A Study to Characterize the Abuse Liability of ALO-02 in Healthy, Non-Dependent, Recreational Opioid Abusers

PLACEBO_COMPARATOR: Treatment A

Drug: Placebo

Placebo solution + Placebo ALO-02 (intact)

EXPERIMENTAL: Treatment B

Drug: intact ALO-02 60 mg/7.2 mg

Placebo solution + ALO-02 60 mg/7.2 mg (intact)

EXPERIMENTAL: Treatment C

Drug: crushed ALO-02 60 mg/7.2 mg

crushed ALO-02 60 mg/7.2 mg in solution + placebo ALO-02 (intact)

ACTIVE_COMPARATOR: Treatment D

Drug: crushed oxycodone IR 60 mg

crushed oxycodone immediate-release (IR) 60 mg in solution + placebo ALO-02 (intact)

EXPERIMENTAL: Treatment E

Drug: crushed ALO-02 40 mg/4.8 mg

crushed ALO-02 40 mg/4.8 mg in solution + placebo ALO-02 (intact)

ACTIVE_COMPARATOR: Treatment F

Drug: crushed oxycodone IR 40 mg

crushed oxycodone immediate-release (IR) 40 mg in solution + placebo ALO-02 (intact)

Drug Liking: Peak Effect (Emax)

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 millimeter (mm) bipolar VAS anchored in the center with a neutral anchor of "neither like nor dislike" (score of 50 mm), on the extreme left with "strong disliking" (score of 0 mm) and on the extreme right with "strong liking" (score of 100 mm). Peak Effect (Emax) = Maximum observed score.

Drug Liking: Area Under Effect Curve (AUE) From 0-2 Hour

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 millimeter (mm) bipolar VAS anchored in the center with a neutral anchor of "neither like nor dislike" (score of 50 mm), on the extreme left with "strong disliking" (score of 0 mm) and on the extreme right with "strong liking" (score of 100 mm). AUE (0-2) = Area under the effect versus time curve from time 0 to 2 hours.

High: Peak Effect (Emax)

High VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score.

High: Area Under Effect Curve (AUE) From 0-2 Hour

High VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-2) = Area under the effect versus time curve from time 0 to 2 hours.

Take Drug Again: Peak Effect (Emax)

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 mm VAS with score ranging from 0 mm to 100 mm (score of 0 mm = "definitely would not", 50 mm = "do not care", and 100 mm = "definitely would"). Emax = Maximum observed score.

Take Drug Again: Mean Effect (Emean)

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 mm VAS with score ranging from 0 mm to 100 mm (score of 0 mm = "definitely would not", 50 mm = "do not care", and 100 mm = "definitely would"). Emax = Maximum observed score.

Take Drug Again: Minimum Effect (Emin)

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 mm VAS with score ranging from 0 mm to 100 mm (score of 0 mm = "definitely would not", 50 mm = "do not care", and 100 mm = "definitely would"). Emax = Maximum observed score.

Take Drug Again Effect at Hours 12, 24 and 36

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 mm VAS with score ranging from 0 mm to 100 mm (score of 0 mm = "definitely would not", 50 mm = "do not care", and 100 mm = "definitely would"). Emax = Maximum observed score.

Overall Drug Liking: Peak Effect (Emax)

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 carry-over effects). A 100 mm VAS is used to assess response based on a score ranging from 0 mm to 100 mm (0 mm = "strong disliking", 50 mm = "neither like nor dislike", and 100 mm= "strong liking"). Emax = Maximum observed score.

Overall Drug Liking: Mean Effect (Emean)

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 carry-over effects). A 100 mm VAS is used to assess response based on a score ranging from 0 mm to 100 mm (0 mm = "strong disliking", 50 mm = "neither like nor dislike", and 100 mm= "strong liking"). Emean = Average observed score.

Overall Drug Liking: Minimum Effect (Emin)

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 carry-over effects). A 100 mm VAS is used to assess response based on a score ranging from 0 mm to 100 mm (0 mm = "strong disliking", 50 mm = "neither like nor dislike", and 100 mm= "strong liking"). Emin= Average observed score.

Overall Drug Liking Effect at Hours 12, 24 and 36

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 carry-over effects). A 100 mm VAS is used to assess response based on a score ranging from 0 mm to 100 mm (0 mm = "strong disliking", 50 mm = "neither like nor dislike", and 100 mm= "strong liking").

Any Drug Effects: Peak Effect (Emax)

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

Any Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour

Any Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x).

Any Drug Effects: Time to Maximum (Peak) Effect (TEmax)

Any Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score.

Good Drug Effects: Peak Effect (Emax)

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

Good Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour

Good Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x).

Good Drug Effects: Time to Maximum (Peak) Effect (TEmax)

Good Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score.

Bad Drug Effects: Peak Effect (Emax)

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

Bad Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour

Bad Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x).

Bad Drug Effects: Time to Maximum (Peak) Effect (TEmax)

Bad Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score.

Feel Sick: Peak Effect (Emax)

Feel Sick VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score.

Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour

Feel Sick VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x).

Feel Sick: Time to Maximum (Peak) Effect (TEmax)

Feel Sick VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score.

Nausea: Peak Effect (Emax)

Nausea VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score.

Nausea: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour

Nausea VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x).

Nausea: Time to Maximum (Peak) Effect (TEmax)

Nausea VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score.

Sleepy: Peak Effect (Emax)

Sleepy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score.

Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour

Sleepy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x).

Sleepy: Time to Maximum (Peak) Effect (TEmax)

Sleepy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm)to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score.

Dizzy: Peak Effect (Emax)

Dizzy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score.

Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour

Dizzy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x).

Dizzy: Time to Maximum (Peak) Effect (TEmax)

Dizzy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score.

Pupillometry: Peak Effect (Emax)

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

Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour

Pupillometry assessments measure change in pupil size (miosis) as an indicator of opioid pharmacological properties. Participants have the size of pupil measured using a pupillometer. Measurements are made in a dimly lit (mesopic) room with controlled lighting conditions. The same eye for each participant was used for all measurements during the study. AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x).

Pupillometry: Time to Maximum (Peak) Effect (TEmax)

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

Time to Reach Maximum Observed Plasma Concentration (Tmax) of Oxycodone, Oxymorphone and Noroxycodone

Participants who received oxycodone and ALO-02 were reported. Oxymorphone and noroxycodone are metabolites of oxycodone.

Drug Liking: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour

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 mm bipolar VAS anchored in the center with a neutral anchor of "neither like nor dislike" (score of 50 mm), on the left with "strong disliking" (score of 0 mm) and on the right with "strong liking" (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time 0 to x hours (0-x).

Drug Liking: Time to Maximum (Peak) Effect (TEmax)

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 mm bipolar VAS anchored in the center with a neutral anchor of "neither like nor dislike" (score of 50 mm), on the left with "strong disliking" (score of 0 mm) and on the right with "strong liking" (score of 100 mm). TEmax = Time to maximum observed score.

High: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour

High VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time 0 to x hours (0-x).

High: Time to Maximum (Peak) Effect (TEmax)

High VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score.

Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of Oxycodone, Oxymorphone and Noroxycodone

Cmax[dn]=Dose normalized maximum observed plasma concentration of participants who received oxycodone and ALO-02 were reported. Oxymorphone and noroxycodone are metabolites of oxycodone.

Maximum Observed Plasma Concentration (Cmax) of Naltrexone and 6-beta-naltrexol

Participants who received ALO-02 were reported. 6-Beta-naltrexol is metabolites of naltrexone.

Time to Reach Maximum Observed Plasma Concentration (Tmax) of Naltrexone and 6-beta-naltrexol

Participants who received ALO-02 were reported. 6-Beta-naltrexol is metabolites of naltrexone.

Plasma Terminal Half-Life (t1/2) of Oxycodone

Participants who received oxycodone and ALO-02 were reported. Oxymorphone and noroxycodone are metabolites of oxycodone.

Area Under the Concentration-Time Curve (AUC) From 0-1 Hour, 0-2 Hour, 0-8 Hour 0-12 Hour and 0-24 Hour of Oxycodone

AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. Participants who received oxycodone were reported.

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Oxycodone

Area under the plasma concentration time-curve from zero to the last quantifiable concentration (AUClast). Participants who received oxycodone were reported.

Dose Normalized Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)dn] of Oxycodone

[AUC (0 - ∞)dn]= Dose normalized area under the plasma concentration versus time curve [AUC(dn)] from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0- t) plus AUC (t - ∞). Participants who received oxycodone were reported. Participants who received oxycodone were reported.

Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)

An AE was any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship. SAE: an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 3 - 7 days following last study drug administration. Symptoms of withdrawal following naloxone administration (naloxone challenge phase) were not collected as adverse events unless they met the criteria for an SAE. AEs included SAEs as well as non-serious AEs which occurred during the trial.

Number of Participants With Clinically Significant Change in Vital Sign Examinations

Vital signs assessment included measurement of heart rate, systolic and diastolic blood pressures, respiratory rate and oral temperature. Criteria for clinically significant change in any vital sign examination was based on investigator's discretion.

Number of Participants With Clinically Significant Change in End Tidal Carbon Dioxide (EtCO2)

End-tidal carbon dioxide concentration in the expired air (EtCO2) was monitored using capnography in a sitting position. Criteria for clinically significant change in EtCO2 was based on investigator's discretion.

Number of Participants With Clinically Significant Change in Oxygen Saturation of Hemoglobin (SpO2)

Oxygen saturation of hemoglobin in blood (SpO2) was monitored using pulse oximetry continuously for 5 hours following dosing in the drug discrimination phase and continuously for 12 hours following dosing in the treatment phase, or longer at the discretion of the investigator. Individual measurements was collected in a sitting position. If SpO2 fall below 90 percent (%), the investigator might had administered oxygen via nasal cannula at a flow rate sufficient to maintain the SpO2 greater than or equal to 90%. Participants with fall in SpO2 below 90% were reported.