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

NCT ID: NCT02248480

Last Updated: 2019-09-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 354 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-10-31
• Study Completion Date: 2015-06-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Duloxetine

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.

Group Type: EXPERIMENTAL

Duloxetine

Intervention Type: DRUG

Administered orally

Placebo

Placebo administered orally once a day for 15 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Administered orally

Interventions

Duloxetine

Administered orally

Intervention Type: DRUG

Placebo

Administered orally

Intervention Type: DRUG

Other Intervention Names

LY248686

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.
• Participants treated with a monoamine oxidase inhibitor (MAoI) within 14 days prior to baseline, or those with the potential need to use MAO inhibitor during the study or within 5 days of discontinuation of investigational drug.
• Participants who answer 'yes' to any of the questions about active suicidal ideation/intent/behaviors occurring within the past month (Columbia-Suicide Severity Rating Scale, suicide ideation section-questions 4 and 5; suicidal behaviors section).
• Participants who have a history of having more than one medical allergy.
• Are non-ambulatory or require the use of crutches or a walker.
• Have frequent falls that could result in hospitalization or could compromise response to treatment.
• Have a primary painful condition that may interfere with assessment of the index joint, i.e., knee.
• Have a history of drug abuse or dependence within the past year, including alcohol and excluding nicotine and caffeine.
• Have a positive urine drug screen for any substances of abuse or excluded medication.
• Have received administration of another investigational drug within the 30 days prior to screening.
• Have had previous exposure to duloxetine or completed/withdrawn from any study investigating duloxetine.
• Pregnant participants, female participants who wish to be pregnant during the clinical study period, or participants who are breast-feeding; or male participants who wish pregnancy of the partner.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shionogi

INDUSTRY

Sponsor Role: collaborator

Eli Lilly and Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

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)

Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

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, , Japan

Countries

Japan

References

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.

Reference Type: DERIVED

PMID: 36269595 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32245696 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32021407 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31505082 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30464579 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30126675 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29713194 (View on PubMed)

Other Identifiers

F1J-JE-HMGX

Identifier Type: OTHER

Identifier Source: secondary_id

14375

Identifier Type: -

Identifier Source: org_study_id