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A Study of LY2951742 in Participants With Mild to Moderate Osteoarthritis Knee Pain

Phase 2
Terminated
Conditions
Osteoarthritis, Knee
Interventions
Other: Placebo- oral
Other: Placebo - SC
Registration Number
NCT02192190
Lead Sponsor
Eli Lilly and Company
Brief Summary

The main purpose of this study is to test if LY2951742 relieves mild to moderate knee pain. The study drugs will be given as an injection under the skin and as an oral capsule. The study will last about 28 weeks for each participant.

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
268
Inclusion Criteria
  • Have osteoarthritis (OA) of the knee joint based on American College of Rheumatology (ACR) criteria and confirmed with X-rays and ACR functional class of I to III
  • Have been on stable dose of prescription Nonsteroidal Anti-Inflammatory Drugs (NSAIDS), celecoxib, tramadol, or acetaminophen of at least 2000 mg per day for at least 20 days in the past month
  • Willing to stop all analgesics for OA pain during the study
  • Experienced pain while walking in the target knee of 50-90 mm inclusive on 0-100 Visual Analog Scale (VAS) with an increase in pain while walking of at least 10 mm following washout of current Osteoarthritis pain medications at screening
Exclusion Criteria
  • Allergic to LY2951742, celecoxib, other NSAIDS, including aspirin, and similar drugs
  • Arthritis of the knee from other causes
  • Uncontrolled hypertension
  • Have OA pain that requires treatment with potent opioids, systemic corticosteroids, intra-articular injections, duloxetine, or venlafaxine
  • Moderate to severe renal impairment
  • Pregnant or lactating

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlacebo- oralPlacebo capsule orally, once daily for approximately 16 weeks. Placebo subcutaneous (SC) once every 4 weeks for 16 weeks (Treatment period = 16 weeks).
PlaceboPlacebo - SCPlacebo capsule orally, once daily for approximately 16 weeks. Placebo subcutaneous (SC) once every 4 weeks for 16 weeks (Treatment period = 16 weeks).
Celecoxib + PlaceboPlacebo - SCCelecoxib 200 milligram (mg) capsule orally once daily for approximately 16 weeks. Placebo SC once every 4 weeks for 16 weeks (Treatment period = 16 weeks).
LY2951742 5 mg + PlaceboLY2951742Placebo capsule orally, once daily for approximately 16 weeks. SC injections of 5 mg LY2951742 once every 4 weeks for 8 weeks followed by placebo SC once every 4 weeks for 8 weeks (Treatment period = 16 weeks).
LY2951742 5 mg + PlaceboPlacebo- oralPlacebo capsule orally, once daily for approximately 16 weeks. SC injections of 5 mg LY2951742 once every 4 weeks for 8 weeks followed by placebo SC once every 4 weeks for 8 weeks (Treatment period = 16 weeks).
LY2951742 5 mg + PlaceboPlacebo - SCPlacebo capsule orally, once daily for approximately 16 weeks. SC injections of 5 mg LY2951742 once every 4 weeks for 8 weeks followed by placebo SC once every 4 weeks for 8 weeks (Treatment period = 16 weeks).
LY2951742 50 mg + PlaceboPlacebo- oralPlacebo capsule orally, once daily for approximately 16 weeks. SC injections of 50 mg LY2951742 once every 4 weeks for 8 weeks followed by placebo SC once every 4 weeks for 8 weeks (Treatment period = 16 weeks).
LY2951742 50 mg + PlaceboPlacebo - SCPlacebo capsule orally, once daily for approximately 16 weeks. SC injections of 50 mg LY2951742 once every 4 weeks for 8 weeks followed by placebo SC once every 4 weeks for 8 weeks (Treatment period = 16 weeks).
LY2951742 120 mg + PlaceboLY2951742Placebo capsule orally, once daily for approximately 16 weeks. SC injections of 120 mg LY2951742 once every 4 weeks for 8 weeks followed by placebo SC once every 4 weeks for 8 weeks (Treatment period = 16 weeks).
LY2951742 120 mg + PlaceboPlacebo- oralPlacebo capsule orally, once daily for approximately 16 weeks. SC injections of 120 mg LY2951742 once every 4 weeks for 8 weeks followed by placebo SC once every 4 weeks for 8 weeks (Treatment period = 16 weeks).
LY2951742 120 mg + PlaceboPlacebo - SCPlacebo capsule orally, once daily for approximately 16 weeks. SC injections of 120 mg LY2951742 once every 4 weeks for 8 weeks followed by placebo SC once every 4 weeks for 8 weeks (Treatment period = 16 weeks).
LY2951742 300 mg + PlaceboLY2951742Placebo capsule orally, once daily for 16 weeks. SC injections of 300 mg LY2951742 once every 4 weeks for 8 weeks followed by placebo SC once every 4 weeks for 8 weeks (Treatment period = 16 weeks).
LY2951742 300 mg + PlaceboPlacebo- oralPlacebo capsule orally, once daily for 16 weeks. SC injections of 300 mg LY2951742 once every 4 weeks for 8 weeks followed by placebo SC once every 4 weeks for 8 weeks (Treatment period = 16 weeks).
LY2951742 300 mg + PlaceboPlacebo - SCPlacebo capsule orally, once daily for 16 weeks. SC injections of 300 mg LY2951742 once every 4 weeks for 8 weeks followed by placebo SC once every 4 weeks for 8 weeks (Treatment period = 16 weeks).
LY2951742 50 mg + PlaceboLY2951742Placebo capsule orally, once daily for approximately 16 weeks. SC injections of 50 mg LY2951742 once every 4 weeks for 8 weeks followed by placebo SC once every 4 weeks for 8 weeks (Treatment period = 16 weeks).
Celecoxib + PlaceboCelecoxibCelecoxib 200 milligram (mg) capsule orally once daily for approximately 16 weeks. Placebo SC once every 4 weeks for 16 weeks (Treatment period = 16 weeks).
Primary Outcome Measures
NameTimeMethod
Change From Baseline to 8 Weeks in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain SubscaleBaseline, 8 Weeks

The 24-question WOMAC Osteoarthritis Index assesses osteoarthritis (OA) symptoms using pain (5 questions), stiffness (2 questions) and physical function (17 questions) subscales. The WOMAC pain subscale was calculated for each participant at each time point for analysis as the mean score (range 0-100 millimeter \[mm\] VAS; 0=very good and 100=very poor) of all 5 questions related to pain. Bayesian posterior adjusted mean was calculated using a Bayesian Normal Dynamic Linear Model (NDLM) dose response model with baseline and pooled investigator site included as baseline covariates.

Secondary Outcome Measures
NameTimeMethod
Number of Participants With a Response Rate Measured by the Outcome Measures for Rheumatology Committee and Osteoarthritis Research Society International Standing Committee for Clinical Trials Response Criteria Initiative (OMERACT-OARSI)8 Weeks

The responders according to OMERACT-OARSI criteria: participants with at least 50 % improvement in pain or in function scores, along with absolute improvement of 20 mm, were considered responders. Alternatively, participants were considered responders if they showed at least 20% improvement and absolute improvement of 10 mm in at least two of the following scores: pain, function and Patients Global Assessment (PGA) scores.

Change From Baseline to 8 Weeks in the WOMAC Total ScoreBaseline, 8 Weeks

The 24-question WOMAC Osteoarthritis Index assesses osteoarthritis symptoms using pain (5 questions), stiffness (2 questions) and physical function (17 questions) subscales.The WOMAC total score was calculated for each participant at each time point for analysis as the mean score (range 0-100 mm VAS; 0=very good and 100=very poor) of 24 questions. LSM mean was calculated using a mixed-effects model repeated measures (MMRM) approach with treatment, visit and the interaction of treatment and visit were fitted as fixed effects in the model and baseline and pooled investigator site as baseline covariates. LSM mean was calculated using a mixed-effects model repeated measures (MMRM) approach with treatment, visit and the interaction of treatment and visit were fitted as fixed effects in the model and baseline and pooled investigator site as baseline covariates.

Change From Baseline to 8 Weeks in the WOMAC Physical Function SubscaleBaseline, 8 Weeks

The 24-question WOMAC Osteoarthritis Index assesses osteoarthritis symptoms using pain (5 questions), stiffness (2 questions) and physical function (17 questions) subscales. The WOMAC Osteoarthritis Index version 3.1 was administered according to the study schedule. The WOMAC physical function subscale was calculated for each participant at each time point for analysis as the mean score (range 0-100 mm VAS; 0=very good and 100=very poor) of all 17 questions related to physical function. Least Square Mean (LSM) was calculated using a mixed-effects model repeated measures (MMRM) approach with treatment, visit and the interaction of treatment and visit were fitted as fixed effects in the model and baseline and pooled investigator site as baseline covariates.

Change in Baseline to 8 Weeks in Patient's Global Assessment of OsteoarthritisBaseline, 8 Weeks

The PGA is a patient-rated instrument that measures their assessment of overall OA symptoms. It is based on the participant's response to the question "Considering all the ways your osteoarthritis affects you, how are you doing today?" using a 100 mm VAS (0=very good and 100=very poor). LSM mean was calculated using a mixed-effects model repeated measures (MMRM) approach with treatment, visit and the interaction of treatment and visit were fitted as fixed effects in the model and baseline and pooled investigator site as baseline covariates.

Change From Baseline to 8 Weeks in the WOMAC Stiffness SubscaleBaseline, 8 Weeks

The 24-question WOMAC Osteoarthritis Index assesses osteoarthritis symptoms using pain (5 questions), stiffness (2 questions) and physical function (17 questions) subscales. The WOMAC stiffness subscale will be calculated for each participant at each time point for analysis as the mean score (range 0-100 mm VAS; 0=very good and 100=very poor) of 2 questions related to stiffness. LSM mean was calculated using a mixed-effects model repeated measures (MMRM) approach with treatment, visit and the interaction of treatment and visit were fitted as fixed effects in the model and baseline and pooled investigator site as baseline covariates. LSM mean was calculated using a mixed-effects model repeated measures (MMRM) approach with treatment, visit and the interaction of treatment and visit were fitted as fixed effects in the model and baseline and pooled investigator site as baseline covariates.

Trial Locations

Locations (37)

Achieve Clinical Research, LLC

🇺🇸

Birmingham, Alabama, United States

Empire Clinical Research

🇺🇸

Upland, California, United States

Medex Healthcare Research, Inc.

🇺🇸

New York, New York, United States

Dream Team Clinical Research

🇺🇸

Anaheim, California, United States

Research Institute of South Florida, Inc.

🇺🇸

Miami, Florida, United States

M&M Medical Center

🇺🇸

Miami, Florida, United States

Drug Studies America

🇺🇸

Marietta, Georgia, United States

Arthritis, Rheumatic & Back Disease Associates

🇺🇸

Voorhees, New Jersey, United States

PharmQuest

🇺🇸

Greensboro, North Carolina, United States

Accurate Clinical Research

🇺🇸

Nassau Bay, Texas, United States

Artemis Institute for Clinical Research

🇺🇸

San Diego, California, United States

Horizons Clinical Research Center

🇺🇸

Denver, Colorado, United States

Avail Clinical Research LLC

🇺🇸

DeLand, Florida, United States

Community Research Foundation Inc

🇺🇸

Miami, Florida, United States

United Osteoporosis Center

🇺🇸

Gainesville, Georgia, United States

Compass Research

🇺🇸

Orlando, Florida, United States

Buynak Clinical Research, P.C.

🇺🇸

Valparaiso, Indiana, United States

ActivMed Practices & Research, Inc

🇺🇸

Methuen, Massachusetts, United States

The Center for Clinical Trials, Inc.

🇺🇸

Biloxi, Mississippi, United States

New Mexico Clinical Research & Osteoporosis Center

🇺🇸

Albuquerque, New Mexico, United States

Family Practice Center of Wooster

🇺🇸

Wooster, Ohio, United States

Drug Trials of America

🇺🇸

Hartsdale, New York, United States

Altoona Center for Clinical Research

🇺🇸

Duncansville, Pennsylvania, United States

Greater Providence Clinical Research, LLC

🇺🇸

Warwick, Rhode Island, United States

Clinical Trials of South Carolina

🇺🇸

Charleston, South Carolina, United States

Quality Research, Inc.

🇺🇸

San Antonio, Texas, United States

Health Research of Hampton Roads Inc

🇺🇸

Newport News, Virginia, United States

National Clinical Research - Norfolk Inc

🇺🇸

Norfolk, Virginia, United States

Clinical Research Associates of Tidewater

🇺🇸

Norfolk, Virginia, United States

AGA Clinical Trials

🇺🇸

Hialeah, Florida, United States

Palm Springs Research Institute

🇺🇸

Hialeah, Florida, United States

iM Research

🇺🇸

West Covina, California, United States

PCPMG Clinical Research Unit

🇺🇸

Greenville, South Carolina, United States

Upstate Clinical Research Associates

🇺🇸

Williamsville, New York, United States

Diablo Clinical Research

🇺🇸

Walnut Creek, California, United States

Renstar Medical Research

🇺🇸

Ocala, Florida, United States

Beacon Clinical Research, LLC

🇺🇸

Brockton, Massachusetts, United States

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