Clinical trial NCT03633448: Study to Evaluate the Pharmacokinetics of Guaifenesin in Adults and Adolescents
Official title: An Open-label, Single-dose, Randomized, Two-way Crossover Study to Evaluate the Pharmacokinetics of Guaifenesin in Adults and Adolescents at Immediate-release Doses of 200 mg and 400 mg.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Lead sponsor: Reckitt Benckiser LLC
Sponsor class: INDUSTRY
First posted: 2018-08-16
Enrollment: 24
Sex: ALL
Minimum age (years): 12
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: Inclusion Criteria:

1. 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:
   1. 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).
   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)
   3. 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.
2. Negative urine pregnancy test at Screening and each Check-in for all female subjects.
3. 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.
4. 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).
5. 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.
6. Non-tobacco users, who had not used nicotine or nicotine-containing products for at least 1 year prior to Day 1 of Period 1.
7. Negative finding on tests for hepatitis B surface antigen (HBsAG), hepatitis C virus (HCV) antibodies, human immunodeficiency virus (HIV).
8. Negative urine screen for drugs of abuse and alcohol at Screening and each Check-in.
9. 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.
10. 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 IRB-approved informed consent/assent form for subjects to participate in the study. Additionally, for subjects \< 18 years of age, a parent(s) or legally authorized representative(s), had to read, sign, and date an IRB-approved informed consent/assent form for subjects \< 18 years of age to participate in the study.
11. Subjects \< 18 years of age must have met the following at-risk requirements:

    1. Frequency - a history of frequent upper respiratory infections (URIs) defined as \> 4 infections per year for adolescents aged ≥ 12 to \< 18 yrs, AND;
    2. Exposure - Another family member in the home who was ill with URI/common cold or a child in the family who was attending preschool or school with ≥ 6 children in the group, AND;
    3. Crowding - Greater than (\>) 4 persons living in the home or \> 3 persons sleeping in one bedroom.

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), including a hemoglobin value \< 12 gm/dL at Screening.
2. Females who were pregnant or nursing.
3. History of hypersensitivity reaction to guaifenesin or to EMLA® cream (eutectic mixture of local anesthetic) or its components (lidocaine + prilocaine as local anesthetic).
4. Receipt of an investigational drug within 30 days prior to Day 1 of Period 1.
5. Abnormal diet (for whatever reason) during the 30 days prior to Day 1 of Period 1.
6. Donation of blood or significant loss of blood within 56 days prior to Day 1 of Period 1.
7. Donation of plasma within 14 days prior to Day 1 of Period 1.
8. Known or suspected use of illicit drugs (i.e., opiates, barbiturates, marijuana, et. al.).
9. 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.
10. 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.
11. 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.
12. 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).

Subject Exclusion Criteria at Check-In

1. Any significant change from Screening in medical history, medication history, alcohol consumption, or tobacco/nicotine use, in the opinion of the PI.
2. 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.
3. 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.
4. If female, a positive urine pregnancy test.
5. Had an acute illness since Screening, unless allowed by Reckitt Benckiser.

Primary outcomes:
measure: Area Under Plasma Concentration-time Curve From Time 0 to the Last Measurable Concentration (AUC(0-t)) of Guaifenesin
timeFrame: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours
measure: Area Under Plasma Concentration-time Curve From Time 0 to Infinity (AUC(0-inf)) of Guaifenesin
timeFrame: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours
measure: Percent of AUC 0-inf Extrapolated (AUC%Extrapolated)
timeFrame: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours
measure: Maximum Observed Plasma Concentration (Cmax) of Guaifenesin
timeFrame: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours
measure: Time to Maximum Observed Concentration (Tmax) of Guaifenesin
timeFrame: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours
measure: Apparent First-order Terminal Elimination Half-life (t½)
timeFrame: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours
measure: Apparent First-order Terminal Elimination Rate Constant (Kel)
timeFrame: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours
Secondary outcomes:
measure: Number of Adverse Events (AEs) of Participants
timeFrame: Upto Day 1
Other outcomes:
Locations:
Study officials:
References: