A Study of Duloxetine (LY248686) in Participants With Chronic Osteoarthritis and Knee Pain in Japan

NCT02248480 | Completed Phase 3 Results

• 2 other identifiers: 14375F1J-JE-HMGX
• Study Type: interventional
• Target: 354
• Locations: 1 country
• Sites: 1

Brief Summary

The main purpose of this study is to evaluate the efficacy of the study drug known as duloxetine in participants with chronic osteoarthritis (OA) and knee pain in Japan.

Conditions

Osteoarthritis of the Knee

Outcome Measures

Primary Outcomes (1)

• Change From Baseline on the Brief Pain Inventory (BPI) 24-Hour Average Pain Score

  Brief Pain Inventory Severity: Average Pain Score: A self-reported scale that measures the severity of pain based on the average pain experienced during the past 24-hours. The severity scores ranged from 0 (no pain) to 10 (pain as severe as you can imagine). Least squares (LS) mean was calculated using a mixed-effects model repeated measures (MMRM) approach including administration groups, observation points, and interaction between the administration groups and observation points as fixed effects, and BPI average pain severity at baseline as covariates.

  Baseline, Week 14

Secondary Outcomes (16)

• Change From Baseline in Patient Global Impression of Improvement (PGI-Improvement)

  Baseline, 14 Weeks

• Change From Baseline on the Clinical Global Impression of Severity (CGI-S)

  Baseline, Week 14

• Change From Baseline on the 36-Item Short-Form Health Survey (SF-36)

  Baseline, Week 14

• Change From Baseline on the Beck Depression Inventory (BDI-II) Total Score

  Baseline, Week 14

• Percentage of Participants With Fall Events From Fall Questionnaire

  Baseline through Week 14

Study Arms (2)

Duloxetine

EXPERIMENTAL

Duloxetine 20 milligram (mg) for first week, 40 mg for second week and 60 mg for next 12 weeks administered orally once daily. Tapering week doses of 40 mg for three days and 20 mg for four days.

Drug: Duloxetine

Placebo

PLACEBO COMPARATOR

Placebo administered orally once a day for 15 weeks.

Drug: Placebo

Interventions

Duloxetine DRUG

Administered orally

Also known as: LY248686

Duloxetine

Placebo DRUG

Administered orally

Placebo

Eligibility Criteria

• Age: 40 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants with present OA.
• Have pain for ≥ 14 days of each month for 3 months prior to study entry.
• Participants must have a score of ≥4 on the BPI average pain score before randomization.
• Females of child-bearing potential must test negative (-) on a pregnancy test.

You may not qualify if:

• Participants who cannot appropriately complete the daily diaries.
• Have a score change of ≧3 on BPI 24-hour average pain score between screening and baseline.
• Participants who have serious cardiovascular, hepatic, renal, endocrine, respiratory, or hematologic illness, peripheral vascular disease, or other medical condition or neuropsychiatric conditions or clinically significant laboratory abnormalities or electrocardiographic abnormalities.
• Participants who have alanine aminotransferase (ALT) or aspartate aminotransferase (AST) higher than 100 international units per liter (IU/L) or total bilirubin higher than 1.6 milligrams/deciliter (mg/dL).
• Participants who have serum creatinine level higher than 2.0 mg/dL, or had renal transplantation or are receiving renal dialysis.
• Participants who have a diagnosis of inflammatory arthritis (that is, rheumatoid arthritis) or an autoimmune disorder (excluding inactive Hashimoto's thyroiditis and Type 1 diabetes).
• Participants who have any previous diagnosis of psychosis, bipolar disorder, or schizoaffective disorder.
• Participants who have major depressive disorder as determined using depression module of the Mini-International Neuropsychiatric Interview (M.I.N.I.).
• Participants who have uncorrected thyroid disease, uncontrolled narrow-angle glaucoma, history of uncontrolled seizures, or uncontrolled or poorly controlled hypertension.
• Participants who have received intrarticular hyaluronate or steroids, joint lavage, or other invasive therapies to the knee in the past 1 month.
• Participants who have had knee arthroscopy of the index knee within the past year or joint replacement of the index knee or osteotomy at anytime.
• Participants who have end-stage osteoarthritis or surgery planned during the trial for the index joint.
• Participants have a prior synovial fluid analysis showing a white blood cell (WBC) ≥2000 cubic millimeters (mm3) that is indicative of a diagnosis other than OA.
• Participants taking any excluded medications that cannot be discontinued.
• Participants anticipated by the investigator to require use of nonsteroidal anti-inflammatory drugs that include acetaminophen, opioid analgesics, or other excluded medication for the duration of the study.

Sponsors & Collaborators

• Eli Lilly and Company: lead
• Shionogi: collaborator

Study Sites (1)

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.

Hyōgo, 651-0086, Japan

Location

Related Publications (7)

• Leaney AA, Lyttle JR, Segan J, Urquhart DM, Cicuttini FM, Chou L, Wluka AE. Antidepressants for hip and knee osteoarthritis. Cochrane Database Syst Rev. 2022 Oct 21;10(10):CD012157. doi: 10.1002/14651858.CD012157.pub2.

  PMID: 36269595 DERIVED

• Itoh N, Tsuji T, Ishida M, Ochiai T, Konno S, Uchio Y. Efficacy of duloxetine for multisite pain in patients with knee pain due to osteoarthritis: An exploratory post hoc analysis of a Japanese phase 3 randomized study. J Orthop Sci. 2021 Jan;26(1):141-148. doi: 10.1016/j.jos.2020.02.013. Epub 2020 Mar 31.

  PMID: 32245696 DERIVED

• Enomoto H, Fujikoshi S, Ogawa K, Tsuji T, Tanaka S. Relationship Between Pain Reduction and Improvement in Health-Related Quality of Life in Patients with Knee Pain Due to Osteoarthritis Receiving Duloxetine: Exploratory Post Hoc Analysis of a Japanese Phase 3 Randomized Study. J Pain Res. 2020 Jan 20;13:181-191. doi: 10.2147/JPR.S211072. eCollection 2020.

  PMID: 32021407 DERIVED

• 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.

  PMID: 31505082 DERIVED

• Itoh N, Tsuji T, Ishida M, Ochiai T, Konno S, Uchio Y. Response to duloxetine in patients with knee pain due to osteoarthritis: an exploratory post hoc analysis of a Japanese Phase III randomized study. J Pain Res. 2018 Oct 26;11:2603-2616. doi: 10.2147/JPR.S176036. eCollection 2018.

  PMID: 30464579 DERIVED

• Enomoto H, Fujikoshi S, Tsuji T, Sasaki N, Tokuoka H, Uchio Y. Efficacy of duloxetine by prior NSAID use in the treatment of chronic osteoarthritis knee pain: A post hoc subgroup analysis of a randomized, placebo-controlled, phase 3 study in Japan. J Orthop Sci. 2018 Nov;23(6):1019-1026. doi: 10.1016/j.jos.2018.07.008. Epub 2018 Aug 17.

  PMID: 30126675 DERIVED

• Uchio Y, Enomoto H, Alev L, Kato Y, Ishihara H, Tsuji T, Ochiai T, Konno S. A randomized, double-blind, placebo-controlled Phase III trial of duloxetine in Japanese patients with knee pain due to osteoarthritis. J Pain Res. 2018 Apr 18;11:809-821. doi: 10.2147/JPR.S164128. eCollection 2018.

  PMID: 29713194 DERIVED

MeSH Terms

Conditions

Osteoarthritis, Knee

Interventions

Duloxetine Hydrochloride

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 22, 2014
• First Posted: September 25, 2014
• Study Start: October 1, 2014
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: September 26, 2019
• Results First Posted: January 16, 2017

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

Locations

JP (1)