A Phase 3b Study to Assess the Efficacy of Duloxetine 60 mg Once Daily Compared With Placebo on the Reduction of Pain Caused by Osteoarthritis of the Knee, in a 13-week, Double-blind, Randomized Study
Overview
- Phase
- Phase 3
- Intervention
- Duloxetine (DLX)
- Conditions
- Osteoarthritis Knee Pain
- Sponsor
- Eli Lilly and Company
- Enrollment
- 424
- Locations
- 1
- Primary Endpoint
- Change From Baseline to 13 Week Endpoint (Baseline Observation Carried Forward [BOCF]) in Brief Pain Inventory (BPI) "24-Hour Average Pain" Item (Question 3) of the BPI-Modified Short Form Score
- Status
- Completed
- Last Updated
- 15 years ago
Overview
Brief Summary
The primary purpose of this study is to determine if duloxetine 60 mg once daily (QD) reduces pain severity in patients with osteoarthritis (OA) knee pain compared with placebo.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female outpatients with osteoarthritis knee pain for greater than or equal to 14 days of each month for 3 months prior to study entry.
- •Have a rating of greater than or equal to 4 on the BPI average pain item (Question 3 of the Brief Pain Inventory \[BPI\] modified short form) at screening and randomization
Exclusion Criteria
- •Have had any previous exposure to duloxetine.
- •Have any previous diagnosis of psychosis, bipolar disorder, or schizoaffective disorder.
- •Have Major Depression Disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, as assessed by the Mini International Neuropsychiatric Interview (Sheehan et al. 1998), or diagnosed within the past year.
- •Have a history of substance abuse or dependence within the past year, excluding nicotine and caffeine.
- •Are taking any excluded medications that cannot be discontinued at screening visit.
- •Have current or pending disability compensation or litigation issues that may compromise response to treatment, in the opinion of the investigator.
- •Have had treatment with a monoamine oxidase inhibitor (MAOI) within 14 days of randomization or the potential need to use an MAOI during the study or within 5 days of discontinuation of study drug.
- •Have a positive urine drug screen for any substance of abuse or excluded medication.
- •Are pregnant or breast-feeding.
- •Have serious cardiovascular, hepatic, renal, respiratory, or hematologic illness, or other medical or psychiatric condition that, in the opinion of the investigator, would compromise participation or be likely to lead to hospitalization during the course of the study.
Arms & Interventions
DLX30-PLA
Per the protocol, patients randomized to the duloxetine group were to receive duloxetine for the entire 13-week acute treatment period. Patients were to start at a 30 mg daily (QD) dose of duloxetine for 1 week, then increase to 60 mg QD of duloxetine for the following 12 weeks. However, due to a study drug labeling error, patients randomized to this group received 30 mg of duloxetine for the initial 1-week, but received placebo instead of receiving 60 mg QD of duloxetine for the next 12 weeks. The resulting unintended, mixed treatment group was labeled as DLX30-PLA throughout this document. Per protocol, the last week of the study (week 14) was intended to be a 1-week taper period. Patients in this treatment group were to receive 30 mg QD of duloxetine during that week, and that did occur per protocol.
Intervention: Duloxetine (DLX)
DLX30-PLA
Per the protocol, patients randomized to the duloxetine group were to receive duloxetine for the entire 13-week acute treatment period. Patients were to start at a 30 mg daily (QD) dose of duloxetine for 1 week, then increase to 60 mg QD of duloxetine for the following 12 weeks. However, due to a study drug labeling error, patients randomized to this group received 30 mg of duloxetine for the initial 1-week, but received placebo instead of receiving 60 mg QD of duloxetine for the next 12 weeks. The resulting unintended, mixed treatment group was labeled as DLX30-PLA throughout this document. Per protocol, the last week of the study (week 14) was intended to be a 1-week taper period. Patients in this treatment group were to receive 30 mg QD of duloxetine during that week, and that did occur per protocol.
Intervention: Placebo (PLA)
PLA-DLX60
Per the protocol, patients randomized to the placebo group were to receive placebo for the entire 13-week acute treatment period. Patients were to start on placebo for the first week, then continue on placebo for the following 12 weeks. However, due to a study drug labeling error, patients in this group received placebo for the initial 1-week, but received 60 mg QD of duloxetine instead of receiving placebo for the next 12 weeks. The resulting unintended, mixed treatment group was labeled as PLA-DLX60 throughout this document. Per protocol, the last week of the study (week 14) was intended to be a 1-week taper period. Patients in this treatment group were to receive placebo that week, and that did occur per protocol.
Intervention: Duloxetine (DLX)
PLA-DLX60
Per the protocol, patients randomized to the placebo group were to receive placebo for the entire 13-week acute treatment period. Patients were to start on placebo for the first week, then continue on placebo for the following 12 weeks. However, due to a study drug labeling error, patients in this group received placebo for the initial 1-week, but received 60 mg QD of duloxetine instead of receiving placebo for the next 12 weeks. The resulting unintended, mixed treatment group was labeled as PLA-DLX60 throughout this document. Per protocol, the last week of the study (week 14) was intended to be a 1-week taper period. Patients in this treatment group were to receive placebo that week, and that did occur per protocol.
Intervention: Placebo (PLA)
Outcomes
Primary Outcomes
Change From Baseline to 13 Week Endpoint (Baseline Observation Carried Forward [BOCF]) in Brief Pain Inventory (BPI) "24-Hour Average Pain" Item (Question 3) of the BPI-Modified Short Form Score
Time Frame: Baseline, 13 weeks
A self-reported measure of the severity of pain based on the average pain over 24-hours. Severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). BOCF endpoint was defined as the baseline value for participants discontinued during acute phase, and defined as the last non-missing observation in the treatment phase for all other randomized participants. Due to the nature of a study drug labeling error which led to a treatment crossover (see Arms), data from protocol-defined treatment groups were compromised. The results from each mixed-treatment group are presented.
Secondary Outcomes
- Number of Participants With Suicidal Behaviors and Ideations From the Columbia Suicide Severity Rating Scale(Baseline through 13 weeks)
- Mean Change From Baseline to Endpoint (13 Week) in Patient's Global Impressions of Improvement Score(Baseline, 13 weeks)
- Mean Change From Baseline to Endpoint (13 Week) in Western Ontario McMaster Universities (WOMAC) Index Score(baseline, 13 weeks)
- Mean Change of Total Score From Baseline to Endpoint (13 Week) of Brief Pain Inventory-Severity (BPI-S) Scale(Baseline, 13 weeks)
- Mean Change of Total Score From Baseline to Endpoint (13 Week) in Brief Pain Inventory- Interference Score(Baseline, 13 weeks)
- Mean Change of Total Score From Baseline to Endpoint (13 Week) in Clinical Global Impressions of Severity (CGI-S)(Baseline, 13 weeks)
- Mean Change of Total Score From Baseline to Endpoint(13 Week) in Intermittent and Constant Osteoarthritis Pain: Knee Version(Baseline, 13 weeks)
- Mean Change of Total Score From Baseline to Endpoint (13 Week) in Profile of Mood States- Brief Form (BPOMS)(Baseline, 13 weeks)
- Mean Change of Total Score From Baseline to Endpoint (13 Week) in European Quality of Life Questionnaire (EQ-5D)(Baseline, 13 weeks)
- Mean Change From Baseline to Endpoint (13 Week) in 36-item Short-Form Health Survey(Baseline, 13 weeks)