A Randomized, Open Label, Single Center, Single Dose, Two Period, Two Sequence, Crossover Bioequivalence Study of Paracetamol in a New Pediatric Paracetamol Oral Suspension Compared to a Marketed Paracetamol Oral Suspension (Panadol Baby & Infant) in Healthy Adult Subjects
Overview
- Phase
- Phase 1
- Intervention
- New Paracetamol Oral Suspension (24 mg/ml)
- Conditions
- Pain
- Sponsor
- HALEON
- Enrollment
- 61
- Locations
- 1
- Primary Endpoint
- The Time of the Maximum Observed Post-dose Concentration (Tmax)
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
The objective of the study is to compare the bioequivalence of a New Paracetamol Oral Suspension 24 milligram/milliliter (mg/ml) with that of an already approved Paracetamol (24 mg/ml) Oral Suspension (Panadol Baby & Infant) when administered to healthy volunteers under fasting condition. Pharmacokinetic parameters will be calculated from plasma concentration data. The rate and extent of absorption of the formulations will be compared.
Detailed Description
This will be a 2-arm, single center, single dose, open-label, randomized, two-sequence, two period crossover, bioequivalence study in healthy adult participants. Participants will be screened for eligibility within 15 days prior to dosing. Participants will receive each of the two study treatments in fasted state during a 6-day (5-overnight stay) residential period at the study site. Participants will receive both treatment regimens in a randomized order with a 72-hour washout period between each dose. During each treatment period, a total of 21 blood samples will be collected which will include a pre-dose blood sample 1 hour before dosing and 20 post-dose blood samples at 5, 10, 20, 30, 40, 50, 60, 80, 90, 120, 150, 180 minutes, 4, 5, 6, 8, 10, 12, 14, 16 hours, for bioanalytical analyses of paracetamol.
Investigators
Eligibility Criteria
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.
- •A participant who is willing and able to comply with scheduled visits, treatment plan, laboratory tests, study restrictions and other study procedures.
- •A participant in good general and mental health with, in the opinion of the investigator or medically qualified designee, as determined by medical evaluation, including medical history, full physical examination, including blood pressure and pulse rate measurement, 12-lead ECG or clinical laboratory tests.
- •A participant with a Body Mass Index (BMI) of 18.5 to 30.0 kg/m\^2; and a total body weight \>50 kg
- •Female participants of childbearing potential and at risk for pregnancy must agree to use a highly effective method of contraception throughout the study and for 7 days after the last dose of assigned treatment.
- •Participant with two consecutive negative tests for active COVID-19, separated by \> 24 hours.
- •Czech citizenship
Exclusion Criteria
- •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 GSKCH 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 before dosing.
- •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.
- •A participant who is pregnant as confirmed by a positive hCG laboratory test or intending to become pregnant over the duration of the study.
- •A participant who is breastfeeding.
- •A participant with known or suspected intolerance or hypersensitivity to the study materials (or closely related compounds) or any of their stated ingredients. This includes paracetamol and excipients in the products e.g. sorbitol, maltitol glycerol etc.
- •A participant unwilling or unable to comply with Lifestyle Considerations.
- •Diagnosis of long QT syndrome or QTc \> 450 msec for males and \> 470 msec for females at screening.
- •A participant with evidence or history of clinically significant laboratory abnormality, hematological, renal, endocrine, pulmonary, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease within the last 5 years that may increase the risk associated with study participation.
- •Any surgical or medical condition which may significantly alter the absorption, distribution, metabolism or excretion of any drug substance but not limited to any of the following:
Arms & Interventions
Test Drug
Participants will receive a single oral dose of either New Paracetamol Oral Suspension (24 mg/ml) or Panadol B\&I Oral Suspension (24 mg/ml paracetamol) on Day 1 (Period 1) and Day 4 (Period 2) under fasting conditions as per the randomization schedule. A wash out period of at least 72-hour will be maintained between each treatment period.
Intervention: New Paracetamol Oral Suspension (24 mg/ml)
Reference Drug
Participants will receive a single oral dose of either New Paracetamol Oral Suspension (24 mg/ml) or Panadol B\&I Oral Suspension (24 mg/ml paracetamol) on Day 1 (Period 1) and Day 4 (Period 2) under fasting conditions as per the randomization schedule. A wash out period of at least 72-hour will be maintained between each treatment period
Intervention: Panadol B&I Oral Suspension (24 mg/ml paracetamol)
Outcomes
Primary Outcomes
The Time of the Maximum Observed Post-dose Concentration (Tmax)
Time Frame: Pre-dose (-1 hour) and 0.08, 0.17, 0.33, 0.5, 0.67, 0.83, 1, 1.33, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 14, 16 hours Post dose.
Blood samples were collected at the indicated time points for for the analysis of tmax. PK parameters were calculated by standard non-compartmental analysis.
The Maximum Observed Post-dose Concentration (Cmax)
Time Frame: Pre-dose (-1 hour) and 0.08, 0.17, 0.33, 0.5, 0.67, 0.83, 1, 1.33, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 14, 16 hours Post dose.
Blood samples were collected at the indicated time points for for the analysis of Cmax. PK parameters were calculated by standard non-compartmental analysis.
The Area Under the Plasma Concentration [AUC] Versus Time Curve Calculated From Time Zero to the Last Measurable Sampling Time Point (Tlast) (AUC [0-tlast])
Time Frame: Pre-dose (-1 hour) and 0.08, 0.17, 0.33, 0.5, 0.67, 0.83, 1, 1.33, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 14, 16 hours Post dose.
Blood samples were collected at the indicated time points for the analysis of AUC (0-tlast). Pharmacokinetic (PK) parameters were calculated by standard non-compartmental analysis.
Secondary Outcomes
- Terminal Elimination Rate Constant (λz)(Pre-dose (-1 hour) and 0.08, 0.17, 0.33, 0.5, 0.67, 0.83, 1, 1.33, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 14, 16 hours Post Dose.)
- Area Under the Plasma Concentration Versus Time Curve Calculated From Time Zero to Infinity [AUC (0-inf)](Pre-dose (-1 hour) and 0.08, 0.17, 0.33, 0.5, 0.67, 0.83, 1, 1.33, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 14, 16 hours Post dose.)
- Percentage of AUC (0-inf) Obtained by Extrapolation (%AUCex)(Pre-dose (-1 hour) and 0.08, 0.17, 0.33, 0.5, 0.67, 0.83, 1, 1.33, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 14, 16 hours Post dose.)