A Study to Assess the Safety, Tolerability and Pharmacokinetics of Multiple Doses of ASP8062 With a Single Dose of Morphine in Recreational Opioid Using Participants

NCT04448561 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 8062-CL-2002UG3DA051392
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Opioid Use Disorder

Keywords

Opioid Use Disorder; pharmacokinetic; ASP8062; morphine

Outcome Measures

Primary Outcomes (13)

• Number of Participants With Adverse Events (AEs)

  Safety was assessed by adverse events (AEs), which included abnormalities identified during a medical test (e.g. laboratory tests, vital signs, electrocardiogram, etc.) if the abnormality induced clinical signs or symptoms, needed active intervention, interruption or discontinuation of study drug or was clinically significant. A Treatment emergent AE (TEAE) was defined as any AE that started or worsened after the first dose of study drug up to 30 days after the last dose of study drug. 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 25)

• Number of Participants With At Least One Event of Suicidal Ideation And/or Suicidal Behavior as Assessed by The Columbia-Suicide Severity Rating Scale (C-SSRS)

  The C-SSRS is a clinician administered assessment tool that evaluates suicidal ideation and behavior. Number of participants with at least one 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 25

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

  The SpO2 was measured using a pulse oximeter placed on the participant's fingertip. Change from baseline in SpO2 was calculated as Day 9 minus Baseline for arms 'ASP8062' and 'Placebo', and Day 10 minus Baseline for arms 'ASP8062 in combination with morphine' and 'Placebo in combination with morphine'. Baseline observation was last non-missing observation prior to first dose.

  'ASP8062' and 'Placebo': Baseline and predose Day 9; 'ASP8062 in combination with morphine' and 'Placebo in combination with morphine': Baseline and predose Day 10

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

  The SpO2 was measured using a pulse oximeter placed on the participant's fingertip. Change from baseline in SpO2 was calculated as Day 9 minus Baseline for arms 'ASP8062' and 'Placebo', and Day 10 minus Baseline for arms 'ASP8062 in combination with morphine' and 'Placebo in combination with morphine'. Baseline observation was last non-missing observation prior to first dose.

  'ASP8062' and 'Placebo': Baseline and 1 hour postdose Day 9; 'ASP8062 in combination with morphine' and 'Placebo in combination with morphine': Baseline and 1 hour postdose Day 10

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

  The SpO2 was measured using a pulse oximeter placed on the participant's fingertip. Change from baseline in SpO2 was calculated as Day 9 minus Baseline for arms 'ASP8062' and 'Placebo', and Day 10 minus Baseline for arms 'ASP8062 in combination with morphine' and 'Placebo in combination with morphine'. Baseline observation was last non-missing observation prior to first dose.

  'ASP8062' and 'Placebo': Baseline and 2 hour postdose Day 9; 'ASP8062 in combination with morphine' and 'Placebo in combination with morphine': Baseline and 2 hour postdose Day 10

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

  The SpO2 was measured using a pulse oximeter placed on the participant's fingertip. Change from baseline in SpO2 was calculated as Day 9 minus Baseline for arms 'ASP8062' and 'Placebo', and Day 10 minus Baseline for arms 'ASP8062 in combination with morphine' and 'Placebo in combination with morphine'. Baseline observation was last non-missing observation prior to first dose.

  'ASP8062' and 'Placebo': Baseline and 4 hour postdose Day 9; 'ASP8062 in combination with morphine' and 'Placebo in combination with morphine': Baseline and 4 hour postdose Day 10

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

  The SpO2 was measured using a pulse oximeter placed on the participant's fingertip. Change from baseline in SpO2 was calculated as Day 9 minus Baseline for arms 'ASP8062' and 'Placebo', and Day 10 minus Baseline for arms 'ASP8062 in combination with morphine' and 'Placebo in combination with morphine'. Baseline observation was last non-missing observation prior to first dose.

  'ASP8062' and 'Placebo': Baseline and 8 hour postdose Day 9; 'ASP8062 in combination with morphine' and 'Placebo in combination with morphine': Baseline and 8 hour postdose Day 10

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

  The SpO2 was measured using a pulse oximeter placed on the participant's fingertip. Change from baseline in SpO2 was calculated as Day 9 minus Baseline for arms 'ASP8062' and 'Placebo', and Day 10 minus Baseline for arms 'ASP8062 in combination with morphine' and 'Placebo in combination with morphine'. Baseline observation was last non-missing observation prior to first dose.

  'ASP8062' and 'Placebo': Baseline and 12 hour postdose Day 9; 'ASP8062 in combination with morphine' and 'Placebo in combination with morphine': Baseline and 12 hour postdose Day 10

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

  End tidal CO2 measurement was obtained per participant utilizing a portable bedside capnography device. Change from baseline in CO2 was calculated as Day 9 minus Baseline for arms 'ASP8062' and 'Placebo', and Day 10 minus Baseline (baseline observation was observation before first dose at Day 9) for arms 'ASP8062 in combination with morphine' and 'Placebo in combination with morphine'.

  'ASP8062' and 'Placebo': Baseline and predose Day 9; 'ASP8062 in combination with morphine' and 'Placebo in combination with morphine': Baseline (observation taken at Day 9), and predose Day 10

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

  End tidal CO2 measurement was obtained per participant utilizing a portable bedside capnography device. Change from baseline in CO2 was calculated as Day 9 minus Baseline for arms 'ASP8062' and 'Placebo', and Day 10 minus Baseline (baseline observation was observation before first dose at Day 9) for arms 'ASP8062 in combination with morphine' and 'Placebo in combination with morphine'.

  'ASP8062' and 'Placebo': Baseline and 1 hour postdose Day 9; 'ASP8062 in combination with morphine' and 'Placebo in combination with morphine': Baseline (observation taken at Day 9), and 1 hour postdose Day 10

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

  End tidal CO2 measurement was obtained per participant utilizing a portable bedside capnography device. Change from baseline in CO2 was calculated as Day 9 minus Baseline for arms 'ASP8062' and 'Placebo', and Day 10 minus Baseline (baseline observation was observation before first dose at Day 9) for arms 'ASP8062 in combination with morphine' and 'Placebo in combination with morphine'.

  'ASP8062' and 'Placebo': Baseline and 2 hour postdose Day 9; 'ASP8062 in combination with morphine' and 'Placebo in combination with morphine': Baseline (observation taken at Day 9), and 2 hour postdose Day 10

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

  End tidal CO2 measurement was obtained per participant utilizing a portable bedside capnography device. Change from baseline in CO2 was calculated as Day 9 minus Baseline for arms 'ASP8062' and 'Placebo', and Day 10 minus Baseline (baseline observation was observation before first dose at Day 9) for arms 'ASP8062 in combination with morphine' and 'Placebo in combination with morphine'.

  'ASP8062' and 'Placebo': Baseline and 4 hour postdose Day 9; 'ASP8062 in combination with morphine' and 'Placebo in combination with morphine': Baseline (observation taken at Day 9), and 4 hour postdose Day 10

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

  End tidal CO2 measurement was obtained per participant utilizing a portable bedside capnography device. Change from baseline in CO2 was calculated as Day 9 minus Baseline for arms 'ASP8062' and 'Placebo', and Day 10 minus Baseline (baseline observation was observation before first dose at Day 9) for arms 'ASP8062 in combination with morphine' and 'Placebo in combination with morphine'.

  'ASP8062' and 'Placebo': Baseline and 8 hour postdose Day 9; 'ASP8062 in combination with morphine' and 'Placebo in combination with morphine': Baseline (observation taken at Day 9), and 8 hour postdose Day 10

Secondary Outcomes (11)

• Pharmacokinetics (PK) of ASP8062 in Plasma: Area Under the Concentration From Time of Dosing to 24 Hours (AUC24)

  'ASP8062': Predose, 0.25, 0.5, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 h postdose Day 9; 'ASP8062 in combination with morphine': Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144 h postdose Day 10

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

  'ASP8062': Predose, 0.25, 0.5, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 h Day 9; 'ASP8062 in combination with morphine': Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144 h postdose Day 10

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

  Predose, 0.25, 0.5, 1.5, 2, 3, 4, 8, 12, 16, 24, 36, 48 h postdose Day 10

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

  Predose, 0.25, 0.5, 1.5, 2, 3, 4, 8, 12, 16, 24, 36, 48 h postdose Day 10

• Pharmacokinetics (PK) of Morphine in Plasma: Cmax

  Predose, 0.25, 0.5, 1.5, 2, 3, 4, 8, 12, 16, 24, 36, 48 h postdose Day 10

Study Arms (2)

ASP8062 in combination with morphine

EXPERIMENTAL

Participants received ASP8062 tablet, orally once daily on days 1 through 10. On day 10, participants also received morphine tablet as single oral dose immediately after the ASP8062 dose.

Drug: ASP8082; Drug: morphine

Placebo in combination with morphine

PLACEBO COMPARATOR

Participants received ASP8062 matching placebo tablet, orally once daily on days 1 through 10. On day 10, participants also received morphine tablet as single oral dose immediately after the ASP8062 matching placebo dose.

Drug: morphine; Drug: Placebo

Interventions

ASP8082 DRUG

oral

ASP8062 in combination with morphine

morphine DRUG

oral

ASP8062 in combination with morphine; Placebo in combination with morphine

Placebo DRUG

oral

Placebo in combination with morphine

Eligibility Criteria

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

You may qualify if:

• Participant is a recreational opioid user who has used opioids for nontherapeutic (recreational) purposes on at least 10 occasions within their lifetime, with at least 1 opioid use in the last 90 days.
• Participant has a body mass index (BMI) range of 18 to 36 kg/m\^2, inclusive and weighs at least 50 kg at screening.
• Female participant 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 28 days after final investigational product (IP) administration.
• Female participant must agree not to breastfeed starting at screening and throughout the study period and for 28 days after final IP administration.
• Female participant must not donate ova starting at first dose of IP and throughout the study period and for 28 days after final IP administration.
• Male participant with female partner(s) of childbearing potential (including breastfeeding partner\[s\]) must agree to use contraception throughout the treatment period and for 90 days after final IP administration.
• Male participant must not donate sperm during the treatment period and for 90 days after final IP administration.
• Male participant with a pregnant partner(s) must agree to remain abstinent or use a condom with spermicide for the duration of the pregnancy throughout the study period and for 90 days after final IP administration.
• Participant agrees to not participate in another interventional study while participating in the present study.

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 any condition which makes the participant unsuitable for study participation.
• Female participant who has been pregnant within 6 months prior to screening or breastfeeding within 3 months prior to screening.
• Participant has a known or suspected hypersensitivity to ASP8062 or morphine and/or other opioids, or any components of the formulations used.
• Participant has had previous exposure with ASP8062.
• Participant has any of the liver function tests (alkaline phosphatase \[ALP\], alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], gamma-glutamyl transferase and total bilirubin \[TBL\]) ≥ 1.5 × upper limit of normal (ULN) on day -1. In such a case, the assessment may be repeated once.
• Participant 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.
• Participant 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.
• Participant has a history of moderate or severe use disorder for any substance other than caffeine or tobacco (based on the Diagnostic and Statistical Manual of Mental Disorders, edition 5 (DSM-5) criteria).
• Participant has a history or presence of any clinically significant psychiatric disorders such as, bipolar 1, schizophrenia, schizoaffective disorder or major depressive disorders.
• Participant has had recent suicidal ideation within the last 12 months or participant who is at significant risk to commit suicide using the Baseline/Screening Columbia-suicide severity rating scale (C-SSRS) at screening and the Since Last Visit C-SSRS on day -1.
• Participant has/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection) or fungal (noncutaneous) infection within 1 week prior to day -1.
• Participant has any clinically significant abnormality following an investigator's review of the physical examination, ECG and protocol-defined clinical laboratory tests at screening or on day -1.
• Participant has a mean pulse \< 50 or \> 90 bpm; mean systolic blood pressure \> 150 mmHg; mean diastolic blood pressure \> 95 mmHg (measurements taken in duplicate after participant has been resting in the supine position for at least 5 minutes) on day -1. If the mean blood pressure exceeds the limits above, 1 additional duplicate may be taken.
• Participant has a mean corrected QT interval using Fridericia's formula (QTcF) of \> 450 msec (for male participants) and \> 470 msec (for female participants) on day -1. If the mean QTcF exceeds the limits above, 1 additional triplicate ECG 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 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

Morphine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

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 24, 2020
• First Posted: June 26, 2020
• Study Start: June 30, 2020
• Primary Completion: September 11, 2020
• Study Completion: September 11, 2020
• Last Updated: November 21, 2024
• Results First Posted: September 29, 2021

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)