Advil Dual Action for Pain

Overseen By Haleon Response Center

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: HALEON

Must not be taking: Anticonvulsants, Herbal remedies

Disqualifiers: Pregnancy, Breastfeeding, Asthma, others

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

Compensation: Varies

Number of Visits: 4

Duration: 12 days

54 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

Yes, you will need to stop taking any medications, including over-the-counter drugs and herbal remedies, at least 2 weeks before the study starts, unless they are systemic contraceptives that you've been using consistently for at least 3 months.

What data supports the effectiveness of the drug Advil Dual Action Liquid Filled Capsules?

Research shows that ibuprofen, a component of Advil Dual Action, is effective in providing faster pain relief compared to some other pain medications, like celecoxib, especially in cases of dental pain. Additionally, liquid capsule formulations, like those used for diclofenac, are absorbed more quickly, which can lead to faster pain relief. ^{1 2 3 4 5}

Is Advil Dual Action generally safe for humans?

Over-the-counter NSAIDs, like those in Advil Dual Action, have been associated with an increased risk of gastrointestinal bleeding, especially if not used as directed. It's important to follow usage instructions carefully to minimize potential risks. ^{1 6 7 8 9}

How is Advil Dual Action different from other pain relief drugs?

Advil Dual Action Liquid Filled Capsules are unique because they combine two active ingredients, ibuprofen and acetaminophen, which work together to provide pain relief. This combination allows for effective pain management with potentially fewer side effects compared to using higher doses of a single ingredient. ^{1 2 5 10 11}

What is the purpose of this trial?

The primary purpose of this study is to demonstrate the bioequivalence of new formulation Advil Dual Action (ADA) liquid filled capsules (Test) compared to the currently marketed ADA Caplet (Reference) under fasted conditions and to assess the relative bioavailability of ADA liquid filled capsules (Test) under fed conditions compared to ADA liquid filled capsules (Reference) under fasted conditions.

Eligibility Criteria

Healthy adults aged 18-55, with a BMI of 18.5 to 30 kg/m^2, can join this pain medication study if they agree to use contraception and follow the study plan. Excluded are those with certain health conditions, drug/alcohol abuse history, recent participation in other studies or blood donations.

Inclusion Criteria

Participant must be willing and able to comply with scheduled visits, treatment plan, and study procedures

Participant must provide a signed and dated informed consent document before any assessment is performed

I am in good physical and mental health with no major health issues.

Exclusion Criteria

Participant must not have certain laboratory abnormalities or vital sign deviations

Participant must not have positive urine drug/alcohol tests or specific consumption habits

Participant must not have participated in other studies involving investigational products within 30 days prior to study entry

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a single oral dose of investigational products in a four-treatment, four-period, four-sequence crossover design with a washout period of 3 days between treatments.

12 days

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Advil Dual Action Liquid Filled Capsules

Trial Overview The trial is testing whether new ADA liquid capsules work the same as ADA caplets for pain relief when fasting and how well these capsules work after eating compared to taking them without food.

Participant Groups

Group I: Sequence 4: Treatment D + Treatment C + Treatment B + Treatment A Experimental Treatment 3 Interventions

Participants will receive a single oral dose of 2 Advil Liqui-gels (ibuprofen 200 mg) under fasted conditions on Day 1 of Period 1 (Treatment D), followed by a single oral dose of 2 ADA liquid filled capsules (125 mg ibuprofen and 250 mg acetaminophen) under fed conditions, 30 minutes after a high-fat high calorie meal on Day 1 of Period 2 (Treatment C), followed by a single oral dose of 2 ADA Caplets (125 mg ibuprofen and 250 mg acetaminophen) under fasted conditions on Day 1 of Period 3 (Treatment B), and further followed by a single oral dose of 2 ADA liquid filled capsules (125 mg ibuprofen and 250 mg acetaminophen) under fasted conditions on Day 1 of Period 4 (Treatment A). There will be a washout period of at least 3 days between each treatment.

Group II: Sequence 3: Treatment C + Treatment A + Treatment D + Treatment B Experimental Treatment 3 Interventions

Participants will receive a single oral dose of 2 ADA liquid filled capsules (125 mg ibuprofen and 250 mg acetaminophen) under fed conditions, 30 minutes after a high-fat high calorie meal on Day 1 of Period 1 (Treatment C), followed by a single oral dose of 2 ADA liquid filled capsules (125 mg ibuprofen and 250 mg acetaminophen) under fasted conditions on Day 1 of Period 2 (Treatment A), followed by a single oral dose of 2 Advil Liqui-gels (ibuprofen 200 mg) under fasted conditions on Day 1 of Period 3 (Treatment D) and further followed by a single oral dose of 2 ADA Caplets (125 mg ibuprofen and 250 mg acetaminophen) under fasted conditions on Day 1 of Period 4 (Treatment B). There will be a washout period of at least 3 days between each treatment.

Group III: Sequence 2: Treatment B + Treatment D + Treatment A + Treatment C Experimental Treatment 3 Interventions

Participants will receive a single oral dose of 2 ADA Caplets (125 mg ibuprofen and 250 mg acetaminophen) under fasted conditions on Day 1 of Period 1 (Treatment B), followed by a single oral dose of 2 Advil Liqui-gels (ibuprofen 200 mg) under fasted conditions on Day 1 of Period 2 (Treatment D), followed by a single oral dose of 2 ADA liquid filled capsules (125 mg ibuprofen and 250 mg acetaminophen) under fasted conditions on Day 1 of Period 3 (Treatment A) and further followed by a single oral dose of ADA liquid filled capsules (125 mg ibuprofen and 250 mg acetaminophen) under fed conditions, 30 minutes after a high-fat high calorie meal on Day 1 of Period 4 (Treatment C). There will be a washout period of at least 3 days between each treatment.

Group IV: Sequence 1: Treatment A + Treatment B + Treatment C + Treatment D Experimental Treatment 3 Interventions

Participants will receive a single oral dose of 2 ADA liquid filled capsules (125 mg ibuprofen and 250 mg acetaminophen) under fasted conditions on Day 1 of Period 1 (Treatment A), followed by a single oral dose of 2 ADA Caplets (125 mg ibuprofen and 250 mg acetaminophen) under fasted conditions on Day 1 of Period 2 (Treatment B), followed by a single oral dose of 2 ADA liquid filled capsules (125 mg ibuprofen and 250 mg acetaminophen) under fed conditions, 30 minutes after a high-fat high calorie meal on Day 1 of Period 3 (Treatment C) and further followed by a single oral dose of 2 Advil Liqui-gels (ibuprofen 200 mg) under fasted conditions on Day 1 of Period 4 (Treatment D). There will be a washout period of at least 3 days between each treatment.

Who Is Running the Clinical Trial?

HALEON

Lead Sponsor

Trials

40

Recruited

6,000+

Findings from Research

In a study involving 132 volunteers, diclofenac-potassium 25 mg liquid capsules showed a lower incidence of erosive gastro-duodenal lesions (53%) compared to acetylsalicylic acid (94%) and had better tolerability than ibuprofen (75%).

The liquid formulation also inhibited gastric mucosal prostaglandin synthesis by 52%, which is comparable to diclofenac tablets (64%) and ibuprofen (50%), indicating that it may provide effective pain relief with a similar safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endoscopic evaluation of the gastro-duodenal tolerance of short-term analgesic treatment with 25 mg diclofenac-K liquid capsules. Hawkey, C., Burnett, I., Gold, MS., et al.[2022]

The study involving 42 healthy subjects showed that the new liquid capsule formulation of diclofenac-K provides faster absorption compared to the traditional tablet form, with a median time to peak concentration (tmax) of about 10 minutes faster.

Both formulations had equivalent overall systemic exposure, but the liquid capsules resulted in nearly double the peak concentration (Cmax), suggesting they may offer a quicker pain relief effect without any safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diclofenac potassium 12.5 mg liquid capsules: earlier and higher exposure to diclofenac. A fasted, single-dose, comparative, bioavailability study versus diclofenac potassium 12.5 mg tablets. Kienzler, JL., Gold, M.[2019]

The new 25 mg liquid capsule formulation of diclofenac-K provides a faster absorption rate compared to the traditional 2 × 12.5 mg tablets, with nearly double the peak concentration (Cmax) of diclofenac in the bloodstream.

Both the liquid capsule and tablet formulations showed equivalent overall systemic exposure to diclofenac, and both were well tolerated by participants, with only one minor drug-related adverse event reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diclofenac potassium 25 mg liquid capsules: earlier and higher exposure to diclofenac. A fasted, single-dose, comparative bioavailability study vs. diclofenac potassium 2 x 12.5 mg tablets. Armogida, M., Gold, M.[2019]

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]

In a study involving 174 patients with moderate to severe pain after dental surgery, ibuprofen liquigels provided significantly faster and more effective pain relief compared to the prescription COX-2 inhibitor celecoxib.

Both ibuprofen liquigels and celecoxib were well tolerated, showing no significant differences in adverse effects, including gastrointestinal issues, suggesting that ibuprofen may be a safer and more effective option for acute pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of nonprescription ibuprofen versus celecoxib for dental pain. Doyle, G., Jayawardena, S., Ashraf, E., et al.[2019]

A study involving 219 caregivers in Australia and New Zealand revealed that while most understood the correct dosage of ibuprofen for children, many lacked knowledge about the correct dosing intervals and maximum daily doses, which could lead to potential safety risks.

The findings highlight significant gaps in caregivers' understanding of ibuprofen's active ingredients, contraindications, and side effects, suggesting a need for improved education and resources to ensure safe administration of this common medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What do Australian & New Zealand caregivers know about children's ibuprofen? The results of an online survey? Mullan, J., Burns, P., Weston, K., et al.[2019]

The study analyzed data from the Australian and Canadian adverse drug reaction databases to assess the safety of over-the-counter (OTC) NSAIDs, specifically their association with gastrointestinal bleeding.

Results showed a two-fold increase in the risk of gastrointestinal bleeding linked to OTC NSAID use, indicating that spontaneous adverse drug reaction reporting can effectively monitor the safety of OTC medicines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential for Detection of Safety Signals for Over-the-Counter Medicines Using National ADR Spontaneous Reporting Data: The Example of OTC NSAID-Associated Gastrointestinal Bleeding. Amatya, E., Fois, R., Williams, KA., et al.[2020]

In a study involving 182 adults with mild-to-moderate acute musculoskeletal pain, 90.7% of participants reported being satisfied or very satisfied with the low-dose diclofenac epolamine (DHEP 12.5-mg) treatment after 72 hours, indicating high treatment satisfaction.

The analgesic effect of DHEP was rapid, with complete pain relief achieved in an average of 49.45 minutes, and the treatment was well tolerated, suggesting it is an effective and safe option for managing acute pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment Satisfaction, Efficacy, and Tolerability of Low-Dose Diclofenac Epolamine Soft Capsules in Acute, Mild, or Moderate Musculoskeletal Pain: A Prospective Open-Label, Single-Arm Interventional Study. Trevisan, CLM., Carraro, A., Baldari, GLA.[2023]

Paracetamol provides modest pain relief for knee or hip osteoarthritis and after craniotomy, with high-quality evidence supporting its efficacy in these conditions.

There is strong evidence that paracetamol is ineffective for acute low back pain, and while adverse events are generally similar to placebo, there is a higher risk of transient liver enzyme elevation with repeated use in spinal pain patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of paracetamol for pain relief: an overview of systematic reviews. Abdel Shaheed, C., Ferreira, GE., Dmitritchenko, A., et al.[2021]

In a study involving 47 healthy adult volunteers, the absorption of diclofenac potassium liquid-filled soft gelatin capsules (DPSGC) was found to be similar whether taken after fasting or with a high-fat meal, indicating consistent efficacy regardless of food intake.

However, food intake significantly reduced the peak concentration (Cmax) of the drug by nearly half and delayed the time to reach peak concentration (Tmax), suggesting that while overall absorption is unaffected, the timing and intensity of the drug's effect may vary with food.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of food intake on the pharmacokinetics of diclofenac potassium soft gelatin capsules: a single-dose, randomized, two-way crossover study. Scallion, R., Moore, KA.[2013]

A study involving 108 patients with severe postepisiotomy pain found that both 25 mg and 50 mg doses of ketoprofen were effective in providing pain relief, showing similar efficacy to 500 mg of dipyrone.

All active treatments significantly outperformed placebo, with over 75% of patients in the active groups rating their pain relief as 'good' or 'excellent', and no adverse events were reported, indicating a good safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analgesic efficacy of liquid ketoprofen compared to liquid dipyrone and placebo administered orally as drops in postepisiotomy pain. Olson, NZ., Sunshine, A., Zighelboim, I., et al.[2015]

References

1. England pubmed.ncbi.nlm.nih.gov

Endoscopic evaluation of the gastro-duodenal tolerance of short-term analgesic treatment with 25 mg diclofenac-K liquid capsules. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Diclofenac potassium 12.5 mg liquid capsules: earlier and higher exposure to diclofenac. A fasted, single-dose, comparative, bioavailability study versus diclofenac potassium 12.5 mg tablets. [2019]

3. Germany pubmed.ncbi.nlm.nih.gov

Diclofenac potassium 25 mg liquid capsules: earlier and higher exposure to diclofenac. A fasted, single-dose, comparative bioavailability study vs. diclofenac potassium 2 x 12.5 mg tablets. [2019]

4. United States 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. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of nonprescription ibuprofen versus celecoxib for dental pain. [2019]

6. England pubmed.ncbi.nlm.nih.gov

What do Australian & New Zealand caregivers know about children's ibuprofen? The results of an online survey? [2019]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Potential for Detection of Safety Signals for Over-the-Counter Medicines Using National ADR Spontaneous Reporting Data: The Example of OTC NSAID-Associated Gastrointestinal Bleeding. [2020]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Treatment Satisfaction, Efficacy, and Tolerability of Low-Dose Diclofenac Epolamine Soft Capsules in Acute, Mild, or Moderate Musculoskeletal Pain: A Prospective Open-Label, Single-Arm Interventional Study. [2023]

9. Australia pubmed.ncbi.nlm.nih.gov

The efficacy and safety of paracetamol for pain relief: an overview of systematic reviews. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Effects of food intake on the pharmacokinetics of diclofenac potassium soft gelatin capsules: a single-dose, randomized, two-way crossover study. [2013]

11. Germany pubmed.ncbi.nlm.nih.gov

Analgesic efficacy of liquid ketoprofen compared to liquid dipyrone and placebo administered orally as drops in postepisiotomy pain. [2015]