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 pai

• Conditions: Osteoarthritic Knee Pain.; MedDRA version: 14.1Level: LLTClassification code 10029877Term: OA kneeSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders; Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

• Registration Number: EUCTR2011-004179-35-DK
• Lead Sponsor: C4Pain ApS

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-11-28
• Last Update Posted: 12 May 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1.Written informed consent (IRB/IEC specific) has been obtained prior to initiation of any protocol required procedures.
2.Male or female between 40 and 75 years of age. Females of childbearing potential must have a negative urine pregnancy test at screening.
3.Body weight >40 kg and <150 kg with a body mass index (BMI) between 19-40 kg/m2 inclusive.
4.Idiopathic osteoarthritic knee pain (index knee) diagnosed in accordance with the American College of Rheumatology (ACR) 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):
a. Knee pain for at least 14 days per month for the 3 months before study entry.
b. Osteophytes (with radiographic evidence).
c. And at least 1 of the following 3 conditions: Age >50, or morning stiffness <30 minutes, or crepitus.
d. 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.
5.For the index knee, the average of the worst daily pain score over the last 14 days prior to day 0 (i.e. days -14 to day -1) 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.
6.Discontinued use of all analgesic medications (including over-the-counter [OTC] analgesics/ Non-Steroidal Anti-Inflammatory Drug (NSAID) at least 3 days prior to visit 2 (subjects are allowed limited use of analgesic medications, refer to section on Permissible Medications/Treatments).
7.Have agreed to maintain the same activity level throughout the course of the study.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 34
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 8

Exclusion Criteria

Have a history of recurrent seizures other than febrile seizures, or a history of frequent and/or severe allergic reactions with multiple medications.
Have a current or recent history 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 increases the risks associated with participation in the study. In addition, subjects with following findings will be excluded:
a. Confirmed Bazett’s corrected QT (QTcB) interval > 450 msec for men and > 470 msec for women at screening.
b. 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,
c. Irregular rhythms other than sinus arrhythmia or occasional supraventricular or ventricular ectopic beats,
d. History of unexplained syncope. Family history of unexplained sudden death or sudden death due to long QT syndrome,
f. T-wave configurations are not of sufficient quality for assessing QT interval determination.
Have an ALAT >2.5 timer ULN at screening.
Have prior renal transplant, current renal dialysis or severe renal insufficiency ( determined by GFR), or serum creatinine laboratory value >1.5 times ULN.

Have active peptic ulcer or gastrointestinal (GI) bleeding.
Have known inflammatory intestinal disease.
Subject with ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease or with congestive heart failure (NYHA II-IV).
Subject with uncontrolled arterial hypertension (>160/90) diabetes mellitus and 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.
Allergic to the active ingredient of etoricoxib or one or more of the excipients.
Pregnant female or breast feeding.
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 antihypertensiva (with the exception of Ca+-antagonists).
Have received treatment within the last 30 days with an investigational study drug
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.

Subject dia

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified