A Study of Newly Formulated Tylenol Tablet (Acetaminophen) and Tylenol 8 Hour (H) Extended Release (ER) Tablet (Acetaminophen) in Healthy Participants

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the bioequivalence of the newly formulated Tylenol tablet (acetaminophen 650 milligram [mg]) with respect to the Tylenol 8 hour (H) extended-release (ER) tablet (acetaminophen 650 mg) in healthy participants under fed conditions.

Official Title
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A Single-dose, Open-label, Randomized, Two-treatment, Two-period, Crossover Study in Healthy Subjects to Assess the Bioequivalence of the Newly Formulated Tylenol® Tablet (Acetaminophen) to the Tylenol® 8H ER Tablet (Acetaminophen) Under Fed Conditions

Conditions
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Healthy

Intervention / Treatment
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* Drug: Acetaminophen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening. If there are abnormalities, they must be consistent with the underlying illness in the study population. This determination must be recorded in the participant's source documents Healthy on the basis of clinical laboratory tests performed at screening. If the results of the serum chemistry panel including liver enzymes, other specific tests, hematology, urinalysis or breathing alcohol test are outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant. This determination must be recorded in the participant's source documents and initialed by the investigator Blood pressure (after the participant is sitting for 5 minutes) between 90 and 140 millimeters of Mercury (mmHg) systolic, inclusive, and no higher than 90 mmHg diastolic Have no history of psychiatric disorder within the 5 years prior to the screening Have no history of gastrointestinal resection that may affect drug absorption Exclusion Criteria: Clinically significant abnormal physical examination, vital signs, or 12 lead ECG at screening as deemed appropriate by the investigator Known allergies, hypersensitivity, or intolerance to acetaminophen or its excipients History of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy, which is considered cured with minimal risk of recurrence) Taken any disallowed therapies as noted in local prescribing information, concomitant therapy before the planned first dose of study drug Use of any prescription or nonprescription medication (including oriental medicines) within 30 days before the first dose of the study drug is scheduled

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Sequence 1: Reference Drug + Test Drug (RT)<br>Participants will receive 8 hour (H) extended-release (ER) acetaminophen tablet orally in period 1 (Reference) followed by newly formulated acetaminophen tablet orally in period 2 (Test). Each period will be separated by a washout period of at least 7 days. | Drug: Acetaminophen<br>* Acetaminophen tablet will be administered orally in treatment sequence 1 and 2.<br>* Other names: Tylenol;|
| Experimental: Treatment Sequence 2: Test Drug + Reference Drug (TR)<br>Participants will receive newly formulated acetaminophen tablet orally in period 1 (Test) followed by 8H ER acetaminophen tablet orally in period 2 (Reference). Each period will be separated by a washout period of at least 7 days. | Drug: Acetaminophen<br>* Acetaminophen tablet will be administered orally in treatment sequence 1 and 2.<br>* Other names: Tylenol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Analyte Concentration (Cmax) | Cmax is the maximum observed analyte concentration. | Up to 24 hours post-dose | 
| Area Under the Concentration-time Curve From Time 0 to Time of the Last Measurable Concentration (AUC [0-last]) | AUC (0-last) is the area under the concentration-time curve from time 0 to time of the last measurable concentration (non-below quantitation limit). | Up to 24 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Concentration-time Curve From Time 0 to Infinite Time (AUC[0-infinity]) | AUC(0-infinity) is the area under the plasma concentration-time curve from time 0 to infinite time, calculated as the sum of AUC (0-last) and C(last)/lambda(z). | Up to 24 hours post-dose | 
| Percentage of Area Under the Concentration-time Curve Extrapolated from Last Measurable Concentration to Infinite Time (extrapolated %AUCinfinity) | Percentage of area under the concentration-time curve extrapolated from last measurable concentration to infinite time (extrapolated %AUCinfinity) is calculated using formula: (AUC [0-infinity] minus (-) AUC [0-last]/AUC [0-infinity])*100. | Up to 24 hours post-dose | 
| Time to Reach the Maximum Observed Analyte Concentration (Tmax) | Tmax is the time to reach the maximum observed analyte plasma concentration. | Up to 24 hours post-dose | 
| Time to Last Measurable Plasma Concentration (T [last]) | Tlast is the time to last measurable plasma concentration. | Up to 24 hours post-dose | 
| Elimination Rate Constant (Lambda [z]) | Lambda (z) is the apparent terminal elimination rate constant determined by linear regression using the terminal log-linear phase of the log transformed concentration-time curve. | Up to 24 hours post-dose | 
| Elimination Half-Life (t 1/2) | t1/2 is defined as apparent is associated terminal elimination half-life associated with the terminal slope (lambda [z]) of the semilogarithmic drug concentration-time curve, calculated as: 0.693/lambda(z). | Up to 24 hours post-dose | 
| Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability | An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. | Up to 41 days |