Evaluation of NaproxenSodium and CodeinePhosphate Combination in Osteoarthritis

Randomized, Double-blind and Placebo-controlled Evaluation of Efficacy and Safety of Naproxen Sodium and Codeine Phosphate Combination in Osteoarthritis

Osteoarthritis (OA) pain treatment has limitations in terms of serious adverse effects and low efficacy. The investigators aimed to evaluate efficacy and safety of naproxen sodium/codeine phosphate combination in these patients.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis
• Intervention / Treatment: Drug: Naproxen Sodium Codeine; Drug: Placebo

Detailed Description

In this prospective, randomized, double blind, placebo controlled clinical trial, 135 patients with osteoarthritis, who were 40-65 years; applied to institution's orthopaedics outpatient clinic; had grade 1, 2, or 3 primary osteoarthritis diagnosed in last 1 year; and had Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score≥40, and Visual Analogue Scale score≥40,were enrolled. Subjects were randomized (1:1) to placebo (n= 67) or combination (n= 68) arms, in which 550 mg naproxen sodium/30mg codeine phosphate was given orally twice a day for 7 days. Rescue medicine was 500 mg paracetamol (max= 6 tablets/day). Demographic characteristics, medical history, adverse events, VAS and WOMAC scores were collected in study visits performed within 10days.The study was approved by local institutional ethics committee and written informed consents were obtained from all participants.

• Study Type: Interventional
• Enrollment (Actual): 135
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Clinical and radiological diagnosis of primary osteoarthritis (knee and hip) in the recent year according to criteria of American College of Rheumatology (ACR)
• Grade 1, 2 or 3 osteoarthritis patients
• Patients 40 to 65 years of age
• Patients with WOMAC score ≥ 40
• Patients with VAS score ≥ 40
• Patients who signed the consent form

Exclusion Criteria:

• Grade 4 osteoarthritis patients / Pregnant or breastfeeding mothers
• Patients with known allergic reaction or intolerance to NSAIDs (nonsteroidal antiinflammatory drugs)
• Patients hypersensitive to naproxen sodium or codeine
• Patients who took another analgesic medicine during 24 hours before and/or a nonsteroidal anti-inflammatory medicine during 72 hours before taking study medicine
• Patients with active gastric or duodenum ulcer
• Patients with renal dysfunction and/or a kidney disease
• Patients with severe liver disease
• Patients with rare hereditary galactose intolerance, Lapp lactase insufficiency or glucose-galactose malabsorption problem
• Patients with depression treated by a medicine from monoamine oxidase class
• Patients with uncontrolled hypertension or patients with hypertension that is hardly controlled with medicines
• Patients with a known medical, psychological disturbance or social status that may negatively affect inclusion into the study or patients who may lead to increase in risk for others with inclusion into the study
• Patients with proven clinically important and unstable systemic medical disease
• Patients who have medical contraindication for study medicine
• Patients who are judged by investigator that they will not adhere or adequately adhere to the study protocol
• Patients who participated into another study with another study medicine in the last 4 week
• Patients who intent to donate blood or blood product during the study period or in the following month of the study completion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Naproxen Sodium Codeine; One tablet twice a day	Drug: Naproxen Sodium Codeine; One tablet twice a day; Other Names: Apranax Plus
PLACEBO_COMPARATOR: Placebo; One tablet twice a day	Drug: Placebo; One tablet twice a day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in Western Ontario Mac Master Questionnaire (WOMAC)	7 days
Change in Visual Analog Scale (VAS)	7 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in pain severity in all visits after treatment from baseline (VAS)	7 days
Functional effects of combination therapy (WOMAC)	7 days
Change in resting pain after treatment from baseline (WOMAC)	7 days
Change in activity pain after treatment from baseline (WOMAC)	7 days
Change in physical function after treatment from baseline (WOMAC)	7 days
Ratio of rescue medicine use (Rescue medication count)	7 days
Collection of adverse event reports to evaluate safety of the medicine	7 days

Collaborators and Investigators

• Sponsor: Istanbul Medeniyet University
• Collaborators: Abdi Ibrahim Ilac San. ve Tic A.S.

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (ACTUAL): November 1, 2014
• Study Completion (ACTUAL): November 1, 2015

Study Registration Dates

• First Submitted: July 9, 2015
• First Submitted That Met QC Criteria: July 16, 2015
• First Posted (ESTIMATE): July 17, 2015

Study Record Updates

• Last Update Posted (ESTIMATE): February 25, 2016
• Last Update Submitted That Met QC Criteria: February 24, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: Osteoarthritis; NAPROXEN SODIUM
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Analgesics, Opioid; Narcotics; Respiratory System Agents; Gout Suppressants; Antitussive Agents; Codeine; Naproxen
• Other Study ID Numbers: NAPCOD2013