A Four-Period, Four-Treatment, Four-Way Relative Bioavailability Study of CL-108 Under Fed and Fasted Conditions

Study Overview
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Brief Summary
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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.

Official Title
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A Single-Dose, Four-Period, Four-Treatment, Four-Way Crossover Relative Bioavailability Study of CL-108 Under Fed and Fasted Conditions

Conditions
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Healthy

Intervention / Treatment
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* Drug: CL-108
* Drug: Vicoprofen
* Drug: Ultracet
* Drug: Phenergan


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A: CL-108 (Fasted)<br>CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fasted condition | Drug: CL-108<br>* Hydrocodone bitartrate/acetaminophen/promethazine 7.5 mg/325 mg/12.5 mg single dose by mouth<br>|
| Experimental: Treatment B: CL-108 (Fed)<br>CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fed condition | Drug: CL-108<br>* Hydrocodone bitartrate/acetaminophen/promethazine 7.5 mg/325 mg/12.5 mg single dose by mouth<br>|
| Active Comparator: Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted)<br>Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fasted condition | Drug: Vicoprofen<br>* Hydrocodone Bitartrate and Ibuprofen 7.5 mg/200 mg single dose tablet by mouth<br>Drug: Ultracet<br>* Tramadol HCl/acetaminophen 37.5 mg/325 mg single dose tablet by mouth<br>Drug: Phenergan<br>* Phenergan (Promethazine HCl, USP) 12.5 mg single dose tablet by mouth<br>* Other names: Promethazine HCl;|
| Active Comparator: Treatment D: Vicoprofen, Ultracet and Phenergan (Fed)<br>Vicoprofen 7.5 mg/200 mg + Ultracet 37.5 mg/325 mg + Phenergan 12.5 mg single dose tablets by mouth under fed condition | Drug: Vicoprofen<br>* Hydrocodone Bitartrate and Ibuprofen 7.5 mg/200 mg single dose tablet by mouth<br>Drug: Ultracet<br>* Tramadol HCl/acetaminophen 37.5 mg/325 mg single dose tablet by mouth<br>Drug: Phenergan<br>* Phenergan (Promethazine HCl, USP) 12.5 mg single dose tablet by mouth<br>* Other names: Promethazine HCl;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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 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) | Estimated by linear regression through at least three data points in the terminal phase of the log concentration-time profile | 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 Terminal Elimination Half-life (T1/2) | Calculated as: T1/2 = ln(2)/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 | 
| 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. | 0 (pre-dose) to 0.25 hours post-dose | 
| AUC0-0.50 for Hydrocodone and Promethazine | AUC0-0.50 measured by Linear Trapezoidal with Linear Interpolation method. | 0 (pre-dose) to 0.5 hours post-dose | 
| AUC0-0.75 for Hydrocodone and Promethazine | AUC0-0.75 measured by Linear Trapezoidal with Linear Interpolation method. | 0 (Pre-dose) to 0.75 hours post-dose | 
| AUC0-1.0 for Hydrocodone and Promethazine | AUC0-1.0 measured by Linear Trapezoidal with Linear Interpolation method. | 0 (pre-dose) to 1.0 hours post-dose | 
| AUC0-1.5 for Hydrocodone and Promethazine | AUC0-1.5 measured by Linear Trapezoidal with Linear Interpolation method. | 0 (pre-dose) to 1.5 hours post-dose | 
| AUC0-2.0 for Hydrocodone and Promethazine | AUC0-2.0 measured by Linear Trapezoidal with Linear Interpolation method. | 0 (pre-dose) to 2 hours post-dose | 
| AUC0-4.0 for Hydrocodone and Promethazine | AUC0-4.0 measured by Linear Trapezoidal with Linear Interpolation method. | 0 (pre-dose) to 4 hours post-dose | 
| 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 | 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 | 
| Area Under the Concentration-time (AUCinf) Curve From Time-zero Extrapolated to Infinity | Calculated as: AUCinf = AUClast + Clast/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 | 
| Percentage of AUCinf [AUCExtrap (%)] Based on Extrapolation | Calculated as: AUCExtrap (%) = (AUC0-inf - AUC0-last)/AUC0-inf *100 | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Elimination rate constant, Elimination half life, Area under the curve, Plasma concentration, Time to plasma concentration