Gastro-protective Effect and Pain Relief Effect of Naxozol Compared to Celecoxib in Patients With Osteoarthritis

A Prospective, Randomized, Double-blinded, Double-dummy, Active-controlled, Multi-center, Interventional Study to Compare Gastro-protective Effect and Pain Relief Effect of Naxozol Compared to Celecoxib in Patients With Osteoarthritis

Naxozol is a combination product of naproxen, a non-steroidal anti-inflammatory drug (NSAID) and esomeprazole, a proton pump inhibitor which is designed to improve symptoms and reduce risk of gastric ulcers in patients at risk of developing NSAID-associated gastric ulcers in the treatment of osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis. The purpose of this study is to investigate whether naxozol protects the gastrointestinal tract effectively compared to celecoxib, a COX-2 inhibitor.

Study Overview

• Status: Unknown
• Conditions: Osteoarthritis
• Intervention / Treatment: Drug: Naproxen/Esomeprazol 500/20mg; Drug: Comparator-Placebo; Drug: Celecoxib 200mg; Drug: Naxozol-Placebo

Detailed Description

A total of 10 orthopedic investigators will participate in this study. The effectiveness in gastro-protection of study drug will be assessed by Leeds Dyspepsia Questionnaire (LDQ). The orthopedic investigators will be trained with this questionnaire administration by an expert gastroenterologist prior to starting this study.

• Study Type: Interventional
• Enrollment (Anticipated): 106
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Seong-Hwan Moon, M.D., Ph.D.; Phone Number: 82 2 2228 5670; Email: shmoon@yuhs.ac
• Study Contact Backup: Name: Ji-Hye Kim; Phone Number: 82 2 2228 2824; Email: CORN@yuhs.ac

Study Locations

• Korea, Republic of
  • Anyang-si, Korea, Republic of
    • Not yet recruiting
    • Hallym University Medical Center
    • Principal Investigator: Moon-Soo Park, M.D.
  • Goyang-si, Korea, Republic of
    • Not yet recruiting
    • Inje University Ilsan Paik Hospital
    • Principal Investigator: Jin-Hwan Kim, M.D.
  • Seongnam-si, Korea, Republic of
    • Not yet recruiting
    • Seoul National University Bundang Hospital
    • Principal Investigator: Ho-Joong Kim, M.D.
  • Seoul, Korea, Republic of
    • Recruiting
    • Severance Hospital
    • Principal Investigator: Seong-Hwan Moon, M.D.
  • Seoul, Korea, Republic of
    • Not yet recruiting
    • Asan Medical Center
    • Principal Investigator: Ho-Seong Lee, M.D.
  • Seoul, Korea, Republic of
    • Not yet recruiting
    • Seoul National University Hospital
    • Principal Investigator: Sang-Hoon Lee, M.D.
  • Seoul, Korea, Republic of
    • Not yet recruiting
    • Hanyang University Seoul Hospital
    • Principal Investigator: Chang-Nam Kang, M.D.
  • Seoul, Korea, Republic of
    • Not yet recruiting
    • Ewha womans university medical center
    • Principal Investigator: Sang-Jin Shin, M.D.
  • Seoul, Korea, Republic of
    • Not yet recruiting
    • Gangnam Severance Hospital
    • Principal Investigator: Woo-Suk Lee, M.D.
  • Seoul, Korea, Republic of
    • Not yet recruiting
    • Seoul ST. Mary's Hospital
    • Principal Investigator: Young-Hoon Kim, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 48 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Koreans given informed consent
• Patients who have ability of reading comprehension and completing questionnaires (EQ-5D and VAS)and have willingness to follow-up 12 weeks
• Patients with osteoarthritis symptoms confirmed by his/her medical history and with pain-VAS of 40 and more

Exclusion Criteria:

• Patients who participate into other interventional study or had participated within 30 days before screening
• Alcohol or drug abuse within 6 months or alcohol consumption of 21 units and more in a week
• Peptic ulcers accompanied with a complication such as bleeding, perforation, penetration or gastric outlet obstruction within 5 years, or a history of active peptic ulcer or peptic ulcer without a complication within 6 months at screening
• Patients who are known with Helicobacter pylori infection but have not received any bacteriostatic treatment
• Known gastroesophageal reflux disease (GERD)
• Any following joint diseases which may significant effect to the efficacy and safety assessments: septic arthritis, inflammatory joint arthritis such as rheumatoid arthritis, gout, recurrent pseudo-pain, Paget's disease, joint fracture, joint ochronosis, acromegaly, hematochromatosis, Wilson's disease, primary osteochondrosis, Ehlers Danlos Syndrome, or other collagen genetic disorder
• Patients who are scheduled admissions to hospital for elective surgery during this study
• History of gastrointestinal cancer
• Gastrointestinal disorders related to drug malabsorption
• Gastrointestinal bleeding, cerebral bleeding, other bleeding disorders, or severe hematological disorders
• Clinically significant diseases such as moderate or severe liver diseases (Child Pough Class II or more), severe heart failure or a history of coronary artery bypass graft (CABG), severe kidney diseases (CrCl<30ml/min)
• Know allergy experiences with any ingredient of study drugs or with other NASIDs or protocol pump inhibitors (PPIs)
• Patients who had had a joint surgery for osteoarthritis within 1 year
• Women of childbearing potential who do not agree with clinically appropriate contraception during this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test Group; Naproxen/Esomeprazol 500/20mg and Comparator-Placebo for 12 weeks	Drug: Naproxen/Esomeprazol 500/20mg; Tablet, b.i.d.; Other Names: Naxozol; Drug: Comparator-Placebo; Capsule (which is identical to Celebrex), o.d.
Active Comparator: Comparator Group; Celecoxib 200mg and Naxozol-Placebo for 12 weeks	Drug: Celecoxib 200mg; Capsule, o.d.; Other Names: Celebrex; Drug: Naxozol-Placebo; Tablet (which is identical to Naxozol), b.i.d.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Leads Dyspepsia Questionnaire (LDQ) Change	Mean change from baseline of Leads Dyspepsia Questionnaire	Baseline, 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean LDQ	Mean value of Leads Dyspepsia Questionnaire at 12 weeks	Baseline, 12 weeks
Gastrointestinal Symptom Rating Scale (GSRS) Change	Mean change from baseline of Gastrointestinal Symptom Rating Scale	Baseline, 12 weeks
Gastrointestinal Adverse Events Rate	Dyspepsia, Diarrhoea, Nausea, Abdominal Pain, Heartburn	Baseline, 12 weeks
Drug Discontinuation Rate Due to Gastrointestinal Adverse Events		Baseline, 12 weeks
Pain Relief Effect, mean change from baseline of Pain Visual Analogue Scale (VAS)	Mean change from baseline of Pain Visual Analogue Scale (VAS)	Baseline, 12 weeks
Quality of Life Change, mean change from baseline of EQ-5D	Mean change from baseline of EQ-5D	Baseline, 12 weeks
Treatment Compliance	Non-compliance is defined less than 80%	Baseline, 12 weeks
Rescue Drugs Usage	Acetaminophen ER 650mg and/or Almagate 500mg will be administrated for control of severe pain events and/or of severe gastrointestinal events.	Baseline, 12 weeks
Adverse Events	Adverse Events and Abnormalities from Vital Signs, Physical Exam, and Clinical Laboratories	Baseline, 12 weeks

Collaborators and Investigators

• Sponsor: Severance Hospital
• Investigators: Study Chair: Seong-Hwan Moon, M.D., Ph.D., Severance Hospital

Study record dates

Study Major Dates

• Study Start: February 1, 2015
• Primary Completion (Anticipated): December 1, 2015
• Study Completion (Anticipated): December 1, 2015

Study Registration Dates

• First Submitted: January 30, 2015
• First Submitted That Met QC Criteria: February 3, 2015
• First Posted (Estimate): February 4, 2015

Study Record Updates

• Last Update Posted (Estimate): March 23, 2015
• Last Update Submitted That Met QC Criteria: March 20, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Osteoarthritis; GSRS; Naxozol; LDQ; Gastroprotective
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; 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; Cyclooxygenase 2 Inhibitors; Gout Suppressants; Celecoxib; Naproxen
• Other Study ID Numbers: Naxozol_P4_1