A Study to Evaluate Ibuprofen (IBU) 62.5 mg and Acetaminophen (APAP) 125 mg/5 ml in an Oral Liquid Suspension Fixed-Dose Combination Product in Children Aged 6 to 11 Years

A Phase I, Single-Center, Open-Label, Single-Dose, Pharmacokinetic Study to Evaluate Ibuprofen (IBU) 62.5 mg and Acetaminophen (APAP) 125 mg/5 ml in an Oral Liquid Suspension Fixed-Dose Combination Product in Children Aged 6 to 11 Years

The purpose of this study will be to characterize the pharmacokinetic (PK) profile of the Fixed-Dose Combination (FDC) IBU 62.5 milligram (mg)/APAP 125 mg per 5 milliliter (mL) suspension in children 6 to 11 years of age, inclusive, to satisfy Pediatric Research Equity Act (PREA) requirements.

This will be a single-center, open-label PK study to assess the pharmacokinetic profile of IBU and APAP from a single oral dose of FDC IBU 62.5 mg/APAP 125 mg per 5 mL liquid suspension in children. Following an overnight fast of at least 8 hours, participants will receive a low-fat breakfast approximately 2.5 hours prior to dosing. The study will enroll approximately 12 children between the ages of 6 and 11 years, inclusive, with the goal of ensuring that at least 10 evaluable participants complete the study.

Inclusion Criteria:

• Participants meeting at least one of the following criteria:

  1. Participant with at least one acute, painful condition (e.g., minor aches and pains due to headache, menstruation, toothache, sports injuries, etc.) requiring use of an oral over the counter (OTC) analgesic within the previous 4 weeks (but not within the 48 hours prior to Day 1, Hour 0 investigational product dosing).
  2. Participant has undergone a non-surgical orthodontic or dental procedure (e.g., placement of an orthodontic appliance or adjustment of braces) within 24 hours prior to dosing.
  3. Participant with post-vaccination pain (post-injection site redness/soreness, joint pain) and/or fever at time of investigational product dosing.
  4. Participants who have a fever at time of investigational product dosing can be enrolled as long as the fever is low-grade (oral temperature less than (<) 37.7 degree Celsius (°C) /100.9 degrees Fahrenheit (ºF)) and, regardless of temperature, the fever has not lasted for more than (>) 48 hours as determined by the Investigator.

• Participants except for medical condition(s) indicating the use of an OTC analgesic or post-immunization pain and/or fever, participants are in normal health as judged by the Investigator upon physical examination of the participant.

• Participants/parent(s)/legal guardian who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

• Participants capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent document and in this protocol. A personally signed and dated informed consent document indicates that the child's parent(s)/legal guardian has been informed of all pertinent aspects of the study.

• Participants with evidence of a personally signed (printed name is acceptable) and dated assent document or verbal assent, indicating the participant is willing to participate in the study. If assent is evaluated not to be obtainable, age and maturity appropriate information should be given verbally to the participants, and the Investigator should document the discussion.

• Participants who are within the 5th and 95th percentiles in physical growth characteristics (i.e., height and weight) by sex as described by the Center for Disease Control and Prevention (CDC) standard growth charts, and body mass index (BMI) based on age and sex.

• Participants must have a total body weight between 48-95 lbs (21.8-43.1 kilogram (kg)).

Exclusion Criteria:

• Participants with evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).

• Participants with any condition or history felt by the Investigator to place the child at risk.

• Participants with history of angioedema and bronchospastic reactivity to aspirin or other non-steroidal anti-inflammatory drug (NSAID).

• Participants with known or suspected intolerance or hypersensitivity to the study materials (or closely related compounds) or any of their stated ingredients: Ibuprofen, or any other NSAID such as aspirin or naproxen, acetaminophen (paracetamol), or topical anesthetics (e.g., EMLA® cream).

• Participants with use of antibiotic therapy within 14 days prior to Day 1.

• Participants using the following:

  1. Ibuprofen, or any other NSAID such as aspirin or naproxen, or acetaminophen (paracetamol) within 48 hours prior to dosing with investigational product.
  2. Other prescription or nonprescription drugs within 2 weeks or 10 half-lives (whichever is longer) prior to dosing with investigational product.
  3. Dietary and herbal supplements within 2 weeks prior to the first dose of investigational product and continuing through the last PK sample on Day 1.

• Participants on treatment with an investigational drug within 90 days (or as determined by the local requirement) or 10 half-lives preceding the first dose of investigational product (whichever is longer).

• Participants who has participated in other studies (including non-medicinal studies) involving investigational product(s) within 30 days prior to signing the Informed Consent Form (ICF)/assent and/or during study participation.

• Fever of greater than 38.3°C or if the participant is too ill to participate in the study, at screening and Day 1/Day 1 of the study.

• Screening supine systolic or diastolic blood pressure (BP) at or above the 90th percentile based on age and height percentiles (by sex) following at least 5 minutes of supine rest.

• Participants with any laboratory result outside of the normal age-appropriate range that is judged by the Investigator to be clinically significant.

• Participants with a positive urine drug screen.

• Investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or Haleon employees, including their family members, directly involved in the conduct of the study.

• Blood withdrawal as part of research or routine medical care, within 8 weeks of admission to the study site that would exceed 1.36 mL/lbs per 8 weeks period, inclusive of medical care and planned sample collection for this study.

• Participants with history of sensitivity to heparin or heparin-induced thrombocytopenia.

• Participants with poor venous access.

• Participants or participant parent(s)/guardians unwilling or unable to comply with the requirements of the protocol.

• Participants who ate or drank grapefruit or grapefruit-related citrus fruits (e.g., Seville oranges, pomelos) from 2 weeks prior to dosing until collection of the final PK blood sample will be excluded as it could interfere with acetaminophen disposition.

• Pregnant female participants of childbearing potential and at risk for pregnancy who are unwilling or unable to agree to an acceptable method of contraception for at least 5 weeks prior to the start of the trial, during the trial and for at least 30 days after the last dose of the investigational product.

• Participants with history of substance abuse.