A Study of Combogesic® 325 in Adolescent Patients With Moderate to Severe Postoperative Pain Associated With Orthopedic Surgery

Inclusion criteria

• Provide written informed consent or consent be provided from parents/legal guardians and assent from participants (where appropriate).
• Be males and females aged at least 12 years and less than 18 years old on both the day of consent and throughout the 24 hour study period.
• Be undergoing planned orthopedic surgery which requires at least 24 hours of hospital inpatient stay.
• Have a clinical indication of acute moderate or severe pain (at least ≥ 50 mm on the VAS scale*) within 6 hours after the completion of surgery associated with orthopedic surgery.
• using a 100mm VAS scale with 0 = no pain and 100 = worst pain imaginable, patients should have a resting VAS pain intensity score of ≥ 50 mm for inclusion. For this study, moderate pain is defined as ≥ 40 mm to ≤ 69 mm and severe pain is defined as a resting VAS of ≥ 70 mm to ≤ 100 mm.
• Have negative HIV and hepatitis B & C test results.

Exclusion criteria

• Has taken any NSAID or acetaminophen containing drug products within 5 half-lives prior to the initial dose of study drug.
• Hypersensitivity to opioids, NSAIDs or acetaminophen or a history of severe/serious drug reaction to NSAIDs or acetaminophen.
• Pregnant or lactating females Known to be pregnant or possibly pregnant.
• Sexually active females of childbearing potential not using adequate contraception* and sexually active males not using adequate contraception**
• Women of childbearing potential who are unwilling to take adequate contraceptive precautions, i.e., a hormonal contraceptive, an intrauterine device, double-barrier method, or abstinence (should the participant become sexually active, she must agree to use a double-barrier method of contraception). A woman of childbearing potential is defined as any female who is less than 2 years post-menopausal or has not undergone a partial or total hysterectomy or surgical sterilization, e.g. bilateral tubal ligation, bilateral oophorectomy.
• Women of childbearing potential who are unwilling to undergo a urine pregnancy test.
• Suffering from a neurological disorder relating to pain perception or any acute or chronic condition that, in the opinion of the Investigator, makes the participant unsuitable from an efficacy or safety perspective.
• In the opinion of the Investigator, unable to understand the visual analogue pain score or comply with the protocol requirements.
• Currently or in last 30 days, has been in a clinical trial involving another study drug.
• Have donated blood or blood products within 30 days prior to study drug administration
• Advanced renal impairment (serum creatinine >132 µmol/L) or a risk for renal failure due to volume depletion.
• Severe known haemopoietic, renal or hepatic disease, or immunosuppressed, including any clinically significant finding from the laboratory tests results (biochemistry and hematology at screening), which, in the opinion of the Investigator, means that it would not be in the participants' best interests to participate in this study.
• History of gastric ulceration or other GI disorders that, in the opinion of the Investigator make the participant unsuitable (e.g. frequent treatment of gastroesophageal reflux disease, inflammatory bowel disease, etc).
• History of severe asthma in the opinion of the investigator.
• Has a history of drug or alcohol abuse
• Suffering from any other disease or condition which, in the opinion of the Investigator, means that it would not be in the participant's best interests to participate in this study.

• Methods of contraception that are deemed adequate have failure rates of < 1%, including: established use of oral contraceptives in conjunction with a barrier method of contraception; injected or implanted hormonal methods of contraception; placement of intrauterine device (IUD) or intrauterine system (IUS); sexual abstinence; hysterectomy; post-menopausal; sterilized; vasectomy. Suitable contraception should be used for the entire study period, from screening to follow-up. Women of childbearing age include all women that have begun puberty and had their first menstrual period until they reach menopause.