Study to Characterize the Pharmacokinetics of 3 Marketed Products Containing 200 mg Guaifenesin in Healthy Volunteers.

Study Overview
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Brief Summary
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Characterize the relative pharmacokinetics (PK) of 3 marketed products containing guaifenesin

Official Title
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A Phase I, Open- Label, Randomized, Multiple-dose, 3-way Crossover Relative Bioavailability Study to Characterize the Pharmacokinetics of the 3 Marketed Products Containing 200 mg Guaifenesin Under Fasted Conditions in Normal Healthy Subjects.

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: Vicks Cough Syrup for Chesty Coughs
* Drug: Robitussin Extra Strength Chest Congestion
* Drug: Organ-I- NR tablet


Participation Criteria
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Eligibility Criteria
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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. Within 15% of ideal body weight (Table of 'Desirable Weights of Adults' Metropolitan Life Insurance Company, 1983). 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. 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 g/dL at screening. If a subject's hemoglobin drops below 11.0 g/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). 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 is 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. Females who are pregnant or nursing. History of sensitivity reaction to guaifenesin. History of or intolerance to lactose. 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, if not approved by Investigator. Test positive for Hepatitis B surface antigen, Hepatitis C antibodies, or HIV at Screening. Subjects who have participated in previous Reckitt Benckiser studies.

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A: Vicks Cough Syrup for Chesty Coughs<br>Vicks Cough immediate-release (IR) syrup 15 mL (containing 200 mg guaifenesin) every 4 hours x 3 doses 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 (containing 200 mg guaifenesin) IR syrup with 240 mL of water<br>|
| Experimental: Treatment B: Robitussin Extra Strength Chest Congestion<br>Robitussin Extra Strength Chest Congestion 5 ml (containing 200 mg guaifenesin) every 4 hours x 3 doses with 240 mL of water after an overnight fast | Drug: Robitussin Extra Strength Chest Congestion<br>* Robitussin Extra Strength Chest Congestion 5 mL (containing 200 mg guaifenesin) IR syrup with 240 mL of water<br>|
| Experimental: Treatment C: Organ-I- NR tablet<br>Organ-I- NR 200 mg guaifenesin tablet every 4 hours x 3 doses with 240 mL of water after an overnight fast | Drug: Organ-I- NR tablet<br>* Organ-I- NR tablet (containing 200 mg guaifenesin) with 240 mL of water<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) of Guaifenesin | Pharmacokinetic Parameter Cmax is 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 and 16 hours | 
| Maximum Measured Plasma Concentration at Steady State (Cmax,ss) of Guaifenesin Following the Third Dose | Pharmacokinetic Parameter Cmax,ss is the Maximum observed plasma concentration following the third dose. | 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 and 16 hours | 
| Observed Plasma Concentration at the End of Dosing Interval at Steady State (Cmin,ss) of Guaifenesin Following the Third Dose | Observed plasma concentration at the end of the dosing interval following the third dose (that is, 4 hours following the third dose). | 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 and 16 hours | 
| Average Plasma Concentration (Cav) of Guaifenesin Following the Third Dose | Average plasma concentration (Cav) following the third dose, calculated as AUC(8-12) divided by the dosing interval, 4. Cav is calculated as AUC(8-12) / dosing interval, 4 | 8, 8.5, 8.75, 9, 9.5, 10, 11 and 12 hours | 
| Time to Maximum Observed Plasma Concentration (Tmax) of Guaifenesin | Pharmacokinetic Parameter Tmax is the 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 and 16 hours | 
| Time to Maximum Observed Plasma Concentration at Steady State (Tmax,ss) of Guaifenesin Following the Third Dose | Pharmacokinetic Parameter Tmax, ss is the time of the maximum observed plasma concentration following the third dose. | 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 and 16 hours | 
| Apparent First-order Terminal Elimination Half-life (T1/2) of Guaifenesin | T1/2 is the 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 and 16 hours | 
| Apparent First-order Terminal Elimination Rate Constant (Kel) of Guaifenesin | Kel is the 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 and 16 hours | 
| Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Measurable Concentration [AUC(0-t)] of Guaifenesin | AUC(0-t) is the 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 and 16 hours | 
| Area Under Plasma Concentration Versus Time Curve From Time 0 to Infinity [AUC(0-inf)] of Guaifenesin | AUC(0-inf) is the area under the plasma concentration versus time curve from time 0 to infinity, calculated as AUC(0-t) + Ct/Kel, where Ct was 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 and 16 hours | 
| Area Under Plasma Concentration Versus Time Curve From 0 to 4 Hours [AUC(0-4)] of Guaifenesin | AUC(0-4) is the area under the plasma concentration versus time curve from time 0 to 4 hours post dose (relative to first dose), as calculated by the linear trapezoidal method. | 0 (Pre-dose), 0.5, 0.75, 1, 1.5, 2, 3 and 4 hours | 
| Area Under Plasma Concentration Versus Time Curve From Time 8 to 12 Hours [AUC(8-12)] of Guaifenesin | AUC(8-12) is the area under the plasma concentration versus time curve from time 8 to 12 hours postdose (relative to first dose), as calculated by the linear trapezoidal method. | 8, 8.5, 8.75, 9, 9.5, 10, 11 and 12 hours | 
| 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 and 16 hours | 
| Accumulation Index (AI) of Guaifenesin | AI is the accumulation index, calculated as AUC(8-12) / AUC(0-4). | 0 (Pre-dose), 0.5, 0.75, 1, 1.5, 2, 3, 4 hours and 8, 8.5, 8.75, 9, 9.5, 10, 11, 12 hours | 
| Degree of Fluctuation (DF) of Guaifenesin | DF is the Degree of Fluctuation Index, calculated as (Cmax,ss - Cmin,ss) / Cav. | 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 and 16 hours | 
| Peak Plasma Concentrations at Steady State (Swing) of Guaifenesin | Pharmacokinetic Parameter Swing is Calculated as (Cmax,ss - Cmin,ss) / Cmin,ss. | 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 and 16 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) | 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 (Period 3) |