A Bioequivalence Study of Advil Dual Action Liquid Filled Capsules (125 mg/250 mg) Versus Advil Dual Action Caplets (125 mg/250 mg) and Bioavailability Assessment of Advil Dual Action Liquid Filled Capsules (125 mg/250 mg) and Advil Liqui-Gels (200 mg) in Healthy Adult Subjects

NCT06802185 | Completed Phase 1

• 1 other identifier: 300219
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pain

Outcome Measures

Primary Outcomes (10)

• Maximum Observed Post-dose Concentration (Cmax) for Ibuprofen Under Fasted Conditions (ADA Liquid Filled Capsules [Treatment A] vs. ADA Caplet [Treatment B])

  Cmax is defined as the maximum observed post-dose concentration for ibuprofen obtained without interpolation. Blood samples will be collected at indicated timepoints for the analysis of Cmax.

  Pre-dose (within 1 hour prior to dosing) and at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.5, 6, 8,10,12,16,20, and 24 hours post dose on Day 1 in each treatment period (each period is of 3 days)

• Area Under the Plasma Concentration Versus Time Curve Calculated from Time 0 to the Last Measurable Sampling Time Point, t (AUC[0-t]) for Ibuprofen Under Fasted Conditions (ADA Liquid Filled Capsules [Treatment A] vs. ADA Caplet [Treatment B])

  AUC(0-t) is defined as the area under the plasma concentration versus time curve calculated from time 0 to the last measurable sampling time point, t, computed using the linear trapezoidal rule. Blood samples will be collected at indicated timepoints for the analysis of AUC(0-t).

  Pre-dose (within 1 hour prior to dosing) and at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.5, 6, 8,10,12,16,20, and 24 hours post dose on Day 1 in each treatment period (each period is of 3 days

• Cmax for Acetaminophen Under Fasted Conditions (ADA Liquid Filled Capsules [Treatment A] vs. ADA Caplet [Treatment B])

  Cmax is defined as the maximum observed post-dose concentration for acetaminophen obtained without interpolation. Blood samples will be collected at indicated timepoints for the analysis of Cmax.

  Pre-dose (within 1 hour prior to dosing) and at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.5, 6, 8,10,12,16,20, and 24 hours post dose on Day 1 in each treatment period (each period is of 3 days)

• AUC(0-t) for Acetaminophen Under Fasted Conditions (ADA Liquid Filled Capsules [Treatment A] vs. ADA Caplet [Treatment B])

  AUC(0-t) is defined as the area under the plasma concentration versus time curve calculated from time 0 to the last measurable sampling time point, t, computed using the linear trapezoidal rule. Blood samples will be collected at indicated timepoints for the analysis of AUC(0-t).

  Pre-dose (within 1 hour prior to dosing) and at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.5, 6, 8,10,12,16,20, and 24 hours post dose on Day 1 in each treatment period (each period is of 3 days)

• Cmax for Ibuprofen (ADA Liquid Filled Capsules Under Fed Conditions [Treatment C] vs. ADA Liquid Filled Capsules Under Fasted Conditions [Treatment A])

  Cmax is defined as the maximum observed post-dose concentration for ibuprofen obtained without interpolation. Blood samples will be collected at indicated timepoints for the analysis of Cmax.

  Pre-dose (within 1 hour prior to dosing) and at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.5, 6, 8,10,12,16,20, and 24 hours post dose on Day 1 in each treatment period (each period is of 3 days)

• AUC(0-t) for Ibuprofen (ADA Liquid Filled Capsules Under Fed Conditions [Treatment C] vs. ADA Liquid Filled Capsules Under Fasted Conditions [Treatment A])

  AUC(0-t) is defined as the area under the plasma concentration versus time curve calculated from time 0 to the last measurable sampling time point, t, computed using the linear trapezoidal rule. Blood samples will be collected at indicated timepoints for the analysis of AUC(0-t).

  Pre-dose (within 1 hour prior to dosing) and at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.5, 6, 8,10,12,16,20, and 24 hours post dose on Day 1 in each treatment period (each period is of 3 days)

• Area Under the Plasma Concentration Versus Time Curve Calculated From Time 0 to Infinity (AUC[0-inf]) for Ibuprofen (ADA Liquid Filled Capsules Under Fed Conditions [Treatment C] vs. ADA Liquid Filled Capsules Under Fasted Conditions [Treatment A])

  AUC(0-inf) is defined as the area under the plasma concentration versus time curve calculated from time 0 to infinity. AUC(0-inf) = AUC(0-t) + C(t)/λz where C(t) is the concentration at the last measurable sampling time point and λz is the terminal elimination rate constant. Blood samples will be collected at indicated timepoints for the analysis of AUC(0-inf).

  Pre-dose (within 1 hour prior to dosing) and at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.5, 6, 8,10,12,16,20, and 24 hours post dose on Day 1 in each treatment period (each period is of 3 days)

• Cmax for Acetaminophen (ADA Liquid Filled Capsules Under Fed Conditions [Treatment C] vs. ADA Liquid Filled Capsules Under Fasted Conditions [Treatment A])

  Cmax is defined as the maximum observed post-dose concentration for acetaminophen obtained without interpolation. Blood samples will be collected at indicated timepoints for the analysis of Cmax.

  Pre-dose (within 1 hour prior to dosing) and at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.5, 6, 8,10,12,16,20, and 24 hours post dose on Day 1 in each treatment period (each period is of 3 days)

• AUC(0-t) for Acetaminophen (ADA Liquid Filled Capsules Under Fed Conditions [Treatment C] vs. ADA Liquid Filled Capsules Under Fasted Conditions [Treatment A])

  AUC(0-t) is defined as the area under the plasma concentration versus time curve calculated from time 0 to the last measurable sampling time point, t, computed using the linear trapezoidal rule. Blood samples will be collected at indicated timepoints for the analysis of AUC(0-t).

  Pre-dose (within 1 hour prior to dosing) and at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.5, 6, 8,10,12,16,20, and 24 hours post dose on Day 1 in each treatment period (each period is of 3 days)

• AUC(0-inf) for Acetaminophen (ADA Liquid Filled Capsules Under Fed Conditions [Treatment C] vs. ADA Liquid Filled Capsules Under Fasted Conditions [Treatment A])

  AUC(0-inf) is defined as the area under the plasma concentration versus time curve calculated from time 0 to infinity. AUC(0-inf) = AUC(0-t) + C(t)/λz where C(t) is the concentration at the last measurable sampling time point and λz is the terminal elimination rate constant. Blood samples will be collected at indicated timepoints for the analysis of AUC(0-inf).

  Pre-dose (within 1 hour prior to dosing) and at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.5, 6, 8,10,12,16,20, and 24 hours post dose on Day 1 in each treatment period (each period is of 3 days)

Secondary Outcomes (19)

• Percentage of AUC(0-inf) Obtained by Extrapolation (%AUCex) for Ibuprofen (Treatment A, Treatment C, Treatment B and Treatment D)

  Pre-dose (within 1 hour prior to dosing) and at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.5, 6, 8,10,12,16,20, and 24 hours post dose on Day 1 in each treatment period (each period is of 3 days)

• AUC(0-inf) for Ibuprofen (Treatment A, Treatment C, Treatment B and Treatment D)

  Pre-dose (within 1 hour prior to dosing) and at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.5, 6, 8,10,12,16,20, and 24 hours post dose on Day 1 in each treatment period (each period is of 3 days)

• Terminal Elimination Rate Constant (λz) for Ibuprofen (Treatment A, Treatment C, Treatment B and Treatment D)

  Pre-dose (within 1 hour prior to dosing) and at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.5, 6, 8,10,12,16,20, and 24 hours post dose on Day 1 in each treatment period (each period is of 3 days)

• Time of the Maximum Observed Post-dose Concentration (tmax) for Ibuprofen (Treatment A, Treatment C, Treatment B and Treatment D)

  Pre-dose (within 1 hour prior to dosing) and at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.5, 6, 8,10,12,16,20, and 24 hours post dose on Day 1 in each treatment period (each period is of 3 days)

• Elimination Half-life (t1/2) for Ibuprofen (Treatment A, Treatment C, Treatment B and Treatment D)

  Pre-dose (within 1 hour prior to dosing) and at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.5, 6, 8,10,12,16,20, and 24 hours post dose on Day 1 in each treatment period (each period is of 3 days)

Study Arms (4)

Sequence 1: Treatment A + Treatment B + Treatment C + Treatment D

EXPERIMENTAL

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.

Drug: ADA Liquid Filled Capsules (Test Product); Drug: ADA Caplets (Reference Product); Drug: Advil Liqui-gels (Reference Product)

Sequence 2: Treatment B + Treatment D + Treatment A + Treatment C

EXPERIMENTAL

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.

Drug: ADA Liquid Filled Capsules (Test Product); Drug: ADA Caplets (Reference Product); Drug: Advil Liqui-gels (Reference Product)

Sequence 3: Treatment C + Treatment A + Treatment D + Treatment B

EXPERIMENTAL

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.

Drug: ADA Liquid Filled Capsules (Test Product); Drug: ADA Caplets (Reference Product); Drug: Advil Liqui-gels (Reference Product)

Sequence 4: Treatment D + Treatment C + Treatment B + Treatment A

EXPERIMENTAL

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.

Drug: ADA Liquid Filled Capsules (Test Product); Drug: ADA Caplets (Reference Product); Drug: Advil Liqui-gels (Reference Product)

Interventions

ADA Liquid Filled Capsules (Test Product) DRUG

ADA liquid filled capsules containing 125 mg ibuprofen and 250 mg acetaminophen.

Sequence 1: Treatment A + Treatment B + Treatment C + Treatment D; Sequence 2: Treatment B + Treatment D + Treatment A + Treatment C; Sequence 3: Treatment C + Treatment A + Treatment D + Treatment B; Sequence 4: Treatment D + Treatment C + Treatment B + Treatment A

ADA Caplets (Reference Product) DRUG

ADA Caplets containing 125 mg ibuprofen and 250 mg acetaminophen.

Sequence 1: Treatment A + Treatment B + Treatment C + Treatment D; Sequence 2: Treatment B + Treatment D + Treatment A + Treatment C; Sequence 3: Treatment C + Treatment A + Treatment D + Treatment B; Sequence 4: Treatment D + Treatment C + Treatment B + Treatment A

Advil Liqui-gels (Reference Product) DRUG

Advil Liqui-gels containing 200 mg ibuprofen.

Sequence 1: Treatment A + Treatment B + Treatment C + Treatment D; Sequence 2: Treatment B + Treatment D + Treatment A + Treatment C; Sequence 3: Treatment C + Treatment A + Treatment D + Treatment B; Sequence 4: Treatment D + Treatment C + Treatment B + Treatment A

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Participant provision of a signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study before any assessment is performed.
• Participant is male or female who, at the time of screening, is between the ages of 18 and 55 years, inclusive. An effort will be made to include similar proportions of males and females in the study.
• Participant who is willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
• A participant in good general and mental health with, in the opinion of the investigator or medically qualified designee, no clinically significant or relevant abnormalities in medical history or upon the physical examination, blood pressure (BP) and pulse rate measurement, 12-lead electrocardiogram (ECG) or clinical laboratory tests, or condition, that would impact the participant's safety, wellbeing or the outcome of the study, if they were to participate in the study, or affect the participant's ability to understand and follow study procedures and requirements.
• Body Mass Index (BMI) of 18.5 to 30.0 kilogram per meter square (kg/m\^2); and a total body weight more than or equal to (\>=) 50.0 kilograms (kg) for males and \>= 45.0 kg for females at screening.
• Female participant of childbearing potential and at risk for pregnancy must agree to use a highly effective method of contraception throughout the study and for at least 30 days after the last dose of assigned treatment.

You may not qualify if:

• A participant who is an employee of the investigational site, either directly involved in the conduct of the study or a member of their immediate family; or an employee of the investigational site otherwise supervised by the investigator; or, a Haleon employee directly involved in the conduct of the study or a member of their immediate family.
• A participant who has participated in other studies (including non-medicinal studies) involving investigational product(s) within 30 days prior to study entry and/or intends to participate in any other study during participation in this study.
• A participant with, in the opinion of the investigator or medically qualified designee, an acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator or medically qualified designee, would make the participant inappropriate for entry into this study.
• Pregnant female participant as confirmed by a positive pregnancy test or intending to become pregnant over the duration of the study.
• Breastfeeding female participant.
• Known or suspected intolerance or hypersensitivity to the study materials (or closely related compounds) or any of their stated ingredients.
• Any history of asthma, urticaria, or other significant allergic diathesis or allergic reaction to any other pain reliever/fever reducer. Participant with uncomplicated seasonal allergic rhinitis can be accepted if expected allergy season is clearly outside enrollment/treatment period.
• Diagnosis of long QT syndrome or QT corrected for heart rate by Fridericia's cube root formula (QTcF) more than (\>) 450 milliseconds (msec) for males and \>470 msec for females at screening.
• Vital sign abnormalities (systolic BP lower than 90 or over 140 millimeters of mercury (mmHg), diastolic BP lower than 50 or over 90 mmHg, or pulse rate less than 50 or over 100 beats per minute) unless determined by the Investigator or medically qualified designee to be not clinically significant. Vital signs may be repeated at the discretion of the Investigator or medically qualified designee.
• Unwilling or unable to comply with the Lifestyle Considerations described in this protocol.
• Use of any medication (including over the counter medications and herbal remedies) within 2 weeks or within less than 10 times the elimination half-life of the respective drug (whichever is longer) before first scheduled study drug administration, or is anticipated to require any concomitant medication during that period or at any time throughout the study. Allowed treatments are:
• \. systemic contraceptives as long as female participant is on stable treatment for at least 3 months before first scheduled study drug administration and continues treatment throughout the study.
• Evidence or history of clinically significant laboratory abnormality, hematological, renal, endocrine, pulmonary, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease in the opinion of the Investigator, or medically qualified designee that may increase the risk associated with study participation.
• Any history of long-term treatment with carbamazepine, phenobarbitone, phenytoin, primidone, rifampicin, St John's Wort or other drugs that induce liver enzymes.
• Clinically relevant chronic or acute infectious illnesses or febrile infections within 2 weeks prior to start of the study.

Sponsors & Collaborators

• HALEON: lead

Study Sites (1)

Spaulding Clinical

West Bend, Wisconsin, 53095, United States

Location

MeSH Terms

Conditions

Pain

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2025
• First Posted: January 31, 2025
• Study Start: January 31, 2025
• Primary Completion: April 12, 2025
• Study Completion: April 12, 2025
• Last Updated: April 23, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months, but an extension can be granted, when justified, for up to another 12 months.

Locations

US (1)