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

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)

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

Study Overview

• Status: Completed
• Conditions: Depressive Disorder, Major
• Intervention / Treatment: Drug: Placebo; Drug: Duloxetine

• Study Type: Interventional
• Enrollment: 327
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo
EXPERIMENTAL: Duloxetine	Drug: Duloxetine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: May 1, 2005
• Primary Completion (ACTUAL): May 1, 2006

Study Registration Dates

• First Submitted: September 4, 2014
• First Submitted That Met QC Criteria: September 4, 2014
• First Posted (ESTIMATE): September 5, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): September 5, 2014
• Last Update Submitted That Met QC Criteria: September 4, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Dopamine Agents; Serotonin and Noradrenaline Reuptake Inhibitors; Duloxetine Hydrochloride
• Other Study ID Numbers: 1208.10