A Study of Acetaminophen/Naproxen Sodium Fixed Combination Tablets in Adolescents 12 to <17 Years of Age With Pain

Study Overview
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Brief Summary
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The purpose of this study is to investigate the population pharmacokinetics of acetaminophen and naproxen from a novel acetaminophen /naproxen sodium fixed combination tablet in adolescents 12 to less than (<) 17 years of age with post-procedure orthodontic pain and to describe the effect of subject-specific covariates, including age and body weight, on inter-subject variability in acetaminophen and naproxen pharmacokinetics in adolescents 12 to <17 years of age with post-procedure orthodontic pain.

Official Title
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An Open-label, Single-dose, Pharmacokinetic Study of Acetaminophen/Naproxen Sodium Fixed Combination Tablets in Adolescents 12 to <17 Years of Age With Orthodontic Pain

Conditions
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Orthodontic Pain

Intervention / Treatment
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* Drug: Acetaminophen/Naproxen Sodium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A parent or a legal guardian of the participant has signed and dated the informed consent document and a written assent has been signed by the participant Has undergone an orthodontic procedure within 72 hours prior to dosing Is otherwise a healthy adolescent between the ages of 12 to less than (<) 17 years at baseline (dosing). Health is defined as the absence of clinically relevant abnormalities as judged by the principle investigator (PI) on the basis of a detailed medical history, physical examination, blood pressure, respiratory rate and pulse rate measurements, and clinical laboratory tests. The responsible PI may request additional investigations or analyses if necessary Has a minimum weight of 72 pounds and has a Body Mass Index (BMI) between the 5th and 95th percentile for their age at dosing Has been fasted for at least 10 hours prior to dose administration of the investigational product Is a non-tobacco user or previous user who completely stopped smoking or using any form of tobacco or nicotine-containing product [including e-cigarettes, cigarettes, non-combusted cigarettes, cigars, smokeless tobacco (such as dip, snuff, snus, and chewing tobacco)] for at least 12 months before screening visit of this study If female, have a negative test for pregnancy at screening and baseline (dosing) Females of childbearing potential and males agree to the contraceptive requirements Is able to comprehend the requirements of the study (based upon clinical site personnel's assessment) and is willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures specified within the protocol Are willing for investigational product of this study to be the only analgesic product used during the study Exclusion Criteria: Use of prescription or non-prescription medications within a period less than 5 half-lives before the first investigational product (IP) administration unless these are contraceptives or occasional use of other medications approved by the Investigator Use of Ibuprofen within 6 hours prior to the dose administration of the investigational product Use of any vitamins, dietary and herbal supplements within seven days before first dose of study drug Has hypersensitivity to acetaminophen, naproxen, other non-steroidal anti-inflammatory drug (NSAIDs), including acetylsalicylic acid, or to any of the ingredients If female, has a positive pregnancy test or is breast-feeding or currently trying to become pregnant Has a positive test for human immunodeficiency virus (HIV) 1 and 2 antibodies, hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (anti-HCV) Has a positive test for drugs of abuse at screening or baseline (dosing) Has difficult venipuncture access and/or refuses to undergo venipuncture Has clinically significant renal or hepatic impairment according to the medically qualified Investigator discretion, or presence of a disease, which in the opinion of the Investigator, would preclude the use of IP Has a history of peptic ulcers, gastrointestinal bleeding of any etiology, bleeding disorders, gastrointestinal disease (including chronic heartburn or gastroesophageal reflux disease, or any other active inflammatory disease of the gastrointestinal tract such as ulcerative colitis or crohn's disease), or has a history of gastrointestinal surgery (including cholecystectomy) that would affect the pharmacokinetic (PK) assessment of the drug or the safety of the participant Has history of substance abuse, as judged by the PI, within 12 months preceding this study Has used alcohol within 24 hours of baseline visit and/or has positive alcohol test in expired air at screening or baseline visit Has used food or beverages containing xanthines (that is, tea, coffee, cola drinks, energy drinks or chocolate) for 48 hours prior to the dosing and during the study period Has used grapefruit and savoy oranges for 48 hours prior to the dosing and during the study period Participating in a clinical trial and/or treated with any investigational product within 3 months preceding the dose of study drug Has preplanned surgery, procedures, or personal commitments that would interfere with the conduct of the study Had an acute blood loss of 50 milliliter (mL) to 249 mL within the 30 days, or 250 mL to 449 mL within the 45 days, or greater than or equal to (>=) 450 mL within the 60 days before first dose administration Has any acute or chronic medical or psychiatric condition(s) that may increase the risk associated with study participation or IP administration or may interfere with the interpretation of study results and, in the judgment of the medically qualified Investigator, would make the participant inappropriate for entry into this study Has any clinically important abnormal value for serum chemistry, hematology, or urinalysis at screening. Laboratory values will generally be within the normal ranges, although minor deviations in tests (except those explicitly specified in the inclusion criteria) that are not considered clinically important by the Investigator are acceptable Is related to persons involved directly or indirectly with the conduct of the study (that is, principal investigator, sub-investigators, study coordinators, other study personnel, employees or contractors of the Sponsor or Johnson & Johnson (J&J) subsidiaries, and the family of each)

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 16 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acetaminophen /Naproxen Sodium<br>Participants with age group 12 to less than (<) 17 years who undergone a non-surgical orthodontic procedure will enroll and receive fixed dose combination of acetaminophen/naproxen sodium tablet orally on baseline (Day 0). | Drug: Acetaminophen/Naproxen Sodium<br>* Fixed dose combination of acetaminophen/naproxen sodium tablet will be administered orally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Apparent Clearance (CL/F) of Acetaminophen/Naproxen Sodium | CL/F is defined as apparent clearance of acetaminophen/naproxen sodium. | Pre-dose up to 48 hours post dose | 
| Apparent Central Volume of Distribution (Vc/F) After Oral Dosing of Acetaminophen/Naproxen Sodium | Vc/F is defined as apparent central volume of distribution after oral dosing of acetaminophen/naproxen sodium. | Pre-dose up to 48 hours post dose | 
| Apparent Peripheral Volume of Distribution (Vp/F) After Oral Dosing of Acetaminophen/Naproxen Sodium | Vp/F is defined as apparent peripheral volume of distribution after oral dosing of acetaminophen/naproxen sodium. | Pre-dose up to 48 hours post dose | 
| Apparent Inter-compartmental Clearance (Q/F) of Acetaminophen/Naproxen Sodium | Q/F is defined as apparent inter-compartmental clearance of acetaminophen/naproxen sodium. | Pre-dose up to 48 hours post dose | 
| First-order Absorption Rate Constant (Ka) of Acetaminophen/Naproxen Sodium | Ka is defined as first-order absorption rate constant of acetaminophen/naproxen sodium. | Pre-dose up to 48 hours post dose | 
| Maximum Plasma Concentration (Cmax) of Acetaminophen/Naproxen Sodium | Cmax is defined as maximum plasma concentration of acetaminophen/naproxen sodium. | Pre-dose up to 48 hours post dose | 
| Time of occurrence of Maximum Plasma Concentration (Tmax) of Acetaminophen/Naproxen Sodium | Tmax is defined as time of occurrence of maximum plasma concentration of acetaminophen/naproxen sodium. | Pre-dose up to 48 hours post dose | 
| Area Under the Plasma Concentration versus Time Curve from Start of Drug Administration Until the Time of the Last Measurable Plasma Concentration (AUC[0-t]) | AUC(0-t) is defined as area under the plasma concentration versus time curve from start of drug administration until the time of the last measurable plasma concentration of acetaminophen/naproxen sodium. | Pre-dose up to 48 hours post dose | 
| Area Under the Plasma Concentration versus Time Curve From Start of Drug Administration Until Infinity (AUC[0-infinite]) | AUC(0-infinite) is defined as area under the plasma concentration versus time curve from start of drug administration until infinity of acetaminophen/naproxen sodium. | Pre-dose up to 48 hours post dose | 
| Terminal Elimination Rate Constant (lambda[z]) of Acetaminophen/Naproxen Sodium | Lambda(z) is defined as terminal elimination rate constant of acetaminophen/naproxen sodium. | Pre-dose up to 48 hours post dose | 
| Half Life (t1/2) of Acetaminophen/Naproxen Sodium | T1/2 is defined as half life of acetaminophen/naproxen sodium. | Pre-dose up to 48 hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events (AEs) | An AE is any untoward medical occurrence that occurs in participants after they have signed an informed consent for the study. The event does not need to have a suspected causal relationship with the investigational product (IP). | Up to 3 days |