Clinical trial NCT03810495: The O'Neil Long Acting Naltrexone Implant (OLANI) Pharmacokinetic (PK)/Safety Study in Healthy Volunteers
Official title: OLANI PK/Safety Study in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Opioid Use Disorder
Keywords: naltrexone
opioids
opioid use disorder
OLANI implant
Lead sponsor: Go Medical Industries Pty Ltd
Sponsor class: INDUSTRY
Collaborators: name: National Institute on Drug Abuse (NIDA)
name: New York State Psychiatric Institute
name: Columbia University
name: Clinilabs, Inc.
First posted: 2019-01-18
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants That Maintain MEC
timeFrame: up to 540 days or until NTX blood levels become undetectable
Secondary outcomes:
measure: Median Cmax of Naltrexone
timeFrame: 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
measure: Tmax of Naltrexone
timeFrame: 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
measure: AUC of Naltrexone
timeFrame: 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
measure: Median Cmax of 6β-naltrexol
timeFrame: 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
measure: Median Tmax of 6β-naltrexol
timeFrame: 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
measure: Time>Minimum Effective Concentration
timeFrame: 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
measure: AUC of 6β-naltrexol
timeFrame: 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
measure: Incidence of Adverse Events (AEs)
timeFrame: Up to 540 days or until NTX blood levels become undetectable
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
Study officials:
affiliation: New York State Psychiatric Institute
name: Adam Bisaga, MD
role: PRINCIPAL_INVESTIGATOR
References: