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
Status and phase
Conditions
Treatments
Details and patient eligibility
About
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.
Full description
This is a single center, single oral dose, open-label, randomized, four-treatment, four period, four sequence, crossover, bioequivalence study of ADA liquid filled capsules (125 milligrams [mg] ibuprofen/250 mg acetaminophen) (Treatment A) versus (vs.) ADA Caplets (125 mg ibuprofen/250 mg acetaminophen) (Treatment B) in healthy adult participants under fasted conditions. The study also includes a bioavailability assessment of ADA liquid filled capsules (125 mg ibuprofen/250 mg acetaminophen) under fed conditions (Treatment C) and Advil Liqui-Gels (200 mg ibuprofen) under fasted conditions (Treatment D). A sufficient number of male and female participants will be screened to randomize approximately 54 to ensure at least 48 evaluable participants complete the entire study. Participants will be randomly assigned to 1 of the 4 treatment sequences and receive a single oral dose of the investigational products per the randomization in each period following a crossover design. There will be a wash-out period of 3 days between investigational product administrations. Blood will be sampled regularly at scheduled times for 24 hours following treatment in each period to assess the pharmacokinetic parameters.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
- 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.
Exclusion criteria
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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.
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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.
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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.
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Pregnant female participant as confirmed by a positive pregnancy test or intending to become pregnant over the duration of the study.
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Breastfeeding female participant.
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Known or suspected intolerance or hypersensitivity to the study materials (or closely related compounds) or any of their stated ingredients.
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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.
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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.
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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.
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Unwilling or unable to comply with the Lifestyle Considerations described in this protocol.
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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.
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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.
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Any history of long-term treatment with carbamazepine, phenobarbitone, phenytoin, primidone, rifampicin, St John's Wort or other drugs that induce liver enzymes.
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Clinically relevant chronic or acute infectious illnesses or febrile infections within 2 weeks prior to start of the study.
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Any surgical or medical condition which may significantly alter the absorption, distribution, metabolism or excretion of any drug substance including, but not limited to any of the following:
- History of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, bowel resection, gastric bypass, gastric stapling or gastric banding (note: this is not applicable for minor abdominal surgery without significant tissue resection, example, appendectomy and herniorrhaphy);
- History of inflammatory bowel disease or gastrointestinal bleeding including peptic ulcers;
- History or current evidence of renal disease or impaired renal function at screening as demonstrated by an estimated glomerular filtration rate (eGFR) less than (<) 80 milliliters per minute per 1.73 meter^2 (ml/min/1.73 m^2) during screening (using the Chronic Kidney Disease Epidemiology Collaboration formula)
- History or current evidence of ongoing hepatic disease or impaired hepatic function at screening.
- A participant will be excluded if more than one of the following lab value deviations are found: 1) aspartate transaminase (AST) (>= 1.2 upper limit of normal [ULN]), alanine transaminase (ALT) (>=1.2 ULN), 2) gamma-glutamyl transpeptidase (GGT) (>=1.2 ULN), alkaline phosphatase (ALP) (>=1.2 ULN), 3) total bilirubin (>2.00 milligrams per deciliter [mg/dL]) or creatine kinase (>=3 ULN). A single deviation from the above values is acceptable and will not exclude the participant, unless specifically advised by the investigator, or medically qualified designee;
- Evidence of urinary obstruction (example, due to benign prostate hyperplasia) or difficulty in voiding at screening;
- History or clinical evidence (on physical examination) at screening of pancreatic injury or pancreatitis.
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Any vaccination, including Coronavirus disease (COVID)-19 vaccine, within 14 days prior to the first dose.
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History of drug abuse within 1 year prior to screening or recreational use of soft drugs (such as marijuana) within 1 month or hard drugs (such as cocaine, phencyclidine [PCP], crack, opioid derivatives including heroin, and amphetamine derivatives) within 3 months prior to dosing.
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History of alcohol abuse within 1 year prior to screening or regular use of alcohol within 6 months prior to screening that exceeds 10 units for women or 15 units for men of alcohol per week (1 unit = 340 milliliters (mL) of beer 5 percent (%), 140 mL of wine 12%, or 45 mL of distilled alcohol 40%).
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Positive urine drug screen or urine alcohol test at screening or Day -1.
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Positive cotinine test at screening or Day -1
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Participant reported regular consumption of beverages or food containing xanthine derivatives or xanthine-related compounds (example, coffee, tea, caffeine-containing sodas and chocolate), equivalent to >= 500 milligrams (mg) xanthine per day.
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Current smoker, defined as the use of tobacco or nicotine products during the 3 months prior to screening until admission to the unit.
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Participant reports consumption of any drug metabolizing enzyme (example, Cytochrome P450 3A4 [CYP3A4] or other cytochrome P450 enzymes) inducing or inhibiting aliments, beverages or food supplements (example, broccoli, Brussels sprouts, grapefruit, grapefruit juice, star fruit, St. John's Wort etcetera [etc.]) within 2 weeks prior to admission to the unit.
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Positive results in any of the serology tests for human immunodeficiency virus (HIV) antigen (Ag) and antibody (Ab), Hepatitis C virus antibody (HCV-Ab), hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (HBcAb) (immunoglobulin [Ig]G + IgM).
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Performance of strenuous physical exercise (body building, high performance sports) from 2 weeks prior to admission and does not agree to refrain throughout the entire study.
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Allergy to skin disinfecting agents, tape, or latex rubber, whenever appropriate substitutions cannot be applied or in the Investigator's or medically qualified designee's opinion may pose a risk to the participant.
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Any condition not identified in the protocol that in the opinion of the investigator or medically qualified designee would confound the evaluation and interpretation of the study data or may put the participant at risk.
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Donation of plasma within 7 days prior to dosing or donation or loss of 500 mL or more of whole blood within 8 weeks prior to dosing.
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Hemoglobin value <12.0 grams per deciliter [g/dL] for males and <11.5 g/dL for females, may repeat at discretion of the Investigator or medically qualified designee at screening or day -1.
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Participant who has previously been enrolled in this study.
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Participant has unsuitable veins for multiple venipunctures/cannulations as assessed by the investigator or delegate at screening.
Trial design
Primary purpose
Allocation
Interventional model
Masking
54 participants in 4 patient groups
Trial contacts and locations
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Central trial contact
Haleon Response Center
Data sourced from clinicaltrials.gov
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