Clinical trial NCT05382091: Evaluation of the O'Neil Long Acting Naltrexone Implant in Opioid Dependent Persons
Official title: A Phase II Multi-Center Safety Study Examining the Use of the O'Neil Long Acting Naltrexone Implant (OLANI) in Opioid Dependent Persons Receiving Repeat Dosing
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Opioid Use Disorder
Keywords: naltrexone
opioids
OLANI implant
opioid use disorder
opioid dependence
opioid receptor antagonist
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: The Emmes Company, LLC
name: University at Buffalo
First posted: 2022-05-19
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will examine the safety and efficacy of the O'Neil Long Acting Naltrexone Implant (OLANI) in persons with opioid dependency who are seeking relapse-prevention treatment. All participants will be treated in an open label manner. No randomization will occur. The OLANI is a long-acting biodegradable form of naltrexone which is implanted in the abdominal region. It is hypothesized that the OLANI will produce blood levels sufficient to block the effects of opioids for an extended period allowing patients to engage in psychosocial treatment and recovery over the long term. After the initial set of implants, participants will be offered 3 sets of single implants 13 weeks, each with an acceptable window of 12-16 weeks after the previous dose.

Detailed description: This is a Phase II, multi-center, open-label study designed to evaluate the safety profile and the efficacy of the OLANI when used in participants who meet the diagnosis of opioid use disorder (OUD), as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), and who will be voluntarily seeking relapse-prevention treatment using the naltrexone (NTX) implant.

Participants eligible for the study have diagnosed OUD, have completed withdrawal from opioids, and are no longer physically dependent at the time of study enrollment. After completing the informed consent process for the study, all participants will receive their initial OLANI set (two implants) implanted subcutaneously by a study surgeon and will be followed by a medical and surgical research team, receiving medical management intervention and blood draws to measure levels of NTX and its metabolite, 6-beta-naltrexol (6BN).

For interested participants, a standard dose of OLANI (standard dose contains 1 x OLANI, for a total of 1.8 g NTX) will be offered 13 weeks (91 days), within an acceptable dosing window of 12-16 weeks (84-112 days) after the initial loading dose, with a preference for participants to receive the dose between 84-91 days. Participants will continue to be offered a repeat standard dose of OLANI every 13 weeks (91 days), within an acceptable dosing window of 12-16 weeks (84-112 days) after their previous dose for a further two repeats. This will result in a maximum of 4 procedures within 36 to 48-weeks. All participants will be followed up until 60 weeks post their initial IP procedure, irrespective of the number of procedures that they have. This will result in a total study duration of 60 weeks for all participants.

Eligibility criteria: Inclusion Criteria:

* All genders between 18 and 65 (inclusive) years old
* Meet criteria for a current (within the previous 12-months) DSM-5 diagnosis of OUD at screening, and voluntarily seeking relapse-prevention treatment with NTX implant
* Completed opioid withdrawal as demonstrated by a negative naloxone challenge test (i.e., has tolerated naloxone 0.8 mg)
* Individuals currently treated with NTX will be eligible to receive the implant at the end of the dosing interval of either Vivitrol or oral NTX
* Have no medical or psychiatric contraindications to treatment either with NTX or with the OLANI, as determined by the site clinician and based on medical history and current health status
* Able to sufficiently speak and understand English and understand study procedures
* Able and willing to provide written informed consent
* Able and willing to provide detailed contact information for both self and for close contact(s) on the locator form
* Able and willing to comply with the requirements and procedures of the protocol, including tolerating a minor surgical procedure with local anesthetic for placement of the implant sets into the subcutaneous tissue of the abdomen
* Have an initial weight between 45.3 and 130 kg (inclusive) or have a BMI of 18.5 to 35.0 (inclusive)
* For female participants of childbearing potential, a willingness to practice an effective method of birth control for the duration of participation in the study. Acceptable methods of birth control are specified on the data collection form and in the Manual of Procedures (MOP), and methods other than those specified are not permitted, except in combination with a study-acceptable method; and willingness to complete urine pregnancy testing to confirm non-pregnant status, as per the study schedule and as requested by the site clinician.

Exclusion Criteria:

* Has a condition, disease state, previous medical history, or observed abnormality(ies) (including physical examination, electrocardiogram \[ECG\], laboratory evaluation, or urinalysis finding) identified during screening that, in the opinion of the site clinician, would preclude safe participation in the study, would affect the ability of the participant to adhere to the protocol, or would interfere with the study assessments, including, but not limited to the following:

  * A significant neurological (including cognitive and psychiatric disorders), hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, hematologic, or metabolic disease, unless currently controlled and stable using protocol-allowed medication(s) for the 30 days immediately preceding the proposed administration of OLANI
  * Has had significant suicidal ideation or behavior within the past year
  * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) value more than three times the upper limit of normal, or a different indicator of clinically significant liver cirrhosis (e.g., bilirubin and albumin will also be assessed)
  * Has a condition (e.g., chronic pain) that requires ongoing treatment with opiate based medication
  * Has any contraindicated medical condition per the approved labelling for NTX containing products
* Has physiological dependence on alcohol and/or sedative-hypnotics that require medical detoxification
* If female, is currently pregnant or breastfeeding, is planning to conceive during the period of study engagement, has a positive blood pregnancy test, or is unwilling to practice effective contraception during study participation
* Has received a NTX implant in the last 12 months
* Has a known hypersensitivity to NTX
* Is not able to provide blood samples due to extensive vein damage
* Has a known hypersensitivity to polylactic acid based materials, including disposable sutures or implants
* Has a known hypersensitivity to local anesthesia
* Is prone to skin rashes, skin irritation, or has a diagnosed or observed skin condition (e.g., recurrent eczema)
* Is tattooed in the proposed implantation area or demonstrates any abnormal skin tissue in the proposed implantation area
* Currently confined or detained in a penal institution or sentenced to such an institution under a criminal or civil statute or detained in other facilities by virtue of statutes.
* Any additional condition(s) that, in the investigator's opinion, would prohibit the participant from completing the study or that would not be in the best interest of the participant.

Primary outcomes:
measure: Treatment Emergent Adverse Events (TEAEs)
timeFrame: time from from placement of first implant set until end of study at 60 weeks.
measure: Adverse Events of Special Interest (AESI)
timeFrame: time from from placement of first implant set until end of study at 60 weeks.
measure: Deaths
timeFrame: time from from placement of first implant set until end of study at 60 weeks.
measure: Serious Adverse Events (SAEs)
timeFrame: time from from placement of first implant set until end of study at 60 weeks.
measure: Adverse events (AEs) causing study discontinuation
timeFrame: time from from placement of first implant set until end of study at 60 weeks.
measure: Opioid overdose events
timeFrame: time from from placement of first implant set until end of study at 60 weeks.
measure: Laboratory abnormalities
timeFrame: time from from placement of first implant set until end of study at 60 weeks.
measure: Suicidality
timeFrame: time from from placement of first implant set until end of study at 60 weeks.
measure: Concomitant medications
timeFrame: time from from placement of first implant set until end of study at 60 weeks.
Secondary outcomes:
measure: AUC0-t of naltrexone
timeFrame: collected before each implant administration (pre-dose), and 3 hours, 7 days, 14 days, 28 days, then every 14 days until next implant procedure. PK sampling is reduced to every 28 days after 12 weeks if the next implant procedure is not completed.
measure: AUC0-t of 6-beta-naltrexol
timeFrame: collected before each implant administration (pre-dose), and 3 hours, 7 days, 14 days, 28 days, then every 14 days until next implant procedure. PK sampling is reduced to every 28 days after 12 weeks if the next implant procedure is not completed.
measure: AUC0-infinity of naltrexone
timeFrame: collected before each implant administration (pre-dose), and 3 hours, 7 days, 14 days, 28 days, then every 14 days until next implant procedure. PK sampling is reduced to every 28 days after 12 weeks if the next implant procedure is not completed.
measure: AUC0-infinity of 6-beta-naltrexol
timeFrame: collected before each implant administration (pre-dose), and 3 hours, 7 days, 14 days, 28 days, then every 14 days until next implant procedure. PK sampling is reduced to every 28 days after 12 weeks if the next implant procedure is not completed.
measure: Cmax of naltrexone
timeFrame: collected before each implant administration (pre-dose), and 3 hours, 7 days, 14 days, 28 days, then every 14 days until next implant procedure. PK sampling is reduced to every 28 days after 12 weeks if the next implant procedure is not completed.
measure: Cmax of 6-beta-naltrexol
timeFrame: collected before each implant administration (pre-dose), and 3 hours, 7 days, 14 days, 28 days, then every 14 days until next implant procedure. PK sampling is reduced to every 28 days after 12 weeks if the next implant procedure is not completed.
measure: Tmax of naltrexone
timeFrame: collected before each implant administration (pre-dose), and 3 hours, 7 days, 14 days, 28 days, then every 14 days until next implant procedure. PK sampling is reduced to every 28 days after 12 weeks if the next implant procedure is not completed.
measure: Tmax of 6-beta-naltrexol
timeFrame: collected before each implant administration (pre-dose), and 3 hours, 7 days, 14 days, 28 days, then every 14 days until next implant procedure. PK sampling is reduced to every 28 days after 12 weeks if the next implant procedure is not completed.
measure: Proportion of participants that maintain a minimum plasma concentration
timeFrame: up to Week 60
measure: Proportion of participants that maintain a minimum plasma concentration
timeFrame: up to Week 60
measure: Abstinence from drugs of abuse by UDS
timeFrame: pre-dose (prior to each implant procedure) and at every study visit through Week 60.
measure: Abstinence from drugs of abuse by Timeline Followback (TLFB)
timeFrame: At every study visit through Week 60 except for days of implant procedures.
measure: Abstinence from alcohol
timeFrame: pre-dose (prior to each implant procedure) and at every study visit through Week 60.
measure: Opioid craving (VAS)
timeFrame: pre-dose (prior to each implant procedure) and at every study visit through Week 60.
measure: Opioid withdrawal (SOWS)
timeFrame: pre-dose (prior to each implant procedure) and at every study visit through Week 60.
measure: Opioid withdrawal (COWS)
timeFrame: pre-dose (prior to each implant procedure) and at every study visit through Week 60.
measure: Hamilton Depression Rating Scale (HDRS)
timeFrame: At every study visit through Week 60 except for days of implant procedures.
measure: Brief Symptom Inventory 18 (BSI-18)
timeFrame: Baseline, Day 28, Day 42, Day 56, Day 84, and then every 28 days until Week 60.
measure: Quality of Life Score (QoL)
timeFrame: Day 28, Day 42, Day 56, Day 84, and then every 28 days until Week 60.
measure: Treatment Satisfaction (TSQM-14)
timeFrame: Repeat implant procedure days and at Week 60.
Other outcomes:
Locations:
Study officials:
affiliation: New York State Psychiatric Institute
name: Adam Bisaga, MD
role: PRINCIPAL_INVESTIGATOR
References: