Study to Evaluate the Pharmacokinetics of Mucinex® 1200 mg Extended-Release Tablet

Study Overview
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Brief Summary
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Characterize and assess PK of guaifenesin in Mucinex® 1200 mg ER Bi-Layer Tablet

Detailed Description
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A Phase I, Open-Label, Single-Dose, Single Period Study to Evaluate the Pharmacokinetics of Mucinex® 1200 mg Extended-Release Bi-Layer Tablet in Normal Healthy Subjects

Official Title
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A Phase I, Open-label, Single-dose, Single Period Study to Evaluate the Pharmacokinetics of Mucinex® 1200 mg Extended-Release Bi-layer Tablet in Normal Healthy Subjects.

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: Mucinex®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females ≥19 to 55 years of age inclusive. All females who were of childbearing potential must have been using one of the following acceptable birth control methods for the time periods specified: Intrauterine device (IUD) in place for at least 3 months prior to Day 1 through 30 days beyond study completion. Barrier method (condom or diaphragm) with spermicide for at least 7 days prior to screening through 30 days beyond study completion. Stable hormonal contraceptive (oral, depo injection, transdermal patch, or vaginal ring) for at least 3 months prior to Day 1 through 30 days beyond completion of study. Note: Abstinence (sexually inactive) was not an acceptable form of contraception; however, abstinent female subjects could have been admitted to the study if they had reported being abstinent at least 14 days prior to screening and they agreed, and signed an Abstinence Statement to the effect, that upon becoming sexually active, they would use a condom with spermicide from that time through 30 days beyond completion of the study. Females of non-childbearing potential must have been surgically sterile (bilateral tubal ligation with surgery at least 6 months prior to Day 1 or hysterectomy and/or bilateral oophorectomy at least 3 months prior to Day 1 or post-menopausal ≥2 years prior to Day 1). A follicle stimulating hormone level (FSH) >40 mIU/mL must have been obtained and in the record for any post-menopausal female. Negative serum pregnancy test at Screening and at Check-in for all female subjects. Good general health as determined by the PI's review of medical history, physical examination, 12-lead electrocardiogram (ECG), vital sign measurements (after 2 minutes resting in the seated position), and clinical laboratory measures. Body mass index (BMI) of 19 to 29 kg/m2, inclusive. (BMI = weight (kg)/[height (m2)]). Non-tobacco users, who had not used nicotine or nicotine-containing products for at least 6 months prior to Day 1. Negative finding on tests for Hepatitis B surface antigen (HBsAG), Hepatitis C virus (HCV) antibodies, human immunodeficiency virus (HIV). Negative urine screen for drugs of abuse and alcohol at Screening and at Check-in. Likely to be compliant with study requirements and complete the study, as determined by the Investigator. Able to read, understand, and sign the informed consent after the nature of the study had been explained and had read, signed, and dated an Institutional Review Board (IRB)-approved informed consent form for subjects to participate in the study. Exclusion Criteria: Clinically significant abnormalities detected by medical history, physical examination, vital sign measurements, ECG findings, or clinical laboratory findings (as determined by the PI). If the subject's hemoglobin dropped below 11.0 gm/dL during the study, the subject may have been dropped from the study at the discretion of the PI/designee. Any disease or condition, which could impact absorption, distribution, metabolism, or elimination of the study drug (as determined by the PI/designee). Females who were pregnant or nursing. History of hypersensitivity reaction to guaifenesin. Receipt of an investigational drug within 30 days prior to Day 1. Abnormal diet (for whatever reason) during the 30 days prior to Day 1. Donation of blood or significant loss of blood within 56 days prior to Day 1. Donation of plasma within 14 days prior to Day 1. Known or suspected use of illicit drugs (i.e., opiates, barbiturates, marijuana, et. al.). The use of any medication, prescription or over-the-counter (OTC) (including herbal supplements) within the 14 days or 5 half-lives of the drug (whichever was longer) prior to Day 1 (with the exception of hormonal contraceptives for women of child-bearing potential). Alcoholism or medicinal product or drug abuse within the past two years or excessive alcohol consumption (more than 10 units per week) [one unit is defined as 5 ounces of wine, 12 ounces of beer, or 1.5 ounces of spirits (i.e., hard liquor such as gin, whiskey, or vodka, et. al.)]. The subject was not to experience tolerance, withdrawal, compulsive use, or substance related problems such as medical complications, disruption in social and family relationships, vocational or financial difficulties, or legal problems. Consumption of grapefruit, pummelo, Seville orange, or grapefruit juice within 14 days prior to dosing on Day 1 through study completion. Consumption of alcohol within the 48 hours prior to dosing on Day 1. Persons involved directly with the conduct of this study (i.e., Investigator, Sub-Investigators, Study Coordinators, etc.) or employees of Reckitt Benckiser and their families.

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 55 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: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mucinex® 1200 mg<br>Mucinex® 1200 mg Extended-Release (ER) Bi-Layer tablet (single dose) | Drug: Mucinex®<br>* Mucinex® 1200 mg ER Bi-Layer tablet<br>* Other names: guaifenesin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) | Pharmacokinetic Parameters (Cmax) Maximum observed plasma concentration. | 0 (pre-dose), 1,2,3,4,5,6,7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 25, 30, 35, 40, 45, 50, and 55 minutes; 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 5, 6, 7, 8, 10, 12, 14, 16 and 24 hours on Day 1 | 
| Time of the Maximum Observed Plasma Concentration (Tmax) | Pharmacokinetic Parameter (Tmax) Time of the maximum observed plasma concentration | 0 (pre-dose), 1,2,3,4,5,6,7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 25, 30, 35, 40, 45, 50, and 55 minutes; 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 5, 6, 7, 8, 10, 12, 14, 16 and 24 hours on Day 1 | 
| Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) | Pharmacokinetic Parameter (AUC0-t) is Area under the plasma concentration versus time curve from time 0 to the time of the last measurable concentration | 0 (pre-dose), 1,2,3,4,5,6,7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 25, 30, 35, 40, 45, 50, and 55 minutes; 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 5, 6, 7, 8, 10, 12, 14, 16 and 24 hours on Day 1 | 
| Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) | Pharmacokinetic Parameter (AUC0-inf) Area under the plasma concentration versus time curve from time 0 to infinity. | 0 (pre-dose), 1,2,3,4,5,6,7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 25, 30, 35, 40, 45, 50, and 55 minutes; 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 5, 6, 7, 8, 10, 12, 14, 16 and 24 hours on Day 1 | 
| Percentage of AUC0-inf Extrapolated Area Under Plasma Concentration Curve Ratio (AUCR) of Guaifenesin | Pharmacokinetic Parameter (AUC%extrap) Percent of AUC0-inf extrapolated AUCR = 100 - (AUC0-t/ AUC0-inf) x 100 | 0 (pre-dose), 1,2,3,4,5,6,7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 25, 30, 35, 40, 45, 50, and 55 minutes; 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 5, 6, 7, 8, 10, 12, 14, 16 and 24 hours on Day 1 | 
| Apparent First-order Terminal Elimination Rate Constant (Kel) | Pharmacokinetic Parameter (Kel) Apparent first-order terminal elimination rate constant | 0 (pre-dose), 1,2,3,4,5,6,7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 25, 30, 35, 40, 45, 50, and 55 minutes; 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 5, 6, 7, 8, 10, 12, 14, 16 and 24 hours on Day 1 | 
| Terminal Elimination Half Life (t1/2) | Pharmacokinetic Parameter (t1/2) is Apparent terminal elimination half-life. | 0 (pre-dose), 1,2,3,4,5,6,7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 25, 30, 35, 40, 45, 50, and 55 minutes; 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 5, 6, 7, 8, 10, 12, 14, 16 and 24 hours on Day 1 | 
| Time at Which the Percentage of Subjects Achieved a Target Concentration of at Least 65 ng/mL (T65) | Pharmacokinetic Parameter (T65) is te time when guaifenesin plasma concentration achieved a target concentration of at least 65 ng/mL. | 0 (pre-dose), 1,2,3,4,5,6,7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 25, 30, 35, 40, 45, 50, and 55 minutes; 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 5, 6, 7, 8, 10, 12, 14, 16 and 24 hours on Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) | Intensity was determined by the Investigator. For symptomatic adverse events (AEs) the following definitions were applied. Mild = AE did not limit usual activities; subject may have experienced slight discomfort. Moderate = AE resulted in some limitation of usual activities; subject may have experienced significant discomfort. Severe = AE resulted in an inability to carry out usual activities; subject may have experienced intolerable discomfort/pain. Relationship to Investigational Medicinal Products (IMP) Unlikely = Slight, but remote, chance that AE was caused by IMP. Possible = Reasonable suspicion that the AE was caused by IMP. Probable = Most likely that AE was caused by IMP. | Up to Day 2 |