Exploratory Dose Ranging Study Assessing APH-1501 for the Treatment of Opioid Addiction

Nanoencapsulated Cannabidiol Time Released Capsules Targeted to Reduce Cravings in the Treatment of Opioid Addiction

The purpose of this study is determine the safety, efficacy and tolerability of a novel drug APH-1501 as a pharmacotherapy for Opioid Dependence. The investigators will evaluate the safety of escalating doses APH-1501.

Study Overview

• Status: Not yet recruiting
• Conditions: Addiction; Opioid Dependence; Opioid Withdrawal
• Intervention / Treatment: Drug: APH-1501; Drug: Placebo

Detailed Description

This is a Phase 2a Exploratory Pilot study assessing the efficacy, immunogenicity and pharmacology of APH-1501, Cannabidiol (CBD), a unique, bioactive component of marijuana, in reducing early attrition and improving outcome in opioid-dependent individual in adults diagnosed with an opioid addiction, ages 21-55 years of age. Subjects will be randomized into 4 groups receiving APH-1501 or placebo over a 30 day period that includes a regimen of reformulated 400, 600 or 800 mg/m2 APH 1501 or placebo. This trial will target opioid-dependent patients who have completed detoxification and are in a treatment facility. During the trial period, participants will be given APH-1501 twice a day for 30 days. Given prior evidence based research on CBD there should be minimum to no side effects to taking APH 1501. The overarching research question for the study is the efficacy of APH 1501, pharmaceutical-grade CBD (>98.5% and < 0.3% Δ9-THC) for clinical use in the treatment of opioid addiction.

This is an intervention model design with three treatment groups, parallel assignment. This study is designed for sufficient time in between dose escalations to allow for interim analysis of safety and tolerability data to be considered for the safest approach to assess the effects of the compound as a therapeutic agent. Randomization will be stratified by the Diagnostic and Statistical Manual (DSM)_V diagnosis taking into account any co-morbid features or dual diagnosis.

• Study Type: Interventional
• Enrollment (Anticipated): 32
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Trevor P Castor; Phone Number: 7819326933; Email: tcastor@aphios.com
• Study Contact Backup: Name: Judith Castor; Phone Number: 7819326933; Email: jlpcastor@aphios.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Ages Eligible for Study: 21 to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Meets DSM-V criteria with a Substance Use Disorder
• Meets protocol-specified criteria for qualification and contraception
• Must consent to random assignment, and be willing to commit to medication ingestion.
• Is willing and able to remain confined in the study unit for the entire duration of each treatment period and comply with restrictions related food, drink and medications
• Voluntarily consents to participate and provides written informed consent prior to any protocol-specific procedures

Exclusion Criteria:

• Has signs, symptoms or history of any condition that, per protocol or in the opinion of the investigator, might compromise:

  1. the safety or well-being of the participant or study staff;
  2. the safety or well-being of the participant's offspring (such as through pregnancy or breast-feeding);
  3. the analysis of results
• Individuals with clinically significant medical disorders or lab abnormalities.
• History of cardiovascular events, head trauma or seizures
• Use of any psychoactive drug or medication at any time of study enrollment and participation
• Having taken any opioid medication in the last 14 days
• Concomitant use of psychotropic medications, with the exception of stable doses (defined as no dosing adjustments in the past two months) of non-monoamine oxidase inhibitor (MAO-I) (antidepressants, non-benzodiazepine anxiolytics, and Attention Deficit -Hyperactivity Disorder(ADHD) medications.
• Pregnant or breastfeeding
• Not using appropriate contraceptive measures ( hormonal, Nuvo-ring, Depo-Provera, IUD) or other barrier protection.
• Psychiatric condition as defined by the DSM-V - Lifetime history of DSM-5 Bipolar I or II Disorder, Schizophrenia or other psychotic disorder. Stably treated Major Depressive Disorder (MDD), Dysthymia, Generalized Anxiety Disorder (GAD), Social Phobia, and Specific Phobia diagnoses are acceptable (i.e. same dose of medication has been prescribed for at least 2 months prior to screening and no changes in current medication expected during course of the trial).
• Hypersensitivity to cannabinoids
• Suicidal ideation or behavior within the past 6 months. Subjects who are believed to be at suicidal or homicidal risk (answers 'yes' on questions 4 or 5 of C-SSRS) will be referred for assessment by a qualified mental health professional.
• Individuals taking an investigational agent within the last 30 days before baseline visit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: APH-1501 400mg; Nano-encapsulated for oral delivery. The study is planned for patients to receive APH 1501 400mg BID( twice daily) for 28 days.	Drug: APH-1501; The investigational drug product APH-1501 is CBD encapsulated in biodegradable polymer nanospheres, is a lyophilized powder intended for oral administration.
Experimental: APH-1501 600mg; Nano-encapsulated for oral delivery. The study is planned for patients to receive APH 1501 600mg BID ( twice daily) for 28 days.	Drug: APH-1501; The investigational drug product APH-1501 is CBD encapsulated in biodegradable polymer nanospheres, is a lyophilized powder intended for oral administration.
Experimental: APH-1501 800mg; Nano-encapsulated for oral delivery. The study is planned for patients to receive APH 1501 800mg BID ( twice daily) for 28 days.	Drug: APH-1501; The investigational drug product APH-1501 is CBD encapsulated in biodegradable polymer nanospheres, is a lyophilized powder intended for oral administration.
Placebo Comparator: Placebo Comparator: Placebo; Nano-encapsulated for oral delivery. The study is planned for patients to receive a placebo dose BID ( twice daily) for 28 days.	Drug: Placebo; The placebo is a sterile pyrogen free lyophilized powder identical in appearance to the experimental drug product.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
[Safety] Incidence of Treatment Emergent Adverse Effects	Number of patients experiencing treatment emergent Adverse Effects(AE's) and Serious Adverse effects(SAE's) during treatment and follow-up. Patients will be asked to complete the Systematic Assessment for Treatment Emergent Events (SAFTEE) The SAFTEE is a questionnaire that rates the current severity of a wide range of somatic, behavioral and affective symptoms in general and specific inquiry formats. It is designed to report adverse health events. Contains ~ 25 detailed questions that systematically address 29 body systems. Responses are rated on five levels of severity.	Baseline through 30 days post final treatment dose up to day 60
[Tolerability] Pharmacokinetics of APH-1501	Blood draws to determine the cannabidiol peak plasma concentration (Cmax).	Baseline, 15 minutes, 30 minutes, 45 minutes, 60 minutes, 120 minutes, 180 minutes 240 minutes, 480 minutes post administered dose
[Tolerability] Pharmacokinetics of APH-1501	Blood draws to determine the cannabidiol time to reach peak serum concentration (Tmax).	Baseline, 15 minutes, 30 minutes, 45 minutes, 60 minutes, 120 minutes, 180 minutes 240 minutes, 480 minutes post first administered dose.
[Tolerability] Pharmacokinetics of APH-1501	Blood draws to determine the cannabidiol time to derermine serum half life (1/2).	Baseline, 15 minutes, 30 minutes, 45 minutes, 60 minutes, 120 minutes, 180 minutes 240 minutes, 480 minutes post first administered dose.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vital signs	Change in Blood pressure - diastolic & systolic (in mmHg).	Baseline, 15 minutes, 30 minutes, 45 minutes, 60 minutes, 120 minutes, 180 minutes 240 minutes, 480 minutes, post first administered dose.
Vital signs	Change in Heart Rate( beats per minute).	Baseline, 15 minutes, 30 minutes, 45 minutes, 60 minutes, 120 minutes, 180 minutes 240 minutes, 480 minutes, post first administered dose.
Vital signs	Change in Respiratory (in breaths per minute).	Baseline, 15 minutes, 30 minutes, 45 minutes, 60 minutes, 120 minutes, 180 minutes 240 minutes, 480 minutes, post first administered dose.
Vital signs	Change in Temp ( in degrees Farenheit).	Baseline, 15 minutes, 30 minutes, 45 minutes, 60 minutes, 120 minutes, 180 minutes 240 minutes, 480 minutes, post first administered dose.
Vital signs	Change in O2 saturation.	Baseline, 15 minutes, 30 minutes, 45 minutes, 60 minutes, 120 minutes, 180 minutes 240 minutes, 480 minutes, post first administered dose.
Vital signs	Change in Electrocardiogram (ECG). ( P Wave and QRS Complex)	Baseline, 15 minutes, 30 minutes, 45 minutes, 60 minutes, 120 minutes, 180 minutes 240 minutes, 480 minutes, post first administered dose.
Vital signs	Change in Blood pressure(in mmHg) diastolic and Systolic.	Day 7,14,21,28 and 60 for followup.
Vital signs	Change in Heart Rate( beats per minute).	Day 7,14,21,28 and 60 for followup.
Vital signs	Change in Respiratory (in breaths per minute).	Day 7,14,21,28 and 60 for followup.
Vital signs	Change in Temp ( in degrees Farenheit).	Day 7,14,21,28 and 60 for followup.
Vital signs	Change in O2 saturation.	Day 7,14,21,28 and 60 for followup.
Vital signs	Change in Electrocardiogram ( EKG) P Wave and QRS Complex	Day 7,14,21,28 and 60 for followup.
Anxiety	Anxiety Assessment using the Beck Anxiety Inventory ( BAI) . The BAI is a self-report measure of anxiety. The total score is calculated by finding the sum of the 21 items. Score of 0-21 = low anxiety Score of 22-35 = moderate anxiety Score of 36 and above = potentially concerning levels of anxiety	Baseline, weeks 1-4 and 1 week post final dose.
Changes in levels of physiological stress	Measure salivary cortisol levels	Baseline through 30 days post final treatment dose up to day 60
Visual Analog Scale for Craving	Changes and potential variations in cue-induced craving will be monitored and measured.	Baseline, weeks 1-4 and 30 days post final treatment up to day 60
Clinical Opiate Withdrawal Scale ( COWS)	Changes and variations in common signs and symptoms of opiate withdrawal will be measured and monitor over time.	Baseline, weeks 1-4 adn 30 days post final treatment up to day 60

Collaborators and Investigators

• Sponsor: Aphios

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2023
• Primary Completion (Anticipated): September 1, 2025
• Study Completion (Anticipated): December 1, 2025

Study Registration Dates

• First Submitted: January 14, 2019
• First Submitted That Met QC Criteria: January 18, 2019
• First Posted (Actual): January 23, 2019

Study Record Updates

• Last Update Posted (Actual): July 27, 2021
• Last Update Submitted That Met QC Criteria: July 26, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Narcotics; Addiction; Cocaine; Substance Use; Cannabis; Mental Disorders; Cannabidiol; Analgesics; Neurotransmitter Uptake Inhibitors; Opioids: Harmful Use
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Narcotic-Related Disorders; Compulsive Behavior; Impulsive Behavior; Opioid-Related Disorders; Behavior, Addictive
• Other Study ID Numbers: APH-1501

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
• product manufactured in and exported from the U.S.: Yes