Study to Evaluate the Pharmacokinetics of Guaifenesin in Adults and Adolescents
Condition: Healthy Subjects
Intervention: Children's Mucinex® Grape Flavor; Children's Mucinex® Grape Flavor
Intervention description: 1 x 200 mg (10 mL) Children's Mucinex® Grape Flavor 100 mg Guaifenesin/5 mL immediate-release formulation; 1 x 400 mg (20 mL) Children's Mucinex® Grape Flavor 100 mg Guaifenesin/5 mL immediate-release formulation
Intervention MeSH terms: Phenylpropanolamine; Guaifenesin; Chlorpheniramine, phenylpropanolamine drug combination
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 12 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers

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.