Healthy Subjects
Conditions
Brief summary
Determine and compare the plasma concentrations of Mucinex® Extended Release (ER) 600 mg bi-layer tablet in normal healthy volunteers in fed and fasting conditions
Interventions
DRUGMucinex®
Mucinex® 600 mg ER bi-layer tablets
Sponsors
Reckitt Benckiser LLC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Informed consent was obtained (i.e. be informed of the nature of the study and given written consent prior to any study procedure). Able to read, understand, and sign the informed consent, after the nature of the study had been explained. 2. Age: 18 to 55 years of age, inclusive. 3. Sex: male or female. 4. Status: Healthy subjects. 5. BMI: ≥18.0 and ≤28.0 kg/m2. 6. No clinically significant findings in vital signs measurements at screening. 7. No clinically significant abnormal laboratory values at screening. 8. No clinically significant findings from a 12-lead electrocardiogram (ECG) at screening. 9. Had no significant diseases or clinically relevant medical condition in the opinion of the Investigator 10. Males who participated in this study were willing to: * remain abstinent \[not engage in sexual intercourse\] from the start of drug administration until 90 days after the end of the study or * used (or their partner used, as applicable) two effective methods of birth control \[condom, diaphragm, cervical cap, vaginal sponge, spermicide, IUD, tubal ligation, vasectomy, or hormonal contraceptives\] from the start of drug administration until 90 days after the end of the study. Females who participated in this study were: * unable to have children (e.g., post-menopausal, hysterectomy); * willing to remain abstinent \[not engage in sexual intercourse\] from 21 days prior to drug administration until 30 days after the end of the study; or * willing to use two effective methods of birth control \[condom, diaphragm, cervical cap, vaginal sponge, spermicide, non-hormonal Intrauterine Device (IUD) (in place for 3 months), tubal ligation, partner has vasectomy, hormonal contraceptives for 3 months prior to drug administration\] from 30 days prior to drug administration until 30 days after the end of the study. 11. Had no clinically significant findings from a physical examination.
Exclusion criteria
1. Employee of Pharma Medica Research Inc. (PMRI) or Reckitt Benckiser. 2. Partner or first-degree relative of any Investigator at PMRI. 3. Known history or presence of any clinically significant medical condition. 4. Known or suspected carcinoma. 5. Presence of hepatic or renal dysfunction. 6. Presence of clinically significant gastrointestinal disease or history of malabsorption within the year preceding the study. 7. Known history or presence of galactose or fructose intolerance, sucrase-isomaltase insufficiency, Lapp lactase insufficiency, galactosemia, or glucose-galactose malabsorption syndrome. 8. Presence of a medical condition requiring regular medication (prescription and/or over-the-counter) with systemic absorption. 9. History of drug or alcohol or medicinal product addiction requiring treatment within the two years preceding the study or excessive alcohol consumption (more than 10 units per week) Note: one unit is defined as 5 ounces of wine, 12 ounces of beer, or 1.5 ounces of spirits. 10. Positive test result for serum Human Chorionic Gonadotropin (hCG) consistent with pregnancy (females only), HIV, Hepatitis B surface antigen or Hepatitis C antibody. 11. Positive test result for urine drugs of abuse (cannabinoids, opiates, amphetamines, cocaine, phencyclidine, tricyclic antidepressants, barbiturates, methadone and benzodiazepines) or urine cotinine. 12. Difficulty fasting or consuming standard meals. 13. Females who were lactating. 14. Did not tolerate venipuncture. 15. Use of tobacco or nicotine-containing products within 12 months prior to drug administration. 16. On a special diet within 30 days prior to drug administration (e.g., liquid, protein, raw food diet). 17. Donation or loss of whole blood (including clinical trials): * ≥50 ml and ≤499 ml within 30 days prior to drug administration * ≥500 ml within 56 days prior to drug administration 18. Females who had started taking hormonal contraceptives or had changed their method or brand of hormonal birth control within 3 months prior to drug administration. 19. Had a tattoo or body piercing within 30 days prior to drug administration. 20. Use of drugs of the monoamine oxidase inhibitor (MAOI) class within 30 days prior to drug administration. 21. Known history or presence of hypersensitivity, intolerance or idiosyncratic reaction to guaifenesin or any other drug substances with similar activity. 22. Previously enrolled in this study. 23. Participated in another clinical trial or received an investigational product within 30 days prior to drug administration. 24. Unable in the opinion of the Investigator to comply fully with the study requirements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of Guaifenesin | 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 20, and 24 hours (Period 1 and 2) | Maximum measured analyte concentration over the sampling period. |
| Area Under Plasma Concentration-time Curve From Time 0 to the Last Measurable Plasma Concentration (AUCt) of Guaifenesin | 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 20, and 24 hours (Period 1 and 2) | The area under the analyte concentration versus time curve, from time zero (0) to the time of the last measurable analyte concentration (t), as calculated by the linear trapezoidal method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Terminal Elimination Rate Constant (Kel) of Guaifenesin | 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 20, and 24 hours (Period 1 and 2) | Elimination rate constant calculated from the slope of the terminal portion of the plasma profile calculated by least-squares regression of log (concentration) versus time. |
| Terminal Elimination Half-life (T½) of Guaifenesin | 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 20, and 24 hours (Period 1 and 2) | Terminal elimination half-life, calculated from the equation: thalf = In(2)/Kel. |
| Time to Maximum Observed Plasma Concentration (Tmax) of Guaifenesin | 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 20, and 24 hours (Period 1 and 2) | Time of the maximum measured analyte concentration over the sampling period. |
| Number of Adverse Events(AEs) Experienced by Participants | Up to period 2 (8.3 days/200 hours) | Intensity determination Mild=AE does not limit usual activities;subject may experience slight discomfort Moderate=AE results in some limitation of usual activities;subject may experience significant discomfort Severe=AE results in an inability to carry out usual activities;subject may experience intolerable discomfort or pain Unassessable/Unclassifiable=Insufficient information to be able to make an assessment Conditional/Unclassified=Insufficient information to make an assessment at present(causality is conditional on additional information) Unrelated=No possibility that the AE was caused by study drug Unlikely=Slight but remote chance that the AE was caused by study drug but the balance of judgment is that it was most likely not due to the study drug Possible=Reasonable suspicion that the AE was caused by the study drug Probable=Most likely that the AE was caused by study drug Certain=The AE was definitely caused by study drug |
| Relative Bioavailability (RF) of Guaifenesin | 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 20, and 24 hours (Period 1 and 2) | Relative bioavailability for each formulation will be defined as: (AUC0-inf Fasting ÷ AUC0-inf Fed) x (Fed dose ÷ Fasting dose) |
| Area Under Plasma Concentration-time Curve From Time 0 to Infinity (AUCinf) of Guaifenesin | 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 20, and 24 hours (Period 1 and 2) | The area under the analyte concentration versus time curve from time zero to infinity. AUCinf = AUCt + Cp/Kel, where Cp is the predicted analyte concentration at the time of the last measurable analyte concentration. |
Participant flow
Recruitment details
This was a single-centre study.
Pre-assignment details
Total Thirty-six (36) subjects were enrolled in the study among them 36 subjects completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Pharmacokinetic (PK) Dataset Treatment A (Test): Single dose Mucinex® 600 mg Extended Release bi-layer tablet by mouth under overnight fasting.
Treatment B (Test): Single dose Mucinex® 600 mg Extended Release bi-layer tablet by mouth under high calorie breakfast fed.
Cohort 1
Period 1 - Treatment A or Treatment B at Sequence AB.
Period 2 - Treatment B or Treatment A at Sequence BA.
Scheduled Washout of 7 days between drug doses.
Cohort 2
Period 1 - Treatment A or Treatment B at Sequence AB.
Period 2 - Treatment B or Treatment A at Sequence BA.
Scheduled Washout of 7 days between drug doses. | 36 |
| Total | 36 |
Baseline characteristics
| Characteristic | Pharmacokinetic (PK) Dataset |
|---|---|
| Age 18 - 40 years | 21 participants |
| Age 41 - 64 years | 15 participants |
| Age, Continuous | 37 years STANDARD_DEVIATION 9 |
| Body Mass Index | 24.7 kg/m² STANDARD_DEVIATION 2.1 |
| Height | 170.8 cm STANDARD_DEVIATION 10.1 |
| Race Asian | 6 participants |
| Race Black or African American | 8 participants |
| Race White | 22 participants |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 19 Participants |
| Weight | 72.3 kg STANDARD_DEVIATION 10.4 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 36 | 0 / 36 |
| other Total, other adverse events | 8 / 36 | 10 / 36 |
| serious Total, serious adverse events | 0 / 36 | 0 / 36 |
Outcome results
Primary
Area Under Plasma Concentration-time Curve From Time 0 to the Last Measurable Plasma Concentration (AUCt) of Guaifenesin
The area under the analyte concentration versus time curve, from time zero (0) to the time of the last measurable analyte concentration (t), as calculated by the linear trapezoidal method.
Time frame: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 20, and 24 hours (Period 1 and 2)
Population: Pharmacokinetic Dataset
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Mucinex® 600 mg (Fast) | Area Under Plasma Concentration-time Curve From Time 0 to the Last Measurable Plasma Concentration (AUCt) of Guaifenesin | 4052.10 ng·h/ml | Standard Deviation 1495.48 |
| Treatment B: Mucinex® 600 mg (Fed) | Area Under Plasma Concentration-time Curve From Time 0 to the Last Measurable Plasma Concentration (AUCt) of Guaifenesin | 4084.90 ng·h/ml | Standard Deviation 1380.2 |
Primary
Maximum Observed Plasma Concentration (Cmax) of Guaifenesin
Maximum measured analyte concentration over the sampling period.
Time frame: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 20, and 24 hours (Period 1 and 2)
Population: Pharmacokinetic (PK) Dataset are the Subjects from whom the observation/estimation of Cmax and AUC measures/parameters will be possible for two periods will be included in the PK dataset.~The PK dataset will be defined prior to the assay of samples.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Mucinex® 600 mg (Fast) | Maximum Observed Plasma Concentration (Cmax) of Guaifenesin | 1066.11 ng/ml | Standard Deviation 429.91 |
| Treatment B: Mucinex® 600 mg (Fed) | Maximum Observed Plasma Concentration (Cmax) of Guaifenesin | 1117.31 ng/ml | Standard Deviation 424.82 |
Secondary
Area Under Plasma Concentration-time Curve From Time 0 to Infinity (AUCinf) of Guaifenesin
The area under the analyte concentration versus time curve from time zero to infinity. AUCinf = AUCt + Cp/Kel, where Cp is the predicted analyte concentration at the time of the last measurable analyte concentration.
Time frame: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 20, and 24 hours (Period 1 and 2)
Population: Pharmacokinetic Dataset
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Mucinex® 600 mg (Fast) | Area Under Plasma Concentration-time Curve From Time 0 to Infinity (AUCinf) of Guaifenesin | 4104.47 ng·h/ml | Standard Deviation 1555.87 |
| Treatment B: Mucinex® 600 mg (Fed) | Area Under Plasma Concentration-time Curve From Time 0 to Infinity (AUCinf) of Guaifenesin | 4092.53 ng·h/ml | Standard Deviation 1382.77 |
Secondary
Number of Adverse Events(AEs) Experienced by Participants
Intensity determination Mild=AE does not limit usual activities;subject may experience slight discomfort Moderate=AE results in some limitation of usual activities;subject may experience significant discomfort Severe=AE results in an inability to carry out usual activities;subject may experience intolerable discomfort or pain Unassessable/Unclassifiable=Insufficient information to be able to make an assessment Conditional/Unclassified=Insufficient information to make an assessment at present(causality is conditional on additional information) Unrelated=No possibility that the AE was caused by study drug Unlikely=Slight but remote chance that the AE was caused by study drug but the balance of judgment is that it was most likely not due to the study drug Possible=Reasonable suspicion that the AE was caused by the study drug Probable=Most likely that the AE was caused by study drug Certain=The AE was definitely caused by study drug
Time frame: Up to period 2 (8.3 days/200 hours)
Population: Pharmacokinetic Dataset~Investigational Medicinal Product(IMP)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A: Mucinex® 600 mg (Fast) | Number of Adverse Events(AEs) Experienced by Participants | TEAE by severity: Mild | 11 Events |
| Treatment A: Mucinex® 600 mg (Fast) | Number of Adverse Events(AEs) Experienced by Participants | TEAE by severity: Moderate | 0 Events |
| Treatment A: Mucinex® 600 mg (Fast) | Number of Adverse Events(AEs) Experienced by Participants | TEAE by severity: Severe | 0 Events |
| Treatment A: Mucinex® 600 mg (Fast) | Number of Adverse Events(AEs) Experienced by Participants | Relationship to IMP: Unassessable/Unclassifiable | 3 Events |
| Treatment A: Mucinex® 600 mg (Fast) | Number of Adverse Events(AEs) Experienced by Participants | Relationship to IMP: Conditional /Unclassified | 0 Events |
| Treatment A: Mucinex® 600 mg (Fast) | Number of Adverse Events(AEs) Experienced by Participants | Relationship to IMP: Unrelated | 2 Events |
| Treatment A: Mucinex® 600 mg (Fast) | Number of Adverse Events(AEs) Experienced by Participants | Relationship to IMP: Unlikely | 0 Events |
| Treatment A: Mucinex® 600 mg (Fast) | Number of Adverse Events(AEs) Experienced by Participants | Relationship to IMP: Possible | 6 Events |
| Treatment A: Mucinex® 600 mg (Fast) | Number of Adverse Events(AEs) Experienced by Participants | Relationship to IMP: Probable | 0 Events |
| Treatment A: Mucinex® 600 mg (Fast) | Number of Adverse Events(AEs) Experienced by Participants | Relationship to IMP: Certain | 0 Events |
| Treatment B: Mucinex® 600 mg (Fed) | Number of Adverse Events(AEs) Experienced by Participants | Relationship to IMP: Possible | 9 Events |
| Treatment B: Mucinex® 600 mg (Fed) | Number of Adverse Events(AEs) Experienced by Participants | TEAE by severity: Mild | 14 Events |
| Treatment B: Mucinex® 600 mg (Fed) | Number of Adverse Events(AEs) Experienced by Participants | Relationship to IMP: Unrelated | 0 Events |
| Treatment B: Mucinex® 600 mg (Fed) | Number of Adverse Events(AEs) Experienced by Participants | TEAE by severity: Moderate | 0 Events |
| Treatment B: Mucinex® 600 mg (Fed) | Number of Adverse Events(AEs) Experienced by Participants | Relationship to IMP: Certain | 0 Events |
| Treatment B: Mucinex® 600 mg (Fed) | Number of Adverse Events(AEs) Experienced by Participants | TEAE by severity: Severe | 0 Events |
| Treatment B: Mucinex® 600 mg (Fed) | Number of Adverse Events(AEs) Experienced by Participants | Relationship to IMP: Unlikely | 0 Events |
| Treatment B: Mucinex® 600 mg (Fed) | Number of Adverse Events(AEs) Experienced by Participants | Relationship to IMP: Unassessable/Unclassifiable | 5 Events |
| Treatment B: Mucinex® 600 mg (Fed) | Number of Adverse Events(AEs) Experienced by Participants | Relationship to IMP: Probable | 0 Events |
| Treatment B: Mucinex® 600 mg (Fed) | Number of Adverse Events(AEs) Experienced by Participants | Relationship to IMP: Conditional /Unclassified | 0 Events |
Secondary
Relative Bioavailability (RF) of Guaifenesin
Relative bioavailability for each formulation will be defined as: (AUC0-inf Fasting ÷ AUC0-inf Fed) x (Fed dose ÷ Fasting dose)
Time frame: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 20, and 24 hours (Period 1 and 2)
Population: Outcome involved analyzing data from both intervention groups (Fed and Fasting) in combination as per the provided formula, therefore, separate analysis for each intervention cannot be reported
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Mucinex® 600 mg (Fast) | Relative Bioavailability (RF) of Guaifenesin | 1.0081 Percent bioavailability | Standard Deviation 0.1655 |
Secondary
Terminal Elimination Half-life (T½) of Guaifenesin
Terminal elimination half-life, calculated from the equation: thalf = In(2)/Kel.
Time frame: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 20, and 24 hours (Period 1 and 2)
Population: Pharmacokinetic Dataset
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Mucinex® 600 mg (Fast) | Terminal Elimination Half-life (T½) of Guaifenesin | 2.46 h | Standard Deviation 2.62 |
| Treatment B: Mucinex® 600 mg (Fed) | Terminal Elimination Half-life (T½) of Guaifenesin | 1.07 h | Standard Deviation 0.29 |
Secondary
Terminal Elimination Rate Constant (Kel) of Guaifenesin
Elimination rate constant calculated from the slope of the terminal portion of the plasma profile calculated by least-squares regression of log (concentration) versus time.
Time frame: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 20, and 24 hours (Period 1 and 2)
Population: Pharmacokinetic Dataset
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Mucinex® 600 mg (Fast) | Terminal Elimination Rate Constant (Kel) of Guaifenesin | 0.3862 1/h | Standard Deviation 0.1717 |
| Treatment B: Mucinex® 600 mg (Fed) | Terminal Elimination Rate Constant (Kel) of Guaifenesin | 0.6788 1/h | Standard Deviation 0.1343 |
Secondary
Time to Maximum Observed Plasma Concentration (Tmax) of Guaifenesin
Time of the maximum measured analyte concentration over the sampling period.
Time frame: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 20, and 24 hours (Period 1 and 2)
Population: Pharmacokinetic Dataset
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Mucinex® 600 mg (Fast) | Time to Maximum Observed Plasma Concentration (Tmax) of Guaifenesin | 0.68 h | Standard Deviation 0.32 |
| Treatment B: Mucinex® 600 mg (Fed) | Time to Maximum Observed Plasma Concentration (Tmax) of Guaifenesin | 3.33 h | Standard Deviation 1.36 |