Clinical trial NCT01018680: A Study Comparing Duloxetine Versus Placebo in Patients Taking a Nonsteroidal Anti-inflammatory Drug (NSAID) for Knee Pain Due to Osteoarthritis
Official title: A Randomized, Placebo-Controlled Trial of Duloxetine Added to Nonsteroidal Anti-inflammatory Drugs in Patients With Knee Pain Due to Osteoarthritis Who Have Had Suboptimal Response to Nonsteroidal Anti-inflammatory Drug Treatment.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Osteoarthritis Knee Pain
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2009-11-25
Enrollment: 524
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study will test the hypothesis that, in patients with knee pain due to osteoarthritis (OA) who are taking nonsteroidal anti-inflammatory drugs (NSAIDs) but still have significant knee pain, duloxetine 60 to 120 milligrams (mg) daily for 10 weeks will provide additional reduction in pain.

Detailed description: Duloxetine has been studied in pain due to osteoarthritis (OA) in 2 previous placebo controlled clinical trials. In clinical practice, when nonsteroidal anti-inflammatory drugs (NSAIDs) are ineffective in reducing pain due to OA, clinicians often add a second agent without discontinuing NSAIDs. In this study, we will investigate whether adding duloxetine to NSAIDs provides additional pain relief and functional improvement in patients with knee pain due to OA.

Eligibility criteria: Inclusion Criteria:

* Present with knee pain due to osteoarthritis (OA) based on OA clinical and radiographic diagnostic criteria.
* Knee Pain for \> 14 days of each month for the 3 months directly preceding study entry.
* Taking nonsteroidal anti-inflammatory drugs (NSAIDs) for knee pain due to OA on most days in the 3 months immediately preceding study entry.

Exclusion Criteria:

* History of intolerance or nonresponsiveness to an adequate trial of duloxetine used for any indication, in the opinion of the investigator.
* Previous diagnosis of psychosis, bipolar disorder, or schizoaffective disorder.
* Have major depressive disorder (MDD) as determined using depression module of the Mini International Neuropsychiatric Interview (MINI).
* Judged clinically by the investigator to be at suicidal risk by examination or using the Columbia Suicide Severity Rating Scale (C-SSRS).
* History of substance abuse or dependence within the past year, excluding nicotine and caffeine.
* Positive urine drug screen for any substance of abuse or excluded medication.
* Opioid dependent in the opinion of the investigator, taking opioids more than 3 days a week, or unwilling to discontinue opioids during the study period.
* Known hypersensitivity to duloxetine or its inactive ingredients.
* History of intolerance or hypersensitivity to NSAIDS, Cyclooxygenase (COX-2) inhibitors, or proton pump inhibitors.
* History of peptic ulcer disease, bleeding disorder, gastrointestinal bleeding, or any abnormal bleeding.
* Baseline hemoglobin measurement of \<11 grams per deciliter (g/dL) for males, or \<10 g/dL for females.
* Serious or unstable cardiovascular, hepatic, renal, metabolic, respiratory, or hematologic illness, symptomatic peripheral vascular disease, or any other medical or psychiatric condition that would compromise participation or be likely to lead to hospitalization or a change in medication during the course of the study.
* Uncorrected thyroid disease, uncontrolled narrow-angle glaucoma, uncontrolled or poorly controlled hypertension, or history of seizures.
* Active liver injury (such as hepatitis) or any degree of hepatic insufficiency (Child-Pugh Class C).
* Frequent falls that could result in hospitalization or could compromise response to treatment.
* Confounding painful condition that may interfere with assessment of the index knee.
* Chronic widespread pain affecting all four quadrants of the body, or diagnosis of fibromyalgia.
* Received intra-articular hyaluronate (Synvisc), steroids, joint lavage, or other invasive therapies to the knee in the past 6 months.
* Arthroscopy of the index knee within the past year or joint replacement of the index knee at anytime.
* Diagnosis of inflammatory arthritis (that is, rheumatoid arthritis, psoriatic arthritis, reactive arthritis, ankylosing spondylitis, etc.) or an autoimmune disorder (excluding inactive Hashimoto's thyroiditis).
* Prior synovial fluid analysis showing a white blood cell count greater than or equal to 2000 cubic millimeters (mm\^3) that is indicative of a diagnosis other than OA, or have a history of gout or pseudogout.
* Radiographic evidence of end-stage (bone on bone) OA in either knee.
* Knee replacement surgery planned within the next 6 months.
* Nonambulatory or requiring the use of crutches, a walker, or more than 1 cane.
* Body mass index (BMI) \>40.

Primary outcomes:
measure: Change From Baseline in the Weekly Mean of the 24-Hour Average Pain Score at 8 Weeks
timeFrame: Baseline, 8 weeks (blinded endpoint)
Secondary outcomes:
measure: Patient Global Impression of Improvement (PGI-I) at 8 Weeks
timeFrame: 8 weeks (blinded endpoint)
measure: Change From Baseline in the Western Ontario and McMaster Universities Index of Osteoarthritis (WOMAC) Pain, Stiffness, and Physical Function Subscale Scores at 8 Weeks
timeFrame: Baseline, 8 weeks (blinded endpoint)
measure: Change From Baseline in the Weekly Mean of the 24-Hour Night Pain and Worst Pain Scores at 8 Weeks
timeFrame: Baseline, 8 weeks (blinded endpoint)
measure: Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) Scores at 8 Weeks
timeFrame: Baseline, 8 weeks (blinded endpoint)
measure: Change From Baseline in the Clinical Global Impression of Severity (CGI-S) at 8 Weeks
timeFrame: Baseline, 8 weeks (blinded endpoint)
measure: Change From Baseline in the Patient Global Assessment of Illness (PGAI) at 8 Weeks
timeFrame: Baseline, 8 weeks (blinded endpoint)
measure: Change From Baseline in the Profile of Mood States-Brief Form (BPOMS) Total and Subscale Scores at 8 Weeks
timeFrame: Baseline, 8 weeks (blinded endpoint)
measure: Percentage of Participants Using Acetaminophen Weekly During the 10-Week Treatment Period
timeFrame: Baseline through 10 weeks (blinded endpoint)
measure: Percentage of Responders as Assessed by the Osteoarthritis Research Society International (OARSI) Response Criteria up to 8 Weeks
timeFrame: Up to 8 weeks (blinded endpoint)
measure: Percentage of Participants Who Achieved a 30 Percent or 50 Percent Reduction in the Weekly Mean of the 24-Hour Average Pain Score up to 8 Weeks
timeFrame: Up to 8 weeks (blinded endpoint)
measure: Percentage of Participants Who Achieved a 30 Percent or 50 Percent Reduction in the Brief Pain Inventory-Severity (BPI-S) Average Pain Score up to 8 Weeks
timeFrame: Up to 8 weeks (blinded endpoint)
measure: Percentage of Participants Who Discontinued Due to an Adverse Event During the 10-Week Treatment Period
timeFrame: Baseline through 10 weeks
Other outcomes:
measure: Percentage of Participants With Abnormal High Hemoglobin A1c (HbA1c) up to 10 Weeks
timeFrame: Up to 10 weeks
measure: Percentage of Participants With Abnormal Weight Gain and Weight Loss up to 10 Weeks
timeFrame: Up to 10 weeks
measure: Percentage of Participants With Abnormal Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) up to 10 Weeks
timeFrame: Up to 10 weeks
measure: Percentage of Participants With Abnormal Pulse Rate up to 10 Weeks
timeFrame: Up to 10 weeks
measure: Percentage of Participants With a Change of Better, Worse, or No Change in Health Outcomes as Measured by Resource Utilization (REU) up to 10 Weeks
timeFrame: Up to 10 weeks
Locations:
city: Tucson
country: United States
facility: 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.
state: Arizona
city: Garden Grove
country: United States
facility: 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.
state: California
city: Long Beach
country: United States
facility: 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.
state: California
city: San Diego
country: United States
facility: 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.
state: California
city: Spring Valley
country: United States
facility: 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.
state: California
city: Wildomar
country: United States
facility: 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.
state: California
city: Boulder
country: United States
facility: 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.
state: Colorado
city: Cromwell
country: United States
facility: 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.
state: Connecticut
city: Deland
country: United States
facility: 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.
state: Florida
city: Ocala
country: United States
facility: 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.
state: Florida
city: Orlando
country: United States
facility: 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.
state: Florida
city: Pembroke Pines
country: United States
facility: 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.
state: Florida
city: Prairie Village
country: United States
facility: 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.
state: Kansas
city: Lexington
country: United States
facility: 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.
state: Kentucky
city: Mt Sterling
country: United States
facility: 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.
state: Kentucky
city: Pasadena
country: United States
facility: 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.
state: Maryland
city: Wheaton
country: United States
facility: 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.
state: Maryland
city: Fall River
country: United States
facility: 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.
state: Massachusetts
city: Weymouth
country: United States
facility: 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.
state: Massachusetts
city: Ann Arbor
country: United States
facility: 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.
state: Michigan
city: Detroit
country: United States
facility: 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.
state: Michigan
city: St Louis
country: United States
facility: 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.
state: Missouri
city: Manlius
country: United States
facility: 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.
state: New York
city: New York
country: United States
facility: 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.
state: New York
city: Staten Island
country: United States
facility: 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.
state: New York
city: Beachwood
country: United States
facility: 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.
state: Ohio
city: Cincinnati
country: United States
facility: 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.
state: Ohio
city: Dayton
country: United States
facility: 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.
state: Ohio
city: Duncansville
country: United States
facility: 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.
state: Pennsylvania
city: Warwick
country: United States
facility: 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.
state: Rhode Island
city: Bellevue
country: United States
facility: 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.
state: Washington
city: Spokane
country: United States
facility: 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.
state: Washington
city: Ponce
country: Puerto Rico
facility: 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.
city: San German
country: Puerto Rico
facility: 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.
city: San Juan
country: Puerto Rico
facility: 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.
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References:
citation: Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW. Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol. 1988 Dec;15(12):1833-40.
citation: Westfall PH, Krishen A. Optimally weighted, fixed sequence and gatekeeper multiple testing procedures. J Stat Plann Infer. 2001;99(1):25-40.
citation: Yue L, Wang J, Enomoto H, Fujikoshi S, Alev L, Cheng YY, Skljarevski V. The Clinical Relevance of Pain Severity Changes: Is There Any Difference Between Asian and Caucasian Patients With Osteoarthritis Pain? Pain Pract. 2020 Feb;20(2):129-137. doi: 10.1111/papr.12835. Epub 2019 Nov 20.
citation: Risser RC, Hochberg MC, Gaynor PJ, D'Souza DN, Frakes EP. Responsiveness of the Intermittent and Constant Osteoarthritis Pain (ICOAP) scale in a trial of duloxetine for treatment of osteoarthritis knee pain. Osteoarthritis Cartilage. 2013 May;21(5):691-4. doi: 10.1016/j.joca.2013.02.007. Epub 2013 Feb 26.
citation: Frakes EP, Risser RC, Ball TD, Hochberg MC, Wohlreich MM. Duloxetine added to oral nonsteroidal anti-inflammatory drugs for treatment of knee pain due to osteoarthritis: results of a randomized, double-blind, placebo-controlled trial. Curr Med Res Opin. 2011 Dec;27(12):2361-72. doi: 10.1185/03007995.2011.633502. Epub 2011 Nov 9.