MedPath

A Study to Characterize the Abuse Liability of Intravenous Oxycodone Alone or in Combination With Intravenous Naltrexone in Healthy, Non-Dependent, Recreational Opioid Users

Phase 1
Completed
Conditions
Healthy
Interventions
Registration Number
NCT01825447
Lead Sponsor
Pfizer
Brief Summary

The main purpose of this study is to simulate if oxycodone and naltrexone combination capsules (ALO-02) were to be tampered with by dissolving and then injecting intravenously for the purpose of getting high.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
89
Inclusion Criteria
  • Healthy subjects
  • Non-dependent, recreational opioid users
  • Must include at least one of these routes of administration: intranasal use on at least 3 occassions in the past year or intravenous use on at least 1 occasion in the past year before Screening (Visit 1).
Exclusion Criteria
  • Diagnosis of substance and/or alcohol dependence
  • Subject has participated in, is currently participating in, or seeking treatment for substance and/or alcohol related disorder
  • History of sleep apnea.

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Treatment APlacebo-
Treatment BOxycodone + Naltrexone-
Treatment COxycodone-
Primary Outcome Measures
NameTimeMethod
High: Area Under Effect Curve (AUE) From 0-2 Hourspre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose

High VAS assesses the effect experienced by the participant on a 100-point unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0) to 'extremely' (score of 100).

High: Peak Effect (Emax)pre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Drug Liking: Area Under Effect Curve (AUE) From 0-2 Hours5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose

Drug liking assesses the degree that a participant likes a drug effect at the time the question is being asked (that is, at the moment). It is scored using a 100-point bipolar visual analogue scale (VAS) anchored in the center with a neutral anchor of

Drug Liking: Peak Effect (Emax)5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Secondary Outcome Measures
NameTimeMethod
Bad Drug Effects: Time to Maximum (Peak) Effect (TEmax)5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Take Drug Again: Mean Effect (Emean)12, 24 h post-dose
Overall Drug Liking: Peak Effect (Emax)12, 24 h post-dose

Overall Drug Liking VAS assesses the participant's global perception of drug liking (that is, effects over the whole course of the drug experience including any carryover effects). A 100-point VAS is used to assess response based on a score ranging from 0 to 100 (0 =

Overall Drug Liking: Mean Effect (Emean)12, 24 h post-dose
Any Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour5 min, 15 min, 30 min, 45 min, 1 h post-dose

Any Drug Effects VAS assesses the effect experienced by the participant on a 100-point unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0) to 'extremely' (score of 100).

Nausea: Area Under Effect Curve (AUE) From 0-2 Hourspre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2 h post-dose
Nausea: Area Under Effect Curve (AUE) From 0-8 Hourspre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8 h post-dose
Drug Liking: Area Under Effect Curve (AUE) From 0-1 Hour5 min, 15 min, 30 min, 45 min, 1 h post-dose

Drug liking assesses the degree that a participant likes a drug effect at the time the question is being asked (that is, at the moment). It is scored using a 100-point bipolar visual analogue scale (VAS) anchored in the center with a neutral anchor of

Drug Liking: Area Under Effect Curve (AUE) From 0-8 Hours5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8 h post-dose
High: Area Under Effect Curve (AUE) From 0-1 Hourpre-dose, 5 min, 15 min, 30 min, 45 min, 1 h post-dose

High VAS assesses the effect experienced by the participant on a 100-point unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0) to 'extremely' (score of 100).

High: Area Under Effect Curve (AUE) From 0-8 Hourspre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8 h post-dose
Feel Sick: Area Under Effect Curve (AUE) From 0-8 Hourspre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8 h post-dose
Nausea: Time to Maximum (Peak) Effect (TEmax)pre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Feel Sick: Time to Maximum (Peak) Effect (TEmax)pre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Plasma Concentration of Oxycodone 5 Minutes Post-Dose (C5min)pre-dose, 5 min post-dose
Plasma Concentration of Oxymorphone 5 Minutes Post-Dose (C5min)pre-dose, 5 min post-dose
Plasma Concentration of Noroxycodone 5 Minutes Post-Dose (C5min)pre-dose, 5 min post-dose
Plasma Concentration of Naltrexone 5 Minutes Post-Dose (C5min)pre-dose, 5 min post-dose
Plasma Concentration of 6-beta-naltrexol 5 Minutes Post-Dose (C5min)pre-dose, 5 min post-dose
Plasma Decay Half-Life (t1/2) of Oxycodonepre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

Plasma Decay Half-Life (t1/2) of Oxymorphonepre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Plasma Decay Half-Life (t1/2) of Noroxycodonepre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Take Drug Again: Peak Effect (Emax)12, 24 h post-dose

Take Drug Again VAS is a subjective assessment of the degree to which a participant would desire to take the drug again if given the opportunity. It is presented on a 100-point bipolar VAS with score ranging from 0 mm to 100 (score of 0 =

Feel Sick: Area Under Effect Curve (AUE) From 0-2 Hourspre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2 h post-dose
Good Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour5 min, 15 min, 30 min, 45 min, 1 h post-dose

Good Drug Effects VAS assesses the effect experienced by the participant on a 100-point unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0) to 'extremely' (score of 100).

Good Drug Effects: Area Under Effect Curve (AUE) From 0-2 Hours5 min, 15 min, 30 min, 45 min, 1, 1.5, 2 h
Any Drug Effects: Area Under Effect Curve (AUE) From 0-2 Hours5 min, 15 min, 30 min, 45 min, 1, 1.5, 2 h post-dose
Any Drug Effects: Area Under Effect Curve (AUE) From 0-8 Hours5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8 h post-dose
Dizzy: Area Under Effect Curve (AUE) From 0-1 Hourpre-dose, 5 min, 15 min, 30 min, 45 min, 1 h post-dose

Dizzy VAS assesses the effect experienced by the participant on a 100-point unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0) to 'extremely' (score of 100).

Dizzy: Area Under Effect Curve (AUE) From 0-2 Hourspre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2 h post-dose
Dizzy: Area Under Effect Curve (AUE) From 0-8 Hourspre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8 h post-dose
Any Drug Effects: Peak Effect (Emax)5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Good Drug Effects: Peak Effect (Emax)5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Bad Drug Effects: Peak Effect (Emax)5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Feel Sick: Peak Effect (Emax)pre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Nausea: Peak Effect (Emax)pre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Sleepy: Peak Effect (Emax)pre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Dizzy: Peak Effect (Emax)pre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Nausea: Area Under Effect Curve (AUE) From 0-1 Hourpre-dose, 5 min, 15 min, 30 min, 45 min, 1 h post-dose

Nausea VAS assesses the effect experienced by the participant on a 100-point unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0) to 'extremely' (score of 100).

Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hourpre-dose, 5 min, 15 min, 30 min, 45 min, 1 h post-dose

Pupillometry assessments measured change in pupil size (miosis) as an indicator of opioid pharmacological properties. The same eye for each participant was used for all measurements during the study. Participants have the size of their pupil measured (in mm) using a pupillometer. Measurements are made in a dimly lit (mesopic) room with controlled lighting conditions.

Pupillometry: Area Under Effect Curve (AUE) From 0-2 Hourspre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2 h post-dose
Pupillometry: Area Under Effect Curve (AUE) From 0-8 Hourspre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8 h post-dose
Pupillometry: Peak Effect (Emax)pre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Pupillometry: Time to Maximum (Peak) Effect (TEmax)pre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Drug Liking: Time to Maximum (Peak) Effect (TEmax)5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
High: Time to Maximum (Peak) Effect (TEmax)pre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Good Drug Effects: Time to Maximum (Peak) Effect (TEmax)5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Good Drug Effects: Area Under Effect Curve (AUE) From 0-8 Hours5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8 h post-dose
Bad Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour5 min, 15 min, 30 min, 45 min, 1 h post-dose

Bad Drug Effects VAS assesses the effect experienced by the participant on a 100-point unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0) to 'extremely' (score of 100).

Bad Drug Effects: Area Under Effect Curve (AUE) From 0-2 Hours5 min, 15 min, 30 min, 45 min, 1, 1.5, 2 h
Bad Drug Effects: Area Under Effect Curve (AUE) From 0-8 Hours5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8 h post-dose
Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hourpre-dose, 5 min, 15 min, 30 min, 45 min, 1 h post-dose

Feel Sick VAS assesses the effect experienced by the participant on a 100-point unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0) to 'extremely' (score of 100).

Sleepy: Area Under Effect Curve (AUE) From 0-1 Hourpre-dose, 5 min, 15 min, 30 min, 45 min, 1 h post-dose

Sleepy VAS assesses the effect experienced by the participant on a 100-point unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0) to 'extremely' (score of 100).

Sleepy: Area Under Effect Curve (AUE) From 0-2 Hourspre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2 h post-dose
Sleepy: Area Under Effect Curve (AUE) From 0-8 Hourspre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8 h post-dose
Any Drug Effects: Time to Maximum (Peak) Effect (TEmax)5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Systemic Clearance (Cl) of Oxymorphonepre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Systemic Clearance (Cl) of Noroxycodonepre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Volume of Distribution at Steady State (Vss) for Oxymorphonepre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Sleepy: Time to Maximum (Peak) Effect (TEmax)pre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Dizzy: Time to Maximum (Peak) Effect (TEmax)pre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Area Under the Curve From Time Zero to Last Quantifiable 6-beta-naltrexol Concentration (AUClast)pre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Plasma Decay Half-Life (t1/2) of Naltrexonepre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Plasma Decay Half-Life (t1/2) of 6-beta-naltrexolpre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Area Under the Oxycodone Concentration-Time Curve (AUC0-1h)pre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose

AUC is a measure of the plasma concentration of the drug over time.

Area Under the Oxymorphone Concentration-Time Curve (AUC0-1h)pre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Area Under the Noroxycodone Concentration-Time Curve (AUC0-1h)pre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Area Under the Naltrexone Concentration-Time Curve (AUC0-1h)pre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Area Under the 6-beta-naltrexol Concentration-Time Curve (AUC0-1h)pre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Area Under the Oxycodone Concentration-Time Curve (AUC0-2h)pre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Area Under the Oxymorphone Concentration-Time Curve (AUC0-2h)pre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Area Under the Noroxycodone Concentration-Time Curve (AUC0-2h)pre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Area Under the Naltrexone Concentration-Time Curve (AUC0-2h)pre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Area Under the 6-beta-naltrexol Concentration-Time Curve (AUC0-2h)pre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Area Under the Oxycodone Concentration-Time Curve (AUC0-8h)pre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Area Under the Oxymorphone Concentration-Time Curve (AUC0-8h)pre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Area Under the Noroxycodone Concentration-Time Curve (AUC0-8h)pre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Area Under the Naltrexone Concentration-Time Curve (AUC0-8h)pre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Area Under the 6-beta-naltrexol Concentration-Time Curve (AUC0-8h)pre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Area Under the Curve From Time Zero to Last Quantifiable Oxycodone Concentration (AUClast)pre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Area Under the Curve From Time Zero to Last Quantifiable Oxymorphone Concentration (AUClast)pre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Area Under the Curve From Time Zero to Last Quantifiable Noroxycodone Concentration (AUClast)pre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Area Under the Curve From Time Zero to Last Quantifiable Naltrexone Concentration (AUClast)pre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Area Under the Curve From Time Zero Extrapolated to Infinity (AUCinf) for Oxycodonepre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Area Under the Curve From Time Zero Extrapolated to Infinity (AUCinf) for Oxymorphonepre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Area Under the Curve From Time Zero Extrapolated to Infinity (AUCinf) for Noroxycodonepre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Area Under the Curve From Time Zero Extrapolated to Infinity (AUCinf) for Naltrexonepre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Area Under the Curve From Time Zero Extrapolated to Infinity (AUCinf) for 6-beta-naltrexolpre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Systemic Clearance (Cl) of Oxycodonepre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose

CL is a quantitative measure of the rate at which a drug substance is removed from the body.

Systemic Clearance (Cl) of Naltrexonepre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Systemic Clearance (Cl) of 6-beta-naltrexolpre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Volume of Distribution at Steady State (Vss) for 6-beta-naltrexolpre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Volume of Distribution at Steady State (Vss) for Oxycodonepre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose

Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state.

Volume of Distribution at Steady State (Vss) for Noroxycodonepre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Volume of Distribution at Steady State (Vss) for Naltrexonepre-dose, 5 min, 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose

Trial Locations

Locations (1)

Pfizer Investigational Site

🇺🇸

Salt Lake City, Utah, United States

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