A Study of Duloxetine in Patients With Osteoarthritis Knee Pain

Osteoarthritis Knee Pain Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00945945
• Other study ID #: 13214
• Secondary ID: F1J-MC-HMGP
• Status: Completed
• Phase: Phase 3
• First received: July 23, 2009
• Last updated: February 11, 2011
• Start date: July 2009
• Est. completion date: May 2010

Study information

• Verified date: February 2011
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 424
• Est. completion date: May 2010
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

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.

• Have a history of recurrent seizures other than febrile seizures.

• Are judged by the investigator to be at suicidal risk.

• Have uncontrolled narrow-angle glaucoma.

• Have acute liver injury (such as hepatitis) or severe cirrhosis (Child- Pugh Class C).

• Have known hypersensitivity to duloxetine or any of the inactive ingredients or patients with frequent or severe allergic reactions to multiple medications.

• Have frequent falls that could result in hospitalization or could compromise response to treatment.

• Have a confounding painful condition that may interfere with assessment of the index joint, that is, knee. (Knee pain should be the predominant pain. Mild OA pain of other joints is allowed.)

• Have a diagnosis of inflammatory arthritis (that is, rheumatoid arthritis) or an autoimmune disorder (excluding inactive Hashimoto's thyroiditis).

• Have received intraarticular hyaluronate or steroids, joint lavage, or other invasive therapies to the knee in the past 3 months.

• Have had knee arthroscopy of the index knee within the past year or joint replacement of the index knee at anytime.

• Have surgery planned during the study for the index joint.

• Have a body mass index (BMI) over 40.

• Use of acupuncture, chiropractic maneuvers, transcutaneous electrical nerve stimulation (TENS), or similar procedures aimed to relieve any kind of pain.

• Patients who are anticipated by the investigator to require use of analgesic agents including but not limited to non-steroidal anti-inflammatory drugs(NSAIDs), acetaminophen/paracetamol, and opioids, or other excluded medication for the duration of the study.

• Are unwilling or unable to comply with the data collection method used to record their patient rated outcome data.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Osteoarthritis
• Osteoarthritis Knee Pain
• Osteoarthritis, Knee

Intervention

Drug:
• Duloxetine (DLX)
dose daily by mouth
• Placebo (PLA)
Placebo Comparator daily by mouth

Locations

Country	Name	City	State
Germany	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Berlin
Germany	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Hamburg
Germany	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Rhaunen
Greece	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Heraklion
Greece	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Kifissia
Greece	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Marousi Attikis
Greece	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Thessaloniki
Puerto Rico	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Ponce
Romania	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Bucharest
Russian Federation	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Moscow
Spain	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Barcelona
Spain	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Getafe
Spain	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	La Coruña
Spain	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Madrid
Sweden	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Malmo
Sweden	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Uddevalla
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Clinton	Utah
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Lake Jackson	Texas
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Montgomery	Alabama
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Morton Grove	Illinois
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Myrtle Beach	South Carolina
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Oregon	Wisconsin
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Phoenix	Arizona
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Prairie Village	Kansas
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Spring Valley	California
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Toledo	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Germany,  Greece,  Puerto Rico,  Romania,  Russian Federation,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	Baseline, 13 weeks	No
Secondary	Number of Participants With Suicidal Behaviors and Ideations From the Columbia Suicide Severity Rating Scale	C-SSRS: scale capturing occurrence, severity, and frequency of suicide-related thoughts and behaviors. Number of patients with suicidal behaviors and ideations are provided. Suicidal behavior: a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation: a "yes" answer to any one of 5 suicidal ideation questions, which includes wish to be dead, and 4 different categories of active suicidal ideation.	Baseline through 13 weeks	Yes
Secondary	Mean Change From Baseline to Endpoint (13 Week) in Patient's Global Impressions of Improvement Score	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). Due to the nature of a study drug labeling error and the resultant treatment crossover (see Arms), the data from both protocol-defined treatment groups were compromised, and the intended comparisons for differences between those treatment groups are considered unevaluable. Secondary efficacy results from the 2 mixed-treatment groups are not presented.	Baseline, 13 weeks	No
Secondary	Mean Change From Baseline to Endpoint (13 Week) in Western Ontario McMaster Universities (WOMAC) Index Score	The WOMAC index (pain, stiffness, physical function subscales) was completed by the patient. The index has 24 questions. Each question is answered using a 5-point Likert scale (0 to 4). The Total score has a range from 0 (none) to 96 (extreme). Due to the nature of a study drug labeling error and the resultant treatment crossover (see Arms), data from both protocol-defined treatment groups were compromised, and the intended comparisons for differences between those treatment groups are considered unevaluable. Secondary efficacy results from the 2 mixed-treatment groups are not presented.	baseline, 13 weeks	No
Secondary	Mean Change of Total Score From Baseline to Endpoint (13 Week) of Brief Pain Inventory-Severity (BPI-S) Scale	Self-reported scale measuring pain severity. Severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). Four questions assess worst pain, least pain, and average pain in the past 24 hours, and pain right now. Total score ranges from 0-40. Due to the nature of a study drug labeling error and resultant treatment crossover, data from both protocol-defined treatment groups were compromised, and the intended comparisons for differences between those treatment groups are considered unevaluable. Secondary efficacy results from the 2 mixed-treatment groups are not presented.	Baseline, 13 weeks	No
Secondary	Mean Change of Total Score From Baseline to Endpoint (13 Week) in Brief Pain Inventory- Interference Score	Interference scores range from 0 (does not interfere) to 10 (completely interferes) on 7 questions assessing interference of pain for general activity, mood, walking ability, normal work, relations with others, sleep, and enjoyment of life. Total score ranges from 0-70. Due to the nature of study drug labeling error and resultant treatment crossover, data from both protocol-defined treatment groups were compromised, and intended comparisons for differences between those treatment groups are considered unevaluable. Secondary efficacy results from the 2 mixed-treatment groups are not presented.	Baseline, 13 weeks	No
Secondary	Mean Change of Total Score From Baseline to Endpoint (13 Week) in Clinical Global Impressions of Severity (CGI-S)	Measures severity of illness at the time of assessment compared with start of treatment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). Due to the nature of a study drug labeling error and the resultant treatment crossover (see Arms), the data from both protocol-defined treatment groups were compromised, and the intended comparisons for differences between those treatment groups are considered unevaluable. Secondary efficacy results from the 2 mixed-treatment groups are not presented.	Baseline, 13 weeks	No
Secondary	Mean Change of Total Score From Baseline to Endpoint(13 Week) in Intermittent and Constant Osteoarthritis Pain: Knee Version	An 11-item questionnaire to individually and jointly assess intermittent and constant pain. Questions assess intensity and impact of pain on activity and emotion. Each item is scored from 0 to 4; higher values indicate higher severity. Total Pain score ranges from 0-44. Due to the nature of study drug labeling error and resultant treatment crossover, data from both protocol-defined treatment groups were compromised, and intended comparisons for differences between those treatment groups are considered unevaluable. Secondary efficacy results from the 2 mixed-treatment groups are not presented.	Baseline, 13 weeks	No
Secondary	Mean Change of Total Score From Baseline to Endpoint (13 Week) in Profile of Mood States- Brief Form (BPOMS)	BPOMS measures mood states and has 6 factors: tension-anxiety, depression-dejection, anxiety-hostility, fatigue, confusion, and vigor. Item scores: 0 (not at all) to 4 (extremely). Each factor scores range from 0-20. Total score = sum of all factor scores minus vigor score. Due to nature of study drug labeling error and resultant treatment crossover, data from both protocol-defined treatment groups were compromised, and intended comparisons for differences between those treatment groups are considered unevaluable. Secondary efficacy results from the 2 mixed-treatment groups are not presented.	Baseline, 13 weeks	No
Secondary	Mean Change of Total Score From Baseline to Endpoint (13 Week) in European Quality of Life Questionnaire (EQ-5D)	Patients rate their health state in 5 domains: mobility, self-care, usual activities, pain, and mood. Score between 1-3 is generated for each domain which is mapped to single index score. Index ranges between 0-1; higher scores indicate better health perceived by patient. Due to nature of study drug labeling error and resultant treatment crossover, data from both protocol-defined treatment groups were compromised, and intended comparisons for differences between those treatment groups are considered unevaluable. Secondary efficacy results from the 2 mixed-treatment groups are not presented.	Baseline, 13 weeks	No
Secondary	Mean Change From Baseline to Endpoint (13 Week) in 36-item Short-Form Health Survey	Self-reported questionnaire with 36 questions covering 8 health domains. Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale, with higher scores indicating better health status or functioning. Due to the nature of a study drug labeling error and the resultant treatment crossover (see Arms), the data from both protocol-defined treatment groups were compromised, and the intended comparisons for differences between those treatment groups are considered unevaluable. Secondary efficacy results from the 2 mixed-treatment groups are not presented.	Baseline, 13 weeks	No