A Double Blind, Randomised, Placebo Controlled Methodological Cross-over Study to Investigate the Senstivity of a Novel Study Design and Endpoints to Treatment Effects of Naproxen in Osteoarthritis

GlaxoSmithKline1 site in 1 country53 target enrollmentSeptember 2008

ConditionsOsteoarthritis

InterventionsNaproxen Placebo

DrugsPlacebo Naproxen

Overview

Phase: Phase 2
Intervention: Naproxen
Conditions: Osteoarthritis
Sponsor: GlaxoSmithKline
Enrollment: 53
Locations: 1
Primary Endpoint: Change from baseline in the time to ascend and descend 11 stairs
Status: Completed
Last Updated: 15 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a methodological study designed to investigate a new model for testing pain agents in the treatment of patients with osteoarthritis (OA). This will be a double-blind, randomised, placebo controlled three-way cross-over study in patients with OA of the knee.

Detailed Description

The study will include an interim analysis after approximately 50 patients have been randomised. Up to 100 patients with painful Osteoarthritis (OA) of the knee may be recruited into the study. Eligible subjects will wash out of all treatments for their OA pain for a minimum of 7 days apart from protocol rescue medication (paracetamol). Following this, subjects will participate in three short term treatment periods with repeated administration of Naproxen (500 mg/twice daily) or placebo for 3 days. Between treatment periods subjects will receive placebo. Endpoints will include objective assessments of function (time to walk and stair climbing) and subjective assessments of pain including current pain, the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and Patient Global Impression of Change. Throughout the study subjects will be asked to rate their pain periodically. Subjects will attend the unit on Day 1 to be dispensed with study medication and to take their first dose in the unit. They will then return to the unit on Days 8, 10, 15, 17, 22 and 24 for pain assessments, with medication dispensed at each of these visits, excluding Day 24.

Registry

clinicaltrials.gov

Start Date

September 2008

End Date

March 2009

Last Updated

15 years ago

Study Type

Interventional

Study Design

Crossover

Sex

All

Investigators

Sponsor

GlaxoSmithKline

Eligibility Criteria

Inclusion Criteria

•A diagnosis of OA of the knee and suitable for the study as determined by a responsible physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
•Male or female between 50 to 75 years of age inclusive.
•A female subject is eligible to participate if she is of non-childbearing potential defined as:
•Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \> 40 MlU/ml and estradiol \< 40 pg/ml (\<140 pmol/L) is confirmatory\].
•Females with menopausal status ( \> 12 months of spontaneous amenorrhea) and receiving hormone replacement therapy (HRT) treatment for more than 3 months.
•BMI within the range 15-35 kg/m2 (inclusive).
•Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
•QTcB or QTcF \< 450 msec; or QTc \< 480 msec in subjects with Bundle Branch Block.
•Have a radiological and clinical diagnosis of OA based upon Arthritis Research Council (ACR) (Appendix 3) criteria affecting at least one knee of a minimum of 3 months in symptom duration prior to screening. An X-ray will be performed at screening if required.
•Have symptomatic OA of at least one knee. The symptoms should be significantly worse in one knee than the other if OA affects both knees.

Exclusion Criteria

•The subject has a positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines. However, a positive drug screen will not automatically exclude a subject if there is a valid explanation for the positive result other than drug abuse e.g. poppy seeds.
•History of regular alcohol consumption within 6 months of the study defined as:
•An average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males), or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females). One unit is equivalent to a half-pint (220mL) of beer or 1 (25ml) measure of spirits or 1 glass (125ml) of wine.
•Intolerance of paracetamol or not response to Non Steriodal Anti Inflammatory Drugs (NSAID) therapy.
•The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
•Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
•Use of anticoagulants (warfarin, heparin) or anti-platelet aggregation agents (excluding low-dose aspirin) or a condition associated with decreased haemostasis.
•Use of prescription or non-prescription drugs within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety. Please also see OA exclusion criteria
•Subject with a known allergy to or judged by the investigator not to be a suitable candidate for naproxen or paracetamol therapy based on medical history, concomitant medications, and concurrent systemic disease as described in the product labelling
•History or presence of gastro-intestinal, hepatic or renal disease or other condition known to interfere with the absorption, distribution, metabolism or excretion of drugs. In particular dyspepsia, peptic ulceration, gastrointestinal bleeding, ulcerative colitis or Crohn´s disease

Arms & Interventions

Active

Intervention: Naproxen

Placebo

Intervention: Placebo

Outcomes

Primary Outcomes

Change from baseline in the time to ascend and descend 11 stairs

Time Frame: Screening, Day 1, Days 8,10,15,17,22,24

Secondary Outcomes

Change from baseline in WOMAC scores(Day 1, Days 8,10,15,17,22,24)
Pain intensity difference as measured on numerical rating scales (NRS) after ascending and descending 11 stairs.(Screening, Day 1,Days 8,10,15,17,22,24)
Pain intensity difference as measured on a numerical rating scales (NRS) after: resting(Screening,Day 1, Days 2 to 7, 9, 11 to 14, 16, 18 to 21, 23, Days 8,10,15,17,22,24)
Patient Global Impression of Change (PGIC).(Days 8,10,15,17,22,24)
Change from baseline in the time to walk 20, 40 and 100m.(Screening, Day 1, Days 8,10,15,17,22,24)
Pain intensity difference as measured on a numerical rating scales (NRS) after: 100m walk(Screening, Day 1, Days 8,10,15,17,22,24)