Mucinex® ER 600 mg Bi-Layer Tablet Fed and Fasted

A Phase I, Open-label, Single-dose, Randomized, 2-way Cross-over Study Designed to Examine the Relative Bioavailability of Guaifenesin When a Mucinex Extended Release 600 mg Bi-layer Tablet is Taken Under Fasted Compared to Fed Conditions in Normal Healthy Volunteers

Determine and compare the plasma concentrations of Mucinex® Extended Release (ER) 600 mg bi-layer tablet in normal healthy volunteers in fed and fasting conditions

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: Mucinex®

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Informed consent was obtained (i.e. be informed of the nature of the study and given written consent prior to any study procedure). Able to read, understand, and sign the informed consent, after the nature of the study had been explained.
2. Age: 18 to 55 years of age, inclusive.
3. Sex: male or female.
4. Status: Healthy subjects.
5. BMI: ≥18.0 and ≤28.0 kg/m2.
6. No clinically significant findings in vital signs measurements at screening.
7. No clinically significant abnormal laboratory values at screening.
8. No clinically significant findings from a 12-lead electrocardiogram (ECG) at screening.
9. Had no significant diseases or clinically relevant medical condition in the opinion of the Investigator

10. Males who participated in this study were 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
    • used (or their partner used, 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 participated in this study were:

    • 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.
11. Had no clinically significant findings from a physical examination.

Exclusion Criteria:

1. Employee of Pharma Medica Research Inc. (PMRI) or Reckitt Benckiser.
2. Partner or first-degree relative of any Investigator at PMRI.
3. Known history or presence of any clinically significant medical condition.
4. Known or suspected carcinoma.
5. Presence of hepatic or renal dysfunction.
6. Presence of clinically significant gastrointestinal disease or history of malabsorption within the year preceding the study.
7. Known history or presence of galactose or fructose intolerance, sucrase-isomaltase insufficiency, Lapp lactase insufficiency, galactosemia, or glucose-galactose malabsorption syndrome.
8. Presence of a medical condition requiring regular medication (prescription and/or over-the-counter) with systemic absorption.

9. History of drug or alcohol or medicinal product addiction requiring treatment within the two years preceding the study 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.

10. Positive test result for serum Human Chorionic Gonadotropin (hCG) consistent with pregnancy (females only), HIV, Hepatitis B surface antigen or Hepatitis C antibody.
11. Positive test result for urine drugs of abuse (cannabinoids, opiates, amphetamines, cocaine, phencyclidine, tricyclic antidepressants, barbiturates, methadone and benzodiazepines) or urine cotinine.
12. Difficulty fasting or consuming standard meals.
13. Females who were lactating.
14. Did not tolerate venipuncture.
15. Use of tobacco or nicotine-containing products within 12 months prior to drug administration.
16. On a special diet within 30 days prior to drug administration (e.g., liquid, protein, raw food diet).

17. 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
18. Females who had started taking hormonal contraceptives or had changed their method or brand of hormonal birth control within 3 months prior to drug administration.
19. Had a tattoo or body piercing within 30 days prior to drug administration.
20. Use of drugs of the monoamine oxidase inhibitor (MAOI) class within 30 days prior to drug administration.
21. Known history or presence of hypersensitivity, intolerance or idiosyncratic reaction to guaifenesin or any other drug substances with similar activity.
22. Previously enrolled in this study.
23. Participated in another clinical trial or received an investigational product within 30 days prior to drug administration.
24. Unable in the opinion of the Investigator to comply fully with the study requirements.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment A: Mucinex® 600 mg (fast); Mucinex® 600 mg ER bi-layer tablet by mouth after 10 hours fasting and subject will fast at least 4 hours post-dose	Drug: Mucinex®; Mucinex® 600 mg ER bi-layer tablets; Other Names: guaifenesin
Experimental: Treatment B: Mucinex® 600 mg (fed); Mucinex® 600 mg ER bi-layer tablet by mouth in fed condition. After an overnight fast of at least 10 hours, subjects will consume a high fat, high calorie breakfast starting 30 minutes prior to drug administration	Drug: Mucinex®; Mucinex® 600 mg ER bi-layer tablets; Other Names: guaifenesin

What is the study measuring?

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, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 20, and 24 hours (Period 1 and 2)
Area Under Plasma Concentration-time Curve From Time 0 to the Last Measurable Plasma 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, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 20, and 24 hours (Period 1 and 2)

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, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 20, and 24 hours (Period 1 and 2)
Area Under Plasma Concentration-time Curve From Time 0 to Infinity (AUCinf) of Guaifenesin	The area under the analyte concentration versus time curve from time zero to infinity. 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, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 20, and 24 hours (Period 1 and 2)
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, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 20, and 24 hours (Period 1 and 2)
Terminal Elimination Half-life (T½) of Guaifenesin	Terminal elimination half-life, calculated from the equation: thalf = 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, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 20, and 24 hours (Period 1 and 2)
Relative Bioavailability (RF) of Guaifenesin	Relative bioavailability for each formulation will be defined as: (AUC0-inf Fasting ÷ AUC0-inf Fed) x (Fed dose ÷ Fasting dose)	0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 20, and 24 hours (Period 1 and 2)
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	Up to period 2 (8.3 days/200 hours)

Collaborators and Investigators

• Sponsor: Reckitt Benckiser LLC

Study record dates

Study Major Dates

• Study Start (Actual): May 29, 2013
• Primary Completion (Actual): August 7, 2013
• Study Completion (Actual): August 7, 2013

Study Registration Dates

• First Submitted: August 20, 2018
• First Submitted That Met QC Criteria: August 24, 2018
• First Posted (Actual): August 28, 2018

Study Record Updates

• Last Update Posted (Actual): March 27, 2019
• Last Update Submitted That Met QC Criteria: March 18, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory System Agents; Expectorants; Guaifenesin
• Other Study ID Numbers: 2013-MUC-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No