A Study for the Treatment of Diabetic Peripheral Neuropathic Pain

Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to determine if duloxetine can help patients with painful diabetic neuropathy.

Official Title
-----------------
A Superiority Study of LY248686 Versus Placebo in the Treatment of Patients With Diabetic Peripheral Neuropathic Pain

Conditions
-----------------
Diabetic Neuropathies

Intervention / Treatment
-----------------
* Drug: Duloxetine hydrochloride - 40 mg
* Drug: placebo
* Drug: Duloxetine hydrochloride - 60 mg


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with pain due to bilateral peripheral neuropathy induced by type 1 or 2 diabetes mellitus. The pain must have been present for at least 6 months and be evaluable in feet, legs, or hands. Participants with hemoglobin A1c (HbA1c) less than or equal to 9.0 percent at Visit 1. Participants in whom HbA1c had been measured 42-70 days before Visit 1 and subsequent HbA1c levels have been within +/- 1.0 percent of the level at Visit 1. Participants with a mean of the 24-hour average pain severity scores (round off to a whole number) of 4 or higher, as calculated from the patient diary for 7 days immediately before Visit 2 Exclusion Criteria: Participants who have undergone renal transplant or who are currently on renal dialysis. Participants who have a history requiring pharmacotherapy within the past year or current history of psychiatric disease, such as mania, bipolar disorder, depression, anxiety disorder, or eating disorder. Participants with hypertension with poor control of blood pressure (systolic blood pressure greater than or equal to 180 millimeters of mercury (mmHg) or diastolic blood pressure greater than or equal to 110 mmHg Participants with alanine transaminase (ALT) or aspartate transaminase (AST) greater than or equal to 100 Units per Liter (U/L) at Visit 1. Participants unable to discontinue prohibited concomitant drugs or concomitant therapies after Visit 1.

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 79 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Duloxetine 60<br>duloxetine 60 milligram (mg) taken orally every day | Drug: Duloxetine hydrochloride - 60 mg<br>* duloxetine 60 mg taken orally every day<br>* Other names: Cymbalta;|
| Experimental: Duloxetine 40<br>Duloxetine 40 mg taken orally every day | Drug: Duloxetine hydrochloride - 40 mg<br>* duloxetine 40 mg taken orally every day<br>* Other names: Cymbalta;|
| Placebo Comparator: Placebo<br>placebo comparator taken orally every day | Drug: placebo<br>* placebo taken orally every day<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline at Week 12 in Average Pain Severity Rating Using Diaries for the Combined Duloxetine Arms (40 mg + 60 mg) | Average pain severity was measured using an 11-point numerical rating scale, collected by diaries and expressed as weekly mean. The scale is a self-reported instrument that measures the severity of pain based on the average pain over the past 24-hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). | Baseline, 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline at Week 12 in Average Pain Severity Rating Score Using Diaries | Average pain severity was measured using an 11-point numerical rating scale, collected by diaries and expressed as weekly mean. The scale is a self-reported instrument that measures the severity of pain based on the average pain over the past 24-hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). | Baseline, 12 weeks | 
| Change From Baseline at Week 12 in Worst Pain Severity Score and Night Pain Severity Score Using Diaries for the Combined Duloxetine Arms (40 mg + 60 mg) | Pain severity for worst pain and night pain as measured by an 11-point numerical rating scale, collected by diaries and expressed as weekly means. A self-reported scale that measures the severity of pain based on the worst pain and night pain experienced over the past 24-hours. The worst pain and night pain severity scores each range from 0 (no pain) to 10 (pain as severe as you can imagine). | Baseline, 12 weeks | 
| Change From Baseline at Week 12 in Worst Pain Severity Score and Night Pain Severity Score Using Diaries | Pain severity for worst pain and night pain as measured by an 11-point numerical rating scale, collected by diaries and expressed as weekly means. A self-reported scale that measures the severity of pain based on the worst pain and night pain experienced over the past 24-hours. The worst pain and night pain severity scores each range from 0 (no pain) to 10 (pain as severe as you can imagine). | Baseline, Week 12 | 
| Patient Global Impression of Improvement Scale at Week 12 in Combined Duloxetine Arms (40 mg + 60 mg) | A scale that measures the patient's perception of improvement at the time of assessment compared with the start of treatment. The score ranges from 1 (very much better) to 7 (very much worse). | Week 12 | 
| Patient Global Impression of Improvement Scale at Week 12 | A scale that measures the patient's perception of improvement at the time of assessment compared with the start of treatment. The score ranges from 1 (very much better) to 7 (very much worse). | Week 12 | 
| Change From Baseline in Brief Pain Inventory Severity Scores at Week 12 for the Combined Duloxetine Arms (40 mg + 60 mg) | A self-reported scale that measures the severity of pain. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). There are 4 questions assessing worst pain, least pain, and average pain in the past 24 hours, and the pain right now. Each question has a total range of scores from 0 to 10. | Baseline, Week 12 | 
| Change From Baseline in Brief Pain Inventory Severity Scores at Week 12 | A self-reported scale that measures the severity of pain. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). There are 4 questions assessing worst pain, least pain, and average pain in the past 24 hours, and the pain right now. Each question has a total range of scores from 0 to 10. | Baseline, Week 12 | 
| Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 for the Combined Duloxetine Arms (40 mg + 60 mg) | The Interference scores range from 0 (does not interfere) to 10 (completely interferes). There are 7 questions assessing the interference of pain in the past 24 hours for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. Each question has a total range of scores from 0 to 10. | Baseline, Week 12 | 
| Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 | The Interference scores range from 0 (does not interfere) to 10 (completely interferes). There are 7 questions assessing the interference of pain in the past 24 hours for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. Each question has a total range of scores from 0 to 10. | Baseline, Week 12 | 
| Change From Baseline in Beck Depression Inventory-II (BDI-II) Total Score at Week 12 for the Combined Duloxetine Arms (40 mg + 60 mg) | A 21-item, patient-completed questionnaire to assess characteristics of depression. Each of the 21 items corresponding to a symptom of depression is summed to give a single score. There is a four-point scale for each item ranging from 0 to 3. Total score ranges from 0 (no depression) to 63 (severe depression). | Baseline, Week 12 | 
| Change From Baseline in Beck Depression Inventory-II (BDI-II) Total Score at Week 12 | A 21-item, patient-completed questionnaire to assess characteristics of depression. Each of the 21 items corresponding to a symptom of depression is summed to give a single score. There is a four-point scale for each item ranging from 0 to 3. Total score ranges from 0 (no depression) to 63 (severe depression). | Baseline, Week 12 |