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

NCT02465866 | Completed Phase 1 Results

• 1 other identifier: CLCT-004
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Healthy

Keywords

Plasma concentration; Time to plasma concentration; Elimination rate constant; Elimination half life; Area under the curve

Outcome Measures

Primary Outcomes (16)

• 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

Study Arms (4)

Treatment A: CL-108 (Fasted)

EXPERIMENTAL

CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fasted condition

Drug: CL-108

Treatment B: CL-108 (Fed)

EXPERIMENTAL

CL-108 single dose tablet (7.5 mg/325 mg/12.5 mg) by mouth under fed condition

Drug: CL-108

Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted)

ACTIVE COMPARATOR

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; Drug: Ultracet; Drug: Phenergan

Treatment D: Vicoprofen, Ultracet and Phenergan (Fed)

ACTIVE COMPARATOR

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; Drug: Ultracet; Drug: Phenergan

Interventions

CL-108 DRUG

Hydrocodone bitartrate/acetaminophen/promethazine 7.5 mg/325 mg/12.5 mg single dose by mouth

Treatment A: CL-108 (Fasted); Treatment B: CL-108 (Fed)

Vicoprofen DRUG

Hydrocodone Bitartrate and Ibuprofen 7.5 mg/200 mg single dose tablet by mouth

Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted); Treatment D: Vicoprofen, Ultracet and Phenergan (Fed)

Ultracet DRUG

Tramadol HCl/acetaminophen 37.5 mg/325 mg single dose tablet by mouth

Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted); Treatment D: Vicoprofen, Ultracet and Phenergan (Fed)

Phenergan DRUG

Phenergan (Promethazine HCl, USP) 12.5 mg single dose tablet by mouth

Also known as: Promethazine HCl

Treatment C: Vicoprofen, Ultracet and Phenergan (Fasted); Treatment D: Vicoprofen, Ultracet and Phenergan (Fed)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Charleston Laboratories, Inc: lead

MeSH Terms

Interventions

hydrocodone tartrate, ibuprofen drug combination; Ultracet; Promethazine; Diphenhydramine

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Phenothiazines; Sulfur Compounds; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Ethylamines; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Chief Commercial Officer
• Organization: Charleston Laboratories, Inc

cliregulatory@charlestonlabs.com

561-748-2007

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice-President, Regulatory Affairs

Study Record Dates

• First Submitted: June 4, 2015
• First Posted: June 9, 2015
• Study Start: November 1, 2014
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: May 2, 2017
• Results First Posted: March 20, 2017

Record last verified: 2017-03