Mucinex® ER 600 mg Bi-layer Tablet Versus Guaifenesin Immediate Release (IR) 200 mg q4h

Study Overview
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Brief Summary
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Demonstrate bioequivalence of guaifenesin in Mucinex® extended release (ER) 600 mg tablet in normal healthy volunteers compared to the immediate release guaifenesin 200 mg tablet reference product marketed

Official Title
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A Phase I, Open-label, Single Dose, Randomized, 2-way Crossover Bioequivalence Study Comparing Mucinex® Extended Release 600 mg Bi-Layer Tablet to a Reference Immediate Release Guaifenesin Tablet (Taken as 200 mg Every 4 Hours [q4h] x 3 Doses) in Normal Healthy Volunteers

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: Informed consent has been obtained (i.e. be informed of the nature of the study and give written consent prior to any study procedure). Able to read, understand, and sign the informed consent, after the nature of the study has been explained. Age: 18 to 55 years of age, inclusive. Sex: Male or female. Status: Healthy subjects. BMI: ≥18.0 and ≤28.0 kg/m2. No clinically significant findings in vital signs measurements at screening. No clinically significant abnormal laboratory values at screening. No clinically significant findings from a 12-lead electrocardiogram (ECG) at screening. Have no significant diseases or clinically relevant medical condition in the opinion of the investigator. Males who participate in this study are willing to: remain abstinent [not engage in sexual intercourse] from the start of drug administration until 90 days after the end of the study or use (or their partner will use, as applicable) two effective methods of birth control [condom, diaphragm, cervical cap, vaginal sponge, spermicide, IUD, tubal ligation, vasectomy, or hormonal contraceptives] from the start of drug administration until 90 days after the end of the study. Females who participate in this study are: unable to have children (e.g., post-menopausal, hysterectomy); willing to remain abstinent [not engage in sexual intercourse] from 21 days prior to drug administration until 30 days after the end of the study; or willing to use two effective methods of birth control [condom, diaphragm, cervical cap, vaginal sponge, spermicide, non-hormonal Intrauterine Device (IUD) (in place for 3 months), tubal ligation, partner has vasectomy, hormonal contraceptives for 3 months prior to drug administration] from 30 days prior to drug administration until 30 days after the end of the study. Have no clinically significant findings from a physical examination. Exclusion Criteria: Subjects to whom any of the following conditions apply must be excluded: Employee of Pharma Medica Research Inc. (PMRI) or Reckitt Benckiser. Partner or first-degree relative of any Investigator at PMRI. Known history or presence of any clinically significant medical condition. Known or suspected carcinoma. Presence of hepatic or renal dysfunction. Presence of clinically significant gastrointestinal disease or history of malabsorption within the last year. Known history or presence of galactose or fructose intolerance, sucrase-isomaltase insufficiency, Lapp lactase insufficiency, galactosemia, or glucose-galactose malabsorption syndrome. Presence of a medical condition requiring regular medication (prescription and/or over-the-counter) with systemic absorption. History of drug or alcohol or medicinal product addiction requiring treatment within the past two years or excessive alcohol consumption (more than 10 units per week) Note: one unit is defined as 5 ounces of wine, 12 ounces of beer, or 1.5 ounces of spirits Positive test result for serum Human Chorionic Gonadotropin (hCG) consistent with pregnancy (females only), HIV, Hepatitis B surface antigen or Hepatitis C antibody. Positive test result for urine drugs of abuse (cannabinoids, opiates, amphetamines, cocaine, phencyclidine, tricyclic antidepressants, barbiturates, methadone and benzodiazepines) or urine cotinine. Difficulty fasting or consuming standard meals. Females who are lactating. Does not tolerate venipuncture. Use of tobacco or nicotine-containing products within 12 months prior to drug administration. On a special diet within 30 days prior to drug administration (e.g., liquid, protein, raw, food diet). Donation or loss of whole blood (including clinical trials): ≥50 ml and ≤499 ml within 30 days prior to drug administration ≥500 ml within 56 days prior to drug administration. Females who have started taking hormonal contraceptives or have changed their method or brand of hormonal birth control within 3 months prior to drug administration. Have had a tattoo or body piercing within 30 days prior to drug administration. Use of drugs of the monoamine oxidase inhibitor (MAOI) class within 30 days prior to drug administration. Known history or presence of hypersensitivity, intolerance or idiosyncratic reaction to guaifenesin or any other drug substances with similar activity. Previously enrolled in this study. Participated in another clinical trial or received an investigational product within 30 days prior to drug administration. Unable in the opinion of the Investigator to comply fully with the study requirements.

Ages Eligible for Study
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Minimum Age: 18 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
Interventional Model Description: 2-Way Crossover
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A: Mucinex® ER 600 mg<br>Mucinex® ER 600 mg bi-layer single dose tablet by mouth under fasting condition. | Drug: Mucinex®<br>* Mucinex® 600 mg single dose ER bi-layer tablet<br>* Other names: guaifenesin;|
| Active Comparator: Treatment B: Guaifenesin 200 mg<br>Guaifenesin 200 mg immediate release (IR) tablet thrice (at 0, 4, and 8 hours) by mouth under fasting condition. | Drug: Mucinex®<br>* Mucinex® 600 mg single dose 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) of Guaifenesin | Maximum measured analyte concentration over the sampling period. | 0 (pre-dose) ,0.25,0.5, 0.75, 1,1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 4.75, 5, 5.5, 6, 7, 8, 8.5, 8.75, 9, 9.5, 10, 11, 12, 14, 16, 20 and 24 hours | 
| Area Under the Plasma Concentration-time Curve From Time 0 to the Last Measurable Concentration (AUCt) of Guaifenesin | The area under the analyte concentration versus time curve, from time zero (0) to the time of the last measurable analyte concentration (t), as calculated by the linear trapezoidal method. | 0 (pre-dose) ,0.25,0.5, 0.75, 1,1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 4.75, 5, 5.5, 6, 7, 8, 8.5, 8.75, 9, 9.5, 10, 11, 12, 14, 16, 20 and 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Maximum Observed Plasma Concentration (Tmax) of Guaifenesin | Time of the maximum measured analyte concentration over the sampling period. | 0 (pre-dose) ,0.25,0.5, 0.75, 1,1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 4.75, 5, 5.5, 6, 7, 8, 8.5, 8.75, 9, 9.5, 10, 11, 12, 14, 16, 20 and 24 hours | 
| Area Under Plasma Concentration-time Curve From Time 0 to Infinity (AUCinf) of Guaifenesin | AUCinf = AUCt + Cp/Kel, where Cp is the predicted analyte concentration at the time of the last measurable analyte concentration. | 0 (pre-dose) ,0.25,0.5, 0.75, 1,1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 4.75, 5, 5.5, 6, 7, 8, 8.5, 8.75, 9, 9.5, 10, 11, 12, 14, 16, 20 and 24 hours | 
| Terminal Elimination Rate Constant (Kel) of Guaifenesin | Elimination rate constant calculated from the slope of the terminal portion of the plasma profile calculated by least squares regression of log (concentration) versus time | 0 (pre-dose) ,0.25,0.5, 0.75, 1,1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 4.75, 5, 5.5, 6, 7, 8, 8.5, 8.75, 9, 9.5, 10, 11, 12, 14, 16, 20 and 24 hours | 
| Terminal Elimination Half-life (T½) of Guaifenesin | Terminal elimination half-life, calculated from the equation: T½ = In(2)/Kel. | 0 (pre-dose) ,0.25,0.5, 0.75, 1,1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 4.75, 5, 5.5, 6, 7, 8, 8.5, 8.75, 9, 9.5, 10, 11, 12, 14, 16, 20 and 24 hours | 
| Relative Bioavailability (RF) of Guaifenesin | RF is measured by (AUCinf ER / AUCinf IR) x (ER dose / IR dose) | 0 (pre-dose) ,0.25,0.5, 0.75, 1,1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 4.75, 5, 5.5, 6, 7, 8, 8.5, 8.75, 9, 9.5, 10, 11, 12, 14, 16, 20 and 24 hours | 
| Number of Adverse Events(AEs) Experienced by Participants | Intensity determination 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; subject may experience intolerable discomfort or pain Unassessable/Unclassifiable=Insufficient information to be able to make an assessment Conditional/Unclassified=Insufficient information to make an assessment at present (causality is conditional on additional information) Unrelated=No possibility that the AE was caused by 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 Possible=Reasonable suspicion that the AE was caused by the study drug Probable=Most likely that the AE was caused by study drug Certain=The AE was definitely caused by study drug Investigational Medicinal Product (IMP) | Up to period 2 (8.3 days/200 hours) |