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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: CL-108; Drug: Vicoprofen; Drug: Ultracet; Drug: Phenergan

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Charleston Laboratories, Inc

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: June 4, 2015
• First Submitted That Met QC Criteria: June 4, 2015
• First Posted (Estimate): June 9, 2015

Study Record Updates

• Last Update Posted (Actual): May 2, 2017
• Last Update Submitted That Met QC Criteria: March 30, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Plasma concentration; Area under the curve; Time to plasma concentration; Elimination rate constant; Elimination half life
• Additional Relevant MeSH Terms: Nutrition Disorders; Malnutrition; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Dermatologic Agents; Anti-Allergic Agents; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Antipruritics; Promethazine
• Other Study ID Numbers: CLCT-004