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Study to Characterize the Pharmacokinetics of 3 Marketed Products Containing 200 mg Guaifenesin in Healthy Volunteers.

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ClinicalTrials.gov Identifier: NCT03643575
Recruitment Status : Completed
First Posted : August 23, 2018
Results First Posted : February 22, 2019
Last Update Posted : March 27, 2019
Sponsor:
Information provided by (Responsible Party):
Reckitt Benckiser LLC ( Reckitt Benckiser Inc. )

Tracking Information
First Submitted Date  ICMJE August 21, 2018
First Posted Date  ICMJE August 23, 2018
Results First Submitted Date  ICMJE October 8, 2018
Results First Posted Date  ICMJE February 22, 2019
Last Update Posted Date March 27, 2019
Actual Study Start Date  ICMJE June 30, 2009
Actual Primary Completion Date July 16, 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 8, 2018)
  • Maximum Observed Plasma Concentration (Cmax) of Guaifenesin [ Time Frame: 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 ]
    Pharmacokinetic Parameter Cmax is the Maximum observed plasma concentration.
  • Maximum Measured Plasma Concentration at Steady State (Cmax,ss) of Guaifenesin Following the Third Dose [ Time Frame: 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 ]
    Pharmacokinetic Parameter Cmax,ss is the Maximum observed plasma concentration following the third dose.
  • Observed Plasma Concentration at the End of Dosing Interval at Steady State (Cmin,ss) of Guaifenesin Following the Third Dose [ Time Frame: 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 ]
    Observed plasma concentration at the end of the dosing interval following the third dose (that is, 4 hours following the third dose).
  • Average Plasma Concentration (Cav) of Guaifenesin Following the Third Dose [ Time Frame: 8, 8.5, 8.75, 9, 9.5, 10, 11 and 12 hours ]
    Average plasma concentration (Cav) following the third dose, calculated as AUC(8-12) divided by the dosing interval, 4. Cav is calculated as AUC(8-12) / dosing interval, 4
  • Time to Maximum Observed Plasma Concentration (Tmax) of Guaifenesin [ Time Frame: 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 ]
    Pharmacokinetic Parameter Tmax is the time of the maximum observed plasma concentration.
  • Time to Maximum Observed Plasma Concentration at Steady State (Tmax,ss) of Guaifenesin Following the Third Dose [ Time Frame: 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 ]
    Pharmacokinetic Parameter Tmax, ss is the time of the maximum observed plasma concentration following the third dose.
  • Apparent First-order Terminal Elimination Half-life (T1/2) of Guaifenesin [ Time Frame: 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 ]
    T1/2 is the apparent first-order terminal elimination half-life, calculated as ln(2)/Kel.
  • Apparent First-order Terminal Elimination Rate Constant (Kel) of Guaifenesin [ Time Frame: 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 ]
    Kel is the apparent first-order terminal elimination rate constant calculated from a semi-log 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., 3 or more non-zero plasma concentrations) in the terminal log-linear phase.
  • Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Measurable Concentration [AUC(0-t)] of Guaifenesin [ Time Frame: 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 ]
    AUC(0-t) is the 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.
  • Area Under Plasma Concentration Versus Time Curve From Time 0 to Infinity [AUC(0-inf)] of Guaifenesin [ Time Frame: 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 ]
    AUC(0-inf) is the area under the plasma concentration versus time curve from time 0 to infinity, calculated as AUC(0-t) + Ct/Kel, where Ct was the last measurable concentration and Kel is the apparent first-order terminal elimination rate constant.
  • Area Under Plasma Concentration Versus Time Curve From 0 to 4 Hours [AUC(0-4)] of Guaifenesin [ Time Frame: 0 (Pre-dose), 0.5, 0.75, 1, 1.5, 2, 3 and 4 hours ]
    AUC(0-4) is the area under the plasma concentration versus time curve from time 0 to 4 hours post dose (relative to first dose), as calculated by the linear trapezoidal method.
  • Area Under Plasma Concentration Versus Time Curve From Time 8 to 12 Hours [AUC(8-12)] of Guaifenesin [ Time Frame: 8, 8.5, 8.75, 9, 9.5, 10, 11 and 12 hours ]
    AUC(8-12) is the area under the plasma concentration versus time curve from time 8 to 12 hours postdose (relative to first dose), as calculated by the linear trapezoidal method.
  • Area Under Plasma Concentration Curve Ratio (AUCR) of Guaifenesin [ Time Frame: 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 ]
    Pharmacokinetic Parameter AUCR is the Ratio of AUC(0-t) to AUC(0-inf). AUCR = AUC(0-t) / AUC(0-inf).
  • Accumulation Index (AI) of Guaifenesin [ Time Frame: 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 ]
    AI is the accumulation index, calculated as AUC(8-12) / AUC(0-4).
  • Degree of Fluctuation (DF) of Guaifenesin [ Time Frame: 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 ]
    DF is the Degree of Fluctuation Index, calculated as (Cmax,ss - Cmin,ss) / Cav.
  • Peak Plasma Concentrations at Steady State (Swing) of Guaifenesin [ Time Frame: 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 ]
    Pharmacokinetic Parameter Swing is Calculated as (Cmax,ss - Cmin,ss) / Cmin,ss.
Original Primary Outcome Measures  ICMJE
 (submitted: August 21, 2018)
  • Maximum Observed Plasma Concentration (Cmax) of Guaifenesin [ Time Frame: 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 ]
  • Maximum Measured Plasma Concentration at Steady State (Cmax,ss) of Guaifenesin Following the Third Dose [ Time Frame: 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 ]
  • Observed Plasma Concentration at the End of Dosing Interval at Steady State (Cmin,ss) of Guaifenesin Following the Third Dose [ Time Frame: 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 ]
  • Average Plasma Concentration (Cav) of Guaifenesin Following the Third Dose [ Time Frame: 8, 8.5, 8.75, 9, 9.5, 10, 11 and 12 hours ]
    Cav is calculated as AUC(8-12) / dosing interval, 4
  • Time to Maximum Observed Plasma Concentration (Tmax) of Guaifenesin [ Time Frame: 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 ]
  • Time to Maximum Observed Plasma Concentration at Steady State (Tmax,ss) of Guaifenesin Following the Third Dose [ Time Frame: 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 ]
  • Apparent First-order Terminal Elimination Half-life (T1/2) of Guaifenesin [ Time Frame: 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 ]
  • Apparent First-order Terminal Elimination Rate Constant (Kel) of Guaifenesin [ Time Frame: 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 ]
  • Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Measurable Concentration [AUC(0-t)] of Guaifenesin [ Time Frame: 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 ]
  • Area Under Plasma Concentration Versus Time Curve From Time 0 to Infinity [AUC(0-inf)] of Guaifenesin [ Time Frame: 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 ]
    AUC(0-inf) = AUC(0-t) + Ct/Kel, where Ct was the last measurable concentration and Kel is the apparent first-order terminal elimination rate constant
  • Area Under Plasma Concentration Versus Time Curve From 0 to 4 Hours [AUC(0-4)] of Guaifenesin [ Time Frame: 0 (Pre-dose), 0.5, 0.75, 1, 1.5, 2, 3 and 4 hours ]
  • Area Under Plasma Concentration Versus Time Curve From Time 8 to 12 Hours [AUC(8-12)] of Guaifenesin [ Time Frame: 8, 8.5, 8.75, 9, 9.5, 10, 11 and 12 hours ]
  • Area Under Plasma Concentration Curve Ratio (AUCR) of Guaifenesin [ Time Frame: 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 ]
    AUCR = AUC(0-t) / AUC(0-inf)
  • Accumulation Index (AI) of Guaifenesin [ Time Frame: 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 ]
    AI = AUC(8-12) / AUC(0-4)
  • Degree of Fluctuation (DF) of Guaifenesin [ Time Frame: 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 ]
    DF = (Cmax,ss - Cmin,ss) / Cav.
  • Peak Plasma Concentrations at Steady State (Swing) of Guaifenesin [ Time Frame: 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 ]
    Swing = (Cmax,ss - Cmin,ss) / Cmin,ss
Change History Complete list of historical versions of study NCT03643575 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 18, 2019)
Number of Participants With Adverse Events (AEs) [ Time Frame: Up to day 2 (Period 3) ]
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.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 21, 2018)
Number of Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Up to day 2 (Period 3) ]
TEAE is defined as any post-dose event.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Characterize the Pharmacokinetics of 3 Marketed Products Containing 200 mg Guaifenesin in Healthy Volunteers.
Official Title  ICMJE 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.
Brief Summary Characterize the relative pharmacokinetics (PK) of 3 marketed products containing guaifenesin
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Healthy Subjects
Intervention  ICMJE
  • Drug: Vicks Cough Syrup for Chesty Coughs
    Vicks Cough Syrup for Chesty Coughs 15 mL (containing 200 mg guaifenesin) IR syrup with 240 mL of water
  • Drug: Robitussin Extra Strength Chest Congestion
    Robitussin Extra Strength Chest Congestion 5 mL (containing 200 mg guaifenesin) IR syrup with 240 mL of water
  • Drug: Organ-I- NR tablet
    Organ-I- NR tablet (containing 200 mg guaifenesin) with 240 mL of water
Study Arms  ICMJE
  • Experimental: Treatment A: Vicks Cough Syrup for Chesty Coughs
    Vicks Cough immediate-release (IR) syrup 15 mL (containing 200 mg guaifenesin) every 4 hours x 3 doses with 240 mL of water after an overnight fast
    Intervention: Drug: Vicks Cough Syrup for Chesty Coughs
  • Experimental: Treatment B: Robitussin Extra Strength Chest Congestion
    Robitussin Extra Strength Chest Congestion 5 ml (containing 200 mg guaifenesin) every 4 hours x 3 doses with 240 mL of water after an overnight fast
    Intervention: Drug: Robitussin Extra Strength Chest Congestion
  • Experimental: Treatment C: Organ-I- NR tablet
    Organ-I- NR 200 mg guaifenesin tablet every 4 hours x 3 doses with 240 mL of water after an overnight fast
    Intervention: Drug: Organ-I- NR tablet
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 21, 2018)
30
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE July 16, 2009
Actual Primary Completion Date July 16, 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 19 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03643575
Other Study ID Numbers  ICMJE 2009-GGE-05
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Reckitt Benckiser LLC ( Reckitt Benckiser Inc. )
Study Sponsor  ICMJE Reckitt Benckiser Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Reckitt Benckiser LLC
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP