Study Evaluating Abuse Potential of Lyrica® in Healthy Non-Drug Dependent Recreational Opioid Users

Study Overview
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Brief Summary
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This is a Phase 4 clinical study in healthy non-drug dependent recreational opioid users to assess the abuse potential of Lyrica when taken alone or in combination with oxycodone.

Detailed Description
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This is a randomized, double-blind, double-dummy, placebo- and active-controlled, 6-treatment, 6-period crossover, single-dose study in healthy male and/or female adult, non drug-dependent recreational opioid users. The study includes Screening, a Qualification Phase, a Treatment Phase and Follow-up. This study will randomize approximately 60 adult male and female (at least 20% female) participants (10 participants in each sequence) in the Treatment Phase to ensure at least 48 participants complete the Treatment Phase of the study. There will be 8 visits to the clinic in total and a follow-up telephone call at the end of the study. The duration of participation will be approximately 16 weeks and 7 of the visits will involve clinic stays of 4 days/3 nights.

Official Title
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A Phase 4 Randomized Double-Blind Double-Dummy Placebo & Active-Controlled Single-Dose Six-Way Crossover Study Evaluating the Abuse Potential of Lyrica® Taken Orally With Oxycodone HCL in Healthy Non-Drug Dependent Recreational Opioid Users

Conditions
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Abuse Potential

Intervention / Treatment
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* Drug: Pregabalin 300mg
* Drug: pregabalin 450 mg
* Drug: Pregabalin 300 mg with oxycodone 20 mg
* Drug: pregabalin 450 mg with oxycodone 20 mg
* Drug: oxycodone 20 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female participants must be 18 to 55 years of age, inclusive, at the time of screening. There must be no less than 20% female participants in the Treatment Phase. Male and female participants who are overtly healthy. Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, vital signs, 12-lead ECG, and/or clinical laboratory tests. Participants must have drug abuse experience with opioids; ie, must have used opioids for non-therapeutic purposes (ie, for psychoactive effects) on at least 10 occasions within the last year and at least once in the 8 weeks before the Screening Visit (Visit 1). Participants must satisfactorily complete both the Naloxone Challenge and the Drug Discrimination. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures. Body mass index (BMI) of 17.5 to 34 kg/m2, inclusive; and a total body weight ≥50 kg (110 lb). Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent document (ICD). Exclusion Criteria: Current or past diagnosis of any type of drug dependence within the past year. Diagnosis of substance and/or alcohol dependence (excluding caffeine and nicotine) will be assessed by the Investigator using the Diagnostic and Statistical Manual-4 (DSM-4) criteria performed at Screening. Current drug use will be allowed if the candidate can produce a negative urine sample and are free of any signs/symptoms of withdrawal. The candidate will be informed if they have a positive breathalyzer test. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing). Any condition possibly affecting drug absorption (eg, gastrectomy) excluding cholecystectomy within 1 year prior to study. Abnormal baseline EtCO2 <35mm Hg or >45 mm Hg. Clinical or laboratory evidence of active hepatitis A infection or a history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C and/or positive testing for HIV, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C antibody (HCVAb). Participants with active suicidal ideation or suicidal behavior within 5 year prior to Screening as determined through the use of the Columbia-Suicide Severity Rating Scale (C-SSRS) or active ideation identified at Screening or on Day 0. Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study. Patients with: sleep apnea, myasthenia gravis and glaucoma. Use of prescription or nonprescription drugs and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of investigational product. Herbal supplements and herbal medications must be discontinued at least 28 days prior to the first dose of study medication. Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives (whichever is longer) preceding the first dose of investigational product used in this study. Positive urine drug screen (UDS) for substances of abuse at each admission in the Qualification and Treatment Phase, excluding tetrahydrocannabinol (THC). If a participant presents with a positive UDS excluding THC at any admission or any visit, the investigator, at his/her discretion, may reschedule a repeat of UDS until the UDS is negative, excluding THC, before the participant is permitted to participate in any phase of the study. Unable to abstain from using THC during the Qualification and Treatment Phase of the study. Has participated in, is currently participating in, or is seeking treatment for substance-and/or alcohol-related disorders (excluding nicotine and caffeine). Has a positive alcohol breathalyzer or urine test at each admission to the study center during qualification and treatment phase. Positive results may be repeated and/or participants re-scheduled at the Investigator's discretions. Participants are heavy smokers or users of other types of nicotine products (>20 cigarettes equivalents per day). Participants are unable to abstain from smoking for at least 2 hours before and at least 8 hours after study drug administration. Screening sitting blood pressure (BP) ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at least 5 minutes rest. If BP is ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), the BP should be repeated 2 more times and the average of the 3 BP values should be used to determine the participant's eligibility. Repeated BP tests should be spaced at least 5 minutes apart. Baseline (screening) 12-lead electrocardiogram (ECG) that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (eg, baseline corrected QT (QTc) interval as determined by the Fridericia method (QTcF) >450 msec, complete left bundle branch block [LBBB], signs of an acute or indeterminate-age myocardial infarction, ST-T interval changes suggestive of myocardial ischemia, second- or third-degree atrioventricular [AV] block, or serious bradyarrhythmias or tachyarrhythmias). If the baseline uncorrected QT interval is >450 msec, this interval should be rate-corrected using the Fridericia method and the resulting QTcF should be used for decision making and reporting. If QTcF exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated 2 more times and the average of the 3 QTcF or QRS values should be used to determine the participant's eligibility. Computer-interpreted ECGs should be overread by a physician experienced in reading ECGs before excluding participants. Participants with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study-specific laboratory and confirmed by a single repeat test, if deemed necessary: Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level 1.5 × upper limit of normal (ULN); Total bilirubin level ≥1.5 × ULN; participants with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is ≤ ULN. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing. History of sensitivity to heparin or heparin-induced thrombocytopenia. Unwilling or unable to comply with the criteria in the Lifestyle Considerations section of this protocol. History of hypersensitivity to pregabalin or oxycodone or any of the components in the formulation of the study products. Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or Sponsor employees, including their family members, directly involved in the conduct of the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Randomized, double-blind, double-dummy, placebo- and active-controlled, 6-treatment, 6-period crossover, single-dose, Williams square design study in healthy male and/or female adult, non drug-dependent recreational opioid users.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lyrica 300 mg<br>Single Dose | Drug: Pregabalin 300mg<br>* Participant will receive an oral dose of pregabalin 300 mg<br>|
| Experimental: Lyrica 450 mg<br>Single Dose | Drug: pregabalin 450 mg<br>* Participant will receive an oral dose of pregabalin 450 mg<br>|
| Experimental: Lyrica 300mg with Oxycodone 20 mg<br>Single Dose | Drug: Pregabalin 300 mg with oxycodone 20 mg<br>* Participant will receive an oral dose of pregabalin 300 mg and oxycodone 20 mg<br>|
| Experimental: Lyrica 450 mg with Oxycodone 20 mg<br>Single Dose | Drug: pregabalin 450 mg with oxycodone 20 mg<br>* Participant will receive an oral dose of pregabalin 450 mg and oxycodone 20 mg<br>|
| Active Comparator: Oxycodone 20 mg<br>Single Dose | Drug: oxycodone 20 mg<br>* Participant will receive an oral dose of oxycodone 20 mg<br>|
| Placebo Comparator: Placebo<br>Single Dose | Drug: Placebo<br>* Participant will receive an oral dose of placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bipolar Visual Analog Scale (VAS) for Drug Liking Maximum Effect (Emax). | Drug liking assesses how much a participant likes or dislikes a drug effect at the time the question (at this moment, my liking this drug is) is being asked. It is scored using a 100 mm visual analogue scale (VAS), where 0 mm = Strong Disliking, 50 mm = Neither Like nor Dislike, and 100 mm = Strong Liking | up to 48 hours after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Unipolar VAS for High - Maximum Effect (Emax) | Maximum effect on the 100 mm visual analog scale for the question I am feeling high where 0 = not at all and 100 = extremely | up to 48 hours after treatment | 
| Bipolar VAS for Take Drug Again | 100 mm visual analog scale at 24, 36, and 48 hours post-dose for the question I would take this drug again where 0 = definitely not, 50 = neutral, and 100 = definitely so. The data from the 24, 36, and 48 hours postdose measurements were combined into a single overall model-adjusted value for 24 to 48 hours post-treatment timeframe by estimation from a mixed model with treatment, period, treatment sequence, time, and treatment*time as fixed effects, subject nested within sequence as a random effect. The compound symmetric covariance matrix was employed. Data from all time points were included | Up to 48 hours after treatment (assessments were made at the following timepoints after each treatment for this outcome measure: 24, 36, and 48 hours) | 
| Bipolar VAS for Overall Drug Liking | 100 mm visual analog scale at 24, 36, and 48 hours post-dose for the question Overall, my liking for this drug is where 0 = definitely not, 50 = neutral, and 100 = definitely so. The data from the 24, 36, and 48 hours postdose measurements were combined into a single overall model-adjusted value for 24 to 48 hours post-treatment timeframe by estimation from a mixed model with treatment, period, treatment sequence, time, and treatment*time as fixed effects, subject nested within sequence as a random effect. The compound symmetric covariance matrix was employed. Data from all time points were included | Up to 48 hours after treatment (assessments were made at the following timepoints after each treatment for this outcome measure: 24, 36, and 48 hours) | 
| Unipolar VAS for Any Drug Effect | 100 mm visual analog scale for the question At this moment, I can feel any drug effects where 0 = not at all and 100 = extremely | up to 48 hours after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lyrica, Pregabalin, Oxycodone, Opioid, Abuse liability