AzTrials
AzTrials

OsteoarthritisPhase 2NCT01619150

A Single Center 2-way Crossover Study to Investigate the Mechanism of Action of Etoricoxib in Subjects With Osteoarthritis Knee Pain

A Phase 2 study of Osteoarthritis, run by C4Pain at 1 site in Denmark.

Completed

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

Official record
Search all trials

Trial summary

The purpose of this study is to investigate which pain mechanisms that can be affected by etoricoxib compared to placebo (inactive medication)in subjects with painful knee osteoarthritis af 4 weeks of treatment. Read more about this study

Who is it for?
Ages 40 to 75 years
Conditions the study is for
Osteoarthritis
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
39 participants
Where
1 siteDenmark
Study dates
Jul 2012to Jul 2013
Phase
Phase 2
Are there results?
None posted in the registry

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 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Written informed consent (IRB/IEC specific) has been obtained prior to initiation of any protocol required procedures.
  • Male or female between 40 and 75 years of age. Females of childbearing potential must have a negative urine pregnancy test at screening.
  • Body weight >40 kg and <150 kg with a body mass index (BMI) between 19-40 kg/m2 inclusive.
  • Idiopathic osteoarthritic knee pain diagnosed in accordance with the American College of Rheumatology modified clinical classification criteria (Altman et al, 1986) and verified radiologically as Kellgren-Lawrence grade I, II or III (Kellgren and Lawrence, 1957) at the index knee. The clinical diagnosis of OA will be confirmed by the ACR clinical and radiographic criteria for classification of idiopathic OA based upon the following criteria (index knee):
  • Knee pain for at least 14 days per month for the 3 months before study entry.
  • Osteophytes (with radiographic evidence).
Show all 11Show fewer
  • And at least 1 of the following 3 conditions: Age >50, or morning stiffness <30 minutes, or crepitus.
  • X-ray images of the knee joints are available confirming OA. X-ray images older than12 months cannot be used. New photos are needed to confirm the diagnostic criteria for OA.
  • For the index knee, the average of the worst daily pain score over the last 14 days prior to day 0 must be 4.0 to 9.0. The 14-day average score will be derived from worst daily pain scores recorded in a diary for the index knee.
  • Discontinued use of all analgesic medications (including over-the-counter analgesics/ Non-Steroidal Anti-Inflammatory Drug at least 3 days prior to visit 2 (subjects are allowed limited use of analgesic medications).
  • Have agreed to maintain the same activity level throughout the course of the study.

Who cannot join

  • Have a history of recurrent seizures other than febrile seizures.
  • Have a history of frequent and/or severe allergic reactions with multiple medications.
  • Have a current or recent history, as determined by the investigator or his delegates, of severe, progressive, and/or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological, psychiatric or cerebral disease which could interfere with the subject's participation in the study.
  • At screening, have an abnormality in the 12-lead ECG that, in the opinion of the investigator, increases the risks associated with participation in the study. In addition, subjects with following findings will be excluded:
  • Confirmed Bazett's corrected QT (QTcB) interval > 450 msec for men and > 470 msec for women at screening. If QTcB is prolonged a second ECG will be taken to confirm the finding; (additional ECGs may be performed if required),
  • Bundle branch blocks and other conduction abnormalities other than mild first degree atrio-ventricular block, left anterior hemi block due to left axis deviation and right bundle branch block of benign origin i.e. not caused by other cardiac disease,
Show all 45Show fewer
  • Irregular rhythms other than sinus arrhythmia or occasional supraventricular or ventricular ectopic beats,
  • History of unexplained syncope,
  • Family history of unexplained sudden death or sudden death due to long QT syndrome,
  • T-wave configurations are not of sufficient quality for assessing QT interval determination, as assessed by the investigator.
  • Have an alanine aminotransaminase > 2.5 times Upper Limit of Normal (ULN) at screening, based on reference ranges of the local laboratory. Moderate or greater hepatic impairment.
  • Have prior renal transplant, current renal dialysis or severe renal insufficiency (determined by a derived glomerular filtration rate using Cockcroft Gault formula of ≤30 ml/min/1,73m² calculated by the local lab), or serum creatinine laboratory value >1.5 times ULN, based on the reference ranges of the local laboratory.
  • Have active peptic ulcer or gastrointestinal bleeding.
  • Have known inflammatory intestinal disease.
  • Subject with ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease.
  • Subject with congestive heart failure (NYHA II-IV).
  • Subject with uncontrolled arterial hypertension (>160/90).
  • Subject with diabetes mellitus and documented atherosclerosis.
  • History of bronchospasms, acute rhinitis, nasal polyps, angioneurotic edema, urticaria or other type of allergic reaction after having used acetylic acid or NSAID, inclusive COX-2 inhibitors.
  • Is allergic to the active ingredient of etoricoxib or one or more of the excipients.
  • Pregnant female, breast feeding or planning a pregnancy during the study period. Females of child-bearing potential, not using a reliable means of contraception.
  • Subject with an active malignancy of any type or a history of malignancy within the last 5 years (except basal cell carcinoma of the skin that has been excised prior to study start).
  • Are taking any excluded medications (analgesic medications) that cannot be discontinued during the screening period (3 days prior to visit 2).
  • Subject in treatment with anticoagulants (with the exception of acetylsalicylic acid), methotrexate or rifampicin or antihypertensives (with the exception of Ca+-antagonists).
  • Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at Visit 1.
  • Have a history of substance abuse or dependence within the past year, excluding nicotine and caffeine.
  • Subject at a high risk of infection (e.g. leg ulcers, indwelling urinary catheter and persistent or recurrent chest infections and subjects who are permanently bed ridden or wheelchair bound).
  • Subject with a history of, or suspected, demyelinating disease of the central nervous system (e.g. multiple sclerosis or optic neuritis).
  • Have an autoimmune disorder (not including psoriasis).
  • Subject that do not fully understand the EPM procedures according to investigator experience.
  • Investigator site personnel directly affiliated with this study and/or their immediate family cannot participate. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.
  • Subject diagnosed with any condition suggestive of a secondary cause of knee OA including but not limited to knee trauma, septic arthritis, inflammatory joint disease, articular fracture, major dysplasia or congenital abnormality, ochronosis, acromegaly, hemochromatosis, Wilson's disease, or primary osteochondromatosis.
  • History of surgery (including arthroscopy) in the index knee within 3 months prior to visit 1 or already planned surgery of the index knee at any time.
  • History of significant prior injury to the index knee within 12 months prior to visit 1.
  • Subject diagnosed with Kellgren and Lawrence grade IV at the index knee.
  • Use of lower extremity assistive devices other than a knee brace or 'shoe lift'. Use of a cane in the hand opposite to the index knee is acceptable.
  • History of prior synovial fluid analysis showing a White Blood Cell count ≥ 2000 mm3 that is indicative of a diagnosis other than OA at the index knee.
  • Have a confounding painful condition that may interfere with assessment of the index knee joint. (Knee pain should be the predominant pain. Mild OA of the hands is allowed, for instance).
  • History of any other musculoskeletal or arthritic condition that may affect the interpretation of clinical efficacy and/or safety data or otherwise contraindicates participation in this clinical study (i.e., currently symptomatic fractures or any concurrent rheumatic disease such as but not limited to fibromyalgia, rheumatoid arthritis, gout, pseudo-gout or Paget's disease and Reiter's syndrome are excluded).
  • Have used corticosteroids prior to baseline:
  • Intra-articular injection of steroids into the index knee or into any other site than the index knee within the previous 3 months,
  • Intra-muscular corticosteroid injections within the previous 3 months,
  • Oral corticosteroids within the previous 1 month.
  • Have initiated or changed their established physiotherapy program within the last 14 day prior to visit 3.
  • Have not recorded a minimum of 10 days of diary data of the last 14 days immediately preceding visit 3.

Trial locations and contacts

1 site in 1 country.

Denmark1 site

  • CCBR A/S

    Aalborg, Aalborg, 9000

Other trials in Denmark

About this study

Official title: A Single Center, Randomized, Double-blind, Placebo-controlled 2-way Crossover Study to Investigate the Mechanism of Action of Etoricoxib in Subjects With Osteoarthritis Knee Pain.

The purpose of this study is to investigate which pain mechanisms that can be affected by etoricoxib compared to placebo (inactive medication)in subjects with painful knee osteoarthritis af 4 weeks of treatment.

Read the detailed description

Study Rationale: The purpose of this study is to investigate which pain mechanisms in subjects with painful knee osteoarthritis can be affected by the peripheral and central actions of etoricoxib as compared to placebo during a 4 week treatment therapy period.

The present study will utilize a set of quantitative mechanism based pain biomarkers to assess peripheral and central pain manifestations in OA and the influence of etoricoxib on those individual manifestations in an attempt to understand and explain clinical pain alleviation.

Study Treatment: Subjects will be randomized to one of the 2 sequences of treatment: Sequence 1 (60 mg/day etoricoxib followed by placebo) or Sequence 2 (placebo followed by 60 mg/day etoricoxib). The two treatment periods of 4 weeks each are separated by a washout period of at least 6 days.

Primary Objective: To assess which pain mechanisms are modulated by 60 mg daily administration of etoricoxib compared to placebo in subjects with osteoarthritic (OA) knee pain during two treatment periods of 4-weeks each.

Secondary Objectives: To evaluate if changes in any of the mechanism based experimental pain assessment parameters can explain changes in clinical outcome parameters.

To profile drug responders- versus non-responders based on pain mechanisms involved.

To investigate if change in inflammatory, bone and cartilage related bio-chemical biomarkers can explain changes in either experimental or clinical pain parameters.

Conditions
Osteoarthritis
Being tested
Etoricoxib, followed by placebo (matching tablet, without active ingredient), Placebo (matching tablet, without active ingredient), followed by etoricoxib
Keywords
knee, osteoarthritis, central sensitization, mechanical detection, pain threshold, quantitative sensory testing, pain biomarkers, COX-2 inhibitors, etoricoxib.
Medical subject headings
Osteoarthritis

What participants receive

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

  • Etoricoxib, followed by placebo (matching tablet, without active ingredient)Drug

    Also called Acoxia®

    Sequence 1: 1 tablet of 60 mg etoricoxib daily for 4 weeks, for oral use. Sequence 2: 1 tablet of matching placebo daily for 4 weeks, for oral use.

  • Placebo (matching tablet, without active ingredient), followed by etoricoxibDrug

    Also called Acoxia®

    Sequence 1: 1 tablet of matching placebo daily for 4 weeks, for oral use. Sequence 2: 1 tablet of 60 mg etoricoxib daily for 4 weeks, for oral use.

Study groups in NCT01619150
Study groupRoleWhat they receive
Etoricoxib, followed by placeboOther4 weeks of treatment with etoricoxib, followed by a wash out period of at least 6 days, followed by another 4 weeks of treatment with placebo.
Receives: Drug: Etoricoxib, followed by placebo (matching tablet, without active ingredient)
Placebo, followed by etoricoxibOther4 weeks of treatment with placebo, followed by a wash out period of at least 6 days, followed by another 4 weeks of treatment with etoricoxib.
Receives: Drug: Placebo (matching tablet, without active ingredient), followed by etoricoxib

What is being measured

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

  1. Change in Experimental mechanism based Pain Measures (EPMs)during two treatment periods of 4-weeks each

    The following EPMs will be applied:

    • Quantitative Sensory Testing (QST) of 3 knee joint pain locations
    • Spreading sensitization
    • Pain areas
    • Wind-up like pain
    • Descending noxious inhibitory control
    • Cuff evoked pain
    • Infrared thermography of both knees

    Measured: The EPMs will be measured: at V3, prior to 1. treatment sequence w/ Medication/Placebo; at V5, after 4 weeks of treatment; at V6, prior to 2. treatment sequence w/ Medication/Placebo; at V8, after 4 weeks of treatment.

Secondary outcomes (1)

  1. Change in Clinical Outcome measures during two treatment periods of 4-weeks each

    Change of pain severity as measured by the daily 24-hour average pain score (APS), night pain and worst daily pain, the following questionnaires: PQAS, BPI, IGIC, PGAC, WOMAC, Dolotest® and PDQ. Furthermore time and pain intensity from a 40 m self-paced walk test and from a 11 step stair climb test.

    Fasting plasma, serum and urine samples will be collected and stored for potential further analysis of e.g. IL-6, IL-8, CTX1, CTX2, TNFα, CCL2, CO1, CO2, sCRP, CRP25, C1M, C2M, C3M, OC, MMP.

    Measured: The Clinical Outcome measures will be measured at screening and throughout the two treatment sequences. The study period is in total 16 weeks. Some measures will be recorded daily, others only at study visits.

Timeline

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

  1. First posted14 Jun 2012 (estimated)
  2. Study startJul 2012
  3. Primary completionJul 2013
  4. Study completionJul 2013

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 2
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Crossover
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
39 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01619150
Sponsor's protocol ID
OSKNEEPA02
Status last verified
Jul 2013
First submitted
7 Jun 2012
Last updated
23 Jul 2013
Results posted
No
Data monitoring committee
No

Publications

  • Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K, Christy W, Cooke TD, Greenwald R, Hochberg M, et al. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum. 1986 Aug;29(8):1039-49. doi: 10.1002/art.1780290816.

    PubMed 3741515

  • Arendt-Nielsen L, Nie H, Laursen MB, Laursen BS, Madeleine P, Simonsen OH, Graven-Nielsen T. Sensitization in patients with painful knee osteoarthritis. Pain. 2010 Jun;149(3):573-581. doi: 10.1016/j.pain.2010.04.003. Epub 2010 Apr 24.

    PubMed 20418016

  • Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW. Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol. 1988 Dec;15(12):1833-40.

    PubMed 3068365

  • Brooks P, Kubler P. Etoricoxib for arthritis and pain management. Ther Clin Risk Manag. 2006 Mar;2(1):45-57.

    PubMed 18360581

  • Cannon CP, Curtis SP, FitzGerald GA, Krum H, Kaur A, Bolognese JA, Reicin AS, Bombardier C, Weinblatt ME, van der Heijde D, Erdmann E, Laine L; MEDAL Steering Committee. Cardiovascular outcomes with etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: a randomised comparison. Lancet. 2006 Nov 18;368(9549):1771-81. doi: 10.1016/S0140-6736(06)69666-9.

    PubMed 17113426

  • Cleeland CS, Nakamura Y, Mendoza TR, Edwards KR, Douglas J, Serlin RC. Dimensions of the impact of cancer pain in a four country sample: new information from multidimensional scaling. Pain. 1996 Oct;67(2-3):267-73. doi: 10.1016/0304-3959(96)03131-4.

    PubMed 8951920

  • Felson DT. Developments in the clinical understanding of osteoarthritis. Arthritis Res Ther. 2009;11(1):203. doi: 10.1186/ar2531. Epub 2009 Jan 30.

    PubMed 19232065

  • Freynhagen R, Baron R, Gockel U, Tolle TR. painDETECT: a new screening questionnaire to identify neuropathic components in patients with back pain. Curr Med Res Opin. 2006 Oct;22(10):1911-20. doi: 10.1185/030079906X132488.

    PubMed 17022849

  • Freynhagen R, Rolke R, Baron R, Tolle TR, Rutjes AK, Schu S, Treede RD. Pseudoradicular and radicular low-back pain--a disease continuum rather than different entities? Answers from quantitative sensory testing. Pain. 2008 Mar;135(1-2):65-74. doi: 10.1016/j.pain.2007.05.004. Epub 2007 Jun 13.

    PubMed 17570589

  • Graven-Nielsen T, Arendt-Nielsen L. Assessment of mechanisms in localized and widespread musculoskeletal pain. Nat Rev Rheumatol. 2010 Oct;6(10):599-606. doi: 10.1038/nrrheum.2010.107. Epub 2010 Jul 27.

    PubMed 20664523

  • Guy and Bonato (Eds). Manual for the ECDEU Assessment Battery. 2nd revised edition. Chevy Chase, MD: National Institute of Mental Health 1976.

  • Imamura M, Imamura ST, Kaziyama HH, Targino RA, Hsing WT, de Souza LP, Cutait MM, Fregni F, Camanho GL. Impact of nervous system hyperalgesia on pain, disability, and quality of life in patients with knee osteoarthritis: a controlled analysis. Arthritis Rheum. 2008 Oct 15;59(10):1424-31. doi: 10.1002/art.24120.

    PubMed 18821657

  • Jansen JP, Gaugris S, Choy EH, Ostor A, Nash JT, Stam W. Cost effectiveness of etoricoxib versus celecoxib and non-selective NSAIDS in the treatment of ankylosing spondylitis. Pharmacoeconomics. 2010;28(4):323-44. doi: 10.2165/11314690-000000000-00000.

    PubMed 20222755

  • Jespersen A, Dreyer L, Kendall S, Graven-Nielsen T, Arendt-Nielsen L, Bliddal H, Danneskiold-Samsoe B. Computerized cuff pressure algometry: A new method to assess deep-tissue hypersensitivity in fibromyalgia. Pain. 2007 Sep;131(1-2):57-62. doi: 10.1016/j.pain.2006.12.012. Epub 2007 Jan 25.

    PubMed 17257757

  • Kristiansen K, Lyngholm-Kjaerby P, Moe C. Introduction and Validation of DoloTest((R)): a new health-related quality of life tool used in pain patients. Pain Pract. 2010 Sep-Oct;10(5):396-403. doi: 10.1111/j.1533-2500.2010.00366.x.

    PubMed 20384966

Questions about this trial

What is this clinical trial studying?

A Phase 2 study of Osteoarthritis, run by C4Pain at 1 site in Denmark.

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 11 inclusion and 45 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 23 Jul 2013. 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 Denmark. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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 in Experimental mechanism based Pain Measures (EPMs)during two treatment periods of 4-weeks each (time frame: The EPMs will be measured: at V3, prior to 1. treatment sequence w/ Medication/Placebo; at V5, after 4 weeks of treatment; at V6, prior to 2. treatment sequence w/ Medication/Placebo; at V8, after 4 weeks of treatment.). 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 NCT01619150, which also lists 26 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 23 Jul 2013; AzTrials last refreshed its copy on 4 Nov 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in