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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04448561
Recruitment Status : Recruiting
First Posted : June 26, 2020
Last Update Posted : July 22, 2020
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )

Brief Summary:

The primary purpose of this study is 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 will also assess the potential for pharmacokinetic interaction between ASP8062 and morphine.


Condition or disease Intervention/treatment Phase
Opioid Use Disorder Drug: ASP8082 Drug: morphine Drug: Placebo Phase 1

Detailed Description:

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

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : June 30, 2020
Estimated Primary Completion Date : October 2020
Estimated Study Completion Date : October 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: ASP8062 in combination with morphine
Participants will receive multiple oral doses of ASP8062 on days 1 through 10. On day 10, participants will also receive a single oral dose of morphine immediately after the ASP8062 dose.
Drug: ASP8082
oral

Drug: morphine
oral

Placebo Comparator: Placebo ASP8062 in combination with morphine
Participants will receive multiple oral doses of placebo on days 1 through 10. On day 10, participants will also receive a single oral dose of morphine immediately after the placebo dose.
Drug: morphine
oral

Drug: Placebo
oral




Primary Outcome Measures :
  1. Number of participants with Adverse Events (AEs) [ Time Frame: Up to day 25 ]
    Adverse events (AEs) will be coded using medical dictionary for regulatory activities (MedDRA). An AE is any untoward medical occurrence in a participant, temporally associated with the use of study Investigational Product (IP), whether or not considered related to the study IP. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study IP. An AE is considered "serious" if, the event: results in death, is life-threatening, requires hospitalization or prolongation to hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or other medically important event.

  2. Number of participants with laboratory value abnormalities and/or adverse events (AEs) [ Time Frame: Up to day 25 ]
    Number of participants with potentially clinically significant laboratory values.

  3. Number of participants with vital sign abnormalities and/or adverse events (AEs) [ Time Frame: Up to day 25 ]
    Number of participants with potentially clinically significant vital sign values.

  4. Number of participants with 12 lead electrocardiogram (ECG) abnormalities and/or Adverse Events (AEs) [ Time Frame: Up to day 25 ]
    Number of participants with potentially clinically significant ECG values.

  5. Number of participants with suicidal ideation and/or suicidal behavior as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Up to day 25 ]
    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 provided 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) will be reported.

  6. Change from baseline in blood oxygen saturation (SpO2) [ Time Frame: Baseline (Day 9) and up to day 10 ]
    The blood oxygen saturation (SpO2) will be measured using a pulse oximeter placed on the participant's fingertip.

  7. Change from baseline in end tidal carbon dioxide (CO2) [ Time Frame: Baseline (Day 9) and up to day 10 ]
    End tidal CO2 measurements will obtained per participant utilizing a portable bedside capnography device.


Secondary Outcome Measures :
  1. Pharmacokinetics (PK) of ASP8062 in plasma: AUC24 [ Time Frame: Up to hour 24 after dosing ]
    Area under the concentration-time curve from the time of dosing to 24 hours (AUC24) will be recorded from the pharmacokinetic (PK) plasma samples collected.

  2. Pharmacokinetics (PK) of ASP8062 in plasma: Cmax [ Time Frame: Up to day 25 ]
    Maximum concentration (Cmax) will be recorded from the pharmacokinetic (PK) plasma samples collected.

  3. Pharmacokinetics (PK) of morphine in plasma: AUCinf [ Time Frame: Up to day 15 ]
    Area under the concentration time curve from the time of dosing extrapolated to time infinity (AUCinf) will be recorded from the pharmacokinetic (PK) plasma samples collected.

  4. Pharmacokinetics (PK) of morphine in plasma: AUClast [ Time Frame: Up to day 15 ]
    Area under the concentration time curve from the time of dosing to the last measurable concentration (AUClast) will be recorded from the pharmacokinetic (PK) plasma samples collected.

  5. Pharmacokinetics (PK) of morphine in plasma: Cmax [ Time Frame: Up to day 15 ]
    Cmax will be recorded from the pharmacokinetic (PK) plasma samples collected.

  6. Pharmacokinetics (PK) of M3G (morphine metabolite) in plasma: AUCinf [ Time Frame: Up to day 15 ]
    AUCinf will be recorded from the pharmacokinetic (PK) plasma samples collected.

  7. Pharmacokinetics (PK) of M3G (morphine metabolite) in plasma: AUClast [ Time Frame: Up to day 15 ]
    AUClast will be recorded from the pharmacokinetic (PK) plasma samples collected.

  8. Pharmacokinetics (PK) of M3G (morphine metabolite) in plasma: Cmax [ Time Frame: Up to day 15 ]
    Cmax will be recorded from the pharmacokinetic (PK) plasma samples collected.

  9. Pharmacokinetics (PK) of M6G (morphine metabolite) in plasma: AUCinf [ Time Frame: Up to day 15 ]
    AUCinf will be recorded from the pharmacokinetic (PK) plasma samples collected.

  10. Pharmacokinetics (PK) of M6G (morphine metabolite) in plasma: AUClast [ Time Frame: Up to day 15 ]
    AUClast will be recorded from the pharmacokinetic (PK) plasma samples collected.

  11. Pharmacokinetics (PK) of M6G (morphine metabolite) in plasma: Cmax [ Time Frame: Up to day 15 ]
    Cmax will be recorded from the pharmacokinetic (PK) plasma samples collected.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04448561


Contacts
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Contact: Astellas Pharma Global Development, Inc. 800-888-7704 Astellas.registration@astellas.com

Locations
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United States, Kansas
Altasciences Clinical Kansas, Inc. Recruiting
Overland Park, Kansas, United States, 66212
Sponsors and Collaborators
Astellas Pharma Global Development, Inc.
Investigators
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Study Director: Executive Medical Director Astellas Pharma Global Development, Inc.
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Responsible Party: Astellas Pharma Global Development, Inc.
ClinicalTrials.gov Identifier: NCT04448561    
Other Study ID Numbers: 8062-CL-2002
First Posted: June 26, 2020    Key Record Dates
Last Update Posted: July 22, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Access to anonymized individual participant level data will not be provided for this trial as it meets one or more of the exceptions described on www.clinicalstudydatarequest.com under "Sponsor Specific Details for Astellas."

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. ):
Opioid Use Disorder
pharmacokinetic
ASP8062
morphine
Additional relevant MeSH terms:
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Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Morphine
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents