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

NCT01619150 | Completed Phase 2

• 1 other identifier: OSKNEEPA02
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Osteoarthritis

Keywords

knee; osteoarthritis; central sensitization; mechanical detection; pain threshold; quantitative sensory testing; pain biomarkers; COX-2 inhibitors; etoricoxib.

Outcome Measures

Primary Outcomes (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

  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)

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

  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.

Study Arms (2)

Etoricoxib, followed by placebo

OTHER

4 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.

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

Placebo, followed by etoricoxib

OTHER

4 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.

Drug: Placebo (matching tablet, without active ingredient), followed by etoricoxib

Interventions

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

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.

Also known as: Acoxia®

Etoricoxib, followed by placebo

Placebo (matching tablet, without active ingredient), followed by etoricoxib DRUG

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.

Also known as: Acoxia®

Placebo, followed by etoricoxib

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.

You may not qualify if:

• 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,
• 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.

Sponsors & Collaborators

• C4Pain: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

CCBR A/S

Aalborg, Aalborg, 9000, Denmark

Location

Related Publications (26)

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MeSH Terms

Conditions

Osteoarthritis

Interventions

Etoricoxib

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Sulfones; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Hans Christian Hoeck, MD PhD

  C4Pain

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2012
• First Posted: June 14, 2012
• Study Start: July 1, 2012
• Primary Completion: July 1, 2013
• Study Completion: July 1, 2013
• Last Updated: July 23, 2013

Record last verified: 2013-07

Locations

DK (1)