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

NCT07225140 | Not Yet Recruiting Phase 3 FDA Drug

• 1 other identifier: AFT-MX-16p
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

Combogesic® 325 contains a combination of ibuprofen and acetaminophen. The purpose of this study is to compare the pain relief effects of Combogesic® 325mg and acetaminophen and to evaluate the safety of Combogesic® 325mg in adolescents between the ages of 12 and \<18 years. What will the study involve for participants?

• Participants will be randomly allocated to one of 3 treatment groups:
• 3 tablets of Combogesic® 325,
• 2 tablets of Combogesic® 325 and 1 tablet of placebo or
• 2 tablets of acetaminophen1000mg and 1 tablet of placebo
• Participants will take 3 tablets every 6 hours with a maximum of 4 doses in 24 hours
• Participants and study doctor will be blinded to the treatment group
• If pain is not sufficiently controlled, opioids may be used as supplementary pain relief at the discretion of the study doctor.
• Participants will complete a patient diary to assess their pain
• Participants will rate the study drug at the end of the treatment. It is expected that Combogesic® tablets (either 2 or 3 tablets per dose) will provide a greater reduction in pain compared to acetaminophen (1000 mg) treatment.

Conditions

Post Operative Pain, Acute

Outcome Measures

Primary Outcomes (1)

• Time-adjusted summed pain intensity difference (SPID) calculated from the visual analogue scale (VAS) pain intensity scores 6 hours after first dose of study medication

  SPID will be derived from the 100 mm Visual Analogue Scale which is the tool used for patients to rate the intensity of their pain on a horizontal 100mm line with 0 on one end and 100 on the other end (0 being no pain and 100 being the worst pain unimaginable). The primary analysis will compare three tablets of Combogesic® against acetaminophen

  From start of exposure to study drug until 6 hours after first dose

Secondary Outcomes (22)

• Time-adjusted SPID0-6 (for 2 tablets of Combogesic vs. acetaminophen) and Time-adjusted SPID0-12, SPID0-18 and SPID0-24 for both doses.

  From start of exposure to study medication up to 24 hours

• The time to onset of pain relief after the first dose of study drug defined as (i) perceptible, (ii) meaningful and (iii) complete pain relief using the three stopwatch method.

  From start of exposure to study medication up to 24 hours

• The maximum VAS pain scores up to 24 hours after the first dose of study medication.

  From start of exposure to study medication up to 24 hours

• The pain intensity (PI) and pain intensity difference (PID) at 6, 12, 18, and 24 hours after first dose.

  From start of exposure to study medication up to 24 hours

• Pain relief as measured on a 5-point categorical scale at 6, 12, 18, and 24 hours after first dose.

  From start of exposure to study medication up to 24 hours

Study Arms (3)

Treatment A- 3 tablets of Combogesic® tablets

EXPERIMENTAL

3 tablets of Combogesic® (acetaminophen 975mg + ibuprofen 292.5 mg, total per dose) will be administered every 6 hours up to a maximum of 4 doses in 24 hours.

Drug: Combogesic® tablets

Treatment B- 2 tablets of Combogesic® + 1 tablets of placebo

EXPERIMENTAL

2 tablets of Combogesic® (acetaminophen 650 mg + ibuprofen 195 mg, total per dose) and 1 tablet of placebo will be administered every 6 hours up to a maximum of 4 doses in 24 hours.

Drug: Combogesic® tablets; Drug: Placebo

Treatment C - 2 tablets of acetaminophen and 1 tablet of placebo

ACTIVE COMPARATOR

2 tablets of acetaminophen (1000 mg total per dose) + 1 tablet of placebo will be administered every 6 hours up to a maximum of 4 doses in 24 hours.

Drug: Acetaminophen 500mg; Drug: Placebo

Interventions

Combogesic® tablets DRUG

The active ingredients of Combogesic® tablets are acetaminophen 325 mg and ibuprofen 97.5 mg.

Also known as: Acetaminophen 325 mg and ibuprofen 97.5 mg

Treatment A- 3 tablets of Combogesic® tablets; Treatment B- 2 tablets of Combogesic® + 1 tablets of placebo

Acetaminophen 500mg DRUG

Each tablet contains acetaminophen 500mg.

Treatment C - 2 tablets of acetaminophen and 1 tablet of placebo

Placebo DRUG

Placebo tablets do not contain any active ingredients

Treatment B- 2 tablets of Combogesic® + 1 tablets of placebo; Treatment C - 2 tablets of acetaminophen and 1 tablet of placebo

Eligibility Criteria

• Age: 12 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.
• Have negative HIV and hepatitis B \& C test results.

You may not qualify if:

• 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

Sponsors & Collaborators

• AFT Pharmaceuticals, Ltd.: lead

Study Sites (1)

Nemours Children's Health

Orlando, Florida, 32827, United States

Location

MeSH Terms

Conditions

Pain, Postoperative

Interventions

Acetaminophen; Ibuprofen

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids

Central Study Contacts

Laura Boddington

CONTACT

+64 9 488 0232 ext 735; laura.boddington@aftpharm.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2025
• First Posted: November 5, 2025
• Study Start: February 1, 2026
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: November 5, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)