Clinical trial NCT04448561: 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
Official title: A Phase 1 Randomized, Placebo-controlled Study to Assess the Safety, Tolerability and Pharmacokinetics of Multiple Doses of ASP8062 With a Single Dose of Morphine in Recreational Opioid Using Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Opioid Use Disorder
Keywords: Opioid Use Disorder
pharmacokinetic
ASP8062
morphine
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2020-06-26
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: Participants were screened for up to 28 days prior to first investigational product administration. Eligible participants were admitted to the clinical unit on day -1 and were residential for a single period of 17 days/16 nights.

Participants were discharged from the clinical unit on day 16 on the condition that all required assessments had been performed and that there were no medical reasons for a longer stay in the clinical unit.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.
* Participant has a positive test for amphetamines, barbiturates, benzodiazepines, cocaine, phencyclidine, alcohol and/or opiates on day -1. Positive tetrahydrocannabinol is not exclusionary and a cannabis intoxication evaluation will be performed. Participant may be reconsidered.
* Participant has used any prescribed or nonprescribed drugs (including vitamins and natural and herbal remedies, e.g., St. John's Wort) in the 2 weeks prior to first IP administration, except for occasional use of acetaminophen (up to 2 g/day), topical dermatological products, including corticosteroid products, hormonal contraceptives and hormone replacement therapy (HRT).
* Participant 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 9 and 10.
* Participant has used any inducer of metabolism (e.g., barbiturates and rifampin) in the 3 months prior to day -1.
* Participant has had significant blood loss, donated approximately 500 mL of whole blood (excluding plasma donation) within 56 days prior to screening or donated plasma within 7 days prior to day -1.
* Participant has a positive serology test for hepatitis B surface antigen, hepatitis C virus antibodies or antibodies to human immunodeficiency virus (HIV) type 1 and/or type 2 at screening.
* Participant has loss of ability to freely provide consent through imprisonment or involuntary incarceration for treatment of either a psychiatric or physical (e.g., infectious disease) illness.
* Participant is an employee of Astellas, the study-related contract research organizations (CROs) or the clinical unit.

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs)
timeFrame: From first dose of study drug up to end of study visit (up to day 25)
measure: 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)
timeFrame: Up to day 25
measure: Change From Baseline in Blood Oxygen Saturation (SpO2) at Predose
timeFrame: 'ASP8062' and 'Placebo': Baseline and predose Day 9; 'ASP8062 in combination with morphine' and 'Placebo in combination with morphine': Baseline and predose Day 10
measure: Change From Baseline in Blood Oxygen Saturation (SpO2) at 1 Hour Postdose
timeFrame: '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
measure: Change From Baseline in Blood Oxygen Saturation (SpO2) at 2 Hour Postdose
timeFrame: '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
measure: Change From Baseline in Blood Oxygen Saturation (SpO2) at 4 Hour Postdose
timeFrame: '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
measure: Change From Baseline in Blood Oxygen Saturation (SpO2) at 8 Hour Postdose
timeFrame: '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
measure: Change From Baseline in Blood Oxygen Saturation (SpO2) at 12 Hour Postdose
timeFrame: '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
measure: Change From Baseline in End Tidal Carbon Dioxide (CO2) at Predose
timeFrame: '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
measure: Change From Baseline in End Tidal Carbon Dioxide (CO2) at 1 Hour Postdose
timeFrame: '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
measure: Change From Baseline in End Tidal Carbon Dioxide (CO2) at 2 Hour Postdose
timeFrame: '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
measure: Change From Baseline in End Tidal Carbon Dioxide (CO2) at 4 Hour Postdose
timeFrame: '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
measure: Change From Baseline in End Tidal Carbon Dioxide (CO2) at 8 Hour Postdose
timeFrame: '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:
measure: Pharmacokinetics (PK) of ASP8062 in Plasma: Area Under the Concentration From Time of Dosing to 24 Hours (AUC24)
timeFrame: '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
measure: Pharmacokinetics (PK) of ASP8062 in Plasma: Maximum Plasma Concentration (Cmax)
timeFrame: '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
measure: Pharmacokinetics (PK) of Morphine in Plasma: Area Under the Concentration From Time of Dosing Extrapolated to Time Infinity (AUCinf)
timeFrame: Predose, 0.25, 0.5, 1.5, 2, 3, 4, 8, 12, 16, 24, 36, 48 h postdose Day 10
measure: Pharmacokinetics (PK) of Morphine in Plasma: Area Under the Concentration Time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast)
timeFrame: Predose, 0.25, 0.5, 1.5, 2, 3, 4, 8, 12, 16, 24, 36, 48 h postdose Day 10
measure: Pharmacokinetics (PK) of Morphine in Plasma: Cmax
timeFrame: Predose, 0.25, 0.5, 1.5, 2, 3, 4, 8, 12, 16, 24, 36, 48 h postdose Day 10
measure: Pharmacokinetics (PK) of Morphine-3β-D-glucuronide(M3G) (Morphine Metabolite) in Plasma: AUCinf
timeFrame: Predose, 0.25, 0.5, 1.5, 2, 3, 4, 8, 12, 16, 24, 36, 48 h postdose Day 10
measure: Pharmacokinetics (PK) of Morphine-3β-D-glucuronide (M3G) (Morphine Metabolite) in Plasma: AUClast
timeFrame: Predose, 0.25, 0.5, 1.5, 2, 3, 4, 8, 12, 16, 24, 36, 48 h postdose Day 10
measure: Pharmacokinetics (PK) of Morphine-3β-D-glucuronide (M3G) (Morphine Metabolite) in Plasma: Cmax
timeFrame: Predose, 0.25, 0.5, 1.5, 2, 3, 4, 8, 12, 16, 24, 36, 48 h postdose Day 10
measure: Pharmacokinetics (PK) of Morphine-6β-D-glucuronide (M6G) (Morphine Metabolite) in Plasma: AUCinf
timeFrame: Predose, 0.25, 0.5, 1.5, 2, 3, 4, 8, 12, 16, 24, 36, 48 h postdose Day 10
measure: Pharmacokinetics (PK) of Morphine-6β-D-glucuronide (M6G) (Morphine Metabolite) in Plasma: AUClast
timeFrame: Predose, 0.25, 0.5, 1.5, 2, 3, 4, 8, 12, 16, 24, 36, 48 h postdose Day 10
measure: Pharmacokinetics (PK) of Morphine-6β-D-glucuronide (M6G) (Morphine Metabolite) in Plasma: Cmax
timeFrame: Predose, 0.25, 0.5, 1.5, 2, 3, 4, 8, 12, 16, 24, 36, 48 h postdose Day 10
Other outcomes:
Locations:
city: Overland Park
country: United States
facility: Altasciences Clinical Kansas, Inc.
state: Kansas
Study officials:
affiliation: Astellas Pharma Global Development, Inc.
name: Executive Medical Director
role: STUDY_DIRECTOR
References: