A Double-Blind, Double-Dummy, Randomized, Active-Comparator, Arthritis Non-Inferiority Study of LT-NS001 versus Naprosyn® for Twelve Weeks in Osteoarthritis Patients to Compare Endoscopic Gastric Ulcer Rates - Nature Trial

• Conditions: osteoarthritis of the knee

• Registration Number: EUCTR2009-018029-57-GB
• Lead Sponsor: ogical Therapeutics Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-03-18
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 534

Inclusion Criteria

Written Informed consent.
• Age 45–80 years, inclusive.
• Osteoarthritis of knee.
• Appropriate candidate for chronic NSAID therapy due to moderate or severe pain on most days in the previous 28 days prior to screening.
• Baseline (pre-dose) index joint WOMAC pain index =40 mm, after a 14 day NSAID washout and with no analgesia on the entire day prior to, and on the day of the WOMAC questionnaire (until completed).
• Body mass index =42 kg/m2.
• Patients of reproductive potential (males and females) agree to use two acceptable methods of birth control during the study. Abstinence is acceptable for patients who sign an additional statement of risk.
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Medical History / Examination:
• Pregnant or nursing women.
• History of documented gastrointestinal bleeding, obstruction or perforation.
• History of a documented symptomatic gastroduodenal ulcer (not including an asymptomatic ulcer detected by endoscopic screening) in the previous 5 years.
• Baseline upper gastroduodenal endoscopy with ulcer or >2 total erosions.
• Inflammatory bowel disease, celiac disease/gluten enteropathy, Whipple’s disease, or other malabsorptive disease.
• Resting supine blood pressure >180 mm Hg systolic or >105 mm Hg diastolic, with no change in anti-hypertensive medication for 28 days prior to Screening if the patient is receiving anti-hypertensive medication.
• New York Heart Association Class III or IV cardiac function.
• Recent (6 months) stroke or myocardial infarction.
• History of cancer except for excised basal cell or squamous cell carcinoma of the skin >3 years ago.
• Active or recurrent infection.
• Psychiatric or neurologic disease precluding participation based on inadequate consent or inability to follow study instructions.
• Any other medical condition that would prohibit study participation in the view of the Principal Investigator.
• Lack of peripheral venous access.
• Active alcohol abuse / drug addiction (including cannabis products) in the previous 2 years.
Medications:
• Allergy to naproxen, acetylsalicylic acid or other NSAID drug.
• Severe naproxen intolerance in the past.
• No intra-articular injections in the 28 days prior to screening.
• Use of a second NSAID including aspirin within 14 days prior to baseline endoscopy, or planned use during study participation.
• Use of an anti-coagulant or anti-platelet drug within 14 days prior to baseline endoscopy or planned use during study participation.
• Use of proton-pump inhibitors (PPI), type 2 histamine blockers (H2 blocker), antacids, binding agents including bile acid sequestrants, pancreatic replacement, cholinesterase inhibitors or specified analgesics including narcotics within 14 days prior to baseline endoscopy or planned use during study participation.
• Treatment with an investigational agent (including device) within 28 days or 5 investigational drug half-lives (whichever is longer) of Screening, current participation in another research study, or participation in more than 3 research studies in the previous 12 months.
Screening Laboratory Tests:
• Positive H. pylori stool antigen test
• Hgb <11.5 gm/dL (women) or <12.5 gm/dL (men).
• Calculated GFR (MDRD) <30 mL/min/1.73 m2.
• AST or ALT >1.5 times upper limit of normal.
• Positive hepatitis B surface antigen (HBsAg).
• Positive anti-hepatitis C (HCV) IgG antibody.
• Positive anti-human immunodeficiency virus (HIV) 1/2 IgG antibody.

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Secondary Objective: Exploratory (for Arm A vs B):<br>1. To compare changes in stiffness, function and total response in an index osteoarthritic knee joint<br>2. To evaluate GI and overall safety of LT-NS001 1200 mg versus Naprosyn® 500 mg b.i.d. for 12 weeks<br>3. To develop population PK data for analysis of covariates;Primary end point(s): Primary (GI Safety): Cumulative incidence of patients with gastric ulcer by endoscopy at week 12 for Arm A versus Arm B;Main Objective: Primary (GI Safety): To compare the cumulative incidence of patients with gastric ulcer by endoscopy (EGD) for Arm A vs Arm B<br>Secondary (for Arm A vs Arm B):<br>1. To demonstrate non-inferior pain control in an index osteoarthritic knee joint<br>2. To compare overall gastric injury rates by EGD<br>3. To compare tolerability and retention on study drug