Pharmacokinetic and Safety Study of Naltrexone Release From Subcutaneous BICX104 Pellets Compared to Vivitrol Injections

Study Overview
=================
Brief Summary
-----------------
This is a Phase 1, 6-month, open-label, multi-center study in parallel groups of randomized healthy volunteers to evaluate the pharmacokinetics and safety of BICX104 implantable subcutaneous naltrexone pellets and Vivitrol intramuscular depot naltrexone injection.

Official Title
-----------------
A Randomized, Open Label, Single Dose Pharmacokinetic and Safety Study of Implantable Long Acting 3-month Naltrexone Subcutaneous Pellets Compared to Naltrexone IM Injection (Vivitrol) in Healthy Volunteers

Conditions
-----------------
Opioid-use Disorder

Intervention / Treatment
-----------------
* Drug: BICX104
* Drug: Vivitrol


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Willing and able to provide informed consent. Female or male subjects aged 18-50 years old. Without current non-remitted DSM-5 (The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) - Substance Use Disorders diagnoses; subjects with a sustained remission diagnosis are not excluded. In good health, as determined by the study physician, based on complete medical history, physical examination, vital signs measurement, ECG, and laboratory tests within normal ranges, to permit treatment. Weight of 100-180 pounds, and a BMI of 18.5 to 30 kg/m2, inclusive. Must agree to comply with all study requirements and be willing to complete entire study. Females of childbearing potential and males willing to practice an effective method(s) of birth control for the duration of participation in the study (<1% failure rate per year). Exclusion Criteria: Is pregnant, is planning to become pregnant or breastfeed infants during the study. Is currently treated with naltrexone or has had a naltrexone implant in the past 2 years or received Vivitrol treatment in the past year. Clinically significant medical/psychological condition or abnormality at screening (i.e., physical examination, electrocardiogram [ECG], hematology or blood chemistry evaluation, or urinalysis findings), including any diagnosis of Hepatitis B, Hepatitis C or HIV infection. Presence of opiates, cocaine, methamphetamine or other significant drugs of abuse in the urine (as determined by urine drug test). Any active hepatitis or hepatic failure or dysfunction evidenced by the following: aspartate transaminase (AST) or alanine transaminase (ALT) higher than 1.5 times the upper limit of normal (1.5xULN), hyperbilirubinemia (bilirubin >10% above ULN), creatine phosphokinase (CPK) higher than 2.5xULN, prolonged prothrombin time (international normalized ratio ≥1.7), ascites, or esophageal variceal disease. Manifestation of suicidal ideation, psychotic symptoms (including significant violent behavior), or psychiatric or neurological disorders that would compromise ability to complete the study. Participation in a methadone program currently or within past 3 years, or 3 or more previous medically supervised detoxification treatments in past 3 years. If a healthy volunteer fails one naloxone challenge, the subject will not be suitable for the study. The only exceptions will be made when a 'false positive' test result is received for the first test. Intolerance and/or hypersensitivity to naltrexone, naloxone, or polylactide-co-polymers such as polylactide-co-glycolide (PLG). Participation in a clinical trial within 30 days of screening. Has a condition which requires or may require treatment with opioid based medication. Is prone to skin rashes, irritation or has a chronic skin condition. Alcohol Use Disorder diagnosis. Has a predisposition to poor response to an implant site reaction, as judged by the study physician. Has a history of keloid formation, connective tissue disease, e.g., scleroderma, or history of recurrent MRSA infections.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BICX104<br>BICX104 is an eroding implantable pellet that contains 1 g naltrexone and 11 mg magnesium stearate that will be inserted subcutaneously. It will be administered once for 84 days. | Drug: BICX104<br>* Erodable implantable pellet containing 1 g naltrexone and 11 mg magnesium stearate.<br>|
| Active Comparator: Vivitrol<br>Vivitrol intramuscular injection containing 380 mg of naltrexone. Three consecutive doses will be administered once every 28 days for 84 days. | Drug: Vivitrol<br>* Intramuscular injection containing 380 mg of naltrexone.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameter: Cmax. | Maximum observed mean plasma concentration [Cmax] of naltrexone and 6-beta-naltrexol. | 140 Days | 
| Pharmacokinetic parameter: Tmax. | Time to mean maximum observed drug concentration (Tmax) of naltrexone and 6-beta-naltrexol. | 140 Days | 
| Pharmacokinetic parameter: Css. | Changes in the mean observed steady state plasma concentration [Css] of naltrexone and 6-beta-naltrexol. | 140 Days | 
| Pharmacokinetic parameter: AUC | Area Under the Plasma Concentration Versus Time Curve (AUC) of naltrexone and 6-beta-naltrexol. | 140 Days | 
| Pharmacokinetic parameter: Tlast ≥ 1ng/ml naltrexone. | Time of Last Quantifiable Plasma Concentration (Tlast) of naltrexone greater than or equal to 1ng/ml. | 140 Days | 
| Pharmacokinetic parameter: Tlast. | Time of Last Quantifiable Plasma Concentration (Tlast) of naltrexone and 6-beta-naltrexol. | 140 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Parameter: AEs | Incidence and severity of adverse events (AEs) | 168 Days |