Healthy Subjects
Conditions
Brief summary
Characterize the relative pharmacokinetics (PK) of 3 marketed products containing guaifenesin
Interventions
Vicks Cough Syrup for Chesty Coughs 15 mL (containing 200 mg guaifenesin) IR syrup with 240 mL of water
DRUGRobitussin Extra Strength Chest Congestion
Robitussin Extra Strength Chest Congestion 5 mL (containing 200 mg guaifenesin) IR syrup with 240 mL of water
DRUGOrgan-I- NR tablet
Organ-I- NR tablet (containing 200 mg guaifenesin) with 240 mL of water
Sponsors
Reckitt Benckiser Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peak Plasma Concentrations at Steady State (Swing) of Guaifenesin | 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. |
| Average Plasma Concentration (Cav) of Guaifenesin Following the Third Dose | 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 |
| Maximum Observed Plasma Concentration (Cmax) of Guaifenesin | 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 | 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 | 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). |
| Time to Maximum Observed Plasma Concentration (Tmax) of Guaifenesin | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) | 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. |
Participant flow
Recruitment details
This was a single-centre study.
Pre-assignment details
A total of 30 subjects entered the study, among them 27 subjects completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Overall Study Treatment A:
Vicks Cough Syrup 15 mL containing 200 mg guaifenesin every 4 hour for 3 doses by mouth after an overnight fast
Treatment B:
Robitussin Extra Strength 5mL syrup containing 200 mg guaifenesin every 4 hour for 3 doses by mouth after an overnight fast
Treatment C:
Organ-I NR Tablet containing 200 mg guaifenesin every 4 hour for 3 doses by mouth after an overnight fast
There was a 7 days washout period between each administration
Participants randomized to receive either Treatment A or Treatment B or Treatment C in 3 Periods (Period 1, 2, 3) of 6 sequence (ABC, BCA, CAB, ACB, BAC, CBA) | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Washout: 7 Days | Adverse Event | 1 | 0 | 0 | 0 | 0 | 0 |
| Washout: 7 Days | Non compliance check in | 0 | 1 | 0 | 0 | 0 | 0 |
| Washout: 7 Days | Withdrew consent due to illness | 0 | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 26.0 years STANDARD_DEVIATION 9.54 |
| Elbow Breadth | 2.661 in STANDARD_DEVIATION 0.214 |
| Frame Size Large | 3 participants |
| Frame Size Medium | 23 participants |
| Frame Size Small | 4 participants |
| Height | 69.65 in STANDARD_DEVIATION 3.246 |
| Race Asian | 1 participants |
| Race Black | 1 participants |
| Race Caucasian | 25 participants |
| Race European/Middle Eastern | 1 participants |
| Race Hispanic | 2 participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 15 Participants |
| Weight | 157.60 lb STANDARD_DEVIATION 22.359 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 28 | 0 / 28 |
| other Total, other adverse events | 5 / 29 | 1 / 28 | 4 / 28 |
| serious Total, serious adverse events | 0 / 29 | 0 / 28 | 0 / 28 |
Outcome results
Primary
Accumulation Index (AI) of Guaifenesin
AI is the accumulation index, calculated as AUC(8-12) / AUC(0-4).
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
Population: PK analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Accumulation Index (AI) of Guaifenesin | 0.7056 Ratio | Standard Deviation 0.1299 |
| Treatment B | Accumulation Index (AI) of Guaifenesin | 0.8420 Ratio | Standard Deviation 0.118 |
| Treatment C | Accumulation Index (AI) of Guaifenesin | 0.8592 Ratio | Standard Deviation 0.1304 |
Primary
Apparent First-order Terminal Elimination Half-life (T1/2) of Guaifenesin
T1/2 is the apparent first-order terminal elimination half-life, calculated as ln(2)/Kel.
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
Population: PK analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Apparent First-order Terminal Elimination Half-life (T1/2) of Guaifenesin | 0.961 hr | Standard Deviation 0.0973 |
| Treatment B | Apparent First-order Terminal Elimination Half-life (T1/2) of Guaifenesin | 1.04 hr | Standard Deviation 0.138 |
| Treatment C | Apparent First-order Terminal Elimination Half-life (T1/2) of Guaifenesin | 0.941 hr | Standard Deviation 0.13 |
Primary
Apparent First-order Terminal Elimination Rate Constant (Kel) of Guaifenesin
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.
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
Population: PK analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Apparent First-order Terminal Elimination Rate Constant (Kel) of Guaifenesin | 0.729 1/hr | Standard Deviation 0.078 |
| Treatment B | Apparent First-order Terminal Elimination Rate Constant (Kel) of Guaifenesin | 0.677 1/hr | Standard Deviation 0.0898 |
| Treatment C | Apparent First-order Terminal Elimination Rate Constant (Kel) of Guaifenesin | 0.750 1/hr | Standard Deviation 0.0987 |
Primary
Area Under Plasma Concentration Curve Ratio (AUCR) of Guaifenesin
Pharmacokinetic Parameter AUCR is the Ratio of AUC(0-t) to AUC(0-inf). AUCR = AUC(0-t) / AUC(0-inf).
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
Population: PK analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Area Under Plasma Concentration Curve Ratio (AUCR) of Guaifenesin | 0.9986 Ratio | Standard Deviation 0.000592 |
| Treatment B | Area Under Plasma Concentration Curve Ratio (AUCR) of Guaifenesin | 0.9982 Ratio | Standard Deviation 0.001138 |
| Treatment C | Area Under Plasma Concentration Curve Ratio (AUCR) of Guaifenesin | 0.9978 Ratio | Standard Deviation 0.001724 |
Primary
Area Under Plasma Concentration Versus Time Curve From 0 to 4 Hours [AUC(0-4)] of Guaifenesin
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.
Time frame: 0 (Pre-dose), 0.5, 0.75, 1, 1.5, 2, 3 and 4 hours
Population: PK analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Area Under Plasma Concentration Versus Time Curve From 0 to 4 Hours [AUC(0-4)] of Guaifenesin | 2013.16 ng*hr/mL | Standard Deviation 785.006 |
| Treatment B | Area Under Plasma Concentration Versus Time Curve From 0 to 4 Hours [AUC(0-4)] of Guaifenesin | 1490.15 ng*hr/mL | Standard Deviation 579.667 |
| Treatment C | Area Under Plasma Concentration Versus Time Curve From 0 to 4 Hours [AUC(0-4)] of Guaifenesin | 1414.18 ng*hr/mL | Standard Deviation 617.126 |
Primary
Area Under Plasma Concentration Versus Time Curve From Time 0 to Infinity [AUC(0-inf)] of Guaifenesin
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.
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
Population: PK analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Area Under Plasma Concentration Versus Time Curve From Time 0 to Infinity [AUC(0-inf)] of Guaifenesin | 5596.33 ng*hr/mL | Standard Deviation 2330.2 |
| Treatment B | Area Under Plasma Concentration Versus Time Curve From Time 0 to Infinity [AUC(0-inf)] of Guaifenesin | 4427.06 ng*hr/mL | Standard Deviation 1721.91 |
| Treatment C | Area Under Plasma Concentration Versus Time Curve From Time 0 to Infinity [AUC(0-inf)] of Guaifenesin | 4232.61 ng*hr/mL | Standard Deviation 1801.69 |
Primary
Area Under Plasma Concentration Versus Time Curve From Time 8 to 12 Hours [AUC(8-12)] of Guaifenesin
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.
Time frame: 8, 8.5, 8.75, 9, 9.5, 10, 11 and 12 hours
Population: PK analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Area Under Plasma Concentration Versus Time Curve From Time 8 to 12 Hours [AUC(8-12)] of Guaifenesin | 1427.70 ng*hr/mL | Standard Deviation 672.821 |
| Treatment B | Area Under Plasma Concentration Versus Time Curve From Time 8 to 12 Hours [AUC(8-12)] of Guaifenesin | 1253.09 ng*hr/mL | Standard Deviation 511.519 |
| Treatment C | Area Under Plasma Concentration Versus Time Curve From Time 8 to 12 Hours [AUC(8-12)] of Guaifenesin | 1198.55 ng*hr/mL | Standard Deviation 511.21 |
Primary
Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Measurable Concentration [AUC(0-t)] of Guaifenesin
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.
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
Population: PK analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Measurable Concentration [AUC(0-t)] of Guaifenesin | 5588.99 ng*hr/mL | Standard Deviation 2329.08 |
| Treatment B | Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Measurable Concentration [AUC(0-t)] of Guaifenesin | 4369.98 ng*hr/mL | Standard Deviation 1708.25 |
| Treatment C | Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Measurable Concentration [AUC(0-t)] of Guaifenesin | 4223.74 ng*hr/mL | Standard Deviation 1798.98 |
Primary
Average Plasma Concentration (Cav) of Guaifenesin Following the Third Dose
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 frame: 8, 8.5, 8.75, 9, 9.5, 10, 11 and 12 hours
Population: PK analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Average Plasma Concentration (Cav) of Guaifenesin Following the Third Dose | 357 ng/mL | Standard Deviation 168 |
| Treatment B | Average Plasma Concentration (Cav) of Guaifenesin Following the Third Dose | 313 ng/mL | Standard Deviation 128 |
| Treatment C | Average Plasma Concentration (Cav) of Guaifenesin Following the Third Dose | 300 ng/mL | Standard Deviation 128 |
Primary
Degree of Fluctuation (DF) of Guaifenesin
DF is the Degree of Fluctuation Index, calculated as (Cmax,ss - Cmin,ss) / Cav.
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
Population: PK analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Degree of Fluctuation (DF) of Guaifenesin | 2.220 Percent fluctuation in concentration | Standard Deviation 0.5508 |
| Treatment B | Degree of Fluctuation (DF) of Guaifenesin | 2.312 Percent fluctuation in concentration | Standard Deviation 0.5221 |
| Treatment C | Degree of Fluctuation (DF) of Guaifenesin | 2.463 Percent fluctuation in concentration | Standard Deviation 0.6758 |
Primary
Maximum Measured Plasma Concentration at Steady State (Cmax,ss) of Guaifenesin Following the Third Dose
Pharmacokinetic Parameter Cmax,ss is the Maximum observed plasma concentration 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
Population: PK analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Maximum Measured Plasma Concentration at Steady State (Cmax,ss) of Guaifenesin Following the Third Dose | 876 ng/mL | Standard Deviation 548 |
| Treatment B | Maximum Measured Plasma Concentration at Steady State (Cmax,ss) of Guaifenesin Following the Third Dose | 765 ng/mL | Standard Deviation 309 |
| Treatment C | Maximum Measured Plasma Concentration at Steady State (Cmax,ss) of Guaifenesin Following the Third Dose | 796 ng/mL | Standard Deviation 317 |
Primary
Maximum Observed Plasma Concentration (Cmax) of Guaifenesin
Pharmacokinetic Parameter Cmax is the Maximum observed plasma concentration.
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
Population: Pharmacokinetic (PK) analyses were performed on the available data of the subjects that completed at least 1 period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Maximum Observed Plasma Concentration (Cmax) of Guaifenesin | 1730 ng/mL | Standard Deviation 723 |
| Treatment B | Maximum Observed Plasma Concentration (Cmax) of Guaifenesin | 1230 ng/mL | Standard Deviation 456 |
| Treatment C | Maximum Observed Plasma Concentration (Cmax) of Guaifenesin | 1110 ng/mL | Standard Deviation 433 |
Primary
Observed Plasma Concentration at the End of Dosing Interval at Steady State (Cmin,ss) of Guaifenesin Following the Third Dose
Observed plasma concentration at the end of the dosing interval following the third dose (that is, 4 hours 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
Population: PK analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Observed Plasma Concentration at the End of Dosing Interval at Steady State (Cmin,ss) of Guaifenesin Following the Third Dose | 60.3 ng/mL | Standard Deviation 33.4 |
| Treatment B | Observed Plasma Concentration at the End of Dosing Interval at Steady State (Cmin,ss) of Guaifenesin Following the Third Dose | 55.1 ng/mL | Standard Deviation 28 |
| Treatment C | Observed Plasma Concentration at the End of Dosing Interval at Steady State (Cmin,ss) of Guaifenesin Following the Third Dose | 73.6 ng/mL | Standard Deviation 59.9 |
Primary
Peak Plasma Concentrations at Steady State (Swing) of Guaifenesin
Pharmacokinetic Parameter Swing is Calculated as (Cmax,ss - Cmin,ss) / Cmin,ss.
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
Population: PK analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Peak Plasma Concentrations at Steady State (Swing) of Guaifenesin | 16.19 Percentage | Standard Deviation 10.03 |
| Treatment B | Peak Plasma Concentrations at Steady State (Swing) of Guaifenesin | 15.62 Percentage | Standard Deviation 8.908 |
| Treatment C | Peak Plasma Concentrations at Steady State (Swing) of Guaifenesin | 0.750 Percentage | Standard Deviation 0.0987 |
Primary
Time to Maximum Observed Plasma Concentration at Steady State (Tmax,ss) of Guaifenesin Following the Third Dose
Pharmacokinetic Parameter Tmax, ss is the time of the maximum observed plasma concentration 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
Population: PK analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Time to Maximum Observed Plasma Concentration at Steady State (Tmax,ss) of Guaifenesin Following the Third Dose | 8.70 hr | Standard Deviation 0.333 |
| Treatment B | Time to Maximum Observed Plasma Concentration at Steady State (Tmax,ss) of Guaifenesin Following the Third Dose | 8.67 hr | Standard Deviation 0.244 |
| Treatment C | Time to Maximum Observed Plasma Concentration at Steady State (Tmax,ss) of Guaifenesin Following the Third Dose | 9.02 hr | Standard Deviation 0.374 |
Primary
Time to Maximum Observed Plasma Concentration (Tmax) of Guaifenesin
Pharmacokinetic Parameter Tmax is the time of the maximum observed plasma concentration.
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
Population: PK analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Time to Maximum Observed Plasma Concentration (Tmax) of Guaifenesin | 2.66 hr | Standard Deviation 2.32 |
| Treatment B | Time to Maximum Observed Plasma Concentration (Tmax) of Guaifenesin | 2.94 hr | Standard Deviation 2 |
| Treatment C | Time to Maximum Observed Plasma Concentration (Tmax) of Guaifenesin | 3.91 hr | Standard Deviation 2.29 |
Secondary
Number of Participants With Adverse Events (AEs)
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.
Time frame: Up to day 2 (Period 3)
Population: PK analyses
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A | Number of Participants With Adverse Events (AEs) | TEAE by severity: Mild | 5 participants |
| Treatment A | Number of Participants With Adverse Events (AEs) | TEAE by severity: Moderate | 2 participants |
| Treatment A | Number of Participants With Adverse Events (AEs) | TEAE by severity: Severe | 0 participants |
| Treatment A | Number of Participants With Adverse Events (AEs) | Relationship to IMP - Unlikely | 5 participants |
| Treatment A | Number of Participants With Adverse Events (AEs) | Relationship to IMP - Possible | 1 participants |
| Treatment A | Number of Participants With Adverse Events (AEs) | Relationship to IMP - Probable | 0 participants |
| Treatment B | Number of Participants With Adverse Events (AEs) | Relationship to IMP - Probable | 0 participants |
| Treatment B | Number of Participants With Adverse Events (AEs) | TEAE by severity: Mild | 1 participants |
| Treatment B | Number of Participants With Adverse Events (AEs) | Relationship to IMP - Unlikely | 1 participants |
| Treatment B | Number of Participants With Adverse Events (AEs) | Relationship to IMP - Possible | 0 participants |
| Treatment B | Number of Participants With Adverse Events (AEs) | TEAE by severity: Moderate | 0 participants |
| Treatment B | Number of Participants With Adverse Events (AEs) | TEAE by severity: Severe | 0 participants |
| Treatment C | Number of Participants With Adverse Events (AEs) | TEAE by severity: Moderate | 1 participants |
| Treatment C | Number of Participants With Adverse Events (AEs) | TEAE by severity: Severe | 0 participants |
| Treatment C | Number of Participants With Adverse Events (AEs) | Relationship to IMP - Probable | 0 participants |
| Treatment C | Number of Participants With Adverse Events (AEs) | Relationship to IMP - Unlikely | 2 participants |
| Treatment C | Number of Participants With Adverse Events (AEs) | TEAE by severity: Mild | 4 participants |
| Treatment C | Number of Participants With Adverse Events (AEs) | Relationship to IMP - Possible | 2 participants |