Study to Evaluate the Pharmacokinetics of Guaifenesin in Adults and Adolescents

NCT03633448 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 2011-GGE-06
• Study Type: interventional
• Target: 24
• Locations: 0 countries
• Sites: N/A

Brief Summary

Evaluate the pharmacokinetics (PK), Safety and tolerability of guaifenesin (Mucinex®) in an immediate-release formulation when a single dose is administered in adolescents and in adults when compared to Children.

Conditions

Healthy Subjects

Outcome Measures

Primary Outcomes (7)

• 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), 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours

• 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), 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours

• Percent of AUC 0-inf Extrapolated (AUC%Extrapolated)

  Percent of AUC 0-inf extrapolated, calculated as (1 - AUC 0-t / AUC 0-inf) x 100.

  0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours

• Maximum Observed Plasma Concentration (Cmax) of Guaifenesin

  Pharmacokinetic Parameter (Cmax) Maximum observed plasma concentration.

  0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours

• Time to Maximum Observed Concentration (Tmax) of Guaifenesin

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

  0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours

• Apparent First-order Terminal Elimination Half-life (t½)

  Apparent first-order terminal elimination half-life, calculated as ln(2)/kel.

  0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours

• Apparent First-order Terminal Elimination Rate Constant (Kel)

  Apparent first-order terminal elimination rate constant calculated from a semilog 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., three or more non-zero plasma concentrations) in the terminal log-linear phase.

  0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours

Secondary Outcomes (1)

• Number of Adverse Events (AEs) of Participants

  Upto Day 1

Study Arms (2)

Mucinex® 1 x 200 mg (10 mL)

EXPERIMENTAL

1 x 200 mg (10 mL) Children's Mucinex® Grape Flavor 100 mg Guaifenesin/5 mL immediate-release formulation

Drug: Children's Mucinex® Grape Flavor

Mucinex® 1 x 400 mg (20 mL)

EXPERIMENTAL

1 x 400 mg (20 mL) Children's Mucinex® Grape Flavor 100 mg Guaifenesin/5 mL immediate-release formulation

Drug: Children's Mucinex® Grape Flavor

Interventions

Children's Mucinex® Grape Flavor DRUG

1 x 200 mg (10 mL) Children's Mucinex® Grape Flavor 100 mg Guaifenesin/5 mL immediate-release formulation

Mucinex® 1 x 200 mg (10 mL)

Eligibility Criteria

• Age: 12 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Males and females ≥ 12 and \< 18 years of age or ≥ 18 and \< 55 years of age.
• All females who were of childbearing potential had to be using one of the following acceptable birth control methods for the time periods specified:
• Intrauterine device (IUD) in place for at least 3 months prior to Day 1 of Period 1 through 30 days beyond study completion (Day 1 of Period 2).
• Barrier method (condom or diaphragm) with spermicide for at least 7 days prior to screening through 30 days beyond study completion (Day 1 of Period 2)
• Stable hormonal contraceptive (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 (Day 1 of Period 2).
• Note: Abstinence (sexually inactive) was not an acceptable form of contraception; however, abstinent female subjects could have been admitted to the study if they agreed, and had signed a statement to the effect, that upon becoming sexually active, would use a condom with spermicide from that time through 30 days beyond completion of the study (Day 1 of Period 2).
• Females ≥ 18 years of age of non-childbearing potential must have been surgically sterile (bilateral tubal ligation with surgery at least 6 months prior to Day 1 of Period 1 or hysterectomy and/or bilateral oophorectomy at least 3 months prior to Day 1 of Period 1) or post-menopausal ≥ 2 years prior to Day 1 of Period 1. A follicle stimulating hormone (FSH) level \> 40 miU/mL must have been obtained and in the record for any post-menopausal female experiencing their last menses \< 2 years prior to Day 1 of Period 1.
• Negative urine pregnancy test at Screening and each Check-in for all female subjects.
• Good general health as determined by the PI's review of medical history, physical examination, vital sign measurements (after 2 minutes resting in the seated position), and clinical laboratory measures.
• For subjects ≥ 18 and \< 55 years of age, body mass index (BMI) of 19 to 29 kg/m2, inclusive. (BMI = weight (kg)/\[height (m)\]2).
• Subjects ≥ 12 and \< 18 years of age had to be \> 5th percentile and less than the 95th percentile for weight and BMI of ≥ 18 to ≤ 28 kg/m2 based on age and gender.
• Non-tobacco users, who had not used nicotine or nicotine-containing products for at least 1 year prior to Day 1 of Period 1.
• Negative finding on tests for hepatitis B surface antigen (HBsAG), hepatitis C virus (HCV) antibodies, human immunodeficiency virus (HIV).
• Negative urine screen for drugs of abuse and alcohol at Screening and each Check-in.
• Likely to be compliant and complete the study, and if \< 18 years of age had parent(s) or legally authorized representative(s) likely to be compliant with study requirements, according to the PI.

You may not qualify if:

• Clinically significant abnormalities detected by medical history, physical examination, vital sign measurements, ECG findings, or clinical laboratory findings (as determined by the PI), including a hemoglobin value \< 12 gm/dL at Screening.
• Females who were pregnant or nursing.
• History of hypersensitivity reaction to guaifenesin or to EMLA® cream (eutectic mixture of local anesthetic) or its components (lidocaine + prilocaine as local anesthetic).
• 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 prior to Day 1 of Period 1.
• Donation of plasma within 14 days prior to Day 1 of Period 1.
• Known or suspected use of illicit drugs (i.e., opiates, barbiturates, marijuana, et. al.).
• The use of any medication on a chronic basis, with the exception of hormonal contraceptives for women of child-bearing potential. An appropriate drug free period for prescription or OTC drugs should have been provided to wash out any especially long half-life drugs.
• Alcoholism or medicinal product or drug abuse within the past two years or excessive alcohol consumption (more than 10 units per week) (one unit was 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.
• Consumption of grapefruit, pummelo, Seville orange or grapefruit juice within 14 days prior to dosing with study medication. Subjects had to be willing to abstain from consuming any of these products during the study.
• Related to persons involved directly or indirectly with the conduct of this study (i.e., PI, Sub-Investigators, Study Coordinators, other study personnel, employees of Reckitt Benckiser, and the families of each).
• Any significant change from Screening in medical history, medication history, alcohol consumption, or tobacco/nicotine use, in the opinion of the PI.
• Reports any known enzyme-inducer, enzyme-inhibitor, or reported chronic exposure to enzyme-inducers such as paint solvents or pesticides since Screening, unless approved by Reckitt Benckiser.
• Reports any other prescription or OTC drug or herbal remedy since Screening (except for low-dose contraceptives, multivitamins, and/or fluoride supplements) unless allowed by Reckitt Benckiser.

Sponsors & Collaborators

• Reckitt Benckiser LLC: lead

Results Point of Contact

• Title: Clinical Research Director, Clinical Research
• Organization: Reckitt Benckiser Inc.

clinicalrequests@rb.com

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2018
• First Posted: August 16, 2018
• Study Start: June 18, 2011
• Primary Completion: July 1, 2011
• Study Completion: July 1, 2011
• Last Updated: June 17, 2019
• Results First Posted: June 17, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share