Pilot Study of the Efficacy and Safety of Q8003 in Patients Who Have Undergone Total Knee Arthroplasty

Condition(s) targeted: Postoperative Pain

Intervention: Q8003 (morphine sulfate and oxycodone hydrochloride) (Drug); Low dose Q8003 (morphine sulfate and oxycodone hydrochloride) (Drug); Percocet (oxycodone and acetaminophen) (Drug)

Phase: Phase 2

Status: Not yet recruiting

Sponsored by: QRxPharma Inc.

Official(s) and/or principal investigator(s):
Patricia T. Richards, MD, Ph.D., Study Director, Affiliation: QRxPharma Inc.

This is a Phase 2 3-arm, open label pilot study of the safety and efficacy of Q8003 in patients who have undergone primary unilateral total knee arthroplasty.

Official title: An Open-Label Pilot Study of the Analgesic Efficacy and Safety Of Q8003 and of the Conversion From IV Morphine PCA Analgesia to Q8003 or to Percocet® in Patients Who Have Undergone Primary Unilateral Total Knee Arthroplasty

Study design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Difference in pain intensity scores from baseline

Secondary outcome: Safety: adverse events, opioid-related signs and symptoms

Detailed description: This Phase 2 study is a 3 arm, open-label pilot study to evaluate:

- whether the flexible high dose Q8003 (based on conversion algorithm) treatment vs the

control arms of either low dose Q8003 (3 mg/2 mg, possibly increasing to 6 mg/4 mg) or 1-2 tablets of Percocet® 5/325 mg will likely be adequate to show separation of the two comparators and prevent excessive dropouts due to lack of efficacy and

- the adequacy of the algorithm to convert IV PCA morphine to oral morphine equivalent

flexible ascending doses of Q8003 administered q4-6h by evaluating safety and analgesic efficacy of Q8003 administered orally over a 48-hour Treatment Period to patients who have undergone primary unilateral total knee arthroplasty

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Male of female, at least 18 years of age at time of enrollment.

- If female, be at least one year post-menopausal, surgically sterile or practicing

effective contraception, be non-lactating, and if of child-bearing potential, have a negative urine pregnancy test result.

- Have a body mass index (BMI) of 38 kg/m2 or less.

- Have undergone a primary unilateral total knee arthroplasty performed under

standardized general, spinal or epidural anesthesia.

- Have developed moderate to severe pain (a score of 2 or more on the 4 point Likert

scale or at least 4 on the 11 point NPRS scale within 6 hours of discontinuing PCA on the morning after surgery).

Exclusion Criteria:

- In the opinion of the Investigator, has a history of pulmonary, cardiovascular

(including uncontrolled hypertension), neurologic, endocrine, hepatic, gastrointestinal, or kidney disease or therapy that, in the opinion of the Investigator, would jeopardize the patient's well being by participation in this study or is mentally or emotionally unsuitable to participate, or unable/unwilling to comply with the study assessments.

- Used opiates continuously (including tramadol) for more than ten days in the past

year.

- Hypersensitivity or poor tolerance to ibuprofen or short term opioids.

- Currently receiving any medications that are not at a stable dose (the same dose for >

2 months prior to date of surgery).

- Was dosed with another investigational drug within 30 days prior to the Screening

Visit or has previously received treatment with Q8003.

- Current therapy with central nervous system depressant medications that might increase

the risks of treatment with opioids (other than those used with surgical anesthesia).

- Current evidence of alcohol abuse (regularly drinks more than 4 units of alcohol per

day; 1 unit = ½ pint of beer, 1 glass of wine, or 1 ounce of spirit).

- History of abusing licit or illicit drug substances within five (5) years of study

entry.

- Has taken drugs known to interact with morphine or oxycodone metabolism, including,

but not limited to, phenothiazines, monoamine oxidase inhibitors (MAOI), amphetamines, and muscle relaxants within the 4 weeks prior to the date of surgery.

West Alabama Research, Inc., Birmingham, Alabama 35209, United States

Arizona Research Center, Phoenix, Arizona 85023, United States

William Beaumont Hospital, Royal Oak, Michigan 48073, United States

Starting date: January 2009
Ending date: April 2009
Last updated: January 6, 2009