Phase 4
N=108
Duloxetine in Patients With Diabetic in Peripheral Neuropathic Pain With or Without Co-morbid Major Depressive Disorder
Diabetic Neuropathies · Depressive Disorder, Major
Bottom Line
View on ClinicalTrials.gov: NCT00844194 ↗Enrolled (actual)
108
Serious AEs
5.6%
Results posted
Oct 2011
Primary outcome: Primary: Change of Brief Pain Inventory (BPI) Average Interference Score From Baseline to Week 12 — -1.4; -2.2 Scores on a scale — p=< 0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 4
- Interventions
- Duloxetine 60 mg QD (Drug); Duloxetine 30 mg QD (Drug); Duloxetine 90 mg QD (Drug); Duloxetine 120 mg QD (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Boehringer Ingelheim
- Primary completion
- Jun 2010
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change of Brief Pain Inventory (BPI) Average Interference Score From Baseline to Week 12 |
-1.7; -2.2; -0.9; -2.6 | — |
| SECONDARY Change of Brief Pain Inventory (BPI) Average Interference Score From Baseline to Week 6 |
-1.2; -2.0 | — |
| SECONDARY Change in BPI Worst Pain During Treatment From Baseline to Week 2 |
-2.2; -1.9 | — |
| SECONDARY Change in Worst Pain (BPI) From Baseline to Week 6 |
-2.6; -3.3 | — |
| SECONDARY Change in Worst Pain (BPI) From Baseline to Week 12 |
-2.8; -3.2 | — |
| SECONDARY Change in Least Pain (BPI) From Baseline to Week 2 |
-1.1; -0.2 | — |
| SECONDARY Change in Least Pain During Treatment (BPI) From Baseline to Week 6 |
-1.7; -1.3 | — |
| SECONDARY Change in Least Pain (BPI) From Baseline to Week 12 |
-1.5; -1.1 | — |
| SECONDARY Change in Average Pain (BPI) From Baseline to Week 2 |
-1.6; -1.1 | — |
| SECONDARY Change in Average Pain During Treatment (BPI) From Baseline to Week 6 |
-2.6; -2.6 | — |
| SECONDARY Change in Average Pain (BPI) From Baseline to Week 12 |
-2.4; -2.2 | — |
| SECONDARY Number of Patients With a Reduction in BPI Average Pain at Week 2 |
29; 9; 19; 3; 5; 2 | — |
| SECONDARY Number of Patients With a Reduction in BPI Average Pain at Week 6 |
42; 17; 30; 12; 14; 6 | — |
| SECONDARY Number of Patients With a Reduction in BPI Average Pain at Week 12 |
42; 17; 30; 11; 6; 4 | — |
| SECONDARY Change in Pain During Treatment (BPI) From Baseline to Week 2 |
-1.4; -1.0 | — |
| SECONDARY Change in Pain (BPI) From Baseline to Week 6 |
-2.0; -1.7 | — |
| SECONDARY Change in Pain During Treatment (BPI) From Baseline to Week 12 |
-1.7; -1.5 | — |
| SECONDARY Change in Relief of Pain (BPI) From the Week Before Baseline to the Week Before Week 2 |
21.5; 18.0 | — |
| SECONDARY Change in Relief of Pain (BPI) From the Week Before Baseline to the Week Before Week 6 |
23.5; 31.7 | — |
| SECONDARY Change in Relief of Pain (BPI) From the Week Before Baseline to the Week Before Week 12 |
30.2; 22.9 | — |
| SECONDARY Change in Interference of Pain With General Activity (BPI) From Baseline to Week 2 |
-1.6; -1.1 | — |
| SECONDARY Change in Interference of Pain With General Activity (BPI) From Baseline to Week 6 |
-1.8; -2.5 | — |
| SECONDARY Change in Interference of Pain With General Activity (BPI) From Baseline to Week 12 |
-2.4; -2.7 | — |
| SECONDARY Change in Interference of Pain With Mood (BPI) From Baseline to Week 2 |
-1.1; -1.5 | — |
| SECONDARY Change in Interference of Pain With Mood (BPI) From Baseline to Week 6 |
-1.4; -3.1 | — |
| SECONDARY Change in Interference of Pain With Mood (BPI) From Baseline to Week 12 |
-1.2; -3.0 | — |
| SECONDARY Change in Interference of Pain With Walking Ability (BPI) From Baseline to Week 2 |
-0.9; -1.0 | — |
| SECONDARY Change in Interference of Pain With Walking Ability (BPI) From Baseline to Week 6 |
-1.3; -2.1 | — |
| SECONDARY Change in Interference of Pain With Walking Ability (BPI) From Baseline to Week 12 |
-1.9; -2.4 | — |
| SECONDARY Change in Interference of Pain With Normal Work (BPI) From Baseline to Week 2 |
-0.9; -0.1 | — |
| SECONDARY Change in Interference of Pain With Normal Work (BPI) From Baseline to Week 6 |
-1.1; -1.3 | — |
| SECONDARY Change in Interference of Pain With Normal Work (BPI) From Baseline to Week 12 |
-1.4; -1.8 | — |
| SECONDARY Change in Interference of Pain With Relations to Other People (BPI) From Baseline to Week 2 |
-0.5; -0.1 | — |
| SECONDARY Change in Interference of Pain With Relations to Other People (BPI) From Baseline to Week 6 |
-0.6; -1.7 | — |
| SECONDARY Change in Interference of Pain With Relations to Other People (BPI) From Baseline to Week 12 |
-0.4; -1.7 | — |
| SECONDARY Change in Interference of Pain With Sleep (BPI) From Baseline to Week 2 |
-0.8; -1.0 | — |
| SECONDARY Change in Interference of Pain With Sleep (BPI) From Baseline to Week 6 |
-1.1; -1.5 | — |
| SECONDARY Change in Interference of Pain With Sleep (BPI) From Baseline to Week 12 |
-1.5; -1.9 | — |
| SECONDARY Change in Interference of Pain With Enjoyment of Life (BPI) From Baseline to Week 2 |
-0.7; -0.6 | — |
| SECONDARY Change in Interference of Pain With Enjoyment of Life (BPI) From Baseline to Week 6 |
-1.2; -2.2 | — |
| SECONDARY Change in Interference of Pain With Enjoyment of Life (BPI) From Baseline to Week 12 |
-0.9; -2.1 | — |
| SECONDARY Patient Global Impression - Improvement (PGI-I) at Week 2 |
3.0; 3.2 | — |
| SECONDARY Patient Global Impression - Improvement (PGI-I) at Week 6 |
2.5; 2.5 | — |
| SECONDARY Patient Global Impression - Improvement (PGI-I) at Week 12 |
2.5; 2.7 | — |
| SECONDARY Change in Beck Depression Inventory Total Score (BDI-II) From Baseline to Week 2 |
-0.9; -3.1 | — |
| SECONDARY Change in Beck Depression Inventory Total Score (BDI-II) From Baseline to Week 6 |
-1.8; -7.3 | — |
| SECONDARY Change in Beck Depression Inventory Total Score (BDI-II) From Baseline to Week 12 |
-1.6; -7.8 | — |
| SECONDARY Change in Hospital Anxiety and Depression Scale (HADS) Anxiety Total Score From Baseline to Week 2 |
-0.7; -1.2 | — |
| SECONDARY Change in HADS Anxiety Total Score From Baseline to Week 6 |
-0.8; -2.2 | — |
| SECONDARY Change in HADS Anxiety Total Score From Baseline to Week 12 |
-1.0; -3.3 | — |
| SECONDARY Change in HADS Depression Total Score From Baseline to Week 2 |
-0.5; -1.6 | — |
| SECONDARY Change in HADS Depression Total Score From Baseline to Week 6 |
-0.8; -3.4 | — |
| SECONDARY Change in HADS Depression Total Score From Baseline to Week 12 |
-0.7; -3.7 | — |
| SECONDARY Change in Short Form Health Survey (SF-12) - Physical Component Summary From Baseline to Week 6 |
4.0; -0.0 | — |
| SECONDARY Change in Short Form Health Survey (SF-12) - Physical Component Summary From Baseline to Week 12 |
3.5; 2.4 | — |
| SECONDARY Change in Short Form Health Survey (SF-12) - Mental Component Summary From Baseline to Week 6 |
-0.9; 5.0 | — |
| SECONDARY Change in Short Form Health Survey (SF-12) - Mental Component Summary From Baseline to Week 12 |
0.7; 6.0 | — |
| SECONDARY Change in Multidimensional Pain Inventory (MPI): Interference of Pain (With Subjective Well-being) From Baseline to Week 6 |
-1.0; -0.9 | — |
| SECONDARY Change in Multidimensional Pain Inventory (MPI): Interference of Pain From Baseline to Week 12 |
-1.1; -1.0 | — |
| SECONDARY Change in Multidimensional Pain Inventory (MPI): Support From Baseline to Week 6 |
-0.4; 0.5 | — |
| SECONDARY Change in Multidimensional Pain Inventory (MPI): Support Which the Patient Received From Baseline to Week 12 |
-0.2; 0.4 | — |
| SECONDARY Change in Multidimensional Pain Inventory (MPI): Pain Severity From Baseline to Week 6 |
-1.2; -1.0 | — |
| SECONDARY Change in Multidimensional Pain Inventory (MPI): Pain Severity From Baseline to Week 12 |
-1.5; -1.2 | — |
| SECONDARY Change in Multidimensional Pain Inventory (MPI): Life Control From Baseline to Week 6 |
0.2; 0.2 | — |
| SECONDARY Change in Multidimensional Pain Inventory (MPI): Life Control From Baseline to Week 12 |
0.4; 0.3 | — |
| SECONDARY Change in Multidimensional Pain Inventory (MPI): Affective Distress From Baseline to Week 6 |
-0.3; -0.5 | — |
| SECONDARY Change in Multidimensional Pain Inventory (MPI): Affective Distress From Baseline to Week 12 |
-0.5; -0.8 | — |
| SECONDARY Change in Multidimensional Pain Inventory (MPI): Negative Responses From Baseline to Week 6 |
-0.1; -0.7 | — |
| SECONDARY Change in Multidimensional Pain Inventory (MPI): Negative Responses From Baseline to Week 12 |
0.1; -0.3 | — |
| SECONDARY Change in Multidimensional Pain Inventory (MPI): Solicitous Responses From Baseline to Week 6 |
-0.2; -0.2 | — |
| SECONDARY Change in Multidimensional Pain Inventory (MPI): Solicitous Responses From Baseline to Week 12 |
-0.2; 0.2 | — |
| SECONDARY Change in Multidimensional Pain Inventory (MPI): Degree to Which Significant Others Display Distracting Responses to the Patient's Pain Behaviors and Complaints From Baseline to Week 6 |
-0.1; -0.1 | — |
| SECONDARY Change in Multidimensional Pain Inventory (MPI): Degree to Which Significant Others Display Distracting Responses to the Patient's Pain Behaviors and Complaints From Baseline to Week 12 |
-0.2; 0.0 | — |
| SECONDARY Change in Multidimensional Pain Inventory (MPI): Household Chores From Baseline to Week 6 |
0.0; -0.1 | — |
| SECONDARY Change in Multidimensional Pain Inventory (MPI): Household Chores From Baseline to Week 12 |
0.1; -0.1 | — |
| SECONDARY Change in Multidimensional Pain Inventory (MPI): Outdoor Work From Baseline to Week 6 |
-1.2; 0.3 | — |
| SECONDARY Change in Multidimensional Pain Inventory (MPI): Outdoor Work From Baseline to Week 12 |
-1.6; 0.6 | — |
| SECONDARY Change in Multidimensional Pain Inventory (MPI): Social Activities From Baseline to Week 6 |
0.1; 0.1 | — |
| SECONDARY Change in Multidimensional Pain Inventory (MPI): Social Activities From Baseline to Week 12 |
0.1; 0.3 | — |
| SECONDARY Change in Multidimensional Pain Inventory (MPI): General Activities From Baseline to Week 6 |
-0.2; 0.1 | — |
| SECONDARY Change in Multidimensional Pain Inventory (MPI): General Activities From Baseline to Week 12 |
-0.3; 0.3 | — |
| SECONDARY Change in Clinical Global Impression - Severity Pain From Baseline to Week 2 |
-0.5; -0.4 | — |
| SECONDARY Change in Clinical Global Impression - Severity Pain From Baseline to Week 6 |
-0.7; -0.8 | — |
| SECONDARY Change in Clinical Global Impression - Severity Pain From Baseline to Week 12 |
-0.8; -1.0 | — |
| SECONDARY Change in Hamilton Depression Score From Baseline to Week 2 |
-0.2; -4.5 | — |
| SECONDARY Change in Hamilton Depression Score From Baseline to Week 6 |
-1.5; -9.3 | — |
| SECONDARY Change in Hamilton Depression Score From Baseline to Week 12 |
-0.8; -9.7 | — |
| SECONDARY Suicidal Thoughts by BDI-II at Week 2 |
67; 27; 3; 1; 0; 0 | — |
| SECONDARY Suicidal Thoughts by BDI-II at Week 6 |
57; 22; 2; 1; 0; 0 | — |
| SECONDARY Suicidal Thoughts by BDI-II at Week 12 |
63; 24; 0; 2; 0; 0 | — |
| SECONDARY Suicidal Thoughts or Behaviours by HAMD-17 at Week 2 |
68; 26; 0; 2; 0; 0 | — |
| SECONDARY Suicidal Thoughts or Behaviours by HAMD-17 at Week 6 |
60; 22; 0; 2; 0; 0 | — |
| SECONDARY Suicidal Thoughts or Behaviours by HAMD-17 at Week 12 |
66; 26; 0; 1; 0; 0 | — |
| SECONDARY Change of Fasting Blood Glucose From Baseline at Week 12 |
14.9; 13.0 | — |
| SECONDARY Change of Glycosylated Hemoglobin A1c (HbA1c) From Baseline at Week 12 |
0.1; 0.1 | — |
| SECONDARY Change of Systolic Blood Pressure From Baseline at Week 12 |
-0.4; -2.8 | — |
| SECONDARY Change of Diastolic Blood Pressure From Baseline at Week 12 |
2.2; -0.6 | — |
| SECONDARY Change of Pulse Rate From Baseline at Week 12 |
2.4; 2.9 | — |
Summary
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.
Eligibility Criteria
Inclusion criteria
- Present with pain due to bilateral peripheral neuropathy (according to International Statistical Classification of Diseases and Related Health Problems 10 (ICD 10).
- 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.
- Male or female outpatients at least 18 years of age.
- 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.
- Educational level and degree of understanding such that they can communicate intelligibly with the investigator and study coordinator.
- Judged to be reliable and agrees to keep all appointments for clinic visits, tests, and procedures required by the protocol.
Exclusion criteria
- Have already a diagnosis of Depression and are currently treated with an antidepressant medication for depression, when entering the study.
- Suffer from pain that cannot be clearly differentiated from or conditions that interfere with the assessment of DPNPain.
- Had a historical exposure to drugs known to cause neuropathy, that could have been responsible for neuropathy.
- Have previously been treated with duloxetine (for DPNP or MDD)
- 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).
- Had a history of substance abuse or dependence within the past year, excluding nicotine and caffeine.
Data sourced from ClinicalTrials.gov (NCT00844194). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.