A Study to Evaluate Withdrawal Effects Following Dosing of Oxycodone/Naltrexone in Methadone-Maintained Subjects

NCT02391571 | Completed Phase 3

• 1 other identifier: ELI-004-2015
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

This single-center study is a randomized, double-blind, active-controlled, multiple-dose, parallel group study to evaluate the potential withdrawal effects, safety and tolerability, and pharmacokinetic and pharmacodynamic effects of multiple doses of oral intact Oxycodone/Naltrexone capsules compared to oxycodone in methadone-maintained opioid-dependent subjects. The study will consist of a Screening Phase, an inpatient Treatment Phase (including a methadone stabilization period, a placebo administration period, a treatment administration period and a safety/washout period), and a Follow-up Phase.

Conditions

Withdrawal Symptoms

Outcome Measures

Primary Outcomes (2)

• Primary: Onset of Withdrawal measured by Subjective Opioid Withdrawal Scale(SOWS)

  To assess the withdrawal effects of intact Oxycodone/Naltrexone following multiple dose administration compared to Oxycodone in methadone-maintained, opioid-dependent subjects (all subjects enrolled in the study N=34) over time using Subjective Opioid Withdrawal Scale(SOWS), a set of 16 questions scored on a scale of 0-4 (not at all to extremely) according to how the subject feels at that moment to the questions asked about withdrawal symptoms. The questions are asked during the placebo period 9 times daily , and daily during treatment administration 9 times a day.

  up to 10 days

• Primary: Onset of Withdrawal measured by Clinician-Rated Opioid Withdrawal Scale (COWS)

  To assess the withdrawal effects of intact Oxycodone/Naltrexone following multiple dose administration compared to Oxycodone in methadone-maintained, opioid-dependent subjects (all subjects enrolled in the study N=34) over time using Clinician-Rated Opioid Withdrawal Scale (COWS), a set of 11 questions scored by a trained clinician that best describes the subject's signs or symptoms of withdrawal at that time. Each are rated on the apparent relationship to opiate withdrawal. These are assessed during the placebo period 9 times daily , and daily during treatment administration 9 times a day. A total score is tallied that determines mild, moderate, moderately severe or severe withdrawal.

  up to 10 days

Secondary Outcomes (3)

• Secondary: Pharmacokinetic Profile of Naltrexone and 6β-Naltrexol in Subjects receiving Oxycodone/Naltrexone

  up to 14 days

• Secondary: Subjective Pharmacodynamic Effects through the use of Visual Analog Scales (VAS)

  up to 14 days

• Secondary: Objective Pharmacodynamic Effects through the use of Pupillometry measurements

  up to 14 days

Study Arms (3)

Oxycodone/Naltrexone

EXPERIMENTAL

Oxycodone/Naltrexone Capsules (over-encapsulated), on days 6-10, every 6 hours (at 09:00, 15:00, 21:00)

Drug: Oxycodone/Naltrexone Capsules

Oxycodone

ACTIVE COMPARATOR

Oxycodone Tablets (Over-encapsulated), on Days 6-10, every 6 hours (at 09:00, 15:00, 21:00)

Drug: Oxycodone

Placebo Lead-In

OTHER

Placebo Lead-In: Placebo Capsules (matching to Active and Experimental) on days 4-5, every 6 hours (at 09:00, 15:00, 21:00)

Drug: Placebo

Interventions

Oxycodone/Naltrexone Capsules DRUG

Oxycodone/Naltrexone to be taken with stable dose of Methadone

Oxycodone/Naltrexone

Oxycodone DRUG

Oxycodone to be taken with stable dose of Methadone

Oxycodone

Placebo DRUG

2 day placebo run in prior to test and active drug phase of study

Placebo Lead-In

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male or female subjects 18 to 55 years of age, inclusive.
• Body mass index (BMI) within the range of 18.0 to 35.0 kg/m2, inclusive, and a minimum weight of 50.0 kg.
• Maintained on a stable methadone regimen. Subjects must be receiving a methadone dose of 50 to 150 mg/day at Screening, with dosage variation ≤20% for at least 14 days prior to the Screening visit and who are willing to remain on their dose at Screening and for the duration of the study.
• The study volunteer has been previously exposed to opioids while on methadone maintenance without relapse occurring, or in the opinion of the methadone maintenance program Director or Physician, is not at undue risk of relapse from participation in the clinical study.

You may not qualify if:

• History or presence of clinically significant abnormality as assessed by physical examination, medical history, 12-lead ECG, vital signs, or laboratory values, which in the opinion of the investigator would jeopardize the safety of the subject or the validity of the study results.
• Clinically significant infection/injury/illness within 1 month prior to Screening.
• Has been diagnosed with cancer within 5 years prior to screening (excluding squamous or basal cell carcinoma of the skin), or has an active malignancy of any type (including squamous or basal cell carcinoma of the skin).
• History of major mental illness that in the opinion of the investigator may affect the ability of the subject to participate in the study. Institutionalized subjects will not be eligible for participation.
• Documented history of a medical condition that, in the opinion of the investigator, would compromise the subject's ability to swallow, absorb, metabolize, or excrete test product, including (but not limited to) intractable nausea and/or vomiting and/or severe gastrointestinal narrowing (pathologic or iatrogenic).
• Documented history of, or currently active, seizure disorder or history of clinically significant head injury or syncope of unknown origin.
• History of severe allergic reaction (including anaphylaxis) to any substance, or previous status asthmaticus, or food allergies/intolerances/restrictions, or special dietary needs which, in the judgment of the investigator, contraindicates the subject's participation in the study.
• History of allergy or hypersensitivity to oxycodone or related drugs (e.g., other opioids) or naltrexone or related drugs (e.g., other antagonists).
• \. An employee of the sponsor or research site personnel directly affiliated with this study or their immediate family member defined as a spouse, parent, child or sibling, whether biological or legally adopted.
• A subject who, in the opinion of the investigator or designee, is considered unsuitable or unlikely to comply with the study protocol for any reason.

Sponsors & Collaborators

• Elite Laboratories, Inc: lead

Study Sites (1)

Vince and Associates

Overland Park, Kansas, 66212, United States

Location

MeSH Terms

Conditions

Substance Withdrawal Syndrome

Interventions

Oxycodone; Naltrexone

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

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; Naloxone

Study Officials

• Debra Kelsh, MD

  Vince and Associates

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2015
• First Posted: March 18, 2015
• Study Start: February 1, 2015
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: August 10, 2016

Record last verified: 2016-08

Locations

US (1)