Clinical trial NCT03643575: Study to Characterize the Pharmacokinetics of 3 Marketed Products Containing 200 mg Guaifenesin in Healthy Volunteers.
Official title: A Phase I, Open- Label, Randomized, Multiple-dose, 3-way Crossover Relative Bioavailability Study to Characterize the Pharmacokinetics of the 3 Marketed Products Containing 200 mg Guaifenesin Under Fasted Conditions in Normal Healthy Subjects.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Lead sponsor: Reckitt Benckiser LLC
Sponsor class: INDUSTRY
First posted: 2018-08-23
Enrollment: 30
Sex: ALL
Minimum age (years): 19
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: Characterize the relative pharmacokinetics (PK) of 3 marketed products containing guaifenesin


Eligibility criteria: Inclusion Criteria:

1. Males and/or females between the ages of 19 and 55 years, inclusive.
2. Females of childbearing potential must be using one of the following acceptable birth control methods:

   1. Intra-uterine device in place for at least 3 months prior to Day 1 of Period 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 (e.g., 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;

   Abstinence is not an acceptable form of contraception; however, abstinent female subjects may be admitted to the study if they agree, and have signed a statement to the effect, that upon becoming sexually active, will use a condom with spermicide from screening through 30 days beyond completion of the study.
3. Females of non-childbearing potential should be surgically sterile (bilateral tubal ligation with surgery at least 6 months prior to study or hysterectomy and/or bilateral oophorectomy at least 3 months prior to Day 1 of Period 1) or postmenopausal \>2 years prior to Day 1 of Period 1. A follicle stimulating hormone (FSH) concentration \>40 miU/mL must be obtained and recorded for any postmenopausal females.
4. Good general health as determined by the Principal Investigator's (PI) review of medical history, physical examination, vital sign measurements, electrocardiogram (ECG), and clinical laboratory measures.
5. Within 15% of ideal body weight (Table of 'Desirable Weights of Adults' Metropolitan Life Insurance Company, 1983).
6. Non-tobacco users, who have not used nicotine or nicotine-containing products for at least 365 days prior to Day 1 of Period 1.
7. Able to read, understand and sign the informed consent after the nature of the study has been explained.
8. Negative urine screen for drugs of abuse and alcohol at screening and each check in.
9. If female, negative finding on serum pregnancy test at screening and each check-in.

Exclusion Criteria:

1. Clinically significant abnormalities detected by medical history, physical examination, vial sign measurements, ECG, or clinical laboratory findings (as determined by the PI/designee) including a hemoglobin value \<12 g/dL at screening. If a subject's hemoglobin drops below 11.0 g/dL during the study, the subject may be dropped from the study at the discretion of the PI.
2. Any disease or condition, which could impact absorption, distribution, metabolism, or elimination of the study drugs (as determined by the PI/designee).
3. 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 is 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.
4. Females who are pregnant or nursing.
5. History of sensitivity reaction to guaifenesin.
6. History of or intolerance to lactose.
7. Receipt of an investigational drug within 30 days prior to Day 1 of Period 1.
8. Abnormal diet (for whatever reason) during the 30 days prior to Day 1 of Period 1.
9. Donation of blood or significant loss of blood within 56 days or plasma within 14 days prior to Day 1 of Period 1.
10. Known or suspected use of illicit drugs.
11. The use of any medication (with the exception of hormonal contraceptives for women of childbearing potential) for 14 days or 5 half-lives of the drug (whichever is longer) prior to Day 1 of Period 1, if not approved by Investigator.
12. Test positive for Hepatitis B surface antigen, Hepatitis C antibodies, or HIV at Screening.
13. Subjects who have participated in previous Reckitt Benckiser studies.

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of Guaifenesin
timeFrame: 0 (Pre-dose), 0.5, 0.75, 1, 1.5, 2, 3, 4, 4.5, 4.75, 5, 5.5, 6, 7, 8, 8.5, 8.75, 9, 9.5, 10, 11, 12, 14 and 16 hours
measure: Maximum Measured Plasma Concentration at Steady State (Cmax,ss) of Guaifenesin Following the Third Dose
timeFrame: 0 (Pre-dose), 0.5, 0.75, 1, 1.5, 2, 3, 4, 4.5, 4.75, 5, 5.5, 6, 7, 8, 8.5, 8.75, 9, 9.5, 10, 11, 12, 14 and 16 hours
measure: Observed Plasma Concentration at the End of Dosing Interval at Steady State (Cmin,ss) of Guaifenesin Following the Third Dose
timeFrame: 0 (Pre-dose), 0.5, 0.75, 1, 1.5, 2, 3, 4, 4.5, 4.75, 5, 5.5, 6, 7, 8, 8.5, 8.75, 9, 9.5, 10, 11, 12, 14 and 16 hours
measure: Average Plasma Concentration (Cav) of Guaifenesin Following the Third Dose
timeFrame: 8, 8.5, 8.75, 9, 9.5, 10, 11 and 12 hours
measure: Time to Maximum Observed Plasma Concentration (Tmax) of Guaifenesin
timeFrame: 0 (Pre-dose), 0.5, 0.75, 1, 1.5, 2, 3, 4, 4.5, 4.75, 5, 5.5, 6, 7, 8, 8.5, 8.75, 9, 9.5, 10, 11, 12, 14 and 16 hours
measure: Time to Maximum Observed Plasma Concentration at Steady State (Tmax,ss) of Guaifenesin Following the Third Dose
timeFrame: 0 (Pre-dose), 0.5, 0.75, 1, 1.5, 2, 3, 4, 4.5, 4.75, 5, 5.5, 6, 7, 8, 8.5, 8.75, 9, 9.5, 10, 11, 12, 14 and 16 hours
measure: Apparent First-order Terminal Elimination Half-life (T1/2) of Guaifenesin
timeFrame: 0 (Pre-dose), 0.5, 0.75, 1, 1.5, 2, 3, 4, 4.5, 4.75, 5, 5.5, 6, 7, 8, 8.5, 8.75, 9, 9.5, 10, 11, 12, 14 and 16 hours
measure: Apparent First-order Terminal Elimination Rate Constant (Kel) of Guaifenesin
timeFrame: 0 (Pre-dose), 0.5, 0.75, 1, 1.5, 2, 3, 4, 4.5, 4.75, 5, 5.5, 6, 7, 8, 8.5, 8.75, 9, 9.5, 10, 11, 12, 14 and 16 hours
measure: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Measurable Concentration [AUC(0-t)] of Guaifenesin
timeFrame: 0 (Pre-dose), 0.5, 0.75, 1, 1.5, 2, 3, 4, 4.5, 4.75, 5, 5.5, 6, 7, 8, 8.5, 8.75, 9, 9.5, 10, 11, 12, 14 and 16 hours
measure: Area Under Plasma Concentration Versus Time Curve From Time 0 to Infinity [AUC(0-inf)] of Guaifenesin
timeFrame: 0 (Pre-dose), 0.5, 0.75, 1, 1.5, 2, 3, 4, 4.5, 4.75, 5, 5.5, 6, 7, 8, 8.5, 8.75, 9, 9.5, 10, 11, 12, 14 and 16 hours
measure: Area Under Plasma Concentration Versus Time Curve From 0 to 4 Hours [AUC(0-4)] of Guaifenesin
timeFrame: 0 (Pre-dose), 0.5, 0.75, 1, 1.5, 2, 3 and 4 hours
measure: Area Under Plasma Concentration Versus Time Curve From Time 8 to 12 Hours [AUC(8-12)] of Guaifenesin
timeFrame: 8, 8.5, 8.75, 9, 9.5, 10, 11 and 12 hours
measure: Area Under Plasma Concentration Curve Ratio (AUCR) of Guaifenesin
timeFrame: 0 (Pre-dose), 0.5, 0.75, 1, 1.5, 2, 3, 4, 4.5, 4.75, 5, 5.5, 6, 7, 8, 8.5, 8.75, 9, 9.5, 10, 11, 12, 14 and 16 hours
measure: Accumulation Index (AI) of Guaifenesin
timeFrame: 0 (Pre-dose), 0.5, 0.75, 1, 1.5, 2, 3, 4 hours and 8, 8.5, 8.75, 9, 9.5, 10, 11, 12 hours
measure: Degree of Fluctuation (DF) of Guaifenesin
timeFrame: 0 (Pre-dose), 0.5, 0.75, 1, 1.5, 2, 3, 4, 4.5, 4.75, 5, 5.5, 6, 7, 8, 8.5, 8.75, 9, 9.5, 10, 11, 12, 14 and 16 hours
measure: Peak Plasma Concentrations at Steady State (Swing) of Guaifenesin
timeFrame: 0 (Pre-dose), 0.5, 0.75, 1, 1.5, 2, 3, 4, 4.5, 4.75, 5, 5.5, 6, 7, 8, 8.5, 8.75, 9, 9.5, 10, 11, 12, 14 and 16 hours
Secondary outcomes:
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Up to day 2 (Period 3)
Other outcomes:
Locations:
Study officials:
References: