A Study to Assess the Abuse Potential of Hydrocodone Extended-Release Tablet in Recreational Opioid Users

NCT01596673 | Completed Phase 1

• 1 other identifier: C33237/1085
• Study Type: interventional
• Target: 100
• Locations: 2 countries
• Sites: 2

Brief Summary

The purpose of this study is to assess the relative abuse potential of the hydrocodone bitartrate extended-release tablet compared to immediate-release hydrocodone bitartrate.

Conditions

Drug Abuse

Outcome Measures

Primary Outcomes (1)

• Drug Liking and Effects Questionnaire (DLEQ)

  The DLEQ measures positive, negative, and any drug effects using bipolar and unipolar VAS. Bipolar VAS range from a strong negative response (score of 0) to a strong positive response (score of 100) with a neutral midpoint (score of 50). Unipolar VAS range from a response of 'none' (score of 0) to 'extremely' (score of 100). Questions include assessments of liking, drowsiness, good effects, bad effects, nausea,and any effects. The primary outcome is question 1 which states: "My liking for this drug is:"

  Phase B: prior to and at designated times up to 24 hours after study drug administration. Phase C:prior to and at set times up to 72 hours after study drug administration

Secondary Outcomes (15)

• Overall drug liking visual analog scale (VAS) score

  24 hours after the start of each study drug administration in phase B and C

• Pharmacokinetic maximum observed (Cmax) plasma concentrations

  Approximately 30 minutes before study drug administration up to 72 hours post study drug administration

• Take drug again Visual Analog Scale

  24 hours after the start of each study drug administration in phase B and C

• Price Value Assessment Questionnaire

  24 hours after the start of each study drug administration in phase B and C

• Addiction Research Center Inventory (ARCI): Morphine Benzedrine Group (MBG) Subscale

  Phase B: prior to and at designated times up to 24 hours after study drug administration. Phase C:prior to and at set times up to 72 hours after study drug administration

Study Arms (4)

BCAD Treatment Group

EXPERIMENTAL

Subjects in this group will receive study drug in the following sequence: Treatment B - 1 intact placebo tablet, hydrocodone bitartrate powder at a dose strength of 45 mg reconstituted in 60 mL of a noncarbonated flavored beverage, and 1 crushed placebo tablet. Treatment C - 1 intact 45-mg hydrocodone bitartrate extended-release tablet, 60 mL of a noncarbonated flavored beverage, and 1 crushed placebo tablet. Treatment A - 1 intact placebo tablet, 60 mL of a noncarbonated flavored beverage, 1 crushed 45-mg hydrocodone bitartrate extended-release tablet. Treatment D - 1 intact placebo tablet, 60 mL of a noncarbonated flavored beverage, and 1 crushed placebo tablet(matching the 45-mg hydrocodone bitartrate extended-release tablet).

Drug: 45-mg hydrocodone bitartrate extended-release tablet (crushed or intact); Drug: Placebo

CDBA Treatment Group

EXPERIMENTAL

Subjects in this group will receive study drug in the following sequence: Treatment C - 1 intact 45-mg hydrocodone bitartrate extended-release tablet, 60 mL of a noncarbonated flavored beverage, and 1 crushed placebo tablet. Treatment D - 1 intact placebo tablet, 60 mL of a noncarbonated flavored beverage, and 1 crushed placebo tablet (matching the 45-mg hydrocodone bitartrate extended-release tablet). Treatment B - 1 intact placebo tablet, hydrocodone bitartrate powder at a dose strength of 45 mg reconstituted in 60 mL of a noncarbonated flavored beverage, and 1 crushed placebo tablet. Treatment A - 1 intact placebo tablet, 60 mL of a noncarbonated flavored beverage, 1 crushed 45-mg hydrocodone bitartrate extended-release tablet.

Drug: 45-mg hydrocodone bitartrate extended-release tablet (crushed or intact); Drug: Placebo

DACB Treatment Group

EXPERIMENTAL

Subjects in this group will receive study drug in the following sequence: Treatment D - 1 intact placebo tablet, 60 mL of a noncarbonated flavored beverage, and 1 crushed placebo tablet(matching the 45-mg hydrocodone bitartrate extended-release tablet). Treatment A - 1 intact placebo tablet, 60 mL of a noncarbonated flavored beverage, 1 crushed 45-mg hydrocodone bitartrate extended-release tablet. Treatment C - 1 intact 45-mg hydrocodone bitartrate extended-release tablet, 60 mL of a noncarbonated flavored beverage, and 1 crushed placebo tablet. Treatment B - 1 intact placebo tablet, hydrocodone bitartrate powder at a dose strength of 45 mg reconstituted in 60 mL of a noncarbonated flavored beverage, and 1 crushed placebo tablet.

Drug: 45-mg hydrocodone bitartrate extended-release tablet (crushed or intact); Drug: Placebo

ABDC Treatment Group

EXPERIMENTAL

Subjects in this group will receive study drug in the following sequence: Treatment A - 1 intact placebo tablet, 60 mL of a noncarbonated flavored beverage, 1 crushed 45-mg hydrocodone bitartrate extended-release tablet. Treatment B - 1 intact placebo tablet, hydrocodone bitartrate powder at a dose strength of 45 mg reconstituted in 60 mL of a noncarbonated flavored beverage, and 1 crushed placebo tablet. Treatment D - 1 intact placebo tablet, 60 mL of a noncarbonated flavored beverage, and 1 crushed placebo tablet(matching the 45-mg hydrocodone bitartrate extended-release tablet). Treatment C - 1 intact 45-mg hydrocodone bitartrate extended-release tablet, 60 mL of a noncarbonated flavored beverage, and 1 crushed placebo tablet.

Drug: 45-mg hydrocodone bitartrate extended-release tablet (crushed or intact); Drug: Placebo

Interventions

45-mg hydrocodone bitartrate extended-release tablet (crushed or intact) DRUG

Phase B: Eligible subjects will be randomized to treatment sequence XY or YX whereby treatment X is 60 mL of a noncarbonated flavored beverage and treatment Y is hydrocodone bitartrate powder at a dose strength of 45-mg reconstituted in 60 mL of a noncarbonated flavored beverage. Phase C: Eligible subjects will be randomly assigned to 1 of 4 treatment arms: Treatment A: intact placebo tablet, 60 mL noncarbonated flavored beverage, 1 crushed 45-mg hydrocodone bitartrate extended-release tablet. Treatment B: intact placebo tablet, hydrocodone bitartrate powder at a dose strength of 45-mg in 60 mL of a noncarbonated flavored beverage and 1 crushed placebo tablet. Treatment C: intact 45-mg hydrocodone bitartrate extended-release tablet, 60 mL noncarbonated flavored beverage, and 1 crushed placebo tablet Treatment D: intact placebo tablet, 60 mL noncarbonated flavored beverage, and 1 crushed placebo tablet.

Also known as: hydrocodone

ABDC Treatment Group; BCAD Treatment Group; CDBA Treatment Group; DACB Treatment Group

Placebo DRUG

Placebo will consist of 60 mL of a non-carbonated beverage without the addition of active treatment

ABDC Treatment Group; BCAD Treatment Group; CDBA Treatment Group; DACB Treatment Group

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Written informed consent is obtained.
• The subject speaks and writes in English.
• The subject is not physically dependent on opioids as demonstrated by successful completion of a naloxone challenge; ie, subject does not exhibit signs or symptoms of opioid withdrawal (as assessed by a Clinical Opiate Withdrawal Scale score of \<5) following administration of intravenous naloxone in the Naloxone Challenge.
• The subject has a history of recreational opioid use to achieve a "high" at least 10 times in the last year and at least on 1 occasion within the 12 weeks before screening. Subjects who abuse multiple drugs should express a preference for opioids.
• The subject is aged 18 through 50 years with a minimum body weight of 50 kg and a body mass index (BMI) of 18.0 through 32.0 kg/m2.
• The subject is in good health as determined by medical and psychiatric history, physical examination, ECG, serum chemistry, hematology, urinalysis, and serology.
• The subject, if a woman, is surgically sterile or 2 years postmenopausal, or if of childbearing potential, is currently using a medically accepted method of contraception and agrees to continue use of this method for the duration of the study (and for 30 days after participation in the study). Acceptable methods of contraception include abstinence, or an intrauterine device (known to have a failure rate of less than 1% per year).
• The subject must have a negative urine drug screen (except for tetrahydrocannabinol) and a negative alcohol test at screening. NOTE: If a subject tests negative for tetrahydrocannabinol at screening, the test result at baseline must be negative for the subject to be considered for enrollment in the study.
• The subject is willing to comply with study restrictions and remain at the study center for the duration of each treatment period during the study.

You may not qualify if:

• The subject has any clinically significant uncontrolled medical conditions (treated or untreated).
• The subject has a clinically significant deviation from normal in the clinical laboratory values or ECG or physical examination findings, as determined by the investigator or the medical monitor.
• The subject is a poor metabolizer of cytochrome P450 (CYP2D6) substrates based on genotyping performed at screening.
• The subject currently or has habitually consumed, within the past 2 years, more than 28 units of alcohol per week for male subjects or 21 units of alcohol per week for female subjects, or has a history or current diagnosis of substance dependence as assessed using by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). NOTE: A unit of alcohol is equal to 1 ounce of hard liquor, 5 ounces of wine, or 8 ounces of beer.
• The subject has participated in, is currently participating in or is seeking treatment for substance-related disorders (excluding nicotine).
• The subject is a heavy smoker (\>20 cigarettes per day), chews tobacco and/or is unable to abstain from smoking for 6 hours during any day, or abstain from caffeine intake for 20 hours during any day.
• The subject is a pregnant or lactating woman. (Any woman becoming pregnant during the study will be withdrawn from the study.)
• The subject has previously participated in a Cephalon-sponsored clinical study with the hydrocodone bitartrate extended-release tablet.
• The subject has any disorder that may interfere with drug absorption, distribution, metabolism, or excretion (including gastrointestinal surgery \[appendectomy allowed\]).
• The subject has a known sensitivity or idiosyncratic reaction to any compound present in hydrocodone or hydromorphone, their related compounds, or to any metabolites, to the solution used for reconstitution of the immediate-release product, or to any compound listed as being present in a study formulation or naloxone.
• The subject has received any investigational drug within 30 days or 5 half-lives (whichever is longer) before the first study drug administration in phase B.
• The subject has used any vitamins within 2 weeks before the first study drug administration in phase B or has used any systemic or topical prescription, or nonprescription medication (ie, over-the-counter \[OTC\] medications \[except acetaminophen or ibuprofen\]) within 2 weeks before the first study drug administration in phase B without evaluation and approval from the medical monitor.
• The subject has used herbal supplements within 2 weeks before the first study drug administration in phase B without evaluation and approval from the medical monitor.
• The subject has donated any plasma within 7 days prior to screening.
• The subject has donated any blood in excess of 450 mL within 56 days prior to screening.

Sponsors & Collaborators

• Cephalon: lead

Study Sites (2)

Cephalon Investigational Site 001

Salt Lake City, Utah, United States

Location

Cephalon Investigational Site 100

Toronto, Ontario, Canada

Location

MeSH Terms

Conditions

Substance-Related Disorders

Interventions

Hydrocodone

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Codeine; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Sponsor's Medical Expert, MD

  Cephalon

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2012
• First Posted: May 11, 2012
• Study Start: March 1, 2012
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2012
• Last Updated: November 21, 2012

Record last verified: 2012-11

Locations

US (1); CA (1)