Bioequivalence Study Comparing Mucinex Extended-release 600 mg Tablets to Immediate-release Guaifenesin 600 mg in Healthy Volunteers

Study Overview
=================
Brief Summary
-----------------
Determine bioequivalence, safety and tolerability of guaifenesin extended-release 600 mg (Mucinex® SE) compared to an immediate-release syrup reference product in normal healthy subjects.

Official Title
-----------------
A Phase I, Open-label, Single-dose, Randomized, 2-way Crossover Bioequivalence Study Comparing Mucinex® SE Extended-Release 600 mg Bi-layer Tablet to a Reference Immediate-Release Guaifenesin 600 mg (Taken as 200 mg q4h) in Normal Healthy Subjects.

Conditions
-----------------
Healthy Subjects

Intervention / Treatment
-----------------
* Drug: Mucinex® SE
* Drug: Vicks Cough Syrup for Chesty Coughs


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Males and/or females between the ages of 19 and 55 years, inclusive. Females of childbearing potential must be using one of the following acceptable birth control methods: Intra-uterine device in place for at least 3 months prior to Day 1 of Period 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 (e.g., oral, depo injection, transdermal patch, or vaginal ring) for at least 3 months prior to Day 1 of Period 1 through 30 days beyond completion of study; Abstinence is not an acceptable form of contraception; however, abstinent female subjects may be admitted to the study if they agree, and have signed a statement to the effect, that upon becoming sexually active, will use a condom with spermicide from screening through 30 days beyond completion of the study. Females of non-childbearing potential should be surgically sterile (bilateral tubal ligation with surgery at least 6 months prior to study or hysterectomy and/or bilateral oophorectomy at least 3 months prior to Day 1 of Period 1) or postmenopausal >2 years prior to Day 1 of Period 1. A follicle stimulating hormone (FSH) concentration >40 miU/mL must be obtained and recorded for any postmenopausal females. Good general health as determined by the Principal Investigator's (PI) review of medical history, physical examination, vital sign measurements, electrocardiogram (ECG), and clinical laboratory measures. Body weight between 50 - 100 kg and body mass index (BMI) within 18 - 30 kg/m2. Non-tobacco users, who have not used nicotine or nicotine-containing products for at least 365 days prior to Day 1 of Period 1. Able to read, understand and sign the informed consent after the nature of the study has been explained. Negative urine screen for drugs of abuse and alcohol at screening and each check in. If female, negative finding on serum pregnancy test at screening and each check-in. Non alcohol or drug abuser - non alcohol abuse is defined as history of less than 4 drinks daily. A drink 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). Exclusion Criteria: Clinically significant abnormalities detected by medical history, physical examination, vial sign measurements, ECG, or clinical laboratory findings (as determined by the PI/designee) including a hemoglobin value <12 gm/dL at screening. If a subject's hemoglobin drops below 11.0 gm/dL during the study, the subject may be dropped from the study at the discretion of the PI. Any disease or condition, which could impact absorption, distribution, metabolism, or elimination of the study drugs (as determined by the PI/designee). Females who are pregnant or nursing. History of sensitivity reaction to guaifenesin. Receipt of an investigational drug within 30 days prior to Day 1 of Period 1. Abnormal diet (for whatever reason) during the 30 days prior to Day 1 of Period 1. Donation of blood or significant loss of blood within 56 days or plasma within 14 days prior to Day 1 of Period 1. Known or suspected use of illicit drugs. The use of any medication (with the exception of hormonal contraceptives for women of childbearing potential) for 14 days or 5 half-lives of the drug (whichever is longer) prior to Day 1 of Period 1. Test positive for Hepatitis B surface antigen, Hepatitis C antibodies, or HIV at Screening.

Ages Eligible for Study
-----------------
Minimum Age: 19 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mucinex® SE 600 mg (extended-release)<br>Single dose of Mucinex® SE extended-release 600 mg bi-layer tablet taken with 240 mL of water after an overnight fast | Drug: Mucinex® SE<br>* Single dose of Mucinex® SE extended-release 600 mg bi-layer tablet<br>* Other names: guaifenesin bi-layer tablet;|
| Active Comparator: Vicks Cough Syrup 200 mg<br>Vicks Cough Syrup for Chesty Coughs 200 mg every 4 hours taken with 240 mL of water after an overnight fast | Drug: Vicks Cough Syrup for Chesty Coughs<br>* Vicks Cough Syrup for Chesty Coughs 15 mL (200 mg guaifenesin q4h) immediate release (IR) syrup<br>* Other names: guaifenesin;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under Plasma Concentration-time Curve From Time 0 to the Last Measurable Concentration (AUC(0-t)) of Guaifenesin | Area under the plasma concentration versus time curve from time 0 to the time of the last measurable concentration, as calculated by the linear trapezoidal method. | 0 (pre-dose), 0.5, 0.75, 1, 1.5, 2, 3, 4, 4.5, 4.75, 5, 5.5, 6, 7, 8, 8.5, 8.75, 9, 9.5, 10, 11, 12, 14, 16 and 24 hours (post-dose) on Day 1 and 2 | 
| Area Under Plasma Concentration-time Curve From Time 0 to Infinity (AUC(0-inf)) of Guaifenesin | Area under the plasma concentration versus time curve from time 0 to infinity, calculated as AUC 0-t + C last/kel, where C last is the last measurable concentration and kel is the apparent first-order terminal elimination rate constant. | 0 (pre-dose), 0.5, 0.75, 1, 1.5, 2, 3, 4, 4.5, 4.75, 5, 5.5, 6, 7, 8, 8.5, 8.75, 9, 9.5, 10, 11, 12, 14, 16 and 24 hours (post-dose) on Day 1 and 2 | 
| Time to Maximum Observed Concentration (Tmax) of Guaifenesin | Pharmacokinetic Parameter (Tmax) Time of the maximum observed plasma concentration. | 0 (pre-dose), 0.5, 0.75, 1, 1.5, 2, 3, 4, 4.5, 4.75, 5, 5.5, 6, 7, 8, 8.5, 8.75, 9, 9.5, 10, 11, 12, 14, 16 and 24 hours (post-dose) on Day 1 and 2 | 
| Area Under Plasma Concentration Curve Ratio (AUCR) of Guaifenesin | Pharmacokinetic Parameter AUCR is the ratio of AUC(0-t) to AUC(0-inf). AUCR = AUC(0-t) / AUC(0-inf) | 0 (pre-dose), 0.5, 0.75, 1, 1.5, 2, 3, 4, 4.5, 4.75, 5, 5.5, 6, 7, 8, 8.5, 8.75, 9, 9.5, 10, 11, 12, 14, 16 and 24 hours (post-dose) on Day 1 and 2 | 
| Apparent Terminal Elimination Rate Constant (Kel) of Guaifenesin | Apparent first-order terminal elimination rate constant calculated from a semi-log plot of the plasma concentration versus time curve. The parameter was calculated by linear least-squares (LS) regression analysis using the maximum number of points (e.g. 3 or more non-zero plasma concentrations) in the terminal log-linear phase. | 0 (pre-dose), 0.5, 0.75, 1, 1.5, 2, 3, 4, 4.5, 4.75, 5, 5.5, 6, 7, 8, 8.5, 8.75, 9, 9.5, 10, 11, 12, 14, 16 and 24 hours (post-dose) on Day 1 and 2 | 
| Apparent Terminal Elimination Half-life (t1/2) of Guaifenesin | Apparent first-order terminal elimination half-life, calculated as ln(2)/kel. | 0 (pre-dose), 0.5, 0.75, 1, 1.5, 2, 3, 4, 4.5, 4.75, 5, 5.5, 6, 7, 8, 8.5, 8.75, 9, 9.5, 10, 11, 12, 14, 16 and 24 hours (post-dose) on Day 1 and 2 | 
| Maximum Observed Plasma Concentration (Cmax) of Guaifenesin | Pharmacokinetic Parameter (Cmax) Maximum observed plasma concentration. | 0 (pre-dose), 0.5, 0.75, 1, 1.5, 2, 3, 4, 4.5, 4.75, 5, 5.5, 6, 7, 8, 8.5, 8.75, 9, 9.5, 10, 11, 12, 14, 16 and 24 hours (post-dose) on Day 1 and 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Adverse Events (AE) of Participants | Mild = AE does not limit usual activities;subject may experience slight discomfort; Moderate = AE results in some limitation of usual activities; subject may experience significant discomfort; Severe = AE results in an inability to carry out usual activities; Probable = Most likely that the AE was caused by study drug; Possible = Reasonable suspicion that the AE was caused by the study drug; Unlikely = Slight but remote chance that the AE was caused by study drug but the balance of judgment is that it was most likely not due to the study drug. | Upto Day 2 |