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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01380093
Other study ID # ALO-01-10-4005
Secondary ID B4541003
Status Completed
Phase Phase 1
First received June 22, 2011
Last updated April 26, 2012
Start date February 2011
Est. completion date May 2011

Study information

Verified date September 2011
Source Pfizer
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug Administration
Study type Interventional

Clinical Trial Summary

The primary purpose of this study is to determine the abuse potential of EMBEDA compared to controlled release morphine when crushed and taken orally by non-dependent recreational opioid users; secondary purposes include to determine the abuse potential of crushed EMBEDA relative to placebo and and to compare the pharmacokinetics and safety of crushed EMBEDA with crushed controlled-release morphine and crushed placebo.


Recruitment information / eligibility

Status Completed
Enrollment 80
Est. completion date May 2011
Est. primary completion date May 2011
Accepts healthy volunteers Accepts Healthy Volunteers
Gender Both
Age group 18 Years to 55 Years
Eligibility Inclusion Criteria:

- Subject is a recreational opioid user who is NOT physically dependent on opioids based on Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition-Text Revision (DSM-IV-TR) criteria, and the Naloxone Challenge. A recreational opioid user is defined as recreationally abusing opioids for non-therapeutic purposes (i.e., for psychoactive effects) on at least 10 occasions within the last year and at least once in the 12 weeks prior to Visit 1.

- Subject is in generally good health as determined by medical history, physical examination, vital signs, clinical laboratory tests, and 12-lead electrocardiogram (ECG).

Exclusion Criteria:

- Has a history or current diagnosis of substance dependence (excluding caffeine and nicotine), as assessed by the Investigator using the DSM IV-TR criteria.

- Has participated in, is currently participating in, or is seeking treatment for substance- and/or alcohol-related disorders (excluding nicotine and caffeine).

- History or presence of any clinically significant illness (e.g., cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic, musculoskeletal, or psychiatric) or any other condition, which in the opinion of the Investigator would jeopardize the safety of the subject or the validity of the study results.

- Has a known allergy or history of hypersensitivity to morphine sulfate, opioids in general, naltrexone hydrochloride (HCl) or similar compounds and/or the known excipients in the investigational drug products.

- Has any condition in which an opioid is contraindicated (e.g., significant respiratory depression, acute or severe bronchial asthma or hypercarbia, or is suspected of having paralytic ileus).

- Females who are pregnant, lactating, or are planning to become pregnant during the course of the study. Females with a positive serum pregnancy test at Visit 1 or at any subsequent study visit will be excluded from participating in the study.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science


Related Conditions & MeSH terms


Intervention

Drug:
Placebo
Single-dose, 2 x microcrystalline cellulose (weighed to equal weights of average tablet/capsule of active comparator) mixed with 150 ml artificially sweetened, non-carbonated beverage
MS Contin (morphine sulfate, controlled release)
Single-dose, 2 x 60 mg morphine sulfate whole tablets manually crushed and mixed with 150 ml artificially sweetened, non-carbonated beverage
EMBEDA (morphine sulfate / naltrexone hydrochloride)
Single-dose, solution 2 x 60 mg morphine sulfate with sequestered 2.4 mg Naltrexone hydrochloride whole capsules manually crushed and mixed with 150 ml artificially sweetened, non-carbonated beverage

Locations

Country Name City State
United States Lifetree Clinical Research Salt Lake City Utah

Sponsors (1)

Lead Sponsor Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Drug Liking: Area Under Effect Curve (AUE) From 0-2 Hours 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 visual analogue scale (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 (0-2) = Area under the effect versus time curve from time 0 to 2 hours (hrs) (0-2). 0.5, 1, 1.5 and 2 hrs post-dose No
Primary 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 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). Emax = Maximum observed score. 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose No
Primary High: Area Under Effect Curve (AUE) From 0-2 Hours High 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 (0-2) = Area under the effect versus time curve from time 0 to 2 hrs (0-2). 0.5, 1, 1.5 and 2 hrs post-dose No
Primary 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 a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score. 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose No
Secondary Drug Liking: Area Under Effect Curve (AUE) From 0-1 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 (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1). 0.5 and 1 hrs post-dose No
Secondary Drug Liking: Area Under Effect Curve (AUE) From 0-4 Hours 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 (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4). 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose No
Secondary Drug Liking: Area Under Effect Curve (AUE) From 0-8 Hours 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 (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8). 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose No
Secondary Drug Liking: Area Under Effect Curve (AUE) From 0-12 Hours 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 (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12). 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose No
Secondary Drug Liking: Area Under Effect Curve (AUE) From 0-24 Hours 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 (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24). 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose No
Secondary 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. 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose No
Secondary High: Area Under Effect Curve (AUE) From 0-1 Hour High 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 (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1). 0.5 and 1 hrs post-dose No
Secondary High: Area Under Effect Curve (AUE) From 0-4 Hours High 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 (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4). 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose No
Secondary High: Area Under Effect Curve (AUE) From 0-8 Hours High 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 (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8). 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose No
Secondary High: Area Under Effect Curve (AUE) From 0-12 Hours High 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 (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12). 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose No
Secondary High: Area Under Effect Curve (AUE) From 0-24 Hours High 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 (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24). 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose No
Secondary 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 a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score. 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose No
Secondary Good Effects: Area Under Effect Curve (AUE) From 0-1 Hour Good effects 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 (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1). 0.5 and 1 hrs post-dose No
Secondary Good Effects: Area Under Effect Curve (AUE) From 0-2 Hours Good effects 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 (0-2) = Area under the effect versus time curve from time 0 to 2 hrs (0-2). 0.5, 1, 1.5 and 2 hrs post-dose No
Secondary Good Effects: Area Under Effect Curve (AUE) From 0-4 Hours Good effects 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 (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4). 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose No
Secondary Good Effects: Area Under Effect Curve (AUE) From 0-8 Hours Good effects 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 (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8). 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose No
Secondary Good Effects: Area Under Effect Curve (AUE) From 0-12 Hours Good effects 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 (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12). 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose No
Secondary Good Effects: Area Under Effect Curve (AUE) From 0-24 Hours Good effects 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 (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24). 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose No
Secondary Good Effects: Peak Effect (Emax) Good effects 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). Emax = Maximum observed score. 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose No
Secondary Good Effects: Time to Maximum (Peak) Effect (TEmax) Good effects 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. 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose No
Secondary Any Effects: Area Under Effect Curve (AUE) From 0-1 Hour Any effects 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 (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1). 0.5 and 1 hrs post-dose No
Secondary Any Effects: Area Under Effect Curve (AUE) From 0-2 Hours Any effects 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 (0-2) = Area under the effect versus time curve from time 0 to 2 hrs (0-2). 0.5, 1, 1.5 and 2 hrs post-dose No
Secondary Any Effects: Area Under Effect Curve (AUE) From 0-4 Hours Any effects 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 (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4). 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose No
Secondary Any Effects: Area Under Effect Curve (AUE) From 0-8 Hours Any effects 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 (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8). 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose No
Secondary Any Effects: Area Under Effect Curve (AUE) From 0-12 Hours Any effects 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 (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12). 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose No
Secondary Any Effects: Area Under Effect Curve (AUE) From 0-24 Hours Any effects 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 (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24). 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose No
Secondary Any Effects: Peak Effect (Emax) Any effects 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). Emax = Maximum observed score. 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose No
Secondary Any Effects: Time to Maximum (Peak) Effect (TEmax) Any effects 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. 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose No
Secondary Bad Effects: Area Under Effect Curve (AUE) From 0-1 Hour Bad effects 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 (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1). 0.5 and 1 hrs post-dose No
Secondary Bad Effects: Area Under Effect Curve (AUE) From 0-2 Hours Bad effects 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 (0-2) = Area under the effect versus time curve from time 0 to 2 hrs (0-2). 0.5, 1, 1.5 and 2 hrs post-dose No
Secondary Bad Effects: Area Under Effect Curve (AUE) From 0-4 Hours Bad effects 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 (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4). 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose No
Secondary Bad Effects: Area Under Effect Curve (AUE) From 0-8 Hours Bad effects 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 (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8). 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose No
Secondary Bad Effects: Area Under Effect Curve (AUE) From 0-12 Hours Bad effects 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 (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12). 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose No
Secondary Bad Effects: Area Under Effect Curve (AUE) From 0-24 Hours Bad effects 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 (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24). 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose No
Secondary Bad Effects: Peak Effect (Emax) Bad effects 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). Emax = Maximum observed score. 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose No
Secondary Bad Effects: Time to Maximum (Peak) Effect (TEmax) Bad effects 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. 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose No
Secondary Nausea: Area Under Effect Curve (AUE) From 0-1 Hour Nausea 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 (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1). Pre-dose, 0.5 and 1 hrs post-dose No
Secondary Nausea: Area Under Effect Curve (AUE) From 0-2 Hours Nausea 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 (0-2) = Area under the effect versus time curve from time 0 to 2 hrs (0-2). Pre-dose, 0.5, 1, 1.5 and 2 hrs post-dose No
Secondary Nausea: Area Under Effect Curve (AUE) From 0-4 Hours Nausea 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 (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4). Pre-dose, 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose No
Secondary Nausea: Area Under Effect Curve (AUE) From 0-8 Hours Nausea 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 (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8). Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose No
Secondary Nausea: Area Under Effect Curve (AUE) From 0-12 Hours Nausea 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 (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12). Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose No
Secondary Nausea: Area Under Effect Curve (AUE) From 0-24 Hours Nausea 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 (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24). Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose No
Secondary 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 a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score. Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose No
Secondary 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 a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score. Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose No
Secondary Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour Feel sick 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 (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1). 0.5 and 1 hrs post-dose No
Secondary Feel Sick: Area Under Effect Curve (AUE) From 0-2 Hours Feel sick 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 (0-2) = Area under the effect versus time curve from time 0 to 2 hrs (0-2). 0.5, 1, 1.5 and 2 hrs post-dose No
Secondary Feel Sick: Area Under Effect Curve (AUE) From 0-4 Hours Feel sick 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 (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4). 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose No
Secondary Feel Sick: Area Under Effect Curve (AUE) From 0-8 Hours Feel sick 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 (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8). 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose No
Secondary Feel Sick: Area Under Effect Curve (AUE) From 0-12 Hours Feel sick 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 (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12). 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose No
Secondary Feel Sick: Area Under Effect Curve (AUE) From 0-24 Hours Feel sick 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 (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24). 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose No
Secondary 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 a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score. 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose No
Secondary 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 a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score. 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose No
Secondary Sleepy: Area Under Effect Curve (AUE) From 0-1 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 (0-1) = Area under the effect versus time curve from time 0 to 1 hr(0-1). 0.5 and 1 hrs post-dose No
Secondary Sleepy: Area Under Effect Curve (AUE) From 0-2 Hours 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 (0-2) = Area under the effect versus time curve from time 0 to 2 hrs (0-2). 0.5, 1, 1.5 and 2 hrs post-dose No
Secondary Sleepy: Area Under Effect Curve (AUE) From 0-4 Hours 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 (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4). 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose No
Secondary Sleepy: Area Under Effect Curve (AUE) From 0-8 Hours 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 (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8). 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose No
Secondary Sleepy: Area Under Effect Curve (AUE) From 0-12 Hours 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 (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12). 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose No
Secondary Sleepy: Area Under Effect Curve (AUE) From 0-24 Hours 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 (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24). 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose No
Secondary 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 a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score. 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose No
Secondary 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. 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose No
Secondary Dizzy: Area Under Effect Curve (AUE) From 0-1 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 (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1). 0.5 and 1 hrs post-dose No
Secondary Dizzy: Area Under Effect Curve (AUE) From 0-2 Hours 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 (0-2) = Area under the effect versus time curve from time 0 to 2 hrs (0-2). 0.5, 1, 1.5 and 2 hrs post-dose No
Secondary Dizzy: Area Under Effect Curve (AUE) From 0-4 Hours 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 (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4). 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose No
Secondary Dizzy: Area Under Effect Curve (AUE) From 0-8 Hours 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 (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8). 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose No
Secondary Dizzy: Area Under Effect Curve (AUE) From 0-12 Hours 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 (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12). 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose No
Secondary Dizzy: Area Under Effect Curve (AUE) From 0-24 Hours 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 (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24). 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose No
Secondary 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 a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score. 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose No
Secondary 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. 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose No
Secondary Overall Drug Liking Effect at 24 Hours 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 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"). 24 hrs post dose No
Secondary Take Drug Again Effect at 24 Hours 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"). 24 hrs post dose No
Secondary Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour 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 had the size of their pupil measured (in mm) using a pupillometer. Measurements were made in a dimly lit (mesopic) room with controlled lighting conditions. AUE (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1). Pre-dose, 0.5 and 1 hrs post-dose No
Secondary Pupillometry: Area Under Effect Curve (AUE) From 0-2 Hours 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 had the size of their pupil measured (in mm) using a pupillometer. Measurements were made in a dimly lit (mesopic) room with controlled lighting conditions. AUE (0-2) = Area under the effect versus time curve from time 0 to 2 hrs (0-2). Pre-dose, 0.5, 1, 1.5 and 2 hrs post-dose No
Secondary Pupillometry: Area Under Effect Curve (AUE) From 0-4 Hours 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 had the size of their pupil measured (in mm) using a pupillometer. Measurements were made in a dimly lit (mesopic) room with controlled lighting conditions. AUE (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4). Pre-dose, 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose No
Secondary Pupillometry: Area Under Effect Curve (AUE) From 0-8 Hours 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 had the size of their pupil measured (in mm) using a pupillometer. Measurements were made in a dimly lit (mesopic) room with controlled lighting conditions. AUE (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8). Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose No
Secondary Pupillometry: Area Under Effect Curve (AUE) From 0-12 Hours 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 had the size of their pupil measured (in mm) using a pupillometer. Measurements were made in a dimly lit (mesopic) room with controlled lighting conditions. AUE (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12). Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose No
Secondary Pupillometry: Area Under Effect Curve (AUE) From 0-24 Hours 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 had the size of their pupil measured (in mm) using a pupillometer. Measurements were made in a dimly lit (mesopic) room with controlled lighting conditions. AUE (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24). Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose No
Secondary Pupillometry: Peak Effect (Emax) 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 had the size of their pupil measured (in mm) using a pupillometer. Measurements were made in a dimly lit (mesopic) room with controlled lighting conditions. Emax = Smallest post-dose pupil size. Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose No
Secondary Pupillometry: Time to Maximum (Peak) Effect (TEmax) 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 had the size of their pupil measured (in mm) using a pupillometer. Measurements were made in a dimly lit (mesopic) room with controlled lighting conditions. TEmax = Time to smallest post-dose pupil size. Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose No
Secondary Time to Reach Maximum Observed Plasma Concentration (Tmax) of Morphine Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose No
Secondary Maximum Observed Plasma Concentration (Cmax) of Morphine Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose No
Secondary Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-1)] of Morphine AUC (0-1) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-1). Pre-dose, 0.5 and 1 hrs post-dose No
Secondary Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-2)] of Morphine AUC (0-2) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-2). Pre-dose, 0.5, 1, 1.5 and 2 hrs post-dose No
Secondary Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-4)] of Morphine AUC (0-4) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-4). Pre-dose, 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose No
Secondary Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-8)] of Morphine AUC (0-8) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-8). Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose No
Secondary Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-12)] of Morphine AUC (0-12) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-12). Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose No
Secondary Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)] of Morphine AUC (0-24) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-24). Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose No
Secondary Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] of Morphine AUC (0 - 8) = Area under the plasma concentration versus time curve (AUC) from time zero to extrapolated infinite time (0 - 8). It is obtained from AUC (0 - t) plus AUC (t - 8). Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose No
Secondary Time to Reach Maximum Observed Plasma Concentration (Tmax) of Naltrexone Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose No
Secondary Maximum Observed Plasma Concentration (Cmax) of Naltrexone Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose No
Secondary Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-1)] of Naltrexone AUC (0-1) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-1). Pre-dose, 0.5 and 1 hrs post-dose No
Secondary Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-2)] of Naltrexone AUC (0-2) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-2). Pre-dose, 0.5, 1, 1.5 and 2 hrs post-dose No
Secondary Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-4)] of Naltrexone AUC (0-4) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-4). Pre-dose, 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose No
Secondary Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-8)] of Naltrexone AUC (0-8) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-8). Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose No
Secondary Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-12)] of Naltrexone AUC (0-12) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-12). Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose No
Secondary Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)] of Naltrexone AUC (0-24) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-24). Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose No
Secondary Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] of Naltrexone AUC (0 - 8) = Area under the plasma concentration versus time curve (AUC) from time zero to extrapolated infinite time (0 - 8). It is obtained from AUC (0 - t) plus AUC (t - 8). Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose No
Secondary Time to Reach Maximum Observed Plasma Concentration (Tmax) of Naltrexone Metabolite (6-beta-naltrexol) Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose No
Secondary Maximum Observed Plasma Concentration (Cmax) of Naltrexone Metabolite (6-beta-naltrexol) Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose No
Secondary Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-1)] of Naltrexone Metabolite (6-beta-naltrexol) AUC (0-1) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-1). Pre-dose, 0.5 and 1 hrs post-dose No
Secondary Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-2)] of Naltrexone Metabolite (6-beta-naltrexol) AUC (0-2) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-2). Pre-dose, 0.5, 1, 1.5 and 2 hrs post-dose No
Secondary Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-4)] of Naltrexone Metabolite (6-beta-naltrexol) AUC (0-4) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-4). Pre-dose, 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose No
Secondary Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-8)] of Naltrexone Metabolite (6-beta-naltrexol) AUC (0-8) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-8). Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose No
Secondary Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-12)] of Naltrexone Metabolite (6-beta-naltrexol) AUC (0-12) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-12). Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose No
Secondary Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)] of Naltrexone Metabolite (6-beta-naltrexol) AUC (0-24) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-24). Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose No
Secondary Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] of Naltrexone Metabolite (6-beta-naltrexol) AUC (0 - 8) = Area under the plasma concentration versus time curve (AUC) from time zero to extrapolated infinite time (0 - 8). It is obtained from AUC (0 - t) plus AUC (t - 8). Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose No