Pharmacokinetic Study of Vivitrol in Healthy Participants

A Bioequivalence Study Comparing Vivitrol and O'Neil Long Acting Naltrexone Implant (OLANI) in Healthy Participants

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.

Study Overview

• Status: Completed
• Conditions: Opioid-use Disorder
• Intervention / Treatment: Drug: Naltrexone 380 MG

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.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 57 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vivitrol (naltrexone); Intramuscular injection of Vivitrol (naltrexone), 380 mg. Six doses given 28 days apart.	Drug: Naltrexone 380 MG; Vivitrol (naltrexone) 380 mg delivered intramuscularly every 28 days; Other Names: Vivitrol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Cmax of Naltrexone (After 1st Dose)	Single-dose PK measurement of the maximum observed plasma naltrexone concentration (Cmax) after dosing on Day 0	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.
Median Tmax of Naltrexone (After 1st Dose)	Single-dose PK measurement of the time to maximum plasma naltrexone concentration (Tmax) after dosing on Day 0	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.
Median AUC0-inf of Naltrexone (After 1st Dose)	Single-dose PK measurement of the area under the plasma concentration-time curve for naltrexone from time 0 extrapolated to infinity (AUC0-inf) after dosing on Day 0	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.
Median Ctrough of Naltrexone (After 1st Dose)	Single-dose PK measurement of naltrexone concentration at the end of the dosing interval (Ctrough) after dosing on Day 0	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.
Median Cmax of 6β-naltrexol (After First Dose)	Single-dose PK measurement of the maximum observed plasma 6β-naltrexol concentration (Cmax) after dosing on Day 0	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.
Median Tmax of 6β-naltrexol (After 1st Dose)	Single-dose PK measurement of the time to maximum plasma 6β-naltrexol concentration (Tmax) after dosing on Day 0	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.
Median AUC0-inf of 6β-naltrexol (After 1st Dose)	Single-dose PK measurement of the area under the plasma concentration-time curve for 6β-naltrexol from time 0 extrapolated to infinity (AUC0-inf) after dosing on Day 0	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.
Median Ctrough of 6β-naltrexol (After 1st Dose)	Single-dose PK measurement of 6β-naltrexol concentration at the end of the dosing interval (Ctrough) after dosing on Day 0	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.
Median Cmax of Naltrexone (After 6th Dose)	PK measurement of the maximum observed plasma naltrexone concentration (Cmax) after 6th dose on Day 140	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
Median Tmax of Naltrexone (After 6th Dose)	PK measurement of the time to maximum plasma naltrexone concentration (Tmax) after dosing on Day 140	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
Median AUC0-inf of Naltrexone (After 6th Dose)	PK measurement of the area under the plasma concentration-time curve for naltrexone from time 0 extrapolated to infinity (AUC0-inf) after dosing on Day 140	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
Median Ctrough of Naltrexone (After 6th Dose)	PK measurement of naltrexone concentration at the end of the dosing interval (Ctrough) after dosing on Day 140	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
Median Cmax of 6β-naltrexol (After 6th Dose)	PK measurement of the maximum observed plasma 6β-naltrexol concentration (Cmax) after dosing on Day 140	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
Median Tmax of 6β-naltrexol (After th Dose)	PK measurement of the time to maximum plasma 6β-naltrexol concentration (Tmax) after dosing on Day 140	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
Median AUC0-inf of 6β-naltrexol (After 6th Dose)	PK measurement of the area under the plasma concentration-time curve for 6β-naltrexol from time 0 extrapolated to infinity (AUC0-inf) after dosing on Day 140	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
Median Ctrough of 6β-naltrexol (After 6th Dose)	PK measurement of 6β-naltrexol concentration at the end of the dosing interval (Ctrough) after dosing on Day 140	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events (AEs)	Proportion of participants reporting AEs	Up to Day 196
Naltrexone Accumulation Ratio (AR) for Cmax	The naltrexone AR was determined for Cmax by dividing the PK parameter for Dose 6 by the PK parameter for Dose 1.	196 days after the 6th dose
Naltrexone Accumulation Ratio (AR) for Ctrough	The naltrexone AR was determined for Crough by dividing the PK parameter for Dose 6 by the PK parameter for Dose 1.	196 days after the 6th dose
Naltrexone Accumulation Ratio (AR) for AUC0-inf	The naltrexone AR was determined for AUC0-inf by dividing the PK parameter for Dose 6 by the PK parameter for Dose 1.	196 days after the 6th dose
6β-naltrexol Accumulation Ratio (AR) for Cmax	The 6β-naltrexol AR was determined for Cmax by dividing the PK parameter for Dose 6 by the PK parameter for Dose 1.	196 days after the 6th dose
6β-naltrexol Accumulation Ratio (AR) for Ctrough	The 6β-naltrexol AR was determined for Ctrough by dividing the PK parameter for Dose 6 by the PK parameter for Dose 1.	196 days after the 6th dose
6β-naltrexol Accumulation Ratio (AR) for AUC0-inf	The 6β-naltrexol AR was determined for AUC0-inf by dividing the PK parameter for Dose 6 by the PK parameter for Dose 1.	196 days after the 6th dose

Collaborators and Investigators

• Sponsor: Go Medical Industries Pty Ltd
• Collaborators: National Institute on Drug Abuse (NIDA); Columbia University; New York State Psychiatric Institute; Clinilabs, Inc.
• Investigators: Principal Investigator: Adam Bisaga, MD, New York State Psychiatric Institute

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2021
• Primary Completion (Actual): April 4, 2022
• Study Completion (Actual): April 4, 2022

Study Registration Dates

• First Submitted: January 17, 2021
• First Submitted That Met QC Criteria: January 19, 2021
• First Posted (Actual): January 20, 2021

Study Record Updates

• Last Update Posted (Actual): February 23, 2024
• Last Update Submitted That Met QC Criteria: February 21, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Opioid Use Disorder; opioids; naltrexone
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Narcotic-Related Disorders; Opioid-Related Disorders; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Alcohol Deterrents; Naltrexone
• Other Study ID Numbers: GM0019; UG3DA047720 (U.S. NIH Grant/Contract); 406190 (Other Identifier: NIH ERA Human Subjects Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No