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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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OLANI PK/Safety Study in Healthy Volunteers

Conditions
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Opioid Use Disorder

Intervention / Treatment
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* Drug: naltrexone implant


Participation Criteria
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Eligibility Criteria
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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.

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: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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naltrexone, opioids, opioid use disorder, OLANI implant