Healthy
Conditions
Keywords
Plasma concentration, Time to plasma concentration, Elimination rate constant, Elimination half life, Area under the curve
Brief summary
This study will compare the relative bioavailability of hydrocodone, acetaminophen, and promethazine in CL-108 (hydrocodone 7.5mg/ acetaminophen 325 mg/ promethazine 12.5 mg) manufactured by Charleston Laboratories, Inc. to hydrocodone in Vicoprofen (hydrocodone 7.5 mg /ibuprofen 200 mg), promethazine 12.5 mg, and acetaminophen in Ultracet (tramadol HCl 37.5 mg/acetaminophen 325 mg) under fasted and fed conditions.
Interventions
DRUGCL-108
Hydrocodone bitartrate/acetaminophen/promethazine 7.5 mg/325 mg/12.5 mg single dose by mouth
DRUGVicoprofen
Hydrocodone Bitartrate and Ibuprofen 7.5 mg/200 mg single dose tablet by mouth
DRUGUltracet
Tramadol HCl/acetaminophen 37.5 mg/325 mg single dose tablet by mouth
DRUGPhenergan
Phenergan (Promethazine HCl, USP) 12.5 mg single dose tablet by mouth
Sponsors
Charleston Laboratories, Inc
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Written informed consent * Subject's body mass index (BMI) must be between 18 and 30kg/m2 (inclusive), and subject must weigh a minimum of 50 kg (110lb) * Abide by study restrictions * Acceptable birth control measures * Ability to attend all study visits * Vital signs as per protocol * Willing to consume high calorie meals within designated time frame
Exclusion criteria
* Clinically significant medical history * Clinically significant abnormal findings * History or presence of allergic or adverse response to hydrocodone, ibuprofen,acetaminophen, any non-steroidal anti-inflammatory drugs (NSAIDs), promethazine, or related drugs. * Has smoked or used tobacco products within 60 days prior to the first dose of study medication * Has donated blood or plasma within 30 days prior to the first dose of study medication * Has participated in another clinical trial (randomized subjects only) within 30 days prior to the first dose of study medication.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Drug Concentration (Cmax) in Plasma Determined Directly From Individual Concentration-time Data | 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, and 48 hours post-dose | Cmax of CL-108 and Vicoprofen + Ultracet + Phenergan were measured in the plasma (the liquid component of the blood in which the blood cells are suspended) in samples collected up to 48 hours post-dose. |
| Time to Reach Maximum Concentration (Tmax) | 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, and 48 hours post-dose | — |
| Last Quantifiable Drug Concentration (Clast) Determined Directly From Individual Concentration-time Data | 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, and 48 hours post-dose | — |
| Time of the Last Quantifiable Concentration (Tlast) | 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, and 48 hours post-dose | — |
| Observed Elimination Rate Constant (λz) | 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, and 48 hours post-dose | Estimated by linear regression through at least three data points in the terminal phase of the log concentration-time profile |
| Observed Terminal Elimination Half-life (T1/2) | 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, and 48 hours post-dose | Calculated as: T1/2 = ln(2)/λz |
| Area Under the Plasma Concentration-time Curve (AUC0-0.25) for Hydrocodone and Promethazine | 0 (pre-dose) to 0.25 hours post-dose | AUC0-0.25 measured by Linear Trapezoidal with Linear Interpolation method. |
| AUC0-0.50 for Hydrocodone and Promethazine | 0 (pre-dose) to 0.5 hours post-dose | AUC0-0.50 measured by Linear Trapezoidal with Linear Interpolation method. |
| AUC0-0.75 for Hydrocodone and Promethazine | 0 (Pre-dose) to 0.75 hours post-dose | AUC0-0.75 measured by Linear Trapezoidal with Linear Interpolation method. |
| AUC0-1.0 for Hydrocodone and Promethazine | 0 (pre-dose) to 1.0 hours post-dose | AUC0-1.0 measured by Linear Trapezoidal with Linear Interpolation method. |
| AUC0-1.5 for Hydrocodone and Promethazine | 0 (pre-dose) to 1.5 hours post-dose | AUC0-1.5 measured by Linear Trapezoidal with Linear Interpolation method. |
| AUC0-2.0 for Hydrocodone and Promethazine | 0 (pre-dose) to 2 hours post-dose | AUC0-2.0 measured by Linear Trapezoidal with Linear Interpolation method. |
| AUC0-4.0 for Hydrocodone and Promethazine | 0 (pre-dose) to 4 hours post-dose | AUC0-4.0 measured by Linear Trapezoidal with Linear Interpolation method. |
| Area Under the Plasma Concentration-time (AUClast) Curve From Time-zero to the Time of the Last Quantifiable Concentration | 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, and 48 hours post-dose | Calculated using the linear trapezoidal rule |
| Area Under the Concentration-time (AUCinf) Curve From Time-zero Extrapolated to Infinity | 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, and 48 hours post-dose | Calculated as: AUCinf = AUClast + Clast/λz |
| Percentage of AUCinf [AUCExtrap (%)] Based on Extrapolation | 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, and 48 hours post-dose | Calculated as: AUCExtrap (%) = (AUC0-inf - AUC0-last)/AUC0-inf \*100 |
Participant flow
Recruitment details
Twenty healthy subjects were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| Overall Subjects | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Period 3 | Withdrawal by Subject | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Overall Subjects |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants |
| Age, Continuous | 52.85 years STANDARD_DEVIATION 17.71 |
| Body Mass Index (BMI) | 25.43 kg/m² STANDARD_DEVIATION 2.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Height | 163.15 cm STANDARD_DEVIATION 10.49 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants |
| Race/Ethnicity, Customized White | 17 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 17 Participants |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 6 Participants |
| Weight | 67.83 kg STANDARD_DEVIATION 10.72 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 19 | 11 / 20 | 20 / 20 | 2 / 19 |
| serious Total, serious adverse events | 0 / 19 | 0 / 20 | 0 / 20 | 0 / 19 |
Outcome results
Primary
Area Under the Concentration-time (AUCinf) Curve From Time-zero Extrapolated to Infinity
Calculated as: AUCinf = AUClast + Clast/λz
Time frame: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, and 48 hours post-dose
Population: ITT population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A: CL-108 (Fasted) | Area Under the Concentration-time (AUCinf) Curve From Time-zero Extrapolated to Infinity | Hydrocodone | 150.2 h*ng/mL | Standard Deviation 57.3 |
| Treatment A: CL-108 (Fasted) | Area Under the Concentration-time (AUCinf) Curve From Time-zero Extrapolated to Infinity | Promethazine (Number of Participants=19,18,20,18) | 96.92 h*ng/mL | Standard Deviation 119.5 |
| Treatment B: CL-108 (Fed) | Area Under the Concentration-time (AUCinf) Curve From Time-zero Extrapolated to Infinity | Promethazine (Number of Participants=19,18,20,18) | 60.72 h*ng/mL | Standard Deviation 29.74 |
| Treatment B: CL-108 (Fed) | Area Under the Concentration-time (AUCinf) Curve From Time-zero Extrapolated to Infinity | Hydrocodone | 155.8 h*ng/mL | Standard Deviation 58.75 |
| Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted) | Area Under the Concentration-time (AUCinf) Curve From Time-zero Extrapolated to Infinity | Hydrocodone | 134.3 h*ng/mL | Standard Deviation 48.2 |
| Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted) | Area Under the Concentration-time (AUCinf) Curve From Time-zero Extrapolated to Infinity | Promethazine (Number of Participants=19,18,20,18) | 88.53 h*ng/mL | Standard Deviation 100.3 |
| Treatment D: Vicoprofen, Ultracet and Phenergan (Fed) | Area Under the Concentration-time (AUCinf) Curve From Time-zero Extrapolated to Infinity | Hydrocodone | 152.4 h*ng/mL | Standard Deviation 56.83 |
| Treatment D: Vicoprofen, Ultracet and Phenergan (Fed) | Area Under the Concentration-time (AUCinf) Curve From Time-zero Extrapolated to Infinity | Promethazine (Number of Participants=19,18,20,18) | 84.13 h*ng/mL | Standard Deviation 76.72 |
Primary
Area Under the Plasma Concentration-time (AUClast) Curve From Time-zero to the Time of the Last Quantifiable Concentration
Calculated using the linear trapezoidal rule
Time frame: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, and 48 hours post-dose
Population: ITT population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A: CL-108 (Fasted) | Area Under the Plasma Concentration-time (AUClast) Curve From Time-zero to the Time of the Last Quantifiable Concentration | Acetaminophen | 19.19 h*ng/mL | Standard Deviation 5.661 |
| Treatment A: CL-108 (Fasted) | Area Under the Plasma Concentration-time (AUClast) Curve From Time-zero to the Time of the Last Quantifiable Concentration | Promethazine (Number of Participants=19,19,20,19) | 75.69 h*ng/mL | Standard Deviation 78.87 |
| Treatment A: CL-108 (Fasted) | Area Under the Plasma Concentration-time (AUClast) Curve From Time-zero to the Time of the Last Quantifiable Concentration | Hydrocodone | 146.2 h*ng/mL | Standard Deviation 56.77 |
| Treatment B: CL-108 (Fed) | Area Under the Plasma Concentration-time (AUClast) Curve From Time-zero to the Time of the Last Quantifiable Concentration | Acetaminophen | 17.85 h*ng/mL | Standard Deviation 4.621 |
| Treatment B: CL-108 (Fed) | Area Under the Plasma Concentration-time (AUClast) Curve From Time-zero to the Time of the Last Quantifiable Concentration | Promethazine (Number of Participants=19,19,20,19) | 66.63 h*ng/mL | Standard Deviation 67.37 |
| Treatment B: CL-108 (Fed) | Area Under the Plasma Concentration-time (AUClast) Curve From Time-zero to the Time of the Last Quantifiable Concentration | Hydrocodone | 151.9 h*ng/mL | Standard Deviation 58.79 |
| Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted) | Area Under the Plasma Concentration-time (AUClast) Curve From Time-zero to the Time of the Last Quantifiable Concentration | Hydrocodone | 130.9 h*ng/mL | Standard Deviation 47.94 |
| Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted) | Area Under the Plasma Concentration-time (AUClast) Curve From Time-zero to the Time of the Last Quantifiable Concentration | Acetaminophen | 18.69 h*ng/mL | Standard Deviation 5.186 |
| Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted) | Area Under the Plasma Concentration-time (AUClast) Curve From Time-zero to the Time of the Last Quantifiable Concentration | Promethazine (Number of Participants=19,19,20,19) | 68.54 h*ng/mL | Standard Deviation 63.24 |
| Treatment D: Vicoprofen, Ultracet and Phenergan (Fed) | Area Under the Plasma Concentration-time (AUClast) Curve From Time-zero to the Time of the Last Quantifiable Concentration | Acetaminophen | 17.85 h*ng/mL | Standard Deviation 4.742 |
| Treatment D: Vicoprofen, Ultracet and Phenergan (Fed) | Area Under the Plasma Concentration-time (AUClast) Curve From Time-zero to the Time of the Last Quantifiable Concentration | Promethazine (Number of Participants=19,19,20,19) | 74.76 h*ng/mL | Standard Deviation 57.53 |
| Treatment D: Vicoprofen, Ultracet and Phenergan (Fed) | Area Under the Plasma Concentration-time (AUClast) Curve From Time-zero to the Time of the Last Quantifiable Concentration | Hydrocodone | 148.5 h*ng/mL | Standard Deviation 56.84 |
Primary
Area Under the Plasma Concentration-time Curve (AUC0-0.25) for Hydrocodone and Promethazine
AUC0-0.25 measured by Linear Trapezoidal with Linear Interpolation method.
Time frame: 0 (pre-dose) to 0.25 hours post-dose
Population: ITT population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A: CL-108 (Fasted) | Area Under the Plasma Concentration-time Curve (AUC0-0.25) for Hydrocodone and Promethazine | Promethazine (Number of Participants=19,19,20,19) | 0.01086 h*ng/mL | Standard Deviation 0.03169 |
| Treatment A: CL-108 (Fasted) | Area Under the Plasma Concentration-time Curve (AUC0-0.25) for Hydrocodone and Promethazine | Hydrocodone | 0.08870 h*ng/mL | Standard Deviation 0.1318 |
| Treatment B: CL-108 (Fed) | Area Under the Plasma Concentration-time Curve (AUC0-0.25) for Hydrocodone and Promethazine | Hydrocodone | 0.03786 h*ng/mL | Standard Deviation 0.1269 |
| Treatment B: CL-108 (Fed) | Area Under the Plasma Concentration-time Curve (AUC0-0.25) for Hydrocodone and Promethazine | Promethazine (Number of Participants=19,19,20,19) | 0.003941 h*ng/mL | Standard Deviation 0.01413 |
| Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted) | Area Under the Plasma Concentration-time Curve (AUC0-0.25) for Hydrocodone and Promethazine | Hydrocodone | 0.1219 h*ng/mL | Standard Deviation 0.2151 |
| Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted) | Area Under the Plasma Concentration-time Curve (AUC0-0.25) for Hydrocodone and Promethazine | Promethazine (Number of Participants=19,19,20,19) | 0.006288 h*ng/mL | Standard Deviation 0.02608 |
| Treatment D: Vicoprofen, Ultracet and Phenergan (Fed) | Area Under the Plasma Concentration-time Curve (AUC0-0.25) for Hydrocodone and Promethazine | Promethazine (Number of Participants=19,19,20,19) | 0.002612 h*ng/mL | Standard Deviation 0.01138 |
| Treatment D: Vicoprofen, Ultracet and Phenergan (Fed) | Area Under the Plasma Concentration-time Curve (AUC0-0.25) for Hydrocodone and Promethazine | Hydrocodone | 0.02250 h*ng/mL | Standard Deviation 0.04577 |
Primary
AUC0-0.50 for Hydrocodone and Promethazine
AUC0-0.50 measured by Linear Trapezoidal with Linear Interpolation method.
Time frame: 0 (pre-dose) to 0.5 hours post-dose
Population: ITT population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A: CL-108 (Fasted) | AUC0-0.50 for Hydrocodone and Promethazine | Hydrocodone | 0.9532 h*ng/mL | Standard Deviation 0.9498 |
| Treatment A: CL-108 (Fasted) | AUC0-0.50 for Hydrocodone and Promethazine | Promethazine (Number of Participants=19,19,20,19) | 0.03535 h*ng/mL | Standard Deviation 0.06239 |
| Treatment B: CL-108 (Fed) | AUC0-0.50 for Hydrocodone and Promethazine | Promethazine (Number of Participants=19,19,20,19) | 0.01570 h*ng/mL | Standard Deviation 0.03508 |
| Treatment B: CL-108 (Fed) | AUC0-0.50 for Hydrocodone and Promethazine | Hydrocodone | 0.2566 h*ng/mL | Standard Deviation 0.6382 |
| Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted) | AUC0-0.50 for Hydrocodone and Promethazine | Hydrocodone | 1.280 h*ng/mL | Standard Deviation 1.271 |
| Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted) | AUC0-0.50 for Hydrocodone and Promethazine | Promethazine (Number of Participants=19,19,20,19) | 0.02692 h*ng/mL | Standard Deviation 0.06096 |
| Treatment D: Vicoprofen, Ultracet and Phenergan (Fed) | AUC0-0.50 for Hydrocodone and Promethazine | Hydrocodone | 0.3163 h*ng/mL | Standard Deviation 0.4305 |
| Treatment D: Vicoprofen, Ultracet and Phenergan (Fed) | AUC0-0.50 for Hydrocodone and Promethazine | Promethazine (Number of Participants=19,19,20,19) | 0.01220 h*ng/mL | Standard Deviation 0.02452 |
Primary
AUC0-0.75 for Hydrocodone and Promethazine
AUC0-0.75 measured by Linear Trapezoidal with Linear Interpolation method.
Time frame: 0 (Pre-dose) to 0.75 hours post-dose
Population: ITT population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A: CL-108 (Fasted) | AUC0-0.75 for Hydrocodone and Promethazine | Hydrocodone | 3.194 h*ng/mL | Standard Deviation 2.379 |
| Treatment A: CL-108 (Fasted) | AUC0-0.75 for Hydrocodone and Promethazine | Promethazine (Number of Participants=19,19,20,19) | 0.1108 h*ng/mL | Standard Deviation 0.109 |
| Treatment B: CL-108 (Fed) | AUC0-0.75 for Hydrocodone and Promethazine | Promethazine (Number of Participants=19,19,20,19) | 0.05549 h*ng/mL | Standard Deviation 0.08128 |
| Treatment B: CL-108 (Fed) | AUC0-0.75 for Hydrocodone and Promethazine | Hydrocodone | 0.8759 h*ng/mL | Standard Deviation 1.645 |
| Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted) | AUC0-0.75 for Hydrocodone and Promethazine | Hydrocodone | 4.027 h*ng/mL | Standard Deviation 3.092 |
| Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted) | AUC0-0.75 for Hydrocodone and Promethazine | Promethazine (Number of Participants=19,19,20,19) | 0.09690 h*ng/mL | Standard Deviation 0.1478 |
| Treatment D: Vicoprofen, Ultracet and Phenergan (Fed) | AUC0-0.75 for Hydrocodone and Promethazine | Hydrocodone | 1.276 h*ng/mL | Standard Deviation 1.629 |
| Treatment D: Vicoprofen, Ultracet and Phenergan (Fed) | AUC0-0.75 for Hydrocodone and Promethazine | Promethazine (Number of Participants=19,19,20,19) | 0.04610 h*ng/mL | Standard Deviation 0.06227 |
Primary
AUC0-1.0 for Hydrocodone and Promethazine
AUC0-1.0 measured by Linear Trapezoidal with Linear Interpolation method.
Time frame: 0 (pre-dose) to 1.0 hours post-dose
Population: ITT population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A: CL-108 (Fasted) | AUC0-1.0 for Hydrocodone and Promethazine | Hydrocodone | 6.383 h*ng/mL | Standard Deviation 3.637 |
| Treatment A: CL-108 (Fasted) | AUC0-1.0 for Hydrocodone and Promethazine | Promethazine (Number of Participants=19,19,20,19) | 0.2578 h*ng/mL | Standard Deviation 0.1999 |
| Treatment B: CL-108 (Fed) | AUC0-1.0 for Hydrocodone and Promethazine | Promethazine (Number of Participants=19,19,20,19) | 0.1457 h*ng/mL | Standard Deviation 0.1649 |
| Treatment B: CL-108 (Fed) | AUC0-1.0 for Hydrocodone and Promethazine | Hydrocodone | 2.046 h*ng/mL | Standard Deviation 3.244 |
| Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted) | AUC0-1.0 for Hydrocodone and Promethazine | Hydrocodone | 7.524 h*ng/mL | Standard Deviation 4.678 |
| Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted) | AUC0-1.0 for Hydrocodone and Promethazine | Promethazine (Number of Participants=19,19,20,19) | 0.2311 h*ng/mL | Standard Deviation 0.3055 |
| Treatment D: Vicoprofen, Ultracet and Phenergan (Fed) | AUC0-1.0 for Hydrocodone and Promethazine | Hydrocodone | 2.722 h*ng/mL | Standard Deviation 3.329 |
| Treatment D: Vicoprofen, Ultracet and Phenergan (Fed) | AUC0-1.0 for Hydrocodone and Promethazine | Promethazine (Number of Participants=19,19,20,19) | 0.1109 h*ng/mL | Standard Deviation 0.1471 |
Primary
AUC0-1.5 for Hydrocodone and Promethazine
AUC0-1.5 measured by Linear Trapezoidal with Linear Interpolation method.
Time frame: 0 (pre-dose) to 1.5 hours post-dose
Population: ITT population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A: CL-108 (Fasted) | AUC0-1.5 for Hydrocodone and Promethazine | Hydrocodone | 14.33 h*ng/mL | Standard Deviation 4.971 |
| Treatment A: CL-108 (Fasted) | AUC0-1.5 for Hydrocodone and Promethazine | Promethazine (Number of Participants=19,19,20,19) | 0.8524 h*ng/mL | Standard Deviation 0.541 |
| Treatment B: CL-108 (Fed) | AUC0-1.5 for Hydrocodone and Promethazine | Promethazine (Number of Participants=19,19,20,19) | 0.5573 h*ng/mL | Standard Deviation 0.4798 |
| Treatment B: CL-108 (Fed) | AUC0-1.5 for Hydrocodone and Promethazine | Hydrocodone | 5.782 h*ng/mL | Standard Deviation 7.049 |
| Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted) | AUC0-1.5 for Hydrocodone and Promethazine | Hydrocodone | 14.95 h*ng/mL | Standard Deviation 6.822 |
| Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted) | AUC0-1.5 for Hydrocodone and Promethazine | Promethazine (Number of Participants=19,19,20,19) | 0.7330 h*ng/mL | Standard Deviation 0.8395 |
| Treatment D: Vicoprofen, Ultracet and Phenergan (Fed) | AUC0-1.5 for Hydrocodone and Promethazine | Hydrocodone | 6.424 h*ng/mL | Standard Deviation 6.742 |
| Treatment D: Vicoprofen, Ultracet and Phenergan (Fed) | AUC0-1.5 for Hydrocodone and Promethazine | Promethazine (Number of Participants=19,19,20,19) | 0.3239 h*ng/mL | Standard Deviation 0.3643 |
Primary
AUC0-2.0 for Hydrocodone and Promethazine
AUC0-2.0 measured by Linear Trapezoidal with Linear Interpolation method.
Time frame: 0 (pre-dose) to 2 hours post-dose
Population: ITT population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A: CL-108 (Fasted) | AUC0-2.0 for Hydrocodone and Promethazine | Hydrocodone | 23.21 h*ng/mL | Standard Deviation 6.24 |
| Treatment A: CL-108 (Fasted) | AUC0-2.0 for Hydrocodone and Promethazine | Promethazine (Number of Participants=19,19,20,19) | 1.938 h*ng/mL | Standard Deviation 1.318 |
| Treatment B: CL-108 (Fed) | AUC0-2.0 for Hydrocodone and Promethazine | Promethazine (Number of Participants=19,19,20,19) | 1.267 h*ng/mL | Standard Deviation 0.9936 |
| Treatment B: CL-108 (Fed) | AUC0-2.0 for Hydrocodone and Promethazine | Hydrocodone | 10.95 h*ng/mL | Standard Deviation 10.34 |
| Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted) | AUC0-2.0 for Hydrocodone and Promethazine | Hydrocodone | 22.53 h*ng/mL | Standard Deviation 8.183 |
| Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted) | AUC0-2.0 for Hydrocodone and Promethazine | Promethazine (Number of Participants=19,19,20,19) | 1.583 h*ng/mL | Standard Deviation 1.689 |
| Treatment D: Vicoprofen, Ultracet and Phenergan (Fed) | AUC0-2.0 for Hydrocodone and Promethazine | Hydrocodone | 11.04 h*ng/mL | Standard Deviation 10.12 |
| Treatment D: Vicoprofen, Ultracet and Phenergan (Fed) | AUC0-2.0 for Hydrocodone and Promethazine | Promethazine (Number of Participants=19,19,20,19) | 0.6735 h*ng/mL | Standard Deviation 0.6328 |
Primary
AUC0-4.0 for Hydrocodone and Promethazine
AUC0-4.0 measured by Linear Trapezoidal with Linear Interpolation method.
Time frame: 0 (pre-dose) to 4 hours post-dose
Population: ITT population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A: CL-108 (Fasted) | AUC0-4.0 for Hydrocodone and Promethazine | Hydrocodone | 54.04 h*ng/mL | Standard Deviation 13.77 |
| Treatment A: CL-108 (Fasted) | AUC0-4.0 for Hydrocodone and Promethazine | Promethazine (Number of Participants=19,19,20,19) | 9.124 h*ng/mL | Standard Deviation 6.271 |
| Treatment B: CL-108 (Fed) | AUC0-4.0 for Hydrocodone and Promethazine | Promethazine (Number of Participants=19,19,20,19) | 5.943 h*ng/mL | Standard Deviation 3.676 |
| Treatment B: CL-108 (Fed) | AUC0-4.0 for Hydrocodone and Promethazine | Hydrocodone | 38.97 h*ng/mL | Standard Deviation 18.47 |
| Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted) | AUC0-4.0 for Hydrocodone and Promethazine | Hydrocodone | 48.35 h*ng/mL | Standard Deviation 12.87 |
| Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted) | AUC0-4.0 for Hydrocodone and Promethazine | Promethazine (Number of Participants=19,19,20,19) | 7.101 h*ng/mL | Standard Deviation 6.159 |
| Treatment D: Vicoprofen, Ultracet and Phenergan (Fed) | AUC0-4.0 for Hydrocodone and Promethazine | Hydrocodone | 35.14 h*ng/mL | Standard Deviation 17.97 |
| Treatment D: Vicoprofen, Ultracet and Phenergan (Fed) | AUC0-4.0 for Hydrocodone and Promethazine | Promethazine (Number of Participants=19,19,20,19) | 4.045 h*ng/mL | Standard Deviation 2.497 |
Primary
Last Quantifiable Drug Concentration (Clast) Determined Directly From Individual Concentration-time Data
Time frame: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, and 48 hours post-dose
Population: ITT population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A: CL-108 (Fasted) | Last Quantifiable Drug Concentration (Clast) Determined Directly From Individual Concentration-time Data | Hydrocodone | 0.556 ng/mL | Standard Deviation 0.354 |
| Treatment A: CL-108 (Fasted) | Last Quantifiable Drug Concentration (Clast) Determined Directly From Individual Concentration-time Data | Promethazine (Number of Participants=19,19,20,19) | 0.611 ng/mL | Standard Deviation 0.936 |
| Treatment A: CL-108 (Fasted) | Last Quantifiable Drug Concentration (Clast) Determined Directly From Individual Concentration-time Data | Acetaminophen | 0.0741 ng/mL | Standard Deviation 0.0297 |
| Treatment B: CL-108 (Fed) | Last Quantifiable Drug Concentration (Clast) Determined Directly From Individual Concentration-time Data | Hydrocodone | 0.523 ng/mL | Standard Deviation 0.412 |
| Treatment B: CL-108 (Fed) | Last Quantifiable Drug Concentration (Clast) Determined Directly From Individual Concentration-time Data | Promethazine (Number of Participants=19,19,20,19) | 0.586 ng/mL | Standard Deviation 1.04 |
| Treatment B: CL-108 (Fed) | Last Quantifiable Drug Concentration (Clast) Determined Directly From Individual Concentration-time Data | Acetaminophen | 0.0917 ng/mL | Standard Deviation 0.0378 |
| Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted) | Last Quantifiable Drug Concentration (Clast) Determined Directly From Individual Concentration-time Data | Acetaminophen | 0.0724 ng/mL | Standard Deviation 0.0291 |
| Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted) | Last Quantifiable Drug Concentration (Clast) Determined Directly From Individual Concentration-time Data | Hydrocodone | 0.465 ng/mL | Standard Deviation 0.315 |
| Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted) | Last Quantifiable Drug Concentration (Clast) Determined Directly From Individual Concentration-time Data | Promethazine (Number of Participants=19,19,20,19) | 0.574 ng/mL | Standard Deviation 0.829 |
| Treatment D: Vicoprofen, Ultracet and Phenergan (Fed) | Last Quantifiable Drug Concentration (Clast) Determined Directly From Individual Concentration-time Data | Hydrocodone | 0.527 ng/mL | Standard Deviation 0.424 |
| Treatment D: Vicoprofen, Ultracet and Phenergan (Fed) | Last Quantifiable Drug Concentration (Clast) Determined Directly From Individual Concentration-time Data | Promethazine (Number of Participants=19,19,20,19) | 0.701 ng/mL | Standard Deviation 0.912 |
| Treatment D: Vicoprofen, Ultracet and Phenergan (Fed) | Last Quantifiable Drug Concentration (Clast) Determined Directly From Individual Concentration-time Data | Acetaminophen | 0.0907 ng/mL | Standard Deviation 0.0428 |
Primary
Maximum Drug Concentration (Cmax) in Plasma Determined Directly From Individual Concentration-time Data
Cmax of CL-108 and Vicoprofen + Ultracet + Phenergan were measured in the plasma (the liquid component of the blood in which the blood cells are suspended) in samples collected up to 48 hours post-dose.
Time frame: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, and 48 hours post-dose
Population: Intended to treat (ITT) population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A: CL-108 (Fasted) | Maximum Drug Concentration (Cmax) in Plasma Determined Directly From Individual Concentration-time Data | Promethazine (Number of Participants=19,19,20,19) | 4.79 ng/mL | Standard Deviation 3.75 |
| Treatment A: CL-108 (Fasted) | Maximum Drug Concentration (Cmax) in Plasma Determined Directly From Individual Concentration-time Data | Hydrocodone | 20.0 ng/mL | Standard Deviation 5.48 |
| Treatment A: CL-108 (Fasted) | Maximum Drug Concentration (Cmax) in Plasma Determined Directly From Individual Concentration-time Data | Acetaminophen | 4.71 ng/mL | Standard Deviation 1.49 |
| Treatment B: CL-108 (Fed) | Maximum Drug Concentration (Cmax) in Plasma Determined Directly From Individual Concentration-time Data | Acetaminophen | 3.27 ng/mL | Standard Deviation 1 |
| Treatment B: CL-108 (Fed) | Maximum Drug Concentration (Cmax) in Plasma Determined Directly From Individual Concentration-time Data | Hydrocodone | 17.9 ng/mL | Standard Deviation 5.8 |
| Treatment B: CL-108 (Fed) | Maximum Drug Concentration (Cmax) in Plasma Determined Directly From Individual Concentration-time Data | Promethazine (Number of Participants=19,19,20,19) | 3.66 ng/mL | Standard Deviation 2.16 |
| Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted) | Maximum Drug Concentration (Cmax) in Plasma Determined Directly From Individual Concentration-time Data | Promethazine (Number of Participants=19,19,20,19) | 4.35 ng/mL | Standard Deviation 2.94 |
| Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted) | Maximum Drug Concentration (Cmax) in Plasma Determined Directly From Individual Concentration-time Data | Hydrocodone | 18.4 ng/mL | Standard Deviation 5.62 |
| Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted) | Maximum Drug Concentration (Cmax) in Plasma Determined Directly From Individual Concentration-time Data | Acetaminophen | 5.02 ng/mL | Standard Deviation 1.66 |
| Treatment D: Vicoprofen, Ultracet and Phenergan (Fed) | Maximum Drug Concentration (Cmax) in Plasma Determined Directly From Individual Concentration-time Data | Acetaminophen | 3.03 ng/mL | Standard Deviation 0.919 |
| Treatment D: Vicoprofen, Ultracet and Phenergan (Fed) | Maximum Drug Concentration (Cmax) in Plasma Determined Directly From Individual Concentration-time Data | Hydrocodone | 17.5 ng/mL | Standard Deviation 3.63 |
| Treatment D: Vicoprofen, Ultracet and Phenergan (Fed) | Maximum Drug Concentration (Cmax) in Plasma Determined Directly From Individual Concentration-time Data | Promethazine (Number of Participants=19,19,20,19) | 4.08 ng/mL | Standard Deviation 1.95 |
Primary
Observed Elimination Rate Constant (λz)
Estimated by linear regression through at least three data points in the terminal phase of the log concentration-time profile
Time frame: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, and 48 hours post-dose
Population: ITT population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A: CL-108 (Fasted) | Observed Elimination Rate Constant (λz) | Hydrocodone | 0.1468 h-1 | Standard Deviation 0.0293 |
| Treatment A: CL-108 (Fasted) | Observed Elimination Rate Constant (λz) | Promethazine (Number of Participants=19,18,20,18) | 0.0429 h-1 | Standard Deviation 0.0129 |
| Treatment A: CL-108 (Fasted) | Observed Elimination Rate Constant (λz) | Acetaminophen | 0.1577 h-1 | Standard Deviation 0.031 |
| Treatment B: CL-108 (Fed) | Observed Elimination Rate Constant (λz) | Hydrocodone | 0.1373 h-1 | Standard Deviation 0.0258 |
| Treatment B: CL-108 (Fed) | Observed Elimination Rate Constant (λz) | Promethazine (Number of Participants=19,18,20,18) | 0.0451 h-1 | Standard Deviation 0.0451 |
| Treatment B: CL-108 (Fed) | Observed Elimination Rate Constant (λz) | Acetaminophen | 0.1359 h-1 | Standard Deviation 0.0223 |
| Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted) | Observed Elimination Rate Constant (λz) | Acetaminophen | 0.1600 h-1 | Standard Deviation 0.0355 |
| Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted) | Observed Elimination Rate Constant (λz) | Hydrocodone | 0.1415 h-1 | Standard Deviation 0.0292 |
| Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted) | Observed Elimination Rate Constant (λz) | Promethazine (Number of Participants=19,18,20,18) | 0.0422 h-1 | Standard Deviation 0.012 |
| Treatment D: Vicoprofen, Ultracet and Phenergan (Fed) | Observed Elimination Rate Constant (λz) | Hydrocodone | 0.1371 h-1 | Standard Deviation 0.0271 |
| Treatment D: Vicoprofen, Ultracet and Phenergan (Fed) | Observed Elimination Rate Constant (λz) | Promethazine (Number of Participants=19,18,20,18) | 0.0458 h-1 | Standard Deviation 0.0145 |
| Treatment D: Vicoprofen, Ultracet and Phenergan (Fed) | Observed Elimination Rate Constant (λz) | Acetaminophen | 0.1412 h-1 | Standard Deviation 0.0218 |
Primary
Observed Terminal Elimination Half-life (T1/2)
Calculated as: T1/2 = ln(2)/λz
Time frame: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, and 48 hours post-dose
Population: ITT population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A: CL-108 (Fasted) | Observed Terminal Elimination Half-life (T1/2) | Hydrocodone | 4.93 hours | Standard Deviation 1.11 |
| Treatment A: CL-108 (Fasted) | Observed Terminal Elimination Half-life (T1/2) | Promethazine (Number of Participants=19,18,20,18) | 17.49 hours | Standard Deviation 5.21 |
| Treatment A: CL-108 (Fasted) | Observed Terminal Elimination Half-life (T1/2) | Acetaminophen | 4.59 hours | Standard Deviation 1.06 |
| Treatment B: CL-108 (Fed) | Observed Terminal Elimination Half-life (T1/2) | Hydrocodone | 5.22 hours | Standard Deviation 0.99 |
| Treatment B: CL-108 (Fed) | Observed Terminal Elimination Half-life (T1/2) | Promethazine (Number of Participants=19,18,20,18) | 15.95 hours | Standard Deviation 3.04 |
| Treatment B: CL-108 (Fed) | Observed Terminal Elimination Half-life (T1/2) | Acetaminophen | 5.22 hours | Standard Deviation 0.79 |
| Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted) | Observed Terminal Elimination Half-life (T1/2) | Acetaminophen | 4.52 hours | Standard Deviation 0.93 |
| Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted) | Observed Terminal Elimination Half-life (T1/2) | Hydrocodone | 5.13 hours | Standard Deviation 1.18 |
| Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted) | Observed Terminal Elimination Half-life (T1/2) | Promethazine (Number of Participants=19,18,20,18) | 17.77 hours | Standard Deviation 5.57 |
| Treatment D: Vicoprofen, Ultracet and Phenergan (Fed) | Observed Terminal Elimination Half-life (T1/2) | Hydrocodone | 5.26 hours | Standard Deviation 1.08 |
| Treatment D: Vicoprofen, Ultracet and Phenergan (Fed) | Observed Terminal Elimination Half-life (T1/2) | Promethazine (Number of Participants=19,18,20,18) | 16.24 hours | Standard Deviation 4.09 |
| Treatment D: Vicoprofen, Ultracet and Phenergan (Fed) | Observed Terminal Elimination Half-life (T1/2) | Acetaminophen | 5.03 hours | Standard Deviation 0.86 |
Primary
Percentage of AUCinf [AUCExtrap (%)] Based on Extrapolation
Calculated as: AUCExtrap (%) = (AUC0-inf - AUC0-last)/AUC0-inf \*100
Time frame: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, and 48 hours post-dose
Population: ITT population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A: CL-108 (Fasted) | Percentage of AUCinf [AUCExtrap (%)] Based on Extrapolation | Hydrocodone | 2.72 Percentage of AUCExtrap | Standard Deviation 1.72 |
| Treatment A: CL-108 (Fasted) | Percentage of AUCinf [AUCExtrap (%)] Based on Extrapolation | Promethazine (Number of Participants=19,18,20,18) | 14.35 Percentage of AUCExtrap | Standard Deviation 7.03 |
| Treatment B: CL-108 (Fed) | Percentage of AUCinf [AUCExtrap (%)] Based on Extrapolation | Promethazine (Number of Participants=19,18,20,18) | 13.54 Percentage of AUCExtrap | Standard Deviation 4.64 |
| Treatment B: CL-108 (Fed) | Percentage of AUCinf [AUCExtrap (%)] Based on Extrapolation | Hydrocodone | 2.68 Percentage of AUCExtrap | Standard Deviation 1.97 |
| Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted) | Percentage of AUCinf [AUCExtrap (%)] Based on Extrapolation | Hydrocodone | 2.65 Percentage of AUCExtrap | Standard Deviation 1.78 |
| Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted) | Percentage of AUCinf [AUCExtrap (%)] Based on Extrapolation | Promethazine (Number of Participants=19,18,20,18) | 15.15 Percentage of AUCExtrap | Standard Deviation 7.86 |
| Treatment D: Vicoprofen, Ultracet and Phenergan (Fed) | Percentage of AUCinf [AUCExtrap (%)] Based on Extrapolation | Hydrocodone | 2.71 Percentage of AUCExtrap | Standard Deviation 2.06 |
| Treatment D: Vicoprofen, Ultracet and Phenergan (Fed) | Percentage of AUCinf [AUCExtrap (%)] Based on Extrapolation | Promethazine (Number of Participants=19,18,20,18) | 14.56 Percentage of AUCExtrap | Standard Deviation 6.28 |
Primary
Time of the Last Quantifiable Concentration (Tlast)
Time frame: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, and 48 hours post-dose
Population: ITT population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A: CL-108 (Fasted) | Time of the Last Quantifiable Concentration (Tlast) | Hydrocodone | 27.80 Hours | Standard Deviation 8.99 |
| Treatment A: CL-108 (Fasted) | Time of the Last Quantifiable Concentration (Tlast) | Promethazine (Number of Participants=19,19,20,19) | 46.76 Hours | Standard Deviation 5.51 |
| Treatment A: CL-108 (Fasted) | Time of the Last Quantifiable Concentration (Tlast) | Acetaminophen | 23.38 Hours | Standard Deviation 2.76 |
| Treatment B: CL-108 (Fed) | Time of the Last Quantifiable Concentration (Tlast) | Promethazine (Number of Participants=19,19,20,19) | 46.77 Hours | Standard Deviation 5.52 |
| Treatment B: CL-108 (Fed) | Time of the Last Quantifiable Concentration (Tlast) | Hydrocodone | 31.21 Hours | Standard Deviation 11.28 |
| Treatment B: CL-108 (Fed) | Time of the Last Quantifiable Concentration (Tlast) | Acetaminophen | 24.01 Hours | Standard Deviation 0.04 |
| Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted) | Time of the Last Quantifiable Concentration (Tlast) | Promethazine (Number of Participants=19,19,20,19) | 46.81 Hours | Standard Deviation 5.37 |
| Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted) | Time of the Last Quantifiable Concentration (Tlast) | Acetaminophen | 23.41 Hours | Standard Deviation 2.69 |
| Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted) | Time of the Last Quantifiable Concentration (Tlast) | Hydrocodone | 28.81 Hours | Standard Deviation 9.84 |
| Treatment D: Vicoprofen, Ultracet and Phenergan (Fed) | Time of the Last Quantifiable Concentration (Tlast) | Hydrocodone | 31.58 Hours | Standard Deviation 11.46 |
| Treatment D: Vicoprofen, Ultracet and Phenergan (Fed) | Time of the Last Quantifiable Concentration (Tlast) | Promethazine (Number of Participants=19,19,20,19) | 46.74 Hours | Standard Deviation 5.51 |
| Treatment D: Vicoprofen, Ultracet and Phenergan (Fed) | Time of the Last Quantifiable Concentration (Tlast) | Acetaminophen | 24.01 Hours | Standard Deviation 0.02 |
Primary
Time to Reach Maximum Concentration (Tmax)
Time frame: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, and 48 hours post-dose
Population: ITT population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A: CL-108 (Fasted) | Time to Reach Maximum Concentration (Tmax) | Hydrocodone | 1.55 hours | Standard Deviation 0.71 |
| Treatment A: CL-108 (Fasted) | Time to Reach Maximum Concentration (Tmax) | Promethazine (Number of Participants=19,19,20,19) | 4.35 hours | Standard Deviation 1.37 |
| Treatment A: CL-108 (Fasted) | Time to Reach Maximum Concentration (Tmax) | Acetaminophen | 0.91 hours | Standard Deviation 0.44 |
| Treatment B: CL-108 (Fed) | Time to Reach Maximum Concentration (Tmax) | Hydrocodone | 3.38 hours | Standard Deviation 1.58 |
| Treatment B: CL-108 (Fed) | Time to Reach Maximum Concentration (Tmax) | Promethazine (Number of Participants=19,19,20,19) | 5.24 hours | Standard Deviation 2.37 |
| Treatment B: CL-108 (Fed) | Time to Reach Maximum Concentration (Tmax) | Acetaminophen | 2.84 hours | Standard Deviation 1.49 |
| Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted) | Time to Reach Maximum Concentration (Tmax) | Acetaminophen | 0.80 hours | Standard Deviation 0.55 |
| Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted) | Time to Reach Maximum Concentration (Tmax) | Hydrocodone | 1.39 hours | Standard Deviation 1.22 |
| Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted) | Time to Reach Maximum Concentration (Tmax) | Promethazine (Number of Participants=19,19,20,19) | 4.90 hours | Standard Deviation 1.72 |
| Treatment D: Vicoprofen, Ultracet and Phenergan (Fed) | Time to Reach Maximum Concentration (Tmax) | Hydrocodone | 3.09 hours | Standard Deviation 1.89 |
| Treatment D: Vicoprofen, Ultracet and Phenergan (Fed) | Time to Reach Maximum Concentration (Tmax) | Promethazine (Number of Participants=19,19,20,19) | 6.45 hours | Standard Deviation 4.59 |
| Treatment D: Vicoprofen, Ultracet and Phenergan (Fed) | Time to Reach Maximum Concentration (Tmax) | Acetaminophen | 2.64 hours | Standard Deviation 1.44 |