Study to Evaluate the Efficacy of Duloxetine in Outpatients With Major Depressive Disorder and Pain

Study Overview
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Brief Summary
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The purpose of this study was to investigate the efficacy of duloxetine versus placebo on pain in outpatients with major depressive disorder (MDD): change in Brief Pain Inventory Short Form (BPI-SF) 24-hour average pain score from baseline over the 8 weeks of treatment

Official Title
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A Ten-week, Randomized, Double-blind Study Evaluating the Efficacy of Duloxetine 60 mg Once Daily Versus Placebo in Outpatients With Major Depressive Disorder and Pain (EU-Pain Enriched Study)

Conditions
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Depressive Disorder, Major

Intervention / Treatment
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* Drug: Duloxetine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female outpatients who meet the criteria for MDD according to the Diagnostic and Statistic Manual of mental disorders, 4th edition (DSM-IV) criteria and confirmed by Mini International Neuropsychiatric Interview (MINI) Montgomery-Asberg Depression Rating Scale (MADRS) score ≥20 at screening and baseline (Visits 1 and 2) Patients must have had at least one previous episode of depression in their medical history Painful physical symptoms (PPS) with a score ≥ 3 on the BPI-SF scale for average pain at screening and baseline Patient aged 18 years or older at the screening visit CGI-Severity score ≥ 4 at Visits 1 and 2 Patients willing and able to comply with the scheduled visits, tests and procedures required by the protocol Written informed consent obtained at the screening visit, in accordance with Good clinical practice (GCP) and local regulatory requirements, prior to any study procedure Exclusion Criteria: Neuro-psychiatric exclusions Lack of response of the current episode to 2 or more adequate courses of antidepressant therapy given at a clinically appropriate dose and for a sufficient length of time in the judgement of the investigator Any anxiety disorder as a primary diagnosis within the past 6 months (including panic disorder, obsessive-compulsive disorder, posttraumatic stress disorder, generalized anxiety disorder, and social phobia). Note: Specific phobias (i.e. agoraphobia, arachnophobia, etc.) will be allowed Any diagnosis of bipolar disorder, schizophrenia, or other psychotic disorders Presence of an Axis II disorder which, in the judgement of the investigator, would interfere with compliance with the study protocol History of serious suicide attempt or patient judged to be at serious suicidal risk in the opinion of the investigator and / or score > 2 for question 10 (suicide) of the MADRS History of drug dependence, including alcohol or benzodiazepines, according to DSM-IV, in the previous year Positive urine screen for drug abuse (cannabis, benzodiazepines, barbiturates, opiates, cocaine, amphetamines) Other medical exclusions Patients requiring continuous treatment with analgesics (> step 2 WHO definition) because of chronic pain (> 6 months) Patients with organic pain syndromes Epilepsy or history of seizure disorder or of a treatment with anticonvulsant medication for epilepsy or seizures Patients with a known diagnosis of raised intraocular pressure or at risk of acute narrow-angle glaucoma Known diagnosis of congenital galactosaemia, glucose or galactose malabsorption syndrome, or lactose deficiency Patients with severely impaired renal function, defined by a creatinine clearance < 30 mL/min (creatinine clearance was calculated by the central laboratory from the screening safety laboratory test Acute liver injury (such as hepatitis) or severe (Child-Pugh Class C) cirrhosis Abnormal initial ECG findings according to investigator's judgement Serious medical illness or clinically significant laboratory abnormalities which, in the judgement of the investigator, are likely to require medication/ intervention or hospitalization during the course of the study Women of childbearing potential not using a medically accepted means of contraception when engaging in sexual intercourse (e.g. intrauterine device, oral contraceptive, contraceptive patch, implant, or barrier devices) Women who are pregnant or breast-feeding Pharmacological and other exclusions Participation in another clinical trial within 30 days prior to screening (Visit 1) Patients who have previously completed or withdrawn from this or any other study investigating duloxetine or have previously been treated with duloxetine Treatment with a monoamine oxidase inhibitor (MAOI) within 14 days prior to Visit 2 or potential need to use a MAOI within 5 days after discontinuation of study drug Treatment with fluoxetine within 28 days prior to Visit 2 Treatment with any of excluded medications (listed in Protocol) within 7 days prior to Visit 2 (excepted MAOI within 14 days and fluoxetine within 28 days) Frequent and/or severe allergic reactions with multiple medications. Known hypersensitivity to duloxetine or any of the inactive ingredients Electro-convulsive Therapy (ECT) or Transcranial Magnetic Stimulation (TMS) within one year prior to screening Initiation or discontinuation of depression-oriented psychotherapeutic treatment (e.g. behavioural therapy, psychoanalytic therapy, cognitive therapy etc.) within 6 weeks prior to screening visit or planned use of such treatment at any time during the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Duloxetine<br> | Drug: Duloxetine<br> <br> |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of 24-hour average pain rated on Brief Pain Inventory-Short Form (BPI-SF) score |  | Up to 8 weeks after drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Montgomery-Asberg Depression Rating Scale (MADRS) total score |  | Up to 8 weeks after drug administration | 
| Time to sustained clinical response for Painful Physical Symptoms (PPS) according BPI-SF score | as defined by 30% reduction from baseline in question 5 (average pain) of the BPI-SF score | Up to 8 weeks after drug administration | 
| Change of patient symptoms rated on Symptom Checklist 90 Revised (SCL-90-R) scale |  | Up to 8 weeks after drug administration | 
| Patients Global Impression (PGI) rated on PGI-improvement scale |  | Up to 8 weeks after drug administration | 
| Clinical Global Impressions (CGIs) by investigator rated on CGI-severity score |  | Up to 8 weeks after drug administration | 
| Clinical Global Impressions (CGIs) by investigator rated on CGI-improvement scale |  | Up to 8 weeks after drug administration | 
| Time to sustained clinical response for overall depression symptoms | as defined by a 50% reduction from baseline in MADRS score | Up to 8 weeks after drug administration | 
| Number of patients with adverse events |  | Up to 8 weeks after drug administration | 
| Number of patients withdrawing due to adverse event |  | Up to 8 weeks after drug administration | 
| Number of patients with clinical significant findings in vital signs | blood pressure, pulse rate | Up to 8 weeks after drug administration | 
| Number of patients with clinical significant findings in weight |  | Up to 8 weeks after drug administration | 
| Number of patients with clinical significant findings in laboratory values |  | Up to 8 weeks after drug administration |