Osteoarthritis Knee PainPhase 3NCT01018680
A Study Comparing Duloxetine Versus Placebo in Patients Taking a Nonsteroidal Anti-inflammatory Drug (NSAID) for Knee Pain Due to Osteoarthritis
A Phase 3 study testing Duloxetine in people with Osteoarthritis Knee Pain, run by Eli Lilly and Company at 35 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Osteoarthritis Knee Pain
- What is being tested?
- Duloxetine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 524 participants
- Where
- 35 sitesin 2 countries
- Study dates
- Nov 2009to Apr 2011
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 25Show fewer
- 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.
Trial locations and contacts
35 sites in 2 countries.
35 sites in 2 countries
United States32 sites
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.
Ann Arbor, Michigan, 48104
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.
Beachwood, Ohio, 44122
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.
Bellevue, Washington, 98007
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.
Boulder, Colorado, 80304
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.
Cincinnati, Ohio, 45219
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.
Cromwell, Connecticut, 06416
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.
Dayton, Ohio, 45406
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.
DeLand, Florida, 32720
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.
Detroit, Michigan, 48235
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.
Duncansville, Pennsylvania, 16635
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.
Fall River, Massachusetts, 02720
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.
Garden Grove, California, 92845
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.
Lexington, Kentucky, 40509
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.
Long Beach, California, 90813
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.
Manlius, New York, 13104
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.
Mount Sterling, Kentucky, 40353
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.
New York, New York, 10021
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.
Ocala, Florida, 34471
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.
Orlando, Florida, 32806
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.
Pasadena, Maryland, 21122
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.
Pembroke Pines, Florida, 33026
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, 66206
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.
San Diego, California, 92123
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.
Spokane, Washington, 99202
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, 91978
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.
St Louis, Missouri, 63141
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.
Staten Island, New York, 10312
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.
Tucson, Arizona, 85704
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.
Warwick, Rhode Island, 02886
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.
Weymouth, Massachusetts, 02190
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.
Wheaton, Maryland, 20902
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.
Wildomar, California, 92595
Puerto Rico3 sites
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, 00732
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.
San German, 00683
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.
San Juan, 00917-5026
About this study
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.
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.
Read the 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.
- Conditions
- Osteoarthritis Knee Pain
- Being tested
- Duloxetine, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DuloxetineDrug
Also called Cymbalta, LY248686
30 milligrams (mg) taken by mouth, once daily for 1 week, followed by 60 to 120 mg taken by mouth, once daily for 9 weeks.
PlaceboDrug
Taken by mouth, once daily for 10 weeks
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
| Duloxetine | Experimental | Not described Receives: Drug: Duloxetine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in the Weekly Mean of the 24-Hour Average Pain Score at 8 Weeks
The weekly mean 24-hour average pain score was calculated from the participant's daily 24-hour average pain ratings using an 11-point numeric rating scale, with scores from 0 (indicating "no pain") to 10 (indicating "the worst possible pain"). The Least Squares Mean estimates were adjusted for baseline, treatment, investigator (pooled), week, treatment*week, and baseline*week.
Measured: Baseline, 8 weeks (blinded endpoint)
Secondary outcomes (12)
Patient Global Impression of Improvement (PGI-I) at 8 Weeks
A scale that measures the participant'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). The Least Squares Mean estimates were adjusted for baseline value of Patient Global Impression of Severity (PGI-S), treatment, investigator (pooled), visit, and treatment*visit. The PGI-S measures participant's perception of severity of illness at the time of assessment. Scores range from 1 (normal, not at all ill) to 7 (extremely ill).
Measured: 8 weeks (blinded endpoint)
Change From Baseline in the Western Ontario and McMaster Universities Index of Osteoarthritis (WOMAC) Pain, Stiffness, and Physical Function Subscale Scores at 8 Weeks
Self-administered questionnaire captures elements of pain, stiffness, and physical disability in participants with osteoarthritis of the knee and/or hip. Index has 24 questions (5 on pain, 2 on stiffness, 17 on physical function). Each question uses a 5-point numeric rating scale ranging from 0 (none) to 4 (extreme). Pain scores range: 0 to 20. Stiffness scores range: 0 to 8. Physical function scores range: 0 to 68. Higher scores=greater impairment. Least Squares Mean estimates were adjusted for baseline value, treatment, investigator (pooled), visit, treatment*visit, and baseline value*visit.
Measured: Baseline, 8 weeks (blinded endpoint)
Change From Baseline in the Weekly Mean of the 24-Hour Night Pain and Worst Pain Scores at 8 Weeks
Weekly mean 24-hour night pain and worst pain values are calculated from the participant's daily assessments of pain at night and worst pain during the previous 24 hours on an 11-point numeric rating scale, with scores from 0 (indicating "no pain") to 10 (indicating "the worst possible pain"). The Least Squares Mean estimates were adjusted for baseline value, treatment, investigator (pooled), week, treatment*week, and baseline*week.
Measured: Baseline, 8 weeks (blinded endpoint)
Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) Scores at 8 Weeks
Measures pain severity and pain interference with function. Severity scores: 0 (no pain) to 10 (severe pain) on each question. Interference scores: 0 (does not interfere) to 10 (completely interferes) on each question assessing interference of pain in past 24 hours for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. Mean interference is the average across the 7 interference items. The Least Squares Mean estimates were adjusted for baseline value, treatment, investigator (pooled), visit, treatment*visit, and baseline*visit.
Measured: Baseline, 8 weeks (blinded endpoint)
Change From Baseline in the Clinical Global Impression of Severity (CGI-S) at 8 Weeks
The CGI-S scale evaluates the severity of illness at the time of assessment. The scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). The CGI-S must be administered by a study physician in the presence of the participant or after having been in the presence of the participant. The Least Squares Mean estimates were adjusted for baseline, treatment, investigator (pooled), visit, treatment*visit, and baseline*visit.
Measured: Baseline, 8 weeks (blinded endpoint)
Change From Baseline in the Patient Global Assessment of Illness (PGAI) at 8 Weeks
The PGAI is a participant-rated measure of the severity of osteoarthritis (OA) of the knee the participant has experienced in the past week as indicated on an 11-point numeric rating scale, with scores ranging from 0 to 10, where greater numbers reflect greater severity. The Least Squares Mean estimates were adjusted for baseline value, treatment, investigator (pooled), visit, treatment*visit, and baseline*visit.
Measured: Baseline, 8 weeks (blinded endpoint)
Change From Baseline in the Profile of Mood States-Brief Form (BPOMS) Total and Subscale Scores at 8 Weeks
30-item BPOMS measures positive and negative aspects of mood states (item score: 0=not at all to 4=extremely). 5 negative factors: tension-anxiety, depression-dejection, anger-hostility, fatigue-inertia, confusion-bewilderment; 1 positive factor: vigor-activity. Factor scores range: 0 to 20; high scores=negative mood (positive mood for vigor). Total score=sum of 5 negative factor scores minus vigor score; range: -20=least disturbed to 100=most disturbed. Least Squares Mean estimates adjusted for baseline value, treatment, investigator (pooled), visit, treatment*visit, and baseline value*visit.
Measured: Baseline, 8 weeks (blinded endpoint)
Percentage of Participants Using Acetaminophen Weekly During the 10-Week Treatment Period
The Least Squares (LS) Mean percentage estimates of participants using acetaminophen was determined during each week individually over the full 10-week treatment period based on participant's daily Yes/No assessments for the use of acetaminophen. The LS Mean estimates for the main effect of treatment (average weekly use) were adjusted for baseline value, treatment, investigator (pooled), week, and treatment*week.
Measured: Baseline through 10 weeks (blinded endpoint)
Percentage of Responders as Assessed by the Osteoarthritis Research Society International (OARSI) Response Criteria up to 8 Weeks
OARSI response is composite Yes/No response assessed at 8 weeks based on decrease in 24-hour average pain ratings, range: 0 ("no pain") to 10 ("worst possible pain"), improvement in functioning (using WOMAC physical function scores, range: 0 [no difficulty] to 68 [extreme difficulty]), and improvement in participant's impression of illness (using PGAI scores, range: 0 to 10; 10=greatest severity). OARSI responder=large response in pain or function components (50% relative and 20% absolute improvement), or moderate response (20% relative and 10% absolute improvement) in 2 of 3 components.
Measured: Up to 8 weeks (blinded endpoint)
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
Response is a dichotomous outcome (Yes/No) indicating at least 30% (or 50%) reduction from baseline to endpoint for the weekly mean of the 24-hour average pain ratings. The weekly mean 24-hour average pain score was calculated from the participant's daily 24-hour average pain rating assessed on an 11-point numeric rating scale, with scores from 0 ("no pain") to 10 ("worst possible pain").
Measured: Up to 8 weeks (blinded endpoint)
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
Response is a dichotomous outcome (Yes/No) indicating at least 30% (or 50%) reduction from baseline to endpoint for BPI-S average pain rating. The BPI-S self-reported scale that measures the severity of pain based on the average pain experienced over the past 24 hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine).
Measured: Up to 8 weeks (blinded endpoint)
Percentage of Participants Who Discontinued Due to an Adverse Event During the 10-Week Treatment Period
Measured: Baseline through 10 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2009 (estimated)
- Study startNov 2009
- Primary completionApr 2011
- Study completionApr 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Osteoarthritis Knee PainStudies of the same condition, open and under way.
- More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 524 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eli Lilly and Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- 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), Study director, Eli Lilly and Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01018680
- Sponsor's protocol ID
- 12909
- Other IDs
- F1J-US-HMGL
- Status last verified
- Sep 2012
- First submitted
- 23 Nov 2009
- Last updated
- 5 Oct 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 3068365Westfall PH, Krishen A. Optimally weighted, fixed sequence and gatekeeper multiple testing procedures. J Stat Plann Infer. 2001;99(1):25-40.
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.
PubMed 31505082Risser 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.
PubMed 23485934Frakes 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.
PubMed 22017192
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01018680
- Acronym / sponsor ID
- 12909
- Conditions
- Osteoarthritis Knee Pain
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 524 participants (actual)
- Lead sponsor
- Eli Lilly and CompanyIndustry (pharma, biotech, devices)
- Study start
- Nov 2009
- Primary completion
- Apr 2011 (actual)
- Study completion
- Apr 2011 (actual)
- First posted
- 25 Nov 2009 (estimated)
- Results
- Posted 5 Oct 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo |
| Duloxetine | Experimental | Drug: Duloxetine |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (25 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DuloxetineAlso: Cymbalta, LY24868630 milligrams (mg) taken by mouth, once daily for 1 week, followed by 60 to 120 mg taken by mouth, once daily for 9 weeks. | Drug | Duloxetine |
| PlaceboTaken by mouth, once daily for 10 weeks | Drug | Placebo |
Primary outcome
Change From Baseline in the Weekly Mean of the 24-Hour Average Pain Score at 8 Weeks
Time frame: Baseline, 8 weeks (blinded endpoint)
The weekly mean 24-hour average pain score was calculated from the participant's daily 24-hour average pain ratings using an 11-point numeric rating scale, with scores from 0 (indicating "no pain") to 10 (indicating "the worst possible pain"). The Least Squares Mean estimates were adjusted for baseline, treatment, investigator (pooled), week, treatment*week, and baseline*week.
12 secondary outcomes
Patient Global Impression of Improvement (PGI-I) at 8 Weeks
Time frame: 8 weeks (blinded endpoint)
Change From Baseline in the Western Ontario and McMaster Universities Index of Osteoarthritis (WOMAC) Pain, Stiffness, and Physical Function Subscale Scores at 8 Weeks
Time frame: Baseline, 8 weeks (blinded endpoint)
Change From Baseline in the Weekly Mean of the 24-Hour Night Pain and Worst Pain Scores at 8 Weeks
Time frame: Baseline, 8 weeks (blinded endpoint)
Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) Scores at 8 Weeks
Time frame: Baseline, 8 weeks (blinded endpoint)
Change From Baseline in the Clinical Global Impression of Severity (CGI-S) at 8 Weeks
Time frame: Baseline, 8 weeks (blinded endpoint)
Change From Baseline in the Patient Global Assessment of Illness (PGAI) at 8 Weeks
Time frame: Baseline, 8 weeks (blinded endpoint)
Change From Baseline in the Profile of Mood States-Brief Form (BPOMS) Total and Subscale Scores at 8 Weeks
Time frame: Baseline, 8 weeks (blinded endpoint)
Percentage of Participants Using Acetaminophen Weekly During the 10-Week Treatment Period
Time frame: Baseline through 10 weeks (blinded endpoint)
Percentage of Responders as Assessed by the Osteoarthritis Research Society International (OARSI) Response Criteria up to 8 Weeks
Time frame: Up to 8 weeks (blinded endpoint)
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
Time frame: Up to 8 weeks (blinded endpoint)
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
Time frame: Up to 8 weeks (blinded endpoint)
Percentage of Participants Who Discontinued Due to an Adverse Event During the 10-Week Treatment Period
Time frame: Baseline through 10 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 3068365Bellamy 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.
- BackgroundWestfall PH, Krishen A. Optimally weighted, fixed sequence and gatekeeper multiple testing procedures. J Stat Plann Infer. 2001;99(1):25-40.
- Derived from this study: PubMed 31505082Yue 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.
- Derived from this study: PubMed 23485934Risser 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.
- Derived from this study: PubMed 22017192Frakes 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.
Related trials for Osteoarthritis Knee Pain
Not yet recruiting
Opioid Reduction and Enhanced Recovery in Orthopaedic Surgery (OREOS)-Knee
Knee Arthroplasty, Total, Partial Knee Arthroplasty
RecruitingPhase 2
Genicular Artery Embolization for Reducing Pain in Medically Refractory Symptomatic Knee Osteoarthritis
Knee Osteoarthritis, Knee Osteoarthritis (Knee OA)
Not yet recruiting
Comparison of High-Intensity and Conventional Physical Therapy in Musculoskeletal Disorders
Low Back Pain, Radicular Syndrome
Recruiting
The Effect of Different Exercise Training Programs on Muscle Oxygenation in Individuals With Knee Osteoarthritis
Osteoarthritis of Knee
Not yet recruiting
Genicular Nerve Radiofrequency Ablation Versus Hyaluronic Acid Injection for Knee Osteoarthritis Pain
Knee Osteoarthritis, Chronic Knee Pain
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
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) study director
Eli Lilly and Company
35 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Duloxetine in people with Osteoarthritis Knee Pain, run by Eli Lilly and Company at 35 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Oct 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 35 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Oct 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in the Weekly Mean of the 24-Hour Average Pain Score at 8 Weeks (time frame: Baseline, 8 weeks (blinded endpoint)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01018680, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2012.