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

• Sponsor: Reckitt Benckiser LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03633487
• Collaborator: (none)
• Enrollment: 24
• Arm: 1
• Actual Duration (Days): 4

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Healthy Subjects	Drug: Mucinex®	Phase 1

Detailed Description

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: 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.
• Actual Study Start Date: Oct 11, 2011
• Actual Primary Completion Date: Oct 15, 2011
• Actual Study Completion Date: Oct 15, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Mucinex® 1200 mg Mucinex® 1200 mg Extended-Release (ER) Bi-Layer tablet (single dose)	Drug: Mucinex®; Mucinex® 1200 mg ER Bi-Layer tablet; Other Names: guaifenesin

Outcome Measures

Primary Outcome Measures

1. Maximum Observed Plasma Concentration (Cmax) [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]

   Pharmacokinetic Parameters (Cmax) Maximum observed plasma concentration.

2. Time of the Maximum Observed Plasma Concentration (Tmax) [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]

   Pharmacokinetic Parameter (Tmax) Time of the maximum observed plasma concentration

3. Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) [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]

   Pharmacokinetic Parameter (AUC0-t) is Area under the plasma concentration versus time curve from time 0 to the time of the last measurable concentration

4. Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) [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]

   Pharmacokinetic Parameter (AUC0-inf) Area under the plasma concentration versus time curve from time 0 to infinity.

5. Percentage of AUC0-inf Extrapolated Area Under Plasma Concentration Curve Ratio (AUCR) of Guaifenesin [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]

   Pharmacokinetic Parameter (AUC%extrap) Percent of AUC0-inf extrapolated AUCR = 100 - (AUC0-t/ AUC0-inf) x 100

6. Apparent First-order Terminal Elimination Rate Constant (Kel) [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]

   Pharmacokinetic Parameter (Kel) Apparent first-order terminal elimination rate constant

7. Terminal Elimination Half Life (t1/2) [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]

   Pharmacokinetic Parameter (t1/2) is Apparent terminal elimination half-life.

8. Time at Which the Percentage of Subjects Achieved a Target Concentration of at Least 65 ng/mL (T65) [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]

   Pharmacokinetic Parameter (T65) is te time when guaifenesin plasma concentration achieved a target concentration of at least 65 ng/mL.

Secondary Outcome Measures

1. Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) [Up to Day 2]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. 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:

1. Intrauterine device (IUD) in place for at least 3 months prior to Day 1 through 30 days beyond study completion.

2. Barrier method (condom or diaphragm) with spermicide for at least 7 days prior to screening through 30 days beyond study completion.

3. 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.

1. Negative serum pregnancy test at Screening and at Check-in for all female subjects.

2. 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.

3. Body mass index (BMI) of 19 to 29 kg/m2, inclusive. (BMI = weight (kg)/[height (m2)]).

4. Non-tobacco users, who had not used nicotine or nicotine-containing products for at least 6 months prior to Day 1.

5. Negative finding on tests for Hepatitis B surface antigen (HBsAG), Hepatitis C virus (HCV) antibodies, human immunodeficiency virus (HIV).

6. Negative urine screen for drugs of abuse and alcohol at Screening and at Check-in.

7. Likely to be compliant with study requirements and complete the study, as determined by the Investigator.

8. 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:

1. 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.

2. Any disease or condition, which could impact absorption, distribution, metabolism, or elimination of the study drug (as determined by the PI/designee).

3. Females who were pregnant or nursing.

4. History of hypersensitivity reaction to guaifenesin.

5. Receipt of an investigational drug within 30 days prior to Day 1.

6. Abnormal diet (for whatever reason) during the 30 days prior to Day 1.

7. Donation of blood or significant loss of blood within 56 days prior to Day 1.

8. Donation of plasma within 14 days prior to Day 1.

9. Known or suspected use of illicit drugs (i.e., opiates, barbiturates, marijuana, et. al.).

10. 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).

11. 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.

12. Consumption of grapefruit, pummelo, Seville orange, or grapefruit juice within 14 days prior to dosing on Day 1 through study completion.

13. Consumption of alcohol within the 48 hours prior to dosing on Day 1.

14. 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.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Reckitt Benckiser LLC

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Reckitt Benckiser LLC
• ClinicalTrials.gov Identifier: NCT03633487
• Other Study ID Numbers: 2011-MUC-05
• First Posted: Aug 16, 2018
• Last Update Posted: Feb 28, 2019
• Last Verified: Feb 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Guaifenesin

Study Results

Participant Flow

Recruitment Details	This was a single-centre study.
Pre-assignment Detail	A total of 24 subjects entered the study; All 24 subjects were included single-period.

Arm/Group Title	Mucinex® 1200 mg
Arm/Group Description	Single dose Mucinex® 1200 mg Extended-Release (ER) Bi-Layer tablet by mouth.
Period Title: Overall Study
STARTED	24
COMPLETED	24
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Mucinex® 1200 mg
Arm/Group Description	Single dose Mucinex® 1200 mg Extended-Release (ER) Bi-Layer tablet by mouth.
Overall Participants	24
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	30.4 (10.95)
Sex: Female, Male (Count of Participants)
Female	7 29.2%
Male	17 70.8%
Race (participants) [Number]
Asian	1 4.2%
Black or African American	1 4.2%
White	22 91.7%
Ethnicity (participants) [Number]
Hispanic or Latino	2 8.3%
Not Hispanic or Latino	22 91.7%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	75.42 (12.711)
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	175.8 (9.65)
Body Mass Index (kg/m²) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m²]	24.220 (2.4480)

Outcome Measures

1. Primary Outcome

Title	Maximum Observed Plasma Concentration (Cmax)
Description	Pharmacokinetic Parameters (Cmax) Maximum observed plasma concentration.
Time Frame	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) population includes subjects with at least one PK sample. Available data from any subjects who vomited within 12 hours after dosing were to be included in the PK data sets.

Arm/Group Title	Mucinex® 1200 mg
Arm/Group Description	Single dose Mucinex® 1200 mg Extended-Release (ER) Bi-Layer tablet by mouth.
Measure Participants	24
Mean (Standard Deviation) [ng/mL]	1634 (769.95)

2. Primary Outcome

Title	Time of the Maximum Observed Plasma Concentration (Tmax)
Description	Pharmacokinetic Parameter (Tmax) Time of the maximum observed plasma concentration
Time Frame	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mucinex® 1200 mg
Arm/Group Description	Single dose Mucinex® 1200 mg Extended-Release (ER) Bi-Layer tablet by mouth.
Measure Participants	24
Mean (Standard Deviation) [hr]	0.9753 (0.61407)

3. Primary Outcome

Title	Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t)
Description	Pharmacokinetic Parameter (AUC0-t) is Area under the plasma concentration versus time curve from time 0 to the time of the last measurable concentration
Time Frame	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mucinex® 1200 mg
Arm/Group Description	Single dose Mucinex® 1200 mg Extended-Release (ER) Bi-Layer tablet by mouth.
Measure Participants	24
Mean (Standard Deviation) [ng*hr/mL]	6515.5 (2765.33)

4. Primary Outcome

Title	Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf)
Description	Pharmacokinetic Parameter (AUC0-inf) Area under the plasma concentration versus time curve from time 0 to infinity.
Time Frame	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mucinex® 1200 mg
Arm/Group Description	Single dose Mucinex® 1200 mg Extended-Release (ER) Bi-Layer tablet by mouth.
Measure Participants	23
Mean (Standard Deviation) [ng*hr/mL]	6733.5 (2831.57)

5. Primary Outcome

Title	Percentage of AUC0-inf Extrapolated Area Under Plasma Concentration Curve Ratio (AUCR) of Guaifenesin
Description	Pharmacokinetic Parameter (AUC%extrap) Percent of AUC0-inf extrapolated AUCR = 100 - (AUC0-t/ AUC0-inf) x 100
Time Frame	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mucinex® 1200 mg
Arm/Group Description	Single dose Mucinex® 1200 mg Extended-Release (ER) Bi-Layer tablet by mouth.
Measure Participants	23
Mean (Standard Deviation) [Percentage of AUC0-inf extrapolated AUCR]	1.950 (2.7458)

6. Primary Outcome

Title	Apparent First-order Terminal Elimination Rate Constant (Kel)
Description	Pharmacokinetic Parameter (Kel) Apparent first-order terminal elimination rate constant
Time Frame	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mucinex® 1200 mg
Arm/Group Description	Single dose Mucinex® 1200 mg Extended-Release (ER) Bi-Layer tablet by mouth.
Measure Participants	23
Mean (Standard Deviation) [1/hr]	0.2644 (0.16374)

7. Primary Outcome

Title	Terminal Elimination Half Life (t1/2)
Description	Pharmacokinetic Parameter (t1/2) is Apparent terminal elimination half-life.
Time Frame	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mucinex® 1200 mg
Arm/Group Description	Single dose Mucinex® 1200 mg Extended-Release (ER) Bi-Layer tablet by mouth.
Measure Participants	23
Mean (Standard Deviation) [hr]	3.374 (1.6383)

8. Primary Outcome

Title	Time at Which the Percentage of Subjects Achieved a Target Concentration of at Least 65 ng/mL (T65)
Description	Pharmacokinetic Parameter (T65) is te time when guaifenesin plasma concentration achieved a target concentration of at least 65 ng/mL.
Time Frame	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mucinex® 1200 mg
Arm/Group Description	Single dose Mucinex® 1200 mg Extended-Release (ER) Bi-Layer tablet by mouth.
Measure Participants	24
Mean (Standard Deviation) [hr]	0.1999 (0.10427)

9. Secondary Outcome

Title	Number of Subjects With Treatment-Emergent Adverse Events (TEAEs)
Description	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.
Time Frame	Up to Day 2

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mucinex® 1200 mg
Arm/Group Description	Single dose Mucinex® 1200 mg Extended-Release (ER) Bi-Layer tablet by mouth.
Measure Participants	24
TEAE by severity: Mild	3 12.5%
TEAE by severity: Moderate	0 0%
TEAE by severity: Severe	0 0%
Relationship to IMP - Definite	0 0%
Relationship to IMP - Probable	0 0%
Relationship to IMP - Possible	1 4.2%
Relationship to IMP - Unlikely	0 0%
Relationship to IMP - None	2 8.3%

Adverse Events

Time Frame	Up to Day 2
Arm/Group Title	Mucinex® 1200 mg
Arm/Group Description	Single dose Mucinex® 1200 mg Extended-Release (ER) Bi-Layer tablet by mouth.
All Cause Mortality
	Mucinex® 1200 mg
	Affected / at Risk (%)	# Events
Total	0/24 (0%)
Serious Adverse Events
	Mucinex® 1200 mg
	Affected / at Risk (%)	# Events
Total	0/24 (0%)
Other (Not Including Serious) Adverse Events
	Mucinex® 1200 mg
	Affected / at Risk (%)	# Events
Total	3/24 (12.5%)
General disorders
Catheter site swelling	1/24 (4.2%)	1
Oedema peripheral	1/24 (4.2%)	1
Nervous system disorders
Headache	1/24 (4.2%)	1
Presyncope	1/24 (4.2%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.