CompletedNCT03810495Updated Nov 12, 2024Results posted

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

A Phase 1 interventional study of naltrexone implant in Opioid Use Disorder, sponsored by Go Medical Industries Pty Ltd. Completed at 1 site in United States. Open to participants aged 18 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-11-12.

Sponsored by Go Medical Industries Pty Ltd · Phase 1, Interventional, and Basic science

Phase: Phase 1
Study type: Interventional
Enrollment: 20
Allocation: Not applicable
Ages: 18 Years to 55 Years
Sex: All

Study 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.

Read the 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.

Conditions studied

Opioid Use Disorder

Browse trials for

Opioid-Related Disorders 1,411

Keywords

naltrexone
opioids
opioid use disorder
OLANI implant

Who can participate

Ages eligible: 18 Years to 55 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

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

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 design

Phase: Phase 1
Primary purpose: Basic science
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 20 participants (actual)

Study arms

Experimental
OLANI (naltrexone implant)
2 OLANI containing 60% naltrexone (1.8 g total) administered one time subcutaneously
Drug: naltrexone implant

Interventions

Drugnaltrexone implant
1.8 g implant containing 60% naltrexone
Also known as: OLANI, O'Neil Long Acting Naltrexone Implant

What researchers measure

Primary outcomes

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

Secondary outcomes

Median Cmax of Naltrexone
Single-dose pharmacokinetic (PK) measurement of the plasma naltrexone concentration (Cmax) after dosing on Day 1
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Up to 540 days or until NTX blood levels become undetectable

Results

Posted Aug 1, 2022

Limitations and caveats

This is a pilot study with a small sample size.

Participant flow

Participant flow — Overall Study
Milestone	OLANI (Naltrexone Implant)
Started	20
Completed	17
Not completed	3
Withdrew: Lost to follow-up	2
Withdrew: Withdrawal by subject	1

Outcome measures

PrimaryPercentage of Participants That Maintain MEC

Percentage of participants who maintain naltrexone (NTX) blood levels of ≥1.33 ng/mL for ≥180 days

Time frame:: up to 540 days or until NTX blood levels become undetectable
Reported as:: Count of participants · Participants

Percentage of Participants That Maintain MEC
Participants	OLANI (Naltrexone Implant)
Percentage of Participants That Maintain MEC	10

SecondaryMedian Cmax of Naltrexone

Single-dose pharmacokinetic (PK) measurement of the plasma naltrexone concentration (Cmax) after dosing on Day 1

Time frame:: 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
Reported as:: Median · ng/mL

Median Cmax of Naltrexone
ng/mL	OLANI (Naltrexone Implant)
Median Cmax of Naltrexone	17.00 (5.38 to 71.4)

SecondaryTmax of Naltrexone

Single-dose PK measurement of the time to reach the maximum (Tmax) naltrexone concentration after dosing on Day 1

Time frame:: 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
Reported as:: Median · day

Tmax of Naltrexone
day	OLANI (Naltrexone Implant)
Tmax of Naltrexone	49.63 (0.47 to 268)

SecondaryAUC of Naltrexone

Single-dose PK measurement of the area under the curve (AUC) for naltrexone after dosing on Day 1

Time frame:: 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
Reported as:: Median · day*ng/mL

AUC of Naltrexone
day*ng/mL	OLANI (Naltrexone Implant)
AUC of Naltrexone	1440.5 (991.1 to 2022)

SecondaryMedian Cmax of 6β-naltrexol

Single-dose PK measurement of the peak plasma 6β-naltrexol concentration after dosing on Day 1

Time frame:: 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
Reported as:: Median · ng/mL

Median Cmax of 6β-naltrexol
ng/mL	OLANI (Naltrexone Implant)
Median Cmax of 6β-naltrexol	23.45 (10.2 to 126)

SecondaryMedian Tmax of 6β-naltrexol

Single-dose PK measurement of the time to reach the maximum 6β-naltrexol concentration after dosing on Day 1

Time frame:: 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
Reported as:: Median · day

Median Tmax of 6β-naltrexol
day	OLANI (Naltrexone Implant)
Median Tmax of 6β-naltrexol	49.70 (1 to 176.3)

SecondaryTime>Minimum Effective Concentration

Time (T) naltrexone remains above the minimum effective concentration (MEC) of 1.33

Time frame:: 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
Reported as:: Median · days

Time>Minimum Effective Concentration
days	OLANI (Naltrexone Implant)
Time>Minimum Effective Concentration	270 (56 to 360)

SecondaryAUC of 6β-naltrexol

Single-dose PK measurement of the AUC for 6β-naltrexol concentration after dosing on Day 1

Time frame:: 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
Reported as:: Median · day*ng/mL

AUC of 6β-naltrexol
day*ng/mL	OLANI (Naltrexone Implant)
AUC of 6β-naltrexol	2856.50 (1484 to 4990)

SecondaryIncidence of Adverse Events (AEs)

Incidence and Severity of AEs

Time frame:: Up to 540 days or until NTX blood levels become undetectable
Reported as:: Number · participants

Incidence of Adverse Events (AEs)
participants	OLANI (Naltrexone Implant)
Participants with at least One Treatment-Emergent Adverse Event	19
Implant site inflammation	7
Vomiting	7
Headache	5
Implant site pruritus	4
Nausea	3
Diarrhoea	3
Upper respiratory tract infection	3
Implant site pain	2
Back pain	2
Weight increased	2

Adverse events

Collected over 18 months. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
OLANI (Naltrexone Implant)	0/20 (0%)	2/20 (10%)	19/20 (95%)

Most frequent serious events

Most frequent serious events
Event	OLANI (Naltrexone Implant)
Stab WoundInjury, poisoning and procedural complications	1/20
VomitingGastrointestinal disorders	1/20

Most frequent other events

Showing 10 of 37

Most frequent other events
Event	OLANI (Naltrexone Implant)
VomitingGastrointestinal disorders	7/20
Implant site inflammationGeneral disorders	7/20
HeadacheNervous system disorders	5/20
Implant site pruritusGeneral disorders	4/20
DiarrhoeaGastrointestinal disorders	3/20
NauseaGastrointestinal disorders	3/20
Upper respiratory tract infectionInfections and infestations	3/20
Implant site painGeneral disorders	2/20
Weight increasedInvestigations	2/20
Back painMusculoskeletal and connective tissue disorders	2/20

Baseline characteristics

Age, Continuous
Age, Continuous(years)	OLANI (Naltrexone Implant)
Mean	38.4 ± 10.77

Sex: Female, Male
Sex: Female, Male(Participants)	OLANI (Naltrexone Implant)
Female	10
Male	10

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	OLANI (Naltrexone Implant)
Hispanic or Latino	7
Not Hispanic or Latino	13
Unknown or Not Reported	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	OLANI (Naltrexone Implant)
American Indian or Alaska Native	0
Asian	1
Native Hawaiian or Other Pacific Islander	0
Black or African American	9
White	5
More than one race	3
Unknown or Not Reported	2

Region of Enrollment
Region of Enrollment(participants)	OLANI (Naltrexone Implant)
United States	20

Body Mass Index (kg/m^2)
Body Mass Index (kg/m^2)(kg/m^2)	OLANI (Naltrexone Implant)
Mean	24.92 ± 3.63

Study locations

1 site

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

References and documents

Study documents

Protocol and statistical analysis plan · Jun 11, 2020
Informed consent form · Jun 18, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Registry details

Key details

Study ID: NCT03810495
Lead sponsor: Go Medical Industries Pty Ltd
Collaborators: National Institute on Drug Abuse (NIDA), New York State Psychiatric Institute, Columbia University, Clinilabs, Inc.
Responsible party: Sponsor
First posted: Jan 18, 2019
Start date: Apr 11, 2019
Primary completion: Mar 18, 2021
Completion: Mar 22, 2021
Results posted: Aug 1, 2022
Last update: Nov 12, 2024

Study contacts

Adam Bisaga, MD

principal investigator · New York State Psychiatric Institute

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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