Abuse Potential of HORIZANT With and Without Oxycodone in Healthy, Nondependent Recreational Opioid Users

NCT06247488 | Completed Phase 4 Results FDA Drug

• 1 other identifier: AR26.3031.2
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the abuse potential of gabapentin enacarbil immediate release capsules taken alone and in combination with oxycodone in healthy adult, non-dependent, recreational opioid users.

Conditions

Abuse Potential

Outcome Measures

Primary Outcomes (1)

• Drug Liking Visual Analog Scale (VAS)

  Mean difference in Drug Liking Emax over 24 hours for Drug Liking ("At this moment, my liking for this drug is"), assessed on a bipolar (0 to 100 points; 0: Strong disliking, 50: Neither like nor dislike, 100: Strong liking) VAS.

  approximately 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 10, and 24 hours postdose in the treatment phase and per period of the treatment phase

Secondary Outcomes (3)

• Overall Drug Liking VAS

  Approximately 12 and 24 hours postdose in the treatment phase and per period of the treatment phase

• Take Drug Again VAS

  Approximately 12 and 24 hours postdose in the treatment phase and per period of the treatment phase

• High VAS

  within 1 hour prior to and approximately 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 10, and 24 hours postdose in the treatment phase and per period of the treatment phase

Study Arms (6)

Placebo

PLACEBO COMPARATOR

oral masked Placebo

Drug: Placebo

Oxycodone 20 mg

ACTIVE COMPARATOR

oral active control

Drug: Oxycodone 20 mg

GE-IR 200mg

EXPERIMENTAL

single oral dose

Drug: GE-IR 200 mg

GE-IR 450 mg

EXPERIMENTAL

single oral dose

Drug: GE-IR 450 mg

GE-IR 200 mg + Oxycodone 20 mg

EXPERIMENTAL

oral doses given together

Drug: Oxycodone 20 mg; Drug: GE-IR 200 mg

GE-IR 450 mg + Oxycodone 20 mg

EXPERIMENTAL

oral doses given together

Drug: Oxycodone 20 mg; Drug: GE-IR 450 mg

Interventions

Placebo DRUG

Participant will receive oral dose of placebo.

Also known as: matching over-encapsulated capsule

Placebo

Oxycodone 20 mg DRUG

Participant will receive oral dose of oxycodone 20 mg.

Also known as: Oxycontin

GE-IR 200 mg + Oxycodone 20 mg; GE-IR 450 mg + Oxycodone 20 mg; Oxycodone 20 mg

GE-IR 200 mg DRUG

Participant will receive oral dose of GE-IR 200 mg and oxycodone 20 mg.

Also known as: Gabapentin Enacarbil, Horizant

GE-IR 200 mg + Oxycodone 20 mg; GE-IR 200mg

GE-IR 450 mg DRUG

Participant will receive oral dose of GE-IR 450 mg and oxycodone 20 mg.

Also known as: Gabapentin Enacarbil, Horizant

GE-IR 450 mg; GE-IR 450 mg + Oxycodone 20 mg

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provision of signed and dated informed consent form (ICF),
• Stated willingness to comply with all study procedures and availability for the duration of the study,
• Male or female, between 18 and 55 years of age, inclusive,
• Current nondependent, recreational opioid user who has used opioid drugs for recreational (nontherapeutic) purposes (i.e., for psychoactive effects) at least 5 times in the subject's lifetime and at least once in the last 12 weeks,
• Body mass index (BMI) within 18.0 kg/m2 to 36.0 kg/m2, inclusive,
• If female, meets 1 of the following criteria:
• If of childbearing potential agrees to use 1 of the accepted contraceptive regimens from at least 30 days prior to the first study treatment administration, during the study, and for at least 30 days after the last dose of the study treatment. An acceptable method of contraception includes 1 of the following:
• Abstinence from heterosexual intercourse,
• Hormonal contraceptives (birth control pills, injectable/implantable/insertable hormonal birth control products, transdermal patch), or
• Intrauterine device (IUD; with or without hormones). Or
• If of childbearing potential agrees to use a double barrier method (e.g., condom and spermicide) during the study and for at least 30 days after the last dose of study treatment.
• If of non-childbearing potential, defined as surgically sterile (i.e., has undergone complete hysterectomy, bilateral oophorectomy or tubal ligation) or is in a postmenopausal state (i.e., at least 1 year without menses without an alternative medical condition and confirmed follicle stimulating hormone (FSH) ≥ 40 milli-International unit (mIU)/mL prior to the first study treatment administration),
• If male and engaging in sexual activity that has the risk of pregnancy must agree to use a double barrier method (e.g., condom and spermicide) and agree to not donate sperm during the study and for at least 90 days after the last dose of study treatment, a male who has a pregnant partner shall be excluded,
• Healthy, as determined by no clinically significant findings from medical history, physical examination, 12-lead ECG, vital signs or clinical laboratory (including hematology, clinical chemistry, urinalysis, and serology \[screening visit only\]) at screening visit and admission, in the opinion of an investigator.
• Negative COVID-19 test prior to each admission.

You may not qualify if:

• History of significant hepatic, renal, cardiovascular, pulmonary, hematologic, neurological, psychiatric, gastrointestinal, endocrine, immunologic, ophthalmologic, or dermatologic disease of any etiology (including infections),
• Presence or history of significant gastrointestinal, liver or kidney disease, or surgery that may affect drug bioavailability with the exception that cholecystectomy is permitted at the discretion of an investigator,
• Presence of any significant respiratory illness or presence or history of chronic respiratory disease (e.g., upper respiratory illness, sleep apnea, emphysema, asthma) at screening (subjects with acute respiratory illness may be rescheduled upon resolution at the discretion of an investigator),
• Personal or family history (first degree relatives) of allergy, hypersensitivity, or drug rash with eosinophilia and systemic symptoms (DRESS) syndrome to gabapentin enacarbil,gabapentin or any drug product including naloxone, opioids (e.g., oxycodone), or related drugs or known excipients of any of the drug products in this study (e.g. lactose),
• History of sensitivity to or poor tolerance of gabapentin enacarbil, gabapentin, pregabalin, naloxone, or oxycodone,
• Female who is lactating at screening,
• Female who is pregnant according to the pregnancy test at screening or prior to the first study treatment administration or planning to become pregnant within 30 days following the last study treatment administration,
• History of substance or alcohol dependence (excluding nicotine and caffeine) within the past 2 years, as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV), and/or subject has ever been in a drug or alcohol rehabilitation program within the last 2 years,
• Is a heavy smoker (\>20 cigarettes per day or nicotine-equivalent) and/or is unable to abstain from smoking or unable to abstain from the use of prohibited nicotine-containing products for at least 1 hour before and 6 hours after study treatment administration (including e-cigarettes, pipes, cigars, chewing tobacco, nicotine topical patches, nicotine gum, or nicotine lozenges),
• Is a heavy opioid user and not likely to be sensitive to a 20 mg dose of oxycodone, in the opinion of an investigator or designee,
• Regularly consumes excessive amounts of caffeine or xanthines within 30 days prior to screening, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, or other caffeinated beverages per day,
• History of suicidal ideation or suicidal behaviour within 2 years of screening, showing suicidal tendency as per the Columbia Suicide Severity Rating Scale (C-SSRS) administered at screening, or is currently at risk of suicide in the opinion of an investigator,
• Has creatinine clearance ≤60ml/min as calculated by the Cockcroft-Gault equation,
• Any history of tuberculosis,
• Positive screening results to human immunodeficiency virus (HIV) 1 and 2 antibodies, hepatitis B virus surface antigen (HBsAg) or hepatitis C virus antibody (HCVAb) tests,

Sponsors & Collaborators

• Arbor Pharmaceuticals, Inc.: lead

Study Sites (1)

Altasciences Clinical Kansas

Overland Park, Kansas, 66212, United States

Location

MeSH Terms

Interventions

Oxycodone; 1-(((alpha-isobutanoyloxyethoxy)carbonyl)aminomethyl)-1-cyclohexaneacetic acid; Gabapentin

Intervention Hierarchy (Ancestors)

Codeine; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Amines; Organic Chemicals; gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Amino Acids; Amino Acids, Peptides, and Proteins

Limitations and Caveats

63 subjects entered the treatment phase and were assessed for adverse events. 11 discontinued over the course of the 6 study periods. 54 subjects were part of the analysis population. This met the study goal for population.

Results Point of Contact

• Title: Vice President of Clinical Development
• Organization: Azurity Pharmaceuticals, Inc.

david.sequeira@azurity.com

(913) 389-7961

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2024
• First Posted: February 8, 2024
• Study Start: January 31, 2022
• Primary Completion: April 25, 2023
• Study Completion: April 25, 2023
• Last Updated: August 12, 2024
• Results First Posted: July 30, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)