Combogesic IV for Acute Pain

Overseen By Laura Boddington

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: AFT Pharmaceuticals, Ltd.

Must not be taking: Anticoagulants, Corticosteroids, NSAIDs, others

Disqualifiers: Allergies, Unstable cardiac, Psychiatric disorder, 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: 12 hours to 5 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new intravenous pain relief medicine called Combogesic® IV, which combines ibuprofen and acetaminophen. The research aims to determine how well children's and teenagers' bodies process this medicine and assess its safety for them. The trial seeks participants aged 2 to under 17 years with acute pain, such as post-surgery or injury pain, who need hospitalization for at least half a day to several days. Participants will receive the medication intravenously every six hours for up to five days and may receive additional pain relief if needed. 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 pain relief option for children and teenagers.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are currently taking anticoagulants or have used systemic corticosteroids recently. It's best to discuss your specific medications with the study doctor.

Is there any evidence suggesting that Combogesic® IV is likely to be safe for children and adolescents?

In earlier studies, Combogesic® IV, a combination of acetaminophen and ibuprofen, was administered to adults for pain relief. These studies showed that 59.3% of patients experienced at least one side effect in the first 48 hours, though these were usually mild.

Acetaminophen can sometimes cause liver damage, especially in high doses or with prolonged use, posing a risk mainly for individuals with existing liver issues. Ibuprofen may cause stomach upset or irritation in some individuals.

This treatment has already received approval for adults, indicating it is generally considered safe for them. The current trial aims to determine its safety for children and teenagers and to understand how their bodies process it. The researchers hope it will be as safe for young people as it is for adults. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Combogesic® IV is unique because it combines acetaminophen and ibuprofen in a single intravenous solution, offering a dual-action approach to managing acute pain. Unlike standard treatments that often require multiple medications taken separately, Combogesic® IV delivers both pain relief and anti-inflammatory benefits in one infusion. This method not only simplifies administration but also potentially enhances pain control by targeting different pain pathways simultaneously. Researchers are excited about its potential for faster, more efficient pain management, which could lead to improved patient outcomes.

What evidence suggests that Combogesic® IV might be an effective treatment for acute pain in children and adolescents?

Research has shown that Combogesic® IV, a combination of acetaminophen and ibuprofen, effectively relieves pain. Studies have found that this combination provides faster pain relief than ibuprofen alone or a placebo. Combogesic® IV is safe and well-tolerated, whether taken once or multiple times. Patients have reported better pain control with this combined treatment compared to using just one of the medications. It is designed for safe use for up to five days. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for children and adolescents aged 2 to less than 17 years who are experiencing acute pain. They must be able to receive intravenous medication and participate in regular blood sampling. The study excludes those with known allergies to ibuprofen or acetaminophen, significant kidney or liver disease, certain heart conditions, bleeding disorders, or any condition that the study doctor thinks could interfere with the trial.

Inclusion Criteria

Is either able to provide written informed consent or consent is provided from parents/legal guardians and assent provided from participants (where appropriate)

Have negative HIV and hepatitis B & C test results

I am between 2 and 16 years old.

Exclusion Criteria

I am allergic or intolerant to common pain relievers like acetaminophen, aspirin, opioids, or NSAIDs.

Considered by the Investigator, for any reason, to be an unsuitable candidate to receive the study drug

History or current diagnosis of a significant psychiatric disorder that would affect the subject's ability to comply with the study requirements

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive Combogesic® IV every 6 hours as necessary, with a maximum of 4 doses within a 24-hour period, for a minimum of 12 hours up to a maximum of 5 days.

12 hours to 5 days

Daily visits for dosing and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including changes in hematology and biochemistry values.

7 days

1-2 visits (in-person or virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Combogesic® IV

Trial Overview The trial is testing Combogesic® IV, a mix of two painkillers: ibuprofen and acetaminophen given by vein. It aims to understand how young patients process this drug and confirm its safety. Participants will get doses based on their weight every six hours as needed for up to five days, with additional opioids allowed if pain persists.

How Is the Trial Designed?

Group I: Combogesic® IV Experimental Treatment 1 Intervention

Combogesic® IV (acetaminophen 10 mg/ml + ibuprofen 3 mg/ml in 100 ml solution for infusion), will be administered by injection into a dedicated indwelling venous cannula, infused over 15 minutes every 6 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/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.

2. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2024/215320Orig1s000SumR.pdf

215320Orig1s000 SUMMARY REVIEW - accessdata.fda.gov An efficacy, safety, and pharmacokinetic study of Combogesic® IV (acetaminophen. 1000 mg + ibuprofen 300 mg, per 100 mL solution for intravenous ...

3. hikma.com hikma.com/news/hikma-pharmaceuticals-receives-permanent-j-code-for-combogesic-iv-acetaminophen-and-ibuprofen-injection-from-centers-for-medicare-medicaid-services-cms/

Hikma Pharmaceuticals Receives Permanent J-Code for ... Time to meaningful pain relief was shorter in the COMBOGESIC® IV group than that in the Ibuprofen IV or placebo groups. COMBOGESIC® IV also ...

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

An open-label, multi-center, single arm, multiple dose study The IV-FDC given every 6 h is safe and well tolerated for up to 5 days. The safety profile was comparable in participants aged < 65, 65–75 and > 75 years.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT07225634?rank=1

A Study of Combogesic® IV (Intravenous) in Pediatric ... Acute pain indications may include but are not limited to post-operative pain associated with musculoskeletal or soft tissue surgery, fractures ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2023/215320s000lbl.pdf

Combogesic IV - accessdata.fda.gov Safety data for the first 48 hours of both studies was pooled. Overall, 59.3% of the patients (N = 182/307) administered COMBOGESIC IV experienced one or ...

7. combogesiciv.com combogesiciv.com/

COMBOGESIC® IV COMBOGESIC® IV contains acetaminophen and ibuprofen. Acetaminophen has been associated with cases of acute liver failure; the risk is higher in those with ...

8. dailymed.nlm.nih.gov dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=b32651c4-7fa0-415b-91eb-854aa1c28f2a

COMBOGESIC- acetaminophen and ibuprofen tablet, film ... COMBOGESIC is indicated in adults for the short-term management of mild to moderate acute pain. ... Because the published safety data on neonatal outcomes ...

9. reference.medscape.com reference.medscape.com/drug/combogesic-IV-acetaminophen-ibuprofen-iv-4000261

Combogesic IV (acetaminophen/ibuprofen IV) dosing, ... Indicated for mild-to-moderate pain and for management of moderate-to-severe pain as an adjunct to opioid analgesics in adults.

10. pdf.hres.ca pdf.hres.ca/dpd_pm/00074462.PDF

PRODUCT MONOGRAPH INCLUDING PATIENT ... COMBOGESIC IV is contraindicated in: • COMBOGESIC IV is contraindicated in patients who are hypersensitive to acetaminophen, ibuprofen or to ...