A Study to Assess the Safety and Efficacy of ASP8062 as an Add-on Therapy to Buprenorphine/Naloxone in Participants With Opioid Use Disorder

NCT05062577 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 8062-CL-2221
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to evaluate the efficacy; safety and tolerability of ASP8062 compared with placebo ASP8062 as add-on therapy to buprenorphine/naloxone.

Conditions

Opioid Use Disorder

Keywords

ASP8062,; Opioid Use Disorder,; OUD,; Buprenorphine/Naloxone

Outcome Measures

Primary Outcomes (2)

• Percentage of participants with >= 80% of urine samples negative for misuse of opioid drugs combined with self-reports negative for opioid use

  Participants will undergo weekly assessments for misuse of opioid drugs through urine drug screening in combination with self-reports of opioid drug misuse. Percentage of participants with \>= 80% of urine samples negative for misuse of opioid drugs combined with self reports negative for opioid use will be reported.

  Up to 12 weeks

• Number of participants with Adverse Events (AEs)

  Adverse events (AEs) will be coded using medical dictionary for regulatory activities (MedDRA). An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study Investigational Product (IP) and other study treatments, whether or not considered related to the study IP and other study treatments. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study IP and other study treatments. This includes events related to the comparator and events related to the (study) procedures. An AE is considered "serious" if, the event: results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or other medically important event.

  Up to 16 weeks

Secondary Outcomes (9)

• The cumulative distribution function (CDF) of the percentage of urine samples negative for misuse of opioid drugs combined with self-reports negative for opioid use

  Up to 12 weeks

• Percentage of participants continuously abstinent from misuse of opioid drugs as assessed by urine samples and self-reports negative for opioid use

  Up to 12 weeks

• Total number of visits of abstinence from misuse of opioid drugs as assessed by urine samples and self-reports negative for opioid use

  Up to 12 weeks

• Number of participants with vital sign abnormalities and/or adverse events (AEs)

  Up to 16 weeks

• Number of participants with laboratory value abnormalities and/or adverse events (AEs)

  Up to 16 weeks

Study Arms (2)

ASP8062 in combination with buprenorphine/naloxone

EXPERIMENTAL

Participants will receive ASP8062 once daily at bedtime (QHS) and buprenorphine/naloxone once daily every morning (QAM) for 12 weeks.

Drug: ASP8062; Drug: buprenorphine/naloxone

Placebo ASP8062 in combination with buprenorphine/naloxone

PLACEBO COMPARATOR

Participants will receive matching placebo once daily at bedtime (QHS) and buprenorphine/naloxone once daily every morning (QAM) for 12 weeks.

Drug: Placebo ASP8062; Drug: buprenorphine/naloxone

Interventions

ASP8062 DRUG

oral

ASP8062 in combination with buprenorphine/naloxone

Placebo ASP8062 DRUG

oral

Placebo ASP8062 in combination with buprenorphine/naloxone

buprenorphine/naloxone DRUG

sublingual

ASP8062 in combination with buprenorphine/naloxone; Placebo ASP8062 in combination with buprenorphine/naloxone

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant has a diagnosis of moderate or severe opioid use disorder (OUD) according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Ed (DSM-5) using the Mini International Neuropsychiatric Interview (MINI) version 7.02.
• Participant is voluntarily seeking treatment for OUD, and is either:
• Currently receiving medication-assisted treatment (MAT) (buprenorphine/naloxone maintenance dose equivalent to 16 mg/4 mg sublingual for \>=28 days prior to screening) for OUD and considered clinically unstable, defined as: currently misusing opioids and has at least 4 positive urine drug screens during the Screening Period (including morphine and metabolites, diacetylmorphine \[heroin\], codeine, oxycodone, hydrocodone, hydromorphone, fentanyl and metabolites, meperidine, propoxyphene, tramadol, oxymorphone and methadone)
• Is not currently receiving MAT for OUD, and has not received MAT (consistently for \> 48 hours) within 60 days prior to screening, and is: willing to initiate buprenorphine/naloxone therapy; considered to be a good candidate for buprenorphine/naloxone treatment based on medical and psychosocial history; able to tolerate buprenorphine/naloxone at the required maintenance dose of 16 mg/4 mg during the 7 days prior to randomization; has a positive urine drug screen at the initial screening visit (Visit 1) (including morphine and metabolites, diacetylmorphine (heroin), codeine, oxycodone, hydrocodone, hydromorphone, fentanyl and metabolites, meperidine, propoxyphene, tramadol, oxymorphone and methadone).
• Participant does not have on-going opioid withdrawal symptoms (a score of \< 11 on the Clinical Opioid Withdrawal Scale (COWS)) at the time of randomization (Day 1).
• Participant has a body mass index range of 18.5 to 45.0 kg/m\^2, inclusive and weighs at least 50 kg at screening.
• Participant has stable living conditions.
• Participant agrees not to make significant changes to current non-medication therapy interventions (e.g., counseling, psychotherapy) in place at the time of Screening throughout the duration of the study.
• Participant agrees not to participate in another interventional study while participating in the present study; defined as from the time of informed consent form (ICF) signature until completion of the last study visit.
• Female participant is not pregnant and at least one of the following conditions apply:
• Not a woman of childbearing potential (WOCBP)
• WOCBP who agrees to follow the contraceptive guidance from the time of informed consent through at least 30 days after final investigational product (IP) administration.
• Female participant must agree not to breastfeed starting at screening and throughout the study period and for 30 days after final IP administration.
• Female participant must not donate ova starting at screening and throughout the study period and for 30 days after final IP administration.
• Male participant with female partner(s) of childbearing potential (including breastfeeding partner) must agree to use contraception throughout the treatment period and for 90 days after final IP administration.

You may not qualify if:

• Participant has received any investigational therapy within 28 days or 5 half-lives, whichever is longer, prior to screening.
• Participant has a history of respiratory depression while on buprenorphine-based or other MAT for OUD.
• Participant has human immunodeficiency virus (HIV) per screening serology test.
• Participant has a positive hepatitis B surface antigen (HbsAg) or detectable hepatitis B DNA. Participants with negative HbsAg, positive hepatitis B core antibody (anti-HBc) and negative hepatitis B surface antibody (anti-HBs) are eligible if hepatitis B DNA is undetectable.
• Current diagnosis of chronic pain and currently treated with opioids other than buprenorphine or buprenorphine/naloxone.
• Current DSM-5 diagnosis of moderate to severe substance use disorder on any other psychoactive substances other than opioids, caffeine or nicotine (e.g., alcohol, sedatives) and the non-opioid substance use disorder(s) are considered primary or coprimary, causing current (last 30 days) significant impairment and/or would interfere with the efficacy and safety assessments.
• Participant has 2 or more positive urine drug screen (UDS) results for barbiturates or benzodiazepines during screening. (Day 1 eligibility will be based on a quick urine test conducted on-site, and not a sample sent to the central lab.)
• Participant has a known or suspected hypersensitivity to ASP8062, buprenorphine, naloxone or any components of the formulations used.
• Participant has previous exposure to ASP8062.
• Participant has a history of suicide attempt or suicidal behavior within 12 months prior to screening or has any suicidal ideation that meets criteria at a level of 4 or 5 by using the Columbia-Suicide Severity Rating Scale (C-SSRS) within 12 months prior to screening or who is at significant risk to commit suicide, as assessed at screening or at Day 1.
• Participant's prescription for buprenorphine/naloxone is unable to be filled at the pharmacy during Screening because they are already receiving an opioid based MAT.
• Participant has any clinically significant liver chemistry test result including aspartate aminotransferase \[AST\] or alanine aminotransferase \[ALT\] result \> 3 times above the upper limit of normal (ULN), and total bilirubin \[TBL\] result \> 1.5 times above the ULN at screening. These assessments may be repeated once, after a reasonable time period (but within the Screening Period).
• Participant has a mean pulse \< 45 or \> 110 beats per minute (unless above the upper bound of the range \[\> 110 beats per minute\] deemed to be secondary to opioid withdrawal); resting systolic blood pressure \> 140 mmHg or \< 90 mmHg, and/or a resting diastolic blood pressure \> 90 mmHg at screening (unless out of range blood pressure is deemed to be secondary to opioid withdrawal). These assessments may be repeated once after a reasonable time period (but within the Screening Period).
• Participant has a clinically significant abnormality on 12-lead electrocardiogram (ECG) at screening or at randomization (Day 1). If the ECG is abnormal an additional ECG can be carried out. If this also gives a clinically significant abnormal result the participant must be excluded.
• Participant has a history of chest pain or palpitation with either exertion or drug use, myocardial infarction, endocarditis (within 12 months of screening), unexplained syncope, cardiac arrest, unexplained cardiac arrhythmias or torsade de pointes, structural heart disease or a family history of Long QT Syndrome.

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

ASP8062; Buprenorphine, Naloxone Drug Combination

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Buprenorphine; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Naloxone; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Executive Medical Director

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2021
• First Posted: September 30, 2021
• Study Start: November 8, 2021
• Primary Completion: February 28, 2023
• Study Completion: February 28, 2023
• Last Updated: November 6, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share