Duloxetine in Patients With Diabetic in Peripheral Neuropathic Pain With or Without Co-morbid Major Depressive Disorder
Duloxetine in Patients With Diabetic in Peripheral Neuropathic Pain With or Without Co-morbid Major Depressive Disorder
The primary objective is to evaluate, separately in diabetic polyneuropathic pain (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. If statistically significant results are obtained for the DPNP patients with MDD,
 then the same evaluation will be performed for the DPNP patients without MDD in another
 confirmatory analysis.

 As secondary objectives the study will compare the two groups (MDD+/MDD-) regarding efficacy
 of duloxetine on BPI severity scales, the distribution of different percentages of pain
 reduction among the patient population, and the patients and physicians impressions of
 severity and improvement of pain.

 The study will also compare treatment outcomes regarding patient-relevant functionality and
 quality of life (QoL) between the two groups (MDD+/MDD-) by evaluating each single BPI
 interference item, the Short Form 12 (SF-12) Health Questionnaire and the West Haven
 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 fasting blood glucose (FBG) and hemoglobin A1c
 (HbA1c) will be evaluated.

 To monitor safety and tolerability, treatment discontinuation rates, treatment emergent
 adverse events, change in vital signs, laboratory results and suicidal thoughts will be
 assessed.
Inclusion criteria:

 1. Present with pain due to bilateral peripheral neuropathy (according to International
 Statistical Classification of Diseases and Related Health Problems 10 (ICD 10).

 2. To qualify for the MDD+ cohort, patients need to meet the ICD-10 criteria for MDD.
 Furthermore, Hamilton rating scale for depression 17 (HAMD-17) scores need to match
 with the ICD-10 criteria for qualification of the MDD+ or MDD- groups.

 3. Male or female outpatients at least 18 years of age.

 4. Females with child bearing potential must test negative for a serum pregnancy test at
 Visit 1. Females of child-bearing potential (not surgically sterilized and between
 menarche and 1 year post-menopause) must agree to utilize medically acceptable and
 reliable means of birth control as determined by the investigator during the study and
 for 1 month following the last dose of the study. Examples of reliable methods include
 use of oral contraceptives or Depo-Clinovir Contraceptive Injection (sterile
 medroxyprogesterone acetate suspension, Pharmacia), partner with vasectomy, diaphragms
 with contraceptive jelly, cervical caps with contraceptive jelly, condoms with
 contraceptive foam, or intrauterine devices. Women who are pregnant or breast-feeding
 may not participate in the study.

 5. Educational level and degree of understanding such that they can communicate
 intelligibly with the investigator and study coordinator.

 6. Judged to be reliable and agrees to keep all appointments for clinic visits, tests,
 and procedures required by the protocol.

 Exclusion criteria:

 1. Have already a diagnosis of Depression and are currently treated with an
 antidepressant medication for depression, when entering the study.

 2. Suffer from pain that cannot be clearly differentiated from or conditions that
 interfere with the assessment of DPNPain.

 3. Had a historical exposure to drugs known to cause neuropathy, that could have been
 responsible for neuropathy.

 4. Have previously been treated with duloxetine (for DPNP or MDD)

 5. Are judged 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).

 6. Had a history of substance abuse or dependence within the past year, excluding
 nicotine and caffeine.