizure disorder, including alcoholic seizures, a family history of seizures, or a history of head trauma that resulted in loss of consciousness or concussion
• Previous exposure to [S,S]-RBX or racemic reboxetine (Edronax®)
• Any serious or unstable medical conditions that, in the opinion of the investigator, would compromise participation in the trial



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

CHRONIC PAINFUL DIABETIC PERIPHERAL NEUROPATHY
MedDRA version: 9.1 Level: LLT Classification code 10012683 Term: Diabetic peripheral neuropathy

Intervention(s)

Product Name: [S,S]-Reboxetine Succinate
Product Code: PNU-165442G
Pharmaceutical Form: Tablet
INN or Proposed INN: [S,S]-reboxetine succinate
Current Sponsor code: PNU-165442G
Other descriptive name: (2S)-2-[(S)-(2-ethoxyphenoxy) phenylmethyl] morpholine succinate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: [S,S]-Reboxetine Succinate
Product Code: PNU-165442G
Pharmaceutical Form: Tablet
INN or Proposed INN: [S,S]-reboxetine succinate
Current Sponsor code: PNU-165442G
Other descriptive name: (2S)-2-[(S)-(2-ethoxyphenoxy) phenylmethyl] morpholine succinate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 4-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): • Daily Pain Rating Scale

Main Objective: • To evaluate the efficacy of [S,S]-RBX in patients with DPN
• To evaluate the safety and tolerability of [S,S]-RBX in patients with DPN

Secondary Objective:

Secondary ID(s)

A6061037