Ibuprofen Liquid Capsules for Impacted Tooth

Overseen By Mamtha Kunshetty, BDS PDGP

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Reckitt Benckiser Healthcare (UK) Limited

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

Disqualifiers: Asthma, Peptic ulcer, Heart failure, others

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

Approved in 7 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of a new ibuprofen liquid capsule for individuals experiencing pain after wisdom teeth removal. Participants will receive either the liquid capsule, a regular ibuprofen tablet, or a placebo (a capsule with no active medicine). The trial aims to determine if the liquid capsule is as effective or more effective than the traditional pill. Individuals who have had two or more wisdom teeth removed and experience moderate to severe pain within six hours post-surgery may be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, allowing participants to contribute to the potential availability of a new pain relief option.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications that could affect pain relief assessments, such as antidepressants, sedatives, or other pain relievers. You also need to avoid medications that might interact with the study drug, like aspirin, other NSAIDs, and certain heart and blood pressure medications.

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

Research shows that ibuprofen, the main treatment in this study, is generally safe for most people. It commonly relieves pain and reduces swelling. However, like all medicines, it can have some side effects.

Studies indicate that ibuprofen liquid capsules can remain in the body for more than 8 hours after ingestion. The capsules might cause stomach discomfort and, in some cases, allergic reactions such as a rash or asthma (wheezing). People allergic to aspirin should exercise caution.

The ibuprofen tablets have similar side effects. They can cause stomach issues and allergic reactions, especially in those sensitive to aspirin. Additionally, ibuprofen might increase the risk of heart attack or stroke, particularly in individuals with existing heart problems.

Overall, both forms of ibuprofen in the study are widely used and considered safe for many people, but awareness of potential side effects is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the Ibuprofen Liquid Capsules because they offer a new way of delivering pain relief compared to standard ibuprofen tablets. Unlike traditional tablets, these liquid capsules may provide faster pain relief after the surgical removal of impacted third molars, thanks to their potentially quicker absorption. This novel delivery method can be a game-changer for patients seeking swift and effective pain management. Plus, by comparing the liquid capsules against both standard tablets and placebos, researchers aim to better understand the pharmacokinetics and dynamics of ibuprofen, paving the way for improved pain relief options.

What evidence suggests that this trial's treatments could be effective for post-operative dental pain?

This trial will compare different forms of ibuprofen for pain relief. Research has shown that ibuprofen, a common pain reliever, reduces pain after dental surgeries, such as wisdom teeth removal. Studies indicate that ibuprofen effectively manages mild to moderate pain. Specifically, ibuprofen liquid capsules, which participants in one arm of this trial may receive, are absorbed faster than regular tablets, potentially leading to quicker pain relief. In one study, more patients taking ibuprofen sodium (a type designed for faster absorption) experienced pain relief within 15 minutes compared to those using regular forms. Overall, ibuprofen, whether in liquid or tablet form, effectively eases pain and swelling. ^{6 7 8 9 10}

Who Is on the Research Team?

Todd Bertoch, MD

Principal Investigator

JBR Clinical Research

Are You a Good Fit for This Trial?

Inclusion Criteria

Has a body weight ≥ 45 kg and a BMI ≥17 kg/m2 and ≤ 30 kg/m2.

Subject has provided written informed consent (for subjects who are below the age of legal consent, parent(s) or legally authorized representative(s) provides written informed consent and the subject provides written assent).

Subject is male or female and aged ≥16 and ≤55 years of age at screening.

Exclusion Criteria

In the opinion of the investigator, any subject with a clinically relevant history of peptic ulceration, gastrointestinal bleeding or perforation, heart failure, renal or hepatic failure, uncontrolled hypertension, nasal polyps, or chronic rhinitis.

A positive urine drugs of abuse test at screening and during the study (with the exception of a positive drugs of abuse screen that is a consequence of permitted prescription medicines) or positive alcohol breathalyser test during the study.

If female, has a positive pregnancy test at screening (serum) or on the day of surgery prior to surgery (urine), or is lactating.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants undergo surgical removal of impacted third molars and receive a single dose of study medication

1 day

1 visit (in-person)

Immediate Post-Treatment Monitoring

Participants are monitored for pain relief and adverse events for 12 hours post-dose

12 hours

Overnight stay (in-person)

Follow-up

Participants return for a follow-up visit for physical assessment and adverse event monitoring

1 week

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Ibuprofen

How Is the Trial Designed?

Group I: Test Product Experimental Treatment 2 Interventions

Ibuprofen 200mg Oral Liquid Capsule, Placebo of Ibuprofen 200mg Oral Tablet

Group II: Reference Product Active Control 2 Interventions

Ibuprofen 200mg Oral Tablet, Placebo of Ibuprofen 200mg Oral Liquid Capsule

Group III: Placebo Placebo Group 2 Interventions

Placebo of Ibuprofen 200mg Oral Liquid Capsule, Placebo of Ibuprofen 200mg Oral Tablet

Ibuprofen is already approved in United States, Canada, European Union, Japan, China, Switzerland for the following indications:

Approved in United States as Advil for:

• Pain relief
• Fever reduction
• Inflammation

Approved in Canada as Motrin for:

• Pain relief
• Fever reduction
• Inflammation

Approved in European Union as Nurofen for:

• Pain relief
• Fever reduction
• Inflammation

Approved in Japan as Ibuprofen for:

• Pain relief
• Fever reduction
• Inflammation

Approved in China as Ibuprofen for:

• Pain relief
• Fever reduction
• Inflammation

Approved in Switzerland as Ibuprofen for:

• Pain relief
• Fever reduction
• Inflammation

Who Is Running the Clinical Trial?

Reckitt Benckiser Healthcare (UK) Limited

Lead Sponsor

Trials

33

Recruited

5,600+

Premier Research

Collaborator

Premier Research Group plc

Collaborator

Premier Research Group plc

Industry Sponsor

Trials

65

Recruited

74,200+

John Ratliff

Premier Research Group plc

Chief Executive Officer since 2024

MBA

Dr. Milena Kanova-Petrova

Premier Research Group plc

Chief Medical Officer since 2024

MD

Published Research Related to This Trial

The European Medicines Agency's Pharmacovigilance Risk Assessment Committee has issued a warning about the serious risks associated with the combination of codeine and ibuprofen, particularly concerning renal and gastrointestinal harms.

This warning highlights the need for careful consideration of the safety profile of this medication combination, emphasizing potential adverse effects that could impact patient health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety warning: combination products containing codeine and ibuprofen. [2023]

The new ibuprofen formulation (IBUNa) demonstrated significantly faster pain relief compared to standard ibuprofen tablets and placebo in a study involving 316 patients with dental pain.

IBUNa not only provided superior overall pain relief but also had a quicker onset of analgesic effect, making it a promising option for treating acute pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Onset of analgesia and efficacy of ibuprofen sodium in postsurgical dental pain: a randomized, placebo-controlled study versus standard ibuprofen. Brain, P., Leyva, R., Doyle, G., et al.[2022]

Intravenous ibuprofen (IVIB) provides significantly higher plasma levels compared to oral ibuprofen, leading to better postoperative pain management and reduced opioid use in a review of 9 studies involving 1062 patients.

IVIB has a favorable safety profile, with fewer adverse events and improved recovery outcomes, making it a strong candidate for inclusion in multimodal pain management strategies for pre- and postoperative care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Narrative Summary of Recently Published Literature on Intravenous Ibuprofen. Southworth, SR., Sellers, JA.[2021]

Over a 10-year period, a total of 29,656,286 units of various ibuprofen formulations were sold in Poland, with only 5 spontaneous reports of adverse effects, indicating that ibuprofen is a very safe medication with rare side effects.

The study suggests that while ibuprofen is generally safe, the current monitoring system for adverse effects in Poland is insufficient and requires enhancements to better detect potential issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of oral ibuprofen--analysis of data from the spontaneous reporting system in Poland. Kuchari, E., Han, S., Karłowicz-Bodalska, K., et al.[2022]

Ibuprofen abuse, particularly through products like Nurofen Plus, can lead to serious complications such as hypokalaemia, which is a low potassium level in the blood.

This case highlights that ibuprofen is often overlooked in standard toxicology screenings, suggesting that it should be considered as a potential cause of hypokalaemia in patients with unexplained symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypokalaemia in ibuprofen and codeine phosphate abuse. Dyer, BT., Martin, JL., Mitchell, JL., et al.[2020]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK542299/

Ibuprofen - StatPearls - NCBI Bookshelf - NIH Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) used to manage various conditions, including inflammatory diseases, rheumatoid disorders, mild to ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05484401?cond=%22Tooth%20Disease%22&intr=%22anti-inflammatory%20agents,%20non-steroidal%22&viewType=Table&rank=1

Ibuprofen Liquid Capsules 2 x 200 mg Efficacy and PK/PD ... This is a single centre, three-arm randomised, double-blind, double-dummy, parallel group, single-dose, active and placebo-controlled efficacy and ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4269818/

Ibuprofen Sodium Is Absorbed Faster than Standard ... Patient diary assessments indicated that significantly more patients treated with IBUNa reported “some” to “complete” pain relief at 15 min (43 vs. 29 % for ...

4. cpdcentre.co.za cpdcentre.co.za/wp-content/uploads/2021/04/Ref-3-Moore-04-21.pdf

Faster, higher, stronger? Evidence for formulation and ... A Cochrane review of ibuprofen in acute pain suggested that rapidly absorbed formulations of salts, or features to speed absorption, provided better ...

5. journals.library.ualberta.ca journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/28210/20708

View of Onset of Action and Efficacy of Ibuprofen Liquigel ... However, IBULG yielded significantly greater odd ratios in meaningful pain relief at 60, 90 and 120 min, but not at 30 min, as compared with IBU ...

6. mayoclinic.org mayoclinic.org/drugs-supplements/ibuprofen-oral-route/description/drg-20070602

Ibuprofen (oral route) - Side effects & dosage Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) used to treat mild to moderate pain, and helps to relieve symptoms of arthritis.

7. dailymed.nlm.nih.gov dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c997ded4-8fd9-46bd-a42b-22ac34d57661

Label: IBUPROFEN capsule, liquid filled - DailyMed Allergy alert: Ibuprofen may cause a severe allergic reaction, especially in people allergic to aspirin. · Stomach bleeding warning: This product contains an ...

8. webmd.com webmd.com/drugs/2/drug-5166-9368/ibuprofen-oral/ibuprofen-oral/details

Ibuprofen (Advil, Caldolor, Motrin) - Uses, Side Effects ... You may take ibuprofen with food or milk if stomach upset occurs. Use an accurate measuring device to measure your ibuprofen oral liquid dose.

9. medsafe.govt.nz medsafe.govt.nz/profs/datasheet/i/ibuprofenGenericCap.pdf

Ibuprofen liquid capsules 400mg Ibuprofen is detected in the plasma for more than 8 hours after administration of Ibuprofen. 5.3 Preclinical safety data. The subchronic and ...

10. dailymed.nlm.nih.gov dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d9fc716a-fba5-45f8-8024-52325799d1dd

Label: MOTRIN IB- ibuprofen capsule, liquid filled - DailyMed asthma (wheezing); shock; skin reddening; rash; blisters. If an allergic reaction occurs, stop use and seek medical help right away. Stomach bleeding warning.