Duloxetine Versus Placebo for Osteoarthritis Knee Pain

Duloxetine 60 to 120 mg Versus Placebo in the Treatment of Patients With Osteoarthritis Knee Pain

The primary purpose of this study is to determine if duloxetine reduces pain severity in patients with osteoarthritis knee pain.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis Knee Pain
• Intervention / Treatment: Drug: placebo; Drug: Duloxetine

• Study Type: Interventional
• Enrollment (Actual): 231
• Phase: Phase 3

Contacts and Locations

Study Locations

• Puerto Rico
  • Hato Rey, Puerto Rico, 00917
    • 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, Puerto Rico, 00935
    • 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.
• Romania
  • Brasov, Romania, 500365
    • 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, Romania, 70266
    • 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.
  • Cluj-Napoca, Romania, 400132
    • 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.
  • Iasi, Romania, 700656
    • 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.
• United States
  • Arizona
    • Chandler, Arizona, United States, 85225
      • 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.
  • California
    • Beverly Hills, California, United States, 90211
      • 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.
    • Northridge, California, United States, 91325
      • 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.
    • Walnut Creek, California, United States, 94598
      • 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.
  • Florida
    • Deland, Florida, United States, 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.
    • Fort Myers, Florida, United States, 33916
      • 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.
    • S. Miami, Florida, United States, 33143
      • 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.
    • Stuart, Florida, United States, 34996
      • 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.
  • Illinois
    • Chicago, Illinois, United States, 60611
      • 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, 60053
      • 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.
  • Massachusetts
    • Billerica, Massachusetts, United States, 01821
      • 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.
    • Waltham, Massachusetts, United States, 02453
      • 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.
    • Westborough, Massachusetts, United States, 01581
      • 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.
  • Nevada
    • Reno, Nevada, United States, 89502
      • 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 Jersey
    • Edison, New Jersey, United States, 08817
      • 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.
    • Stratford, New Jersey, United States, 08084
      • 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.
    • Toms River, New Jersey, United States, 08755
      • 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.
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74135
      • 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.
  • Texas
    • Lake Jackson, Texas, United States, 77566
      • 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.
    • Waco, Texas, United States, 76708
      • 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.
    • Wichita Falls, Texas, United States, 76309
      • 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.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female outpatients with osteoarthritis knee pain.

Exclusion Criteria:

• 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.
• Acute liver injury (such as hepatitis) or severe cirrhosis.
• Previous exposure to duloxetine.
• Body Mass Index (BMI) over 40.
• Major depressive disorder.
• Daily use of narcotics.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; duloxetine 30 mg, daily (QD), by mouth (PO) for 1 week then duloxetine 60 mg QD, PO for 6 weeks then duloxetine 60 mg or 120 mg QD, PO for 6 weeks	Drug: Duloxetine; Other Names: Cymbalta; LY248686
Placebo Comparator: B; placebo daily (QD), by mouth (PO) for 13 weeks	Drug: placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weekly Change From Baseline in the 24-Hour Average Pain Rating Using an 11-Point Numerical Likert Scale Patient Diary	This is an ordinal scale assessing the 24-hour average pain with scores from 0 (no pain) to 10 (worst possible pain).	Over 13 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Global Impression of Improvement at 13 Week Endpoint	A scale that measures the patient's perception of improvement at the time of assessment. The score ranges from 1 (very much better) to 7 (very much worse).	13 Weeks
Change From Baseline to 13 Week Endpoint in Western Ontario and McMaster Osteoarthritis Index (WOMAC) - Pain Subscale	The WOMAC index (pain, stiffness, physical function subscales) will be completed by the patient. The pain subscale has 5 questions on pain associated with every day tasks. Each question is answered using a 5-point Likert scale (0 to 4). The pain subscale has a range of scores of 0 (none) to 20 (extreme).	Baseline and 13 Weeks
Change From Baseline to 13 Week Endpoint in Western Ontario and McMaster Osteoarthritis Index (WOMAC) - Stiffness Subscale	The WOMAC index (pain, stiffness, physical function subscales) will be completed by the patient. The stiffness subscale has 2 questions on stiffness associated with time of day (morning versus later in the day). Each question is answered using a 5-point Likert scale (0 to 4). The pain subscale has a range of scores of 0 (none) to 8 (extreme).	Baseline and 13 Weeks
Change From Baseline to 13 Week Endpoint in Western Ontario and McMaster Osteoarthritis Index (WOMAC) - Physical Function Subscale	The WOMAC index (pain, stiffness, physical function subscales) will be completed by the patient. The physical function subscale has 17 questions on physical function difficulties with every day tasks. Each question is answered using a 5-point Likert scale (0 to 4). The physical function subscale has a range of scores of 0 (none) to 68 (extreme).	Baseline and 13 Weeks
Change From Baseline to 13 Week Endpoint in Western Ontario and McMaster Osteoarthritis Index (WOMAC) - Total Score	The WOMAC index (pain, stiffness, physical function subscales) will be 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).	Baseline and 13 Weeks
Change From Baseline to 13 Week Endpoint in Weekly Mean of the 24-Hour Worst Pain Score	This is an ordinal scale with scores from 0 (no pain) to 10 (worst possible pain). The value is the change from baseline in the weekly mean of the 24-hour worst pain score on the scale.	Baseline and 13 Weeks
Weekly Change From Baseline in the 24-Hour Worst Pain Score	This is an ordinal scale with scores from 0 (no pain) to 10 (worst possible pain). The value is the change from baseline in the weekly mean of the 24-hour worst pain score on the scale.	Over 13 Weeks
Change From Baseline to 13 Week Endpoint in Weekly Mean of 24-Hour Average Pain in the Re-Randomized Treatment Phase	This is an ordinal scale with scores from 0 (no pain) to 10 (worst possible pain). This value is the change from baseline in the weekly mean of the 24-hour average pain score on the scale.	Baseline and 13 Weeks
Change From Baseline to 13 Week Endpoint in Clinical Global Impression of Severity	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.	Baseline and 13 Weeks
Change From Baseline to 13 Week Endpoint in Brief Pain Inventory (BPI) - Worst Pain Score	A self-reported scale that measures the severity of pain based on the worst pain experienced over the past 24-hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine).	Baseline and 13 Weeks
Change From Baseline to 13 Week Endpoint in Brief Pain Inventory - Least Pain Score	A self-reported scale that measures the severity of pain based on the least pain experienced over the past 24-hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine).	Baseline and 13 Weeks
Change From Baseline to 13 Week Endpoint in Brief Pain Inventory - Average Pain Score	A 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).	Baseline and 13 Weeks
Change From Baseline to 13 Week Endpoint in Brief Pain Inventory - Pain Right Now Score	A self-reported scale that measures the severity of pain based on the pain right now. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine).	Baseline and 13 Weeks
Change From Baseline to 13 Week Endpoint in Brief Pain Inventory Interference Score - General Activity	A self-reported scale that measures the interference of pain in the past 24 hours on general acitivity. The Interference scores range from 0 (does not interfere) to 10 (completely interferes).	Baseline and 13 Weeks
Change From Baseline to 13 Week Endpoint in Brief Pain Inventory Interference Score - Mood	A self-reported scale that measures the interference of pain in the past 24 hours on mood. The Interference scores range from 0 (does not interfere) to 10 (completely interferes).	Baseline and 13 Weeks
Change From Baseline to 13 Week Endpoint in Brief Pain Inventory Interference Score - Walking Ability	A self-reported scale that measures the interference of pain in the past 24 hours on walking ability. The Interference scores range from 0 (does not interfere) to 10 (completely interferes).	Baseline and 13 Weeks
Change From Baseline to 13 Week Endpoint in Brief Pain Inventory Interference Score - Normal Work	A self-reported scale that measures the interference of pain in the past 24 hours on normal work. The Interference scores range from 0 (does not interfere) to 10 (completely interferes).	Baseline and 13 Weeks
Change From Baseline to 13 Week Endpoint in Brief Pain Inventory Interference Score - Relations With Other People	A self-reported scale that measures the interference of pain in the past 24 hours on relations with other people. The Interference scores range from 0 (does not interfere) to 10 (completely interferes).	Baseline and 13 Weeks
Change From Baseline to 13 Week Endpoint in Brief Pain Inventory Interference Score - Sleep	A self-reported scale that measures the interference of pain in the past 24 hours on sleep. The Interference scores range from 0 (does not interfere) to 10 (completely interferes).	Baseline and 13 Weeks
Change From Baseline to 13 Week Endpoint in Brief Pain Inventory Interference Score - Enjoyment of Life	A self-reported scale that measures the interference of pain in the past 24 hours on enjoyment of life. The Interference scores range from 0 (does not interfere) to 10 (completely interferes).	Baseline and 13 Weeks
Change From Baseline to 13 Week Endpoint in Brief Pain Inventory Average Interference	A self-reported scale that measures interference of pain on average of the 7 questions assessing the interference of pain for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. The average Interference scores range from 0 (does not interfere) to 10 (completely interferes).	Baseline and 13 Weeks
Response to Treatment - The Number of Participants With a >= 30% Reduction of Weekly Mean in 24-Hour Average Pain Severity Ratings	Number of participants who experienced a response to treatment, which was defined as having a >=30% reduction of the weekly mean in 24-hour average pain severity ratings. This is an ordinal scale with scores from 0 (no pain) to 10 (worst possible pain).	Over 13 Weeks
Response to Treatment - The Number of Participants With a >=30% Reduction of Weekly Mean in 24-Hour Average Pain Severity Ratings in the Re-Randomized Treatment Phase	Number of participants who experienced a response to treatment, which was defined as having a >=30% reduction of the weekly mean in 24-hour average pain severity ratings. Response to treatment over the last 6 weeks of the trial (after patients were re-randomized) were compared to baseline measures.	Over 13 Weeks
Change From Baseline to 13 Week Endpoint in Medical Outcomes Study Short Form-36 (SF-36) - Mental Health Component Summary	A self-reported questionnaire that consists of 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. The mental component summary (MCS) has been constructed based on the 8 SF-36 domains.	Baseline and 13 Weeks
Change From Baseline to 13 Week Endpoint in Medical Outcomes Study Short Form-36 (SF-36) - Physical Component Summary	A self-reported questionnaire that consists of 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. The physical component summary (PCS) has been constructed based on the 8 SF-36 domains.	Baseline and 13 Weeks
Change From Baseline to 13 Week Endpoint in Euro-Quality of Life - 5 Dimensions (EQ-5D): US Based Index Score	The EQ-5D is an assessment of one's overall health. Consists of 5 items. Patients choose 1 of 3 options that best describe the status of each item. The EQ-5D US based index scores range from -0.11 to 1.0 where a score of 1.0 indicates perfect health. A positive change from baseline indicates health improvement.	Baseline and 13 Weeks
Change From Baseline to 13 Week Endpoint in Beck Depression Inventory-II - Total Score	A 21-item, patient-completed questionnaire to assess characteristics of depression. Each of the 21 items corresponding to a symptom of depression is summed to give a single score. There is a four-point scale for each item ranging from 0 to 3. Total score of 0-13 is considered minimal range, 14-19 is mild, 20-28 is moderate, and 29-63 is severe.	Baseline and 13 Weeks
Change From Baseline to 13 Week Endpoint in Hospital Anxiety and Depression Scale (HADS) - Anxiety Subscale	A 14-item questionnaire with 2 subscales: anxiety and depression. Each item is rated on a 4-point scale, giving maximum scores of 21 for anxiety and depression. Scores of 11 or more on either subscale are considered to be a significant 'case' of psychological morbidity, while scores of 8-10 represent 'borderline' and 0-7, 'normal.'	Baseline and 13 Weeks
Statistically Significant Change From Baseline to 13 Week Endpoint in Laboratory Data - Chemistry Analytes: Alkaline Phosphatase	Change from baseline to endpoint in alkaline phosphatase using central laboratory reference ranges.	Baseline and 13 Weeks
Statistically Significant Change From Baseline to 13 Week Endpoint in Laboratory Data - Chemistry Analytes: Uric Acid	Change from baseline to endpoint in uric acid using central laboratory reference ranges.	Baseline and 13 Weeks
Change From Baseline to 13 Week Endpoint in Vital Signs - Pulse Rate	Pulse rate (heart rate) measured in the sitting position.	Baseline and 13 Weeks
Change From Baseline to 13 Week Endpoint in Vital Signs - Blood Pressure (BP) Diastolic	Diastolic blood pressure measured in the sitting position.	Baseline and 13 Weeks
Change From Baseline to 13 Week Endpoint in Vital Signs - Blood Pressure (BP) Systolic	Systolic blood pressure measured in the sitting position.	Baseline and 13 Weeks
Change From Baseline to 13 Week Endpoint in Vital Signs - Weight		Baseline and 13 Weeks

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

General Publications

• Williamson OD, Schroer M, Ruff DD, Ahl J, Margherita A, Sagman D, Wohlreich MM. Onset of response with duloxetine treatment in patients with osteoarthritis knee pain and chronic low back pain: a post hoc analysis of placebo-controlled trials. Clin Ther. 2014 Apr 1;36(4):544-51. doi: 10.1016/j.clinthera.2014.02.009. Epub 2014 Mar 17.
• 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.
• Hochberg MC, Wohlreich M, Gaynor P, Hanna S, Risser R. Clinically relevant outcomes based on analysis of pooled data from 2 trials of duloxetine in patients with knee osteoarthritis. J Rheumatol. 2012 Feb;39(2):352-8. doi: 10.3899/jrheum.110307. Epub 2011 Dec 1.

Helpful Links

• Lilly Clinical Trial Registry

Study record dates

Study Major Dates

• Study Start: November 1, 2006
• Primary Completion (Actual): October 1, 2007
• Study Completion (Actual): October 1, 2007

Study Registration Dates

• First Submitted: December 6, 2006
• First Submitted That Met QC Criteria: December 6, 2006
• First Posted (Estimate): December 7, 2006

Study Record Updates

• Last Update Posted (Estimate): August 19, 2009
• Last Update Submitted That Met QC Criteria: July 7, 2009
• Last Verified: July 1, 2009

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; 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: 10546 (Other Identifier: CTEP); F1J-MC-HMEP