Combogesic for Postoperative Pain

Overseen By Laura Boddington

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: AFT Pharmaceuticals, Ltd.

Must not be taking: NSAIDs, Acetaminophen

Disqualifiers: Pregnancy, Neurological disorders, Renal disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 24 hours

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a new pain relief drug, Combogesic® 325mg, is more effective than acetaminophen for managing post-surgery pain. The study compares the pain relief from Combogesic, which combines ibuprofen and acetaminophen, with that of acetaminophen alone. Participants will take different combinations of these medications and report their pain levels. The trial seeks adolescents who have undergone planned orthopedic surgery and are experiencing moderate to severe pain. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the development of a potentially new standard in pain management.

Do I have to stop taking my current medications for the trial?

Yes, you must stop taking any NSAID or acetaminophen-containing drugs before starting the trial, as specified in the exclusion criteria.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that combining acetaminophen and ibuprofen, as found in Combogesic®, is generally safe. One study found that this combination is safe in both single and multiple doses and provides better pain relief than acetaminophen alone. Another study demonstrated that a similar combination administered through an IV every 6 hours was safe for up to 5 days.

Overall, these studies suggest that the combination of acetaminophen and ibuprofen is effective and has a strong safety record. It is unlikely to cause serious side effects, making it a safer option compared to stronger painkillers like opioids.

This trial will compare Combogesic® with acetaminophen alone to determine which is more effective for pain relief and to further assess its safety in teenagers. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Combogesic® for postoperative pain because it combines acetaminophen and ibuprofen in one tablet, offering a multi-mechanism approach to pain relief. Unlike traditional options that often rely on opioids or single-agent NSAIDs, Combogesic® targets pain through different pathways, potentially enhancing effectiveness and reducing the need for high doses of any one medication. This combination could lead to better pain control with fewer side effects, making it an attractive alternative to current postoperative pain management strategies.

What evidence suggests that Combogesic® 325 might be an effective treatment for postoperative pain?

Research has shown that taking acetaminophen and ibuprofen together, as in Combogesic®, relieves pain more effectively than taking either one alone. One study found this combination reduced pain more effectively than using just acetaminophen or ibuprofen. Another study demonstrated that people required less additional pain medication when using this combination. In this trial, participants will receive different formulations of Combogesic® or acetaminophen alone. Combogesic® may provide significant pain relief, potentially more than acetaminophen alone. Overall, this combination is often as effective as, or even better than, some stronger painkillers. ^{4 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adolescents aged 12-17 who are experiencing moderate to severe pain after orthopedic surgery. They must be able to take oral medication and keep a pain diary. Those with known allergies to ibuprofen or acetaminophen, significant health issues, or taking certain medications that could interfere with the study can't participate.

Inclusion Criteria

I am experiencing moderate to severe pain.

Have negative HIV and hepatitis B & C test results

Provide written informed consent or consent be provided from parents/legal guardians and assent from participants (where appropriate)

Exclusion Criteria

I am a woman able to have children but refuse to take a pregnancy test.

I have advanced kidney problems or am at risk due to low body fluids.

History of severe asthma in the opinion of the investigator

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive randomized treatment with Combogesic® 325 or acetaminophen, taking 3 tablets every 6 hours with a maximum of 4 doses in 24 hours

24 hours

Continuous monitoring during hospital stay

Follow-up

Participants are monitored for safety and effectiveness after treatment, including adverse effects and pain relief assessment

7 days

1 visit (in-person) and daily diary entries

What Are the Treatments Tested in This Trial?

Interventions

• Combogesic® 325

Trial Overview The study tests Combogesic® 325mg (ibuprofen and acetaminophen combo) against just acetaminophen for postoperative pain relief in teens. Participants will receive either Combogesic® or acetaminophen alongside a placebo without knowing which one they're getting, and may use opioids if needed.

How Is the Trial Designed?

Group I: Treatment B- 2 tablets of Combogesic® + 1 tablets of placebo Experimental Treatment 2 Interventions

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.

Group II: Treatment A- 3 tablets of Combogesic® tablets Experimental Treatment 1 Intervention

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.

Group III: Treatment C - 2 tablets of acetaminophen and 1 tablet of placebo Active Control 2 Interventions

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.

Who Is Running the Clinical Trial?

AFT Pharmaceuticals, Ltd.

Lead Sponsor

Trials

5

Recruited

920+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2791549/

Combined acetaminophen and ibuprofen for pain relief after ... Maxigesic tablets provide superior pain relief after oral surgery to acetaminophen or ibuprofen alone.

2. sciencedirect.com sciencedirect.com/science/article/pii/S0149291818303825

Analgesic Efficacy of an Acetaminophen/Ibuprofen Fixed ... The analysis of time-adjusted SPID48 showed that FDC 975/292.5 provided more effective pain relief than placebo, acetaminophen, or ibuprofen (all, P < 0.001).

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38609589/

Effect of an intravenous acetaminophen/ibuprofen fixed ... This study aimed to evaluate the acetaminophen/ibuprofen combination effectiveness in reducing analgesic requirements and pain intensity in patients undergoing ...

4. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2724188

Effect of Combination of Paracetamol (Acetaminophen ... The combination of paracetamol 1000 mg and ibuprofen 400 mg did not only result in the lowest morphine consumption, but it also resulted in ...

5. tandfonline.com tandfonline.com/doi/full/10.1080/00325481.2024.2382671

Ibuprofen/acetaminophen fixed-dose combination as an ... Across studies, IBU/APAP FDCs consistently demonstrated pain relief similar to or better than opioid and nonopioid comparators and reliably ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6371943/

An integrated safety analysis of combined acetaminophen and ... Overall, the FDC is well tolerated and has a strong safety profile at single and multiple doses with improved efficacy over monotherapy.

7. sciencedirect.com sciencedirect.com/science/article/pii/S0753332221004923

An open-label, multi-center, single arm, multiple dose study Study tested safety of an IV fixed dose combination of acetaminophen and ibuprofen. •. The IV-FDC given every 6 h is safe and well tolerated for up to 5 days.

8. dovepress.com dovepress.com/article/download/43967

an integrated safety analysis of combined acetaminophen ... Analgesic efficacy of an acetaminophen/ibuprofen fixed-dose combination in moderate to severe postoperative dental pain: a randomized, double-blind, parallel-.