Painful diabetic polyneuropathy according to ICD-10 with or without co-morbid Major Depressive Disorder according to ICD-10 (F32 and F33). MedDRA version: 9.1 Level: LLT Classification code 10012685 Term: Diabetic polyneuropathy MedDRA version: 9.1 Level: LLT Classification code 10025453 Term: Major depressive disorder NOS
Conditions
Interventions
Trade Name: ARICLAIM
Product Name: Ariclaim
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Duloxetine
CAS Number: 136434349
Other descriptive name: DULOXETINE HYDROCHLORIDE
Concentration unit
Sponsors
Boehringer Ingelheim Pharma GmbH & Co. KG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Male or female patients of =18 years of age that meet the International Conference of Diseases (ICD-10) criteria for DPNP and have a score of = 4 on the BPI 24-hour average pain item at visit 2. • To qualify for the MDD+ cohort, patients need to meet the ICD-10 criteria for MDD (F32 and F33 according to ICD-10). Furthermore, the HAMD-17 scores need to match with the ICD-10 criteria for qualification of the MDD+ (with MDD) or MDD- (without MDD) groups, i.e. a HAMD-17 total score of =16 is required to qualify for MDD+ and =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Have already a diagnosis of depression and are currently treated for depression, when entering the study. • Are judged at Visits 1 and 2 to be at suicidal risk by the clinical investigator or as defined by a score of 2 or greater on question 9 of the Beck Depression Inventory-II (BDI-II). • Had a historical exposure to drugs known to cause neuropathy (for example, vincristine), or a history of a medical condition, including pernicious anaemia and hypothyroidism, that could have been responsible for neuropathy. • Suffer from pain that cannot be clearly differentiated from or conditions that interfere with the assessment of the diabetic neuropathy pain. Examples of painful conditions that could be confused with diabetic neuropathy pain include peripheral vascular disease (ischemic pain); neurological disorders unrelated to diabetic neuropathy (for example, phantom limb pain from amputation); skin condition in the area of the neuropathy that could alter sensation (for example, plantar ulcer); other painful conditions, (for example, arthritis). • Have unstable glycemic control as assessed by glycosylated hemoglobin (HbA1c) =12% prior to Visit 2. • Have previously been treated with duloxetine. • Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry (Visit 1). • Had a history of substance abuse or dependence within the past year, excluding nicotine and caffeine. • Have a positive urine screen for drug abuse (cannabinoids, cocaine, opiates including methadone, or amphetamines, barbiturates, benzodiazepines) at Visit 1 (screening). • Have serious or unstable cardiovascular, hepatic, renal, respiratory, or hematologic illness, symptomatic peripheral vascular disease, or other medical condition (including unstable hypertension) or psychiatric conditions that, in the opinion of investigator, would compromise participation or be likely to lead to hospitalization during the course of the study. • Have acute liver injury (such as hepatitis) or severe cirrhosis (Child-Pugh Class C). • Are taking any excluded medications that cannot be discontinued at Visit 1. • Received treatment with a monoamine oxidase inhibitor (MAOI) within 14 days prior to Visit 2 or the potential need to take within 5 days after discontinuation from the study or may need to use a MAOI during the study. • Received treatment with fluoxetine within 30 days prior to Visit 2.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to evaluate, separately in DPNP patients with and without co-morbid major depressive disorder (MDD), whether duloxetine given as 60 mg to 120 mg once daily (QD) leads to a clinically relevant improvement as measured by the change in Brief Pain Inventory (BPI) 24 hours average interference score from baseline to after 12 weeks. A clinically relevant improvement will be demonstrated if the confidence interval for the mean change from baseline does not lie above the clinically relevant change of -1.35. ;Secondary Objective: In secondary evaluations, the efficacy of duloxetine will be evaluated within the groups (MMD+ and MDD-) by assessing the changes in the BPI severity scores, the percentage of patients with various reductions in BPI average pain, and the patients' and physicians' impressions of severity and improvement in pain. In addition, patient-rated functionality and quality of life will also be evaluated within the groups looking at each individual BPI interference item, the SF-12 Health Questionnaire and the Multidimensional Pain Inventory (MPI). As a third group of secondary objectives the efficacy of duloxetine of the psychological symptoms (e.g. depression) of DPNP patients with or without depression will be assessed using the Hamilton Depression Scale, the Beck Depression Inventory-II and the Hospital Anxiety and Depression Scale. Further the effect of duloxetine treatment on FBG and HbA1c and several safety parameters will be evaluated. ;Primary end point(s): The primary endpoint is the change from baseline of the BPI 24 h average interference score after 12 weeks of treatment with duloxetine 60-120 mg once daily (QD) in patients with DPNP with and without co-morbid MDD (MDD+ and MDD- respectively). | — |
Countries
Germany
Outcome results
None listed