Clinical trial NCT04716881: Pharmacokinetic Study of Vivitrol in Healthy Participants
Official title: A Bioequivalence Study Comparing Vivitrol and O'Neil Long Acting Naltrexone Implant (OLANI) in Healthy Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Opioid-use Disorder
Keywords: naltrexone
opioids
Opioid Use Disorder
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: 2021-01-20
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Maximum age (years): 57
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: This is a Phase I, single-center, single arm, open-label study, to establish the pharmacokinetic (PK) parameters of Vivitrol 380 mg IM injection (IP), a US Food and Drug Administration (FDA) approved medication.

Detailed description: This is a Phase I, single-center, single arm, open-label study, to establish the PK parameters of Vivitrol 380 mg IM injection (IP), a US FDA approved medication. Participants will be healthy volunteers with no significant medical or mental health disorders, who have completed participation in clinical trial GM0017 (i.e. have received the OLANI treatment and have subsequently provided two consecutive plasma levels of naltrexone (NTX) \<0.1ng/mL).

This study will examine the PK profile of Vivitrol IM 380 mg over 6 doses for a treatment period of 196 days. Intense sampling will occur after the 1st and 6th dose of Vivitrol. Participants will be without a DSM 5 - Substance Related Disorders classification. Participants will be required to undergo a Naloxone Challenge Test (NCT) to confirm opiate naivety before administration of the IP. No randomization will occur.

Eligibility criteria: Inclusion Criteria:

* Have completed GM0017 (i.e. been administered OLANI (3.6 gram) and provided two consecutive monthly blood samples of NTX below 0.1 ng/mL)
* Men or women between ≥18 and \<58 years old Without 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 an injection of NTX to allow for investigational drug administration in the intramuscular tissue
* Have an initial weight between 45.3 and 81.6 kilograms (inclusive) or have a BMI inclusive of 18.5 to 30.0.

Exclusion Criteria:

* Is currently on active NTX medication.
* Positive UDS at screening for illicit substances.
* Has a condition which requires treatment with opioid based medication.
* Has a known hypersensitivity to NTX.
* Is prone to skin rashes, irritation or has a skin condition such as recurrent eczema that is likely to impact the injection site area, or as determined by the evaluating physician.
* Demonstrates any abnormal skin tissue in the proposed injection area.
* Is pregnant or planning to be. Women need to have negative pregnancy test at screening. Women need to agree to practice an effective method of contraception throughout participation.
* Participant is breastfeeding or planning to be.
* Has a current significant neurological (including cognitive and psychiatric disorders),
* 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.
* ALT or 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 MINI 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, 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.
* Is allergic to any of the ingredients in Vivitrol or the diluent used to mix Vivitrol (i.e. carboxymethylcellulose sodium, polysorbate 20, sodium chloride, sodium hydroxide and hydrochloric acid as pH adjusters, in water for injection).

Primary outcomes:
measure: Median Cmax of Naltrexone (After 1st Dose)
timeFrame: 1st dose: Day 0 (predose), 1, 2, 4, 8, 12 hours, 24 hours (Day 1), Days 1.5, 1.75, 2, 3, 5, 7, 10, 14, 17, 21, 24, and 28.
measure: Median Tmax of Naltrexone (After 1st Dose)
timeFrame: 1st dose: Day 0 (predose), 1, 2, 4, 8, 12 hours, 24 hours (Day 1), Days 1.5, 1.75, 2, 3, 5, 7, 10, 14, 17, 21, 24, and 28.
measure: Median AUC0-inf of Naltrexone (After 1st Dose)
timeFrame: 1st dose: Day 0 (predose), 1, 2, 4, 8, 12 hours, 24 hours (Day 1), Days 1.5, 1.75, 2, 3, 5, 7, 10, 14, 17, 21, 24, and 28.
measure: Median Ctrough of Naltrexone (After 1st Dose)
timeFrame: 1st dose: Day 0 (predose), 1, 2, 4, 8, 12 hours, 24 hours (Day 1), Days 1.5, 1.75, 2, 3, 5, 7, 10, 14, 17, 21, 24, and 28.
measure: Median Cmax of 6β-naltrexol (After First Dose)
timeFrame: 1st dose: Day 0 (predose), 1, 2, 4, 8, 12 hours, 24 hours (Day 1), Days 1.5, 1.75, 2, 3, 5, 7, 10, 14, 17, 21, 24, and 28.
measure: Median Tmax of 6β-naltrexol (After 1st Dose)
timeFrame: 1st dose: Day 0 (predose), 1, 2, 4, 8, 12 hours, 24 hours (Day 1), Days 1.5, 1.75, 2, 3, 5, 7, 10, 14, 17, 21, 24, and 28.
measure: Median AUC0-inf of 6β-naltrexol (After 1st Dose)
timeFrame: 1st dose: Day 0 (predose), 1, 2, 4, 8, 12 hours, 24 hours (Day 1), Days 1.5, 1.75, 2, 3, 5, 7, 10, 14, 17, 21, 24, and 28.
measure: Median Ctrough of 6β-naltrexol (After 1st Dose)
timeFrame: 1st dose: Day 0 (predose), 1, 2, 4, 8, 12 hours, 24 hours (Day 1), Days 1.5, 1.75, 2, 3, 5, 7, 10, 14, 17, 21, 24, and 28.
measure: Median Cmax of Naltrexone (After 6th Dose)
timeFrame: 6th dose: Day 140 (1, 2, 4, 8 & 12 hours), 141, 141.5, 141.75, 142, 143, 145, 147, 150, 154, 157, 161, 164, 168, 182 and 196
measure: Median Tmax of Naltrexone (After 6th Dose)
timeFrame: 6th dose: Day 140 (1, 2, 4, 8 & 12 hours), 141, 141.5, 141.75, 142, 143, 145, 147, 150, 154, 157, 161, 164, 168, 182 and 196
measure: Median AUC0-inf of Naltrexone (After 6th Dose)
timeFrame: 6th dose: Day 140 (1, 2, 4, 8 & 12 hours), 141, 141.5, 141.75, 142, 143, 145, 147, 150, 154, 157, 161, 164, 168, 182 and 196
measure: Median Ctrough of Naltrexone (After 6th Dose)
timeFrame: 6th dose: Day 140 (1, 2, 4, 8 & 12 hours), 141, 141.5, 141.75, 142, 143, 145, 147, 150, 154, 157, 161, 164, 168, 182 and 196
measure: Median Cmax of 6β-naltrexol (After 6th Dose)
timeFrame: 6th dose: Day 140 (1, 2, 4, 8 & 12 hours), 141, 141.5, 141.75, 142, 143, 145, 147, 150, 154, 157, 161, 164, 168, 182 and 196
measure: Median Tmax of 6β-naltrexol (After th Dose)
timeFrame: 6th dose: Day 140 (1, 2, 4, 8 & 12 hours), 141, 141.5, 141.75, 142, 143, 145, 147, 150, 154, 157, 161, 164, 168, 182 and 196
measure: Median AUC0-inf of 6β-naltrexol (After 6th Dose)
timeFrame: 6th dose: Day 140 (1, 2, 4, 8 & 12 hours), 141, 141.5, 141.75, 142, 143, 145, 147, 150, 154, 157, 161, 164, 168, 182 and 196
measure: Median Ctrough of 6β-naltrexol (After 6th Dose)
timeFrame: 6th dose: Day 140 (1, 2, 4, 8 & 12 hours), 141, 141.5, 141.75, 142, 143, 145, 147, 150, 154, 157, 161, 164, 168, 182 and 196
Secondary outcomes:
measure: Adverse Events (AEs)
timeFrame: Up to Day 196
measure: Naltrexone Accumulation Ratio (AR) for Cmax
timeFrame: 196 days after the 6th dose
measure: Naltrexone Accumulation Ratio (AR) for Ctrough
timeFrame: 196 days after the 6th dose
measure: Naltrexone Accumulation Ratio (AR) for AUC0-inf
timeFrame: 196 days after the 6th dose
measure: 6β-naltrexol Accumulation Ratio (AR) for Cmax
timeFrame: 196 days after the 6th dose
measure: 6β-naltrexol Accumulation Ratio (AR) for Ctrough
timeFrame: 196 days after the 6th dose
measure: 6β-naltrexol Accumulation Ratio (AR) for AUC0-inf
timeFrame: 196 days after the 6th dose
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: