The O'Neil Long Acting Naltrexone Implant (OLANI) Pharmacokinetic (PK)/Safety Study in Healthy Volunteers

OLANI PK/Safety Study in Healthy Volunteers

This study will examine the pharmacokinetic profile and safety of the O'Neil Long Acting Naltrexone Implant (OLANI) overtime in healthy volunteers. All participants will be treated in an open label manner. No randomization will occur. It is hypothesized that the OLANI will provide sustained therapeutic doses of naltrexone (NTX) for periods up to 6 months via a single subcutaneous application of 2 OLANIs.

Study Overview

• Status: Completed
• Conditions: Opioid Use Disorder
• Intervention / Treatment: Drug: naltrexone implant

Detailed Description

Naltrexone (NTX) is a nonspecific pure opioid antagonist with a high affinity for the µ-opioid receptor. It blocks the effects of opioids by competitive binding at opiate receptors. NTX is used primarily in the management of opiate and alcohol dependence. It is available in the United States (US) as 2 formulations; a once daily oral formulation (Revia) and a once monthly intramuscular injection (Vivitrol). While NTX is a potent antagonist and efficiently blocks the effects of exogenous opiates such as heroin, the success of NTX for the treatment of opiate dependence has been limited by poor patient compliance. Therefore, the development of a sustained release NTX formulation (in excess of 1 month) would be of great benefit for the treatment of opioid use disorder.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men or women between the ages of 18 and 55 years old (inclusive)
• Without The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM 5) - Substance Related Disorders classification; in sustained remission is not exclusionary
• Able and willing to comply with the requirements of the protocol
• Able and willing to provide written informed consent
• Willing to undergo a minor surgical procedure under local anesthetic to allow for investigational drug administration in the subcutaneous tissue
• BMI inclusive of 18.5 to 30.0
• Have an initial weight between 45.3 and 81.6 kilograms (inclusive)

Exclusion Criteria:

• Positive urine drug screen (UDS) at screening for illicit substances.
• Is currently on naltrexone medication.
• Has had a naltrexone implant in the past 24 months.
• Has received treatment with an extended naltrexone product (e.g. Vivitrol) in the past 12 months.
• Has a condition which requires treatment with opioid based medication.
• Has a known hypersensitivity to naltrexone.
• Has a known hypersensitivity to poly-lactic based materials e.g. biodegradable sutures, surgical implants or previous biodegradable implants.
• Has a known hypersensitivity to local anesthesia.
• Is prone to skin rashes, irritation or has a skin condition such as recurrent eczema that is likely to impact the implant site area, or as determined by the evaluating physician.
• Demonstrates any abnormal skin tissue in the proposed implantation area.
• Is pregnant or planning to be. Women need to have negative blood pregnancy test at screening. Women need to agree to practice dual contraceptives.
• Participant is breastfeeding or planning to be.
• Has a current significant neurological (including cognitive and psychiatric disorders), hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, hematological or metabolic disease unless currently controlled and stable with protocol-allowed medication 30 days prior to proposed investigational product administration.
• Any clinically important abnormal finding as determined by medical history, physical examination, ECG or clinical laboratory tests.
• Any additional condition(s) that in the investigator's opinion would prohibit the participant from completing the study or would not be in the best interest of the participant.
• Alanine aminotransferase (ALT) or aspartate transaminase (AST) > 3 times the upper end of the laboratory normal range.
• Any methadone use 14 days prior to screening, and up to Study Day 0.
• Current DSM-5 diagnosis of schizophrenia, bipolar, anxiety, or depressive disorder, confirmed by The Mini International Neuropsychiatric Interview (MINI) diagnostic interview assessment, or currently treated with medications for anxiety or depression. Past history (in remission DSM-5 classification) of anxiety or depression is not exclusionary.
• Any elevated risk for suicide measured using the Columbia Suicide Severity Rating Scale (C-SSRS), endorsing any of the items in the past month (C-SSRS, Lifetime)
• Is participating or intending to participate in any other clinical trial during the duration of this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OLANI (naltrexone implant); 2 OLANI containing 60% naltrexone (1.8 g total) administered one time subcutaneously	Drug: naltrexone implant; 1.8 g implant containing 60% naltrexone; Other Names: OLANI; O'Neil Long Acting Naltrexone Implant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants That Maintain MEC	Percentage of participants who maintain naltrexone (NTX) blood levels of ≥1.33 ng/mL for ≥180 days	up to 540 days or until NTX blood levels become undetectable

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Cmax of Naltrexone	Single-dose pharmacokinetic (PK) measurement of the plasma naltrexone concentration (Cmax) after dosing on Day 1	pre-dose, at 3, 6, and 12 hours (± 60 minutes) after dosing; 24 and 48 hours (± 2 hours) after dosing; day 4 (± 1 day), day 8 (± 2 days); days 14, 21, 28, 35, 42, 49 and 56 (± 3 days); then every 30 days (± 10 days) up to 540 days
Tmax of Naltrexone	Single-dose PK measurement of the time to reach the maximum (Tmax) naltrexone concentration after dosing on Day 1	pre-dose, at 3, 6, and 12 hours (± 60 minutes) after dosing; 24 and 48 hours (± 2 hours) after dosing; day 4 (± 1 day), day 8 (± 2 days); days 14, 21, 28, 35, 42, 49 and 56 (± 3 days); then every 30 days (± 10 days) up to 540 days
AUC of Naltrexone	Single-dose PK measurement of the area under the curve (AUC) for naltrexone after dosing on Day 1	pre-dose, at 3, 6, and 12 hours (± 60 minutes) after dosing; 24 and 48 hours (± 2 hours) after dosing; day 4 (± 1 day), day 8 (± 2 days); days 14, 21, 28, 35, 42, 49 and 56 (± 3 days); then every 30 days (± 10 days) up to 540 days
Median Cmax of 6β-naltrexol	Single-dose PK measurement of the peak plasma 6β-naltrexol concentration after dosing on Day 1	pre-dose, at 3, 6, and 12 hours (± 60 minutes) after dosing; 24 and 48 hours (± 2 hours) after dosing; day 4 (± 1 day), day 8 (± 2 days); days 14, 21, 28, 35, 42, 49 and 56 (± 3 days); then every 30 days (± 10 days) up to 540 days
Median Tmax of 6β-naltrexol	Single-dose PK measurement of the time to reach the maximum 6β-naltrexol concentration after dosing on Day 1	pre-dose, at 3, 6, and 12 hours (± 60 minutes) after dosing; 24 and 48 hours (± 2 hours) after dosing; day 4 (± 1 day), day 8 (± 2 days); days 14, 21, 28, 35, 42, 49 and 56 (± 3 days); then every 30 days (± 10 days) up to 540 days
Time>Minimum Effective Concentration	Time (T) naltrexone remains above the minimum effective concentration (MEC) of 1.33	pre-dose, at 3, 6, and 12 hours (± 60 minutes) after dosing; 24 and 48 hours (± 2 hours) after dosing; day 4 (± 1 day), day 8 (± 2 days); days 14, 21, 28, 35, 42, 49 and 56 (± 3 days); then every 30 days (± 10 days) up to 540 days
AUC of 6β-naltrexol	Single-dose PK measurement of the AUC for 6β-naltrexol concentration after dosing on Day 1	pre-dose, at 3, 6, and 12 hours (± 60 minutes) after dosing; 24 and 48 hours (± 2 hours) after dosing; day 4 (± 1 day), day 8 (± 2 days); days 14, 21, 28, 35, 42, 49 and 56 (± 3 days); then every 30 days (± 10 days) up to 540 days
Incidence of Adverse Events (AEs)	Incidence and Severity of AEs	Up to 540 days or until NTX blood levels become undetectable

Collaborators and Investigators

• Sponsor: Go Medical Industries Pty Ltd
• Collaborators: National Institute on Drug Abuse (NIDA); Columbia University; New York State Psychiatric Institute; Clinilabs, Inc.
• Investigators: Principal Investigator: Adam Bisaga, MD, New York State Psychiatric Institute

Study record dates

Study Major Dates

• Study Start (Actual): April 11, 2019
• Primary Completion (Actual): March 18, 2021
• Study Completion (Actual): March 22, 2021

Study Registration Dates

• First Submitted: January 17, 2019
• First Submitted That Met QC Criteria: January 17, 2019
• First Posted (Actual): January 18, 2019

Study Record Updates

• Last Update Posted (Actual): October 13, 2022
• Last Update Submitted That Met QC Criteria: September 19, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: opioid use disorder; opioids; naltrexone; OLANI implant
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Narcotic-Related Disorders; Opioid-Related Disorders; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Alcohol Deterrents; Naltrexone
• Other Study ID Numbers: GM0017; UG3DA047720 (U.S. NIH Grant/Contract); 240358 (Other Identifier: NIH ERA Human Subjects Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No