Efficacy and Safety of Celecoxib/Acetaminophen Versus Celecoxib for Diagnosed Osteoarthritis in Acute Exacerbation

Efficacy and Safety Study of the Fixed-dose Combination of Celecoxib/Acetaminophen Compared to Celecoxib for the Treatment of Pain in Patients Diagnosed With Osteoarthritis in Acute Exacerbation

This is a Phase III, longitudinal, multicenter, randomized, double-blind clinical trial designed to evaluate the efficacy and safety of a fixed-dose combination of celecoxib and acetaminophen compared to celecoxib monotherapy for the treatment of pain associated with acute exacerbations of osteoarthritis.

Researchers will evaluate the efficacy and safety of a fixed-dose combination of celecoxib and acetaminophen compared to celecoxib monotherapy for the treatment of pain in patients with osteoarthritis experiencing an acute exacerbation over a 6-week follow-up period. Adverse events related to the study interventions will be recorded throughout the follow-up phase.

Participants will:

Be randomized into one of three intervention groups (A, B, or C).

Attend five scheduled clinic visits (Day 0, and Weeks 1, 2, 4, and 6 of follow-up).

Be permitted to take 500 mg of naproxen as rescue medication, if needed, with prior authorization from the principal investigator.

Inclusion Criteria:

• Voluntarily agrees to participate in the study and provides written informed consent.
• Prior diagnosis of knee or hip osteoarthritis based on clinical criteria (according to the American College of Rheumatology (ACR) criteria described in Annex 5).
• Pain in the affected joint with exacerbation lasting no more than 3 weeks.
• Patient reports moderate to severe pain intensity (VAS ≥ 40 mm).
• For women of childbearing potential (a woman is considered fertile after menarche and until postmenopause unless permanently sterile), they must agree to use at least ONE of the following contraceptive methods during the study:

Barrier methods: diaphragm, cervical cap, male condom, female condom, spermicide foam, sponge, or film.

Hormonal methods: combined oral contraceptives, injectable contraceptives, subdermal implant, contraceptive patch.

Intrauterine device (IUD): copper or silver IUD, Levonorgestrel intrauterine system (IUS), and/or combinations of the above as deemed acceptable by the physician.

Women are considered not of childbearing potential if they meet at least ONE of the following criteria:

Postmenopausal. Premenopausal woman with at least ONE of the following: hysterectomy, bilateral salpingectomy, or bilateral oophorectomy.

Male subjects must agree to use a male condom as a contraceptive method during the study.

• At the discretion of the Principal Investigator (PI) or treating physician, the subject has an indication for treatment with the investigational product and may derive clinical benefit from it.

Exclusion Criteria:

• Intolerance or allergy to the investigational product or any of its components (as reported in the medical history and patient interview).
• Participation in another clinical study involving an investigational treatment or participation in one within the last two weeks prior to the study start.
• Potential study bias due to employment or relationship with the research center, sponsor, or being part of a vulnerable population.
• Medical conditions affecting prognosis that prevent outpatient management, to be evaluated by the Principal Investigator for subject inclusion relevance.
• History of advanced, severe, progressive, or unstable disease of any kind that may interfere with efficacy and safety assessments or pose a special risk to the patient.
• Medical contraindication to the investigational product.
• History of allergic reaction to NSAIDs (Non-Steroidal Anti-Inflammatory Drugs), Acetaminophen, or known hypersensitivity to any formulation components.
• Significant gastrointestinal disorders, such as gastric ulcers, Crohn's disease, ulcerative colitis, or gastrointestinal bleeding.
• Prior opioid treatment within the last five days, as reported in the medical history.
• History of treatment failure with COX-2 selective inhibitors, as documented in the medical history.
• History of chronic somatic pain unrelated to knee or hip osteoarthritis (e.g., fibromyalgia, metastatic disease, or Paget's disease).
• History of alcohol or drug abuse within the past year.
• Current treatment with NSAIDs, including COX-2 inhibitors, within the last 72 hours before signing informed consent (except for aspirin used for cardioprotective purposes).
• History of arthroscopy, viscosupplementation, or intra-articular steroid use in the last three months.
• Previous surgery on the affected joint within the last six months.
• Major trauma in the affected joint within the last three weeks.
• History of chronic liver failure (Child-Pugh A, B, or C).
• History of acute or severe renal failure (glomerular filtration rate <30 ml/min/1.73 m²), as reported in the medical history.
• Significant coagulation disorders (e.g., Von Willebrand disease, hemophilia, vitamin K deficiency) or current use of anticoagulants.

Oncologic patients (except basal cell carcinoma) or those with severe illnesses that, according to the investigator, have a poor prognosis or a life expectancy of less than one year, including severe mental illness.

• Patients with symptoms suggestive of active COVID-19 infection (e.g., fever, cough, dyspnea) and/or contact within the last 14 days with a suspected or confirmed COVID-19 patient.
• Positive pregnancy test, pregnant women, those currently breastfeeding, or those planning pregnancy during the study period.