A Study to Assess the Effect of a Single Dose of ASP8062 on the Multiple Dose Safety, Tolerability and Pharmacokinetics of Buprenorphine/Naloxone in Participants With Opioid Use Disorder

NCT04447287 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 8062-CL-2003UG3DA051392
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

The primary purpose of this study was to assess the safety and tolerability of multiple doses of buprenorphine/naloxone alone and buprenorphine/naloxone in combination with a single dose of ASP8062. This study also assessed the potential for pharmacokinetic interaction between ASP8062 and buprenorphine/naloxone.

Conditions

Opioid Use Disorder

Keywords

Suboxone®; Opioid Use Disorder; buprenorphine/naloxone; ASP8062; pharmacokinetic

Outcome Measures

Primary Outcomes (13)

• Number of Participants With Adverse Events (AEs)

  An AE is defined as any untoward medical occurrence in a participant administered an Investigational Product (IP) and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding; abnormal laboratory test result or other safety assessment, symptom, or disease temporally associated with the use of IP whether or not considered related to the IP. A treatment-emergent adverse event (TEAE) was defined as an AE with onset at any time from first dosing until last scheduled procedure. AEs were considered serious (SAEs) if the AE resulted in death, was life-threatening, resulted in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, resulted in congenital anomaly, or birth defect or required inpatient hospitalization or led to prolongation of hospitalization.

  From first dose of study drug up to end of study visit (up to day 27)

• Number of Participants With Suicidal Ideation and/or Suicidal Behavior as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)

  The Columbia-Suicide Severity Rating Scale (C-SSRS) is a clinician administered assessment tool that evaluates suicidal ideation and behavior. Number of participants that have an affirmative response to the 5 items for suicidal ideation (1. Wish to be dead, 2. Non-specific active suicidal thoughts, 3. Active suicidal ideation with any methods (not plan) without intent to act, 4. Active suicidal ideation with some intent to act, without specific plan, 5. Active suicidal ideation with specific plan and intent) and/or to the 5 items for suicidal behavior (1. Preparatory acts or behavior, 2. Aborted attempt, 3. Interrupted attempt, 4. Actual attempt, 5. Completed suicide) were reported.

  Up to day 27

• Change From Baseline in Blood Oxygen Saturation (SpO2) at Predose

  The blood oxygen saturation (SpO2 was measured using a pulse oximeter placed on the participant's fingertip. Change from baseline in SpO2 was calculated as Day 11 minus Baseline for arm 'buprenorphine/naloxone', and Day 12 minus Baseline for arms 'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone'. Baseline observation was last non-missing observation prior to first dose.

  'buprenorphine/naloxone': Baseline and 1 hour postdose Day 11; 'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone': Baseline and 1 hour postdose Day 12

• Change From Baseline in Blood Oxygen Saturation (SpO2) at 1 Hour Postdose

  The blood oxygen saturation (SpO2) was measured using a pulse oximeter placed on the participant's fingertip. Change from baseline in SpO2 was calculated as Day 11 minus Baseline for arm 'buprenorphine/naloxone', and Day 12 minus Baseline for arms 'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone'. Baseline observation was last non-missing observation prior to first dose.

  'buprenorphine/naloxone': Baseline and 1 hour postdose Day 11; 'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone': Baseline and 1 hour postdose Day 12

• Change From Baseline in Blood Oxygen Saturation (SpO2) at 2 Hour Postdose

  The blood oxygen saturation (SpO2) was measured using a pulse oximeter placed on the participant's fingertip. Change from baseline in SpO2 was calculated as Day 11 minus Baseline for arm 'buprenorphine/naloxone', and Day 12 minus Baseline for arms 'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone'. Baseline observation was last non-missing observation prior to first dose.

  'buprenorphine/naloxone': Baseline and 2 hour postdose Day 11; 'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone': Baseline and 2 hour postdose Day 12

• Change From Baseline in Blood Oxygen Saturation (SpO2) at 4 Hour Postdose

  The blood oxygen saturation (SpO2) was measured using a pulse oximeter placed on the participant's fingertip. Change from baseline in SpO2 was calculated as Day 11 minus Baseline for arm 'buprenorphine/naloxone', and Day 12 minus Baseline for arms 'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone'. Baseline observation was last non-missing observation prior to first dose.

  'buprenorphine/naloxone': Baseline and 4 hour postdose Day 11; 'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone': Baseline and 4 hour postdose Day 12

• Change From Baseline in Blood Oxygen Saturation (SpO2) at 8 Hour Postdose

  The blood oxygen saturation (SpO2) was measured using a pulse oximeter placed on the participant's fingertip. Change from baseline in SpO2 was calculated as Day 11 minus Baseline for arm 'buprenorphine/naloxone', and Day 12 minus Baseline for arms 'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone'. Baseline observation was last non-missing observation prior to first dose.

  'buprenorphine/naloxone': Baseline and 8 hour postdose Day 11; 'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone': Baseline and 8 hour postdose Day 12

• Change From Baseline in Blood Oxygen Saturation (SpO2) at 12 Hour Postdose

  The blood oxygen saturation (SpO2) was measured using a pulse oximeter placed on the participant's fingertip. Change from baseline in SpO2 was calculated as Day 11 minus Baseline for arm 'buprenorphine/naloxone', and Day 12 minus Baseline for arms 'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone'. Baseline observation was last non-missing observation prior to first dose.

  'buprenorphine/naloxone': Baseline and 12 hour postdose Day 11; 'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone': Baseline and 12 hour postdose Day 12

• Change From Baseline in End Tidal Carbon Dioxide (CO2) at Predose

  End tidal CO2 measurements was obtained per participant utilizing a portable bedside capnography device. Change from baseline in CO2 was calculated as Day 12 minus Baseline for arms 'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone'.

  'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone': Baseline and predose Day 12

• Change From Baseline in End Tidal Carbon Dioxide (CO2) at 1 Hour Postdose

  End tidal CO2 measurements was obtained per participant utilizing a portable bedside capnography device. Change from baseline in CO2 was calculated as Day 11 minus Baseline for arm 'buprenorphine/naloxone', and Day 12 minus Baseline for arms 'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone'.

  'buprenorphine/naloxone': Baseline and 1 hour postdose Day 11; 'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone': Baseline and 1 hour postdose Day 12

• Change From Baseline in End Tidal Carbon Dioxide (CO2) at 2 Hour Postdose

  End tidal CO2 measurements was obtained per participant utilizing a portable bedside capnography device. Change from baseline in CO2 was calculated as Day 11 minus Baseline for arm 'buprenorphine/naloxone', and Day 12 minus Baseline for arms 'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone'.

  'buprenorphine/naloxone': Baseline and 2 hour postdose Day 11; 'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone': Baseline and 2 hour postdose Day 12

• Change From Baseline in End Tidal Carbon Dioxide (CO2) at 4 Hour Postdose

  End tidal CO2 measurements was obtained per participant utilizing a portable bedside capnography device. Change from baseline in CO2 was calculated as Day 11 minus Baseline for arm 'buprenorphine/naloxone', and Day 12 minus Baseline for arms 'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone'.

  'buprenorphine/naloxone': Baseline and 4 hour postdose Day 11; 'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone': Baseline and 4 hour postdose Day 12

• Change From Baseline in End Tidal Carbon Dioxide (CO2) at 8 Hour Postdose

  End tidal CO2 measurements was obtained per participant utilizing a portable bedside capnography device. Change from baseline in CO2 was calculated as Day 11 minus Baseline for arm 'buprenorphine/naloxone', and Day 12 minus Baseline for arms 'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone'.

  'buprenorphine/naloxone': Baseline and 8 hour postdose Day 11; 'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone': Baseline and 8 hour postdose Day 12

Secondary Outcomes (9)

• Pharmacokinetics (PK) of ASP8062 in Plasma: Area Under the Concentration-time Curve From the Time of Dosing Extrapolated to Time Infinity (AUCinf)

  Predose on day 12 and at the following postdose time points on day 12: 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144, 168, 216 and 264 hour(s)

• Pharmacokinetics (PK) of ASP8062 in Plasma: Area Under the Concentration-time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast)

  Predose on day 12 and at the following postdose time points on day 12: 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144, 168, 216 and 264 hour(s)

• Pharmacokinetics (PK) of ASP8062 in Plasma: Maximum Concentration (Cmax)

  Predose on day 12 and at the following postdose time points on day 12: 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144, 168, 216 and 264 hour(s)

• Pharmacokinetics (PK) of Buprenorphine in Plasma: Area Under the Concentration-time Curve From the Time of Dosing to 24 Hours (AUC24)

  Predose on day 11 and at the following postdose time points on day 11: 0.25, 0.5, 1, 1.5, 2, 3, 4, 8, 12 and 16 hour(s)

• Pharmacokinetics (PK) of Buprenorphine in Plasma: Cmax

  Predose on day 11 and at the following postdose time points on day 11: 0.25, 0.5, 1, 1.5, 2, 3, 4, 8, 12 and 16 hour(s)

Study Arms (2)

ASP8062 in combination with buprenorphine/naloxone

EXPERIMENTAL

Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. In the Investigational Period participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.

Drug: ASP8062; Drug: buprenorphine/naloxone

Placebo ASP8062 in combination with buprenorphine/naloxone

PLACEBO COMPARATOR

Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. In the Investigational Period participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. After randomization on day 12, participants received a single oral dose of placebo concomitantly with buprenorphine/naloxone. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.

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

Also known as: Suboxone®

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

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Subject has a body mass index range of 18 to 36 kg/m\^2, inclusive and weighs at least 50 kg at screening.
• Subject has a diagnosis of moderate or severe opioid use disorder (OUD) according to the Diagnostic and Statistical Manual of Mental Disorders, edition 5 (DSM-5) at screening.
• Subject tests positive for opioids at screening and/or on day -1 or subject shows signs of opioid withdrawal on day -1.
• Subject is willing to take buprenorphine/naloxone and is not taking buprenorphine or buprenorphine/naloxone at screening.
• Female subject is not pregnant and at least 1 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 subject must agree not to breastfeed starting at screening and throughout the study period and for 30 days after final IP administration.
• Female subject must not donate ova starting at first dose of IP and throughout the study period and for 30 days after final IP administration.
• Male subject with female partner(s) of childbearing potential (including breastfeeding partner) must agree to use contraception throughout the study period and for 90 days after final IP administration.
• Male subject must not donate sperm during the treatment period and for 90 days after final IP administration.
• Male subject with pregnant partner(s) must agree to remain abstinent or use a condom and spermicide for the duration of the pregnancy throughout the study period and for 90 days after final IP administration.
• Subject agrees not to participate in another interventional study while participating in the present study.
• Subject must be willing to abstain from smoking (including use of tobacco containing products and nicotine or nicotine-containing products \[e.g., electronic vapes\] from at least 1 hour predose through at least 8 hours postdose on days 11 and 12.

You may not qualify if:

• Subject has received any investigational therapy within 28 days or 5 half-lives, whichever is longer, prior to screening.
• Subject has any condition which makes the subject unsuitable for study participation.
• Female subject who has been pregnant within 6 months prior to screening or breastfeeding within 3 months prior to screening.
• Subject has a known or suspected hypersensitivity to ASP8062, buprenorphine, naloxone or any components of the formulations used.
• Subject has had previous exposure with ASP8062.
• Subject has any of the liver function tests (alkaline phosphatase \[ALP\], alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], gamma-glutamyl transferase and total bilirubin \[TBL\]) \> 2 × upper limit of normal (ULN) on day -1. In such a case, the assessment may be repeated once.
• Subject has any clinically significant history of allergic conditions (including drug allergies, asthma or anaphylactic reactions, but excluding untreated, asymptomatic, seasonal allergies) prior to first IP administration.
• Subject has any history or evidence of any clinically significant cardiovascular, gastrointestinal, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, renal and/or other major disease or malignancy with exception of history of cholecystectomy.
• Subject has current or recent diagnosis (within the last 12 months) of moderate or severe alcohol, sedative, hypnotic, anxiolytic, cocaine or any other substance use disorder (except for opioids, caffeine, tobacco or nicotine) according to the DSM-5 at screening.
• Subject has a history or presence of any clinically significant psychiatric disorders such as, bipolar 1, schizophrenia, schizoaffective disorder or major depressive disorders.
• Subject tests positive for alcohol, benzodiazepine or methadone on day -1. Subject tests positive for buprenorphine on day -1.
• Subject has had recent suicidal ideation within the last 12 months or subject who is at significant risk to commit suicide using the Columbia-Suicide Severity Rating Scale (C-SSRS) at screening or since the last visit on day -1.
• Subject has/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection) or fungal (noncutaneous) infection within 1 week prior to day -1.
• Subject has any clinically significant abnormality following physical examination, electrocardiogram (ECG) and protocol-defined clinical laboratory tests at screening or on day -1.
• Subject has a mean pulse \< 45 or \> 110 beats per minute (unless out of range \[\> 110 beats per minute\] pulse is deemed to be secondary to opioid withdrawal); mean systolic blood pressure \> 150 mmHg; mean diastolic blood pressure \> 95 mmHg (unless out of range blood pressure is deemed to be secondary to opioid withdrawal)(measurements taken in duplicate after subject has been resting in the supine position for at least 5 minutes; pulse will be measured automatically) on day -1. If the mean blood pressure exceeds the limits above, 1 additional duplicate may be taken.

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Altasciences Clinical Kansas, Inc.

Overland Park, Kansas, 66212, United States

Location

Related Publications (1)

• Ito M, Walzer M, Beth Blauwet M, Spence A, Heo N, Kelsh D, Blahunka P, Erdman J, Nour Alsharif M, Marek GJ. A phase 1b study to investigate the potential interactions between ASP8062 and buprenorphine/naloxone in patients with opioid use disorder. J Psychopharmacol. 2023 Feb;37(2):144-154. doi: 10.1177/02698811221149657. Epub 2023 Feb 3.

  PMID: 36738100 DERIVED

Related Links

• Link to results and other applicable study documents on the Astellas Clinical Trials website
• Link to plain language summary of the study on the Trial Results Summaries website

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

Results Point of Contact

• Title: Clinical Trial Disclosure
• Organization: Astellas Pharma Global Development, Inc.

astellas.resultsdisclosure@astellas.com

800-888-7704

Study Officials

• Executive Medical Director

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2020
• First Posted: June 25, 2020
• Study Start: June 29, 2020
• Primary Completion: November 25, 2020
• Study Completion: November 25, 2020
• Last Updated: November 21, 2024
• Results First Posted: January 12, 2022

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)