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Osteoarthritis of the KneePhase 3NCT02248480

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

A Phase 3 study testing Duloxetine in people with Osteoarthritis of the Knee, run by Eli Lilly and Company at 1 site in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 40 to 79 years
Conditions the study is for
Osteoarthritis of the Knee
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
354 participants
Where
1 siteJapan
Study dates
Oct 2014to Jun 2015
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 to 79 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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).
Show all 26Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

Japan1 site
  • 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

Other trials in Japan

About this study

Official title: Effect of Duloxetine 60 mg Versus Placebo in Patients With Chronic Osteoarthritis and Knee Pain in Japan

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.

Being tested
Duloxetine, Placebo
Medical subject headings
Osteoarthritis, Knee

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DuloxetineDrug

    Also called LY248686

    Administered orally

  • PlaceboDrug

    Administered orally

Study groups in NCT02248480
Study groupRoleWhat they receive
DuloxetineExperimentalDuloxetine 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.
Receives: Drug: Duloxetine
PlaceboPlacebo comparatorPlacebo administered orally once a day for 15 weeks.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline, Week 14

Secondary outcomes (16)
  1. Change From Baseline in Patient Global Impression of Improvement (PGI-Improvement)

    Patient's Global Impressions of Improvement Scale: PGI-I measures a participant's perception of improvement at the time of assessment compared with the start of treatment. Score ranges from 1 (very much better) to 7 (very much worse). 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 PGI-severity at baseline as covariates.

    Measured: Baseline, 14 Weeks

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

    CSI-S measures severity of illness at the time of assessment compared with start of treatment with scores ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). 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 baseline data as covariates.

    Measured: Baseline, Week 14

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

    36-item Short-Form Health Survey: SF-36 Health Status Survey is a generic, health-related scale assessing participant's quality of life on 8 domains: physical functioning, social functioning, bodily pain, vitality, mental health, role-physical, role-emotional and general health. Domain scores: general health (range: 5-25); physical functioning (range: 10-30); role-physical (range: 4-8); role-emotional (range: 3-15); social functioning (range: 2-10); bodily pain (range: 2-12); vitality (range: 4-20); mental health (range: 5-25). Each raw scale score was converted to a scale score ranging from 0-100 points, , with higher values representing a better outcome [(Raw score) - min{raw score}] / (max {raw score} - min{raw score}) x 100]. Least squares (LS) mean was calculated using Analysis of covariance (ANCOVA) approach including administration groups as fixed effects, and baseline data as covariate.

    Measured: Baseline, Week 14

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

    Beck Depression Inventory-II: BDI-II is a 21-item, participant-completed questionnaire to assess characteristics of depression. Each of the 21 items corresponding to symptoms of depression were scored on a 4-point scale ranging from 0 to 3 and was summed to give a single score. A total score of 0-13 was considered minimal range, 14-19 was mild, 20-28 was moderate, and 29-63 was severe. Least squares (LS) mean was calculated using a ANCOVA approach' including administration groups as fixed effects, and baseline data as covariate.

    Measured: Baseline, Week 14

  5. Percentage of Participants With Fall Events From Fall Questionnaire

    Participants evaluated their experience with and details of falls which were recorded.

    Measured: Baseline through Week 14

  6. Change From Baseline on the Western Ontario and McMaster Osteoarthritis Index (WOMAC) Questionnaire Total Score

    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 total score was calculated for each participant at each time point for analysis as the mean total score, range 0 (none) -96 (extreme). 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 baseline data as covariates.

    Measured: Baseline, Week 14

  7. Change From Baseline on the Patient Global Assessment Illness (PGAI) Score

    Measured: Baseline, Week 14

  8. Change From Baseline on the 5 Dimension (EQ-5D) Version of the European Quality of Life Instrument

    The EQ-5D is a generic, multidimensional, health-related, quality-of-life instrument and was completed on five dimensions (mobility, self care, usual activities, pain/discomfort and anxiety/depression) to measure health-related quality of life on a scale from 0-1, with the higher score indicating a better health state perceived by the participant. The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood using a three level scale (no problem, some problems, and major problems). These combinations of attributes were converted into a weighted health-state Index Score according to the Japan population-based algorithm. Least squares (LS) mean was calculated using an ANCOVA approach including administration groups as fixed effects, and baseline data as covariate.

    Measured: Baseline, Week 14

  9. Change in Baseline in Brief Pain Inventory Severity and Interference Scores (BPI-S, BPI-I) Change From Baseline in BPI Pain Severity Items and Interference Items Score

    BPI-S and BPI-I are self-reported scales measuring severity of pain and interference on function. Severity scores: 0 (no pain) to 10 (severe pain) on each question assessing worst pain, least pain, and average pain in past 24 hours, and pain right now. 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. Average interference = average of non-missing scores of individual interference items. 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 baseline data as covariates.

    Measured: Baseline, Week 14

  10. Percentage of Participants With a 30% and 50% Reduction in Average Pain Score on Weekly Mean of the 24-Hour Average Pain Score on the 11-Point Numeric Rating Scale

    24-hour average pain severity scores were recorded daily on an 11-point Likert scale, an ordinal scale, with scores ranging from 0 (no pain) to 10 (worst possible pain). The 11-point Likert scale was also used for assessment of average pain within 24-hours.

    Measured: Baseline,Week 14

  11. Change From Baseline on Weekly Mean of the 24-Hour Average Pain and Worst Pain Score

    24-hour average pain severity scores were recorded daily on an 11-point Likert scale, an ordinal scale, with scores ranging from 0 (no pain) to 10 (worst possible pain). The 11-point Likert scale was also used for assessment of average pain and worst pain within 24-hours. 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 baseline data as covariates.

    Measured: Baseline, Week 14

  12. Percentage of Participants With Reduction of ≥30% and ≥50% in BPI 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).

    Measured: Baseline, Week 14

  13. Percentage of Participants With a Responder Rate Based on OMERACT-OARSI Criteria

    A responder is required to meet at least one condition: reduction of ≥50% and ≥2 score in Weekly Mean of the 24-Hour Average Pain Score, reduction of ≥50% or ≥13.6 score in WOMAC (difficulty in dairy activity) and meet ≥2 out of following 3 conditions: reduction of ≥20% and ≥1 score in Weekly Mean of the 24-Hour Average Pain, reduction of ≥20% and ≥6.8 score in WOMAC (difficulty in dairy activity), PGAI score ≥2.

    Measured: Baseline, Week 14

  14. Change From Baseline on the WOMAC Questionnaire Pain Subscale

    The WOMAC index (pain, stiffness, physical function subscales) was completed by the participant.The pain subscale had 5 questions on pain associated with every day tasks. Each question was answered using a 5-point Likert scale (0 to 4). The pain subscale has a range of scores of 0 (none) to 20 (extreme). 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, baseline data as covariates.

    Measured: Baseline, 14 Weeks

  15. Change From Baseline on the WOMAC Questionnaire Stiffness Subscale

    The WOMAC index (pain, stiffness, physical function subscales) will be completed by the participant.The stiffness subscale had 2 questions on stiffness associated with time of day (morning versus later in the day). Each question was answered using a 5-point Likert scale (0 to 4). The stiffness subscale has a range of scores of 0 (none) to 8 (extreme). 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, baseline data as covariates.

    Measured: Baseline, 14 Weeks

  16. Change From Baseline on the WOMAC Questionnaire Physical Function Subscale

    The WOMAC osteoarthritis scale consists of 24 items in 3 subscales: pain, stiffness, and physical function. The physical function subscale rates participant pain during stair use, rising from sitting, standing, bending, walking, getting in/out of a car, shopping, putting on/taking off socks, rising from bed, lying in bed, getting in/out of the bath, sitting, getting on/off the toilet, heavy household duties, and light household duties. Each question was answered using a 5-point Likert scale (0 to 4). Physical Function Subscale has a range of scores of 0 (none) to 68 (extreme). 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, baseline data as covariates.

    Measured: Baseline, 14 Weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Sep 2014 (estimated)
  2. Study startOct 2014
  3. Primary completionJun 2015
  4. Study completionJun 2015

Resources

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
354 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02248480
Sponsor's protocol ID
14375
Other IDs
F1J-JE-HMGX
Status last verified
Sep 2019
First submitted
22 Sep 2014
Last updated
26 Sep 2019
Data monitoring committee
No
Individual data sharing
Yes: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

Publications

  • 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.

    PubMed 36269595
  • 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.

    PubMed 32245696
  • 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.

    PubMed 32021407
  • 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 31505082
  • 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.

    PubMed 30464579
  • 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.

    PubMed 30126675
  • 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.

    PubMed 29713194

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Duloxetine in people with Osteoarthritis of the Knee, run by Eli Lilly and Company at 1 site in Japan.

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 4 inclusion and 26 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 26 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Japan. 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 16 Jan 2017). 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 on the Brief Pain Inventory (BPI) 24-Hour Average Pain Score (time frame: Baseline, Week 14). 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 NCT02248480, which also lists 7 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 26 Sep 2019.

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