A Study to Assess the Safety, Tolerability and Pharmacoki... | NCT04448561

NCT04448561

ID	Type	Description	Link
UG3DA051392	U.S. NIH Grant/Contract		View source

Status Module

Sponsor/Collaborators Module

Name	Class
National Institute on Drug Abuse (NIDA)	NIH

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
ASP8082	Drug	oral	ASP8062 in combination with morphine
morphine

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.

Secondary Outcomes

Measure	Description	Time Frame
Pharmacokinetics (PK) of ASP8062 in Plasma: Area Under the Concentration From Time of Dosing to 24 Hours (AUC24)	AUC24 was recorded from the PK plasma samples collected. Samples for AUC24 were collected for arm 'ASP8062' at Day 9, and for arm 'ASP8062 in combination with morphine' at Day 10.	'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

Eligibility Module

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.

Contacts/Locations Module

Name	Affiliation	Role
Executive Medical Director	Astellas Pharma Global Development, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Altasciences Clinical Kansas, Inc.		Overland Park	Kansas	66212	United States

References Module

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

ID	Title	Description
FG000	ASP8062 in Combination With Morphine	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.
FG001	Placebo in Combination With Morphine

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Jul 30, 2020

ID	Title	Description
BG000	ASP8062 in Combination With Morphine	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.
BG001	Placebo in Combination With Morphine	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.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00016 BG0018 BG00224

Categories

TEAE

Title	Measurements
	OG0007 OG00111 OG0023 OG003

Primary

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.

The analysis population was the SAF.

Posted

Count of Participants

Participants

Up to day 25

ID	Title	Description
OG000	ASP8062	Participants received ASP8062 tablet, orally once daily on days 1 through 9.
OG001	ASP8062 in Combination With Morphine	Participants received ASP8062 tablet, orally once on day 10. On day 10, participants also received morphine tablet as single oral dose immediately after the ASP8062 dose.
OG002	Placebo

Primary

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.

SAF population with available data at each time point.

Posted

Mean

Standard Deviation

percentage of oxygen saturation

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

ID	Title	Description
OG000	ASP8062	Participants received ASP8062 tablet, orally once daily on days 1 through 9.
OG001	ASP8062 in Combination With Morphine	Participants received ASP8062 tablet, orally once on day 10. On day 10, participants also received morphine tablet as single oral dose immediately after the ASP8062 dose.
OG002	Placebo	Participants received ASP8062 matching placebo tablet, orally once daily on days 1 through 9.

Primary

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

SAF population with available data at each time point.

Posted

Mean

Standard Deviation

percentage of oxygen saturation

'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

ID	Title	Description
OG000	ASP8062	Participants received ASP8062 tablet, orally once daily on days 1 through 9.
OG001	ASP8062 in Combination With Morphine	Participants received ASP8062 tablet, orally once on day 10. On day 10, participants also received morphine tablet as single oral dose immediately after the ASP8062 dose.
OG002	Placebo	Participants received ASP8062 matching placebo tablet, orally once daily on days 1 through 9.

Primary

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

SAF population with available data at each time point.

Posted

Mean

Standard Deviation

percentage of oxygen saturation

'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

ID	Title	Description
OG000	ASP8062	Participants received ASP8062 tablet, orally once daily on days 1 through 9.
OG001	ASP8062 in Combination With Morphine	Participants received ASP8062 tablet, orally once on day 10. On day 10, participants also received morphine tablet as single oral dose immediately after the ASP8062 dose.
OG002	Placebo	Participants received ASP8062 matching placebo tablet, orally once daily on days 1 through 9.

Primary

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

SAF population with available data at each time point.

Posted

Mean

Standard Deviation

percentage of oxygen saturation

'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

ID	Title	Description
OG000	ASP8062	Participants received ASP8062 tablet, orally once daily on days 1 through 9.
OG001	ASP8062 in Combination With Morphine	Participants received ASP8062 tablet, orally once on day 10. On day 10, participants also received morphine tablet as single oral dose immediately after the ASP8062 dose.
OG002	Placebo	Participants received ASP8062 matching placebo tablet, orally once daily on days 1 through 9.

Primary

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

SAF population with available data at each time point.

Posted

Mean

Standard Deviation

percentage of oxygen saturation

'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

ID	Title	Description
OG000	ASP8062	Participants received ASP8062 tablet, orally once daily on days 1 through 9.
OG001	ASP8062 in Combination With Morphine	Participants received ASP8062 tablet, orally once on day 10. On day 10, participants also received morphine tablet as single oral dose immediately after the ASP8062 dose.
OG002	Placebo	Participants received ASP8062 matching placebo tablet, orally once daily on days 1 through 9.

Primary

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

SAF population with available data at each time point.

Posted

Mean

Standard Deviation

percentage of oxygen saturation

'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

ID	Title	Description
OG000	ASP8062	Participants received ASP8062 tablet, orally once daily on days 1 through 9.
OG001	ASP8062 in Combination With Morphine	Participants received ASP8062 tablet, orally once on day 10. On day 10, participants also received morphine tablet as single oral dose immediately after the ASP8062 dose.
OG002	Placebo	Participants received ASP8062 matching placebo tablet, orally once daily on days 1 through 9.

Primary

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'.

SAF population with available data at each time point.

Posted

Mean

Standard Deviation

mmHg

'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

ID	Title	Description
OG000	ASP8062	Participants received ASP8062 tablet, orally once daily on days 1 through 9.
OG001	ASP8062 in Combination With Morphine	Participants received ASP8062 tablet, orally once on day 10. On day 10, participants also received morphine tablet as single oral dose immediately after the ASP8062 dose.
OG002	Placebo	Participants received ASP8062 matching placebo tablet, orally once daily on days 1 through 9.

Primary

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

SAF population with available data at each time point.

Posted

Mean

Standard Deviation

mmHg

'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

ID	Title	Description
OG000	ASP8062	Participants received ASP8062 tablet, orally once daily on days 1 through 9.
OG001	ASP8062 in Combination With Morphine	Participants received ASP8062 tablet, orally once on day 10. On day 10, participants also received morphine tablet as single oral dose immediately after the ASP8062 dose.
OG002	Placebo	Participants received ASP8062 matching placebo tablet, orally once daily on days 1 through 9.

Primary

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

SAF population with available data at each time point.

Posted

Mean

Standard Deviation

mmHg

'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

ID	Title	Description
OG000	ASP8062	Participants received ASP8062 tablet, orally once daily on days 1 through 9.
OG001	ASP8062 in Combination With Morphine	Participants received ASP8062 tablet, orally once on day 10. On day 10, participants also received morphine tablet as single oral dose immediately after the ASP8062 dose.
OG002	Placebo	Participants received ASP8062 matching placebo tablet, orally once daily on days 1 through 9.

Primary

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

SAF population with available data at each time point.

Posted

Mean

Standard Deviation

mmHg

'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

ID	Title	Description
OG000	ASP8062	Participants received ASP8062 tablet, orally once daily on days 1 through 9.
OG001	ASP8062 in Combination With Morphine	Participants received ASP8062 tablet, orally once on day 10. On day 10, participants also received morphine tablet as single oral dose immediately after the ASP8062 dose.
OG002	Placebo	Participants received ASP8062 matching placebo tablet, orally once daily on days 1 through 9.

Primary

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

SAF population with available data at each time point.

Posted

Mean

Standard Deviation

mmHg

'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

ID	Title	Description
OG000	ASP8062	Participants received ASP8062 tablet, orally once daily on days 1 through 9.
OG001	ASP8062 in Combination With Morphine	Participants received ASP8062 tablet, orally once on day 10. On day 10, participants also received morphine tablet as single oral dose immediately after the ASP8062 dose.
OG002	Placebo	Participants received ASP8062 matching placebo tablet, orally once daily on days 1 through 9.

Secondary

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

AUC24 was recorded from the PK plasma samples collected. Samples for AUC24 were collected for arm 'ASP8062' at Day 9, and for arm 'ASP8062 in combination with morphine' at Day 10.

The analysis population was Pharmacokinetic Analysis Set (PKAS) with available data at each time point. PKAS consisted of all participants who received at least 1 dose of ASP8062 for which concentration data were available to facilitate derivation of at least 1 pharmacokinetic parameter of ASP8062.

Posted

Mean

Standard Deviation

nanogram*hour per milliliter(ng*h/mL)

'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

ID	Title	Description
OG000	ASP8062	Participants received ASP8062 tablet, orally once daily on days 1 through 9.
OG001	ASP8062 in Combination With Morphine	Participants received ASP8062 tablet, orally once on day 10. On day 10, participants also received morphine tablet as single oral dose immediately after the ASP8062 dose.

Secondary

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

Cmax was recorded from the PK plasma samples collected. Samples for Cmax were collected for arm 'ASP8062' at Day 9, and for arm 'ASP8062 in combination with morphine' at Day 10.

The analysis population was PKAS with available data at each time point.

Posted

Mean

Standard Deviation

nanogram per milliliter (ng/mL)

'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

ID	Title	Description
OG000	ASP8062	Participants received ASP8062 tablet, orally once daily on days 1 through 9.
OG001	ASP8062 in Combination With Morphine	Participants received ASP8062 tablet, orally once on day 10. On day 10, participants also received morphine tablet as single oral dose immediately after the ASP8062 dose.

Units	Counts
Participants

Secondary

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

AUCinf was recorded from the PK plasma samples collected.

The analysis population was PKAS with available data at each time point. Insufficient number of samples were available for calculation for AUCinf.

Posted

Mean

Standard Deviation

ng*h/mL

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

ID	Title	Description
OG000	ASP8062 in Combination With Morphine	Participants received ASP8062 tablet, orally once on day 10. On day 10, participants also received morphine tablet as single oral dose immediately after the ASP8062 dose.
OG001	Placebo in Combination With Morphine	Participants received ASP8062 matching placebo tablet, orally once on day 10. On day 10, participants also received morphine tablet as single oral dose immediately after the ASP8062 matching placebo dose.

Units	Counts
Participants

Secondary

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

AUClast was recorded from the PK plasma samples collected.

The analysis population was PKAS.

Posted

Mean

Standard Deviation

ng*h/mL

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

ID	Title	Description
OG000	ASP8062 in Combination With Morphine	Participants received ASP8062 tablet, orally once on day 10. On day 10, participants also received morphine tablet as single oral dose immediately after the ASP8062 dose.
OG001	Placebo in Combination With Morphine	Participants received ASP8062 matching placebo tablet, orally once on day 10. On day 10, participants also received morphine tablet as single oral dose immediately after the ASP8062 matching placebo dose.

Units	Counts
Participants	OG000

Secondary

Pharmacokinetics (PK) of Morphine in Plasma: Cmax

Cmax was recorded from the PK plasma samples collected.

The analysis population was PKAS.

Posted

Mean

Standard Deviation

ng/mL

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

ID	Title	Description
OG000	ASP8062 in Combination With Morphine	Participants received ASP8062 tablet, orally once on day 10. On day 10, participants also received morphine tablet as single oral dose immediately after the ASP8062 dose.
OG001	Placebo in Combination With Morphine	Participants received ASP8062 matching placebo tablet, orally once on day 10. On day 10, participants also received morphine tablet as single oral dose immediately after the ASP8062 matching placebo dose.

Units	Counts
Participants	OG000

Secondary

Pharmacokinetics (PK) of Morphine-3β-D-glucuronide(M3G) (Morphine Metabolite) in Plasma: AUCinf

AUCinf was recorded from the PK plasma samples collected.

The analysis population was PKAS with available data at each time point. Insufficient number of samples were available for calculation for AUCinf.

Posted

Mean

Standard Deviation

ng*h/mL

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

ID	Title	Description
OG000	ASP8062 in Combination With Morphine	Participants received ASP8062 tablet, orally once on day 10. On day 10, participants also received morphine tablet as single oral dose immediately after the ASP8062 dose.
OG001	Placebo in Combination With Morphine	Participants received ASP8062 matching placebo tablet, orally once on day 10. On day 10, participants also received morphine tablet as single oral dose immediately after the ASP8062 matching placebo dose.

Units	Counts
Participants

Secondary

Pharmacokinetics (PK) of Morphine-3β-D-glucuronide (M3G) (Morphine Metabolite) in Plasma: AUClast

AUClast was recorded from the PK plasma samples collected.

The analysis population was PKAS.

Posted

Mean

Standard Deviation

ng*h/mL

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

ID	Title	Description
OG000	ASP8062 in Combination With Morphine	Participants received ASP8062 tablet, orally once on day 10. On day 10, participants also received morphine tablet as single oral dose immediately after the ASP8062 dose.
OG001	Placebo in Combination With Morphine	Participants received ASP8062 matching placebo tablet, orally once on day 10. On day 10, participants also received morphine tablet as single oral dose immediately after the ASP8062 matching placebo dose.

Units	Counts
Participants	OG000

Secondary

Pharmacokinetics (PK) of Morphine-3β-D-glucuronide (M3G) (Morphine Metabolite) in Plasma: Cmax

Cmax was recorded from the PK plasma samples collected.

The analysis population was PKAS.

Posted

Mean

Standard Deviation

ng/mL

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

ID	Title	Description
OG000	ASP8062 in Combination With Morphine	Participants received ASP8062 tablet, orally once day 10. On day 10, participants also received morphine tablet as single oral dose immediately after the ASP8062 dose.
OG001	Placebo in Combination With Morphine	Participants received ASP8062 matching placebo tablet, orally once on day 10. On day 10, participants also received morphine tablet as single oral dose immediately after the ASP8062 matching placebo dose.

Units	Counts
Participants	OG000

Secondary

Pharmacokinetics (PK) of Morphine-6β-D-glucuronide (M6G) (Morphine Metabolite) in Plasma: AUCinf

AUCinf was recorded from the PK plasma samples collected.

The analysis population was the PKAS with available at each time point. The analysis population was PKAS with available data at each time point. Insufficient number of samples were available for calculation for AUCinf.

Posted

Mean

Standard Deviation

ng*h/mL

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

ID	Title	Description
OG000	ASP8062 in Combination With Morphine	Participants received ASP8062 tablet, orally once on day 10. On day 10, participants also received morphine tablet as single oral dose immediately after the ASP8062 dose.
OG001	Placebo in Combination With Morphine	Participants received ASP8062 matching placebo tablet, orally once on day 10. On day 10, participants also received morphine tablet as single oral dose immediately after the ASP8062 matching placebo dose.

Units	Counts
Participants

Secondary

Pharmacokinetics (PK) of Morphine-6β-D-glucuronide (M6G) (Morphine Metabolite) in Plasma: AUClast

AUClast was recorded from the PK plasma samples collected.

The analysis population was the PKAS.

Posted

Mean

Standard Deviation

ng*h/mL

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

ID	Title	Description
OG000	ASP8062 in Combination With Morphine	Participants received ASP8062 tablet, orally once on day 10. On day 10, participants also received morphine tablet as single oral dose immediately after the ASP8062 dose.
OG001	Placebo in Combination With Morphine	Participants received ASP8062 matching placebo tablet, orally once on day 10. On day 10, participants also received morphine tablet as single oral dose immediately after the ASP8062 matching placebo dose.

Units	Counts
Participants	OG000

Secondary

Pharmacokinetics (PK) of Morphine-6β-D-glucuronide (M6G) (Morphine Metabolite) in Plasma: Cmax

Cmax was recorded from the PK plasma samples collected.

The analysis population was the PKAS.

Posted

Mean

Standard Deviation

ng/mL

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

ID	Title	Description
OG000	ASP8062 in Combination With Morphine	Participants received ASP8062 tablet, orally once on day 10. On day 10, participants also received morphine tablet as single oral dose immediately after the ASP8062 dose.
OG001	Placebo Combination With Morphine	Participants received ASP8062 matching placebo tablet, orally once on day 10. On day 10, participants also received morphine tablet as single oral dose immediately after the ASP8062 matching placebo dose.

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	ASP8062	Participants received ASP8062 tablet, orally once daily on days 1 through 9.	16	16	7	16
EG001	ASP8062 in Combination With Morphine	Participants received ASP8062 tablet, orally once on day 10. On day 10, participants also received morphine tablet as single oral dose immediately after the ASP8062 dose.	15	15	11	15
EG002	Placebo	Participants received ASP8062 matching placebo tablet, orally once daily on days 1 through 9. On day 10, participants also received morphine tablet as single oral dose immediately after the ASP8062 matching placebo dose.	8	8	3	8
EG003	Placebo in Combination With Morphine	Participants received ASP8062 matching placebo tablet, orally once on day 10. On day 10, participants also received morphine tablet as single oral dose immediately after the ASP8062 matching placebo dose.	8	8	7	8

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Vertigo	Ear and labyrinth disorders	MedDRA v 23.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected15 at risk EG0020 events0 affected8 at risk EG0031 events1 affected8 at risk
Vision blurred	Eye disorders	MedDRA v 23.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected15 at risk EG0020 events0 affected8 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA v 23.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected15 at risk EG0020 events0 affected8 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA v 23.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected15 at risk EG0020 events0 affected8 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA v 23.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected15 at risk EG0020 events0 affected8 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA v 23.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0012 events2 affected15 at risk EG0020 events0 affected8 at risk EG003
Haematochezia	Gastrointestinal disorders	MedDRA v 23.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected15 at risk EG0020 events0 affected8 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA v 23.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0016 events6 affected15 at risk EG0020 events0 affected8 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA v 23.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0015 events5 affected15 at risk EG0020 events0 affected8 at risk EG003
Asthenia	General disorders	MedDRA v 23.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected15 at risk EG0020 events0 affected8 at risk EG003
Feeling abnormal	General disorders	MedDRA v 23.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected15 at risk EG0020 events0 affected8 at risk EG003
Feeling of relaxation	General disorders	MedDRA v 23.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected15 at risk EG0020 events0 affected8 at risk EG003
Infusion site extravasation	General disorders	MedDRA v 23.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected15 at risk EG0020 events0 affected8 at risk EG003
Vessel puncture site haemorrhage	General disorders	MedDRA v 23.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0012 events1 affected15 at risk EG0020 events0 affected8 at risk EG003
Furuncle	Infections and infestations	MedDRA v 23.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected15 at risk EG0020 events0 affected8 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA v 23.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected15 at risk EG0021 events1 affected8 at risk EG003
Lipase increased	Investigations	MedDRA v 23.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected15 at risk EG0020 events0 affected8 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA v 23.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected15 at risk EG0020 events0 affected8 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA v 23.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected15 at risk EG0020 events0 affected8 at risk EG003
Dizziness	Nervous system disorders	MedDRA v 23.0	Systematic Assessment	EG0003 events2 affected16 at risk EG0011 events1 affected15 at risk EG0020 events0 affected8 at risk EG003
Head discomfort	Nervous system disorders	MedDRA v 23.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected15 at risk EG0020 events0 affected8 at risk EG003
Headache	Nervous system disorders	MedDRA v 23.0	Systematic Assessment	EG0003 events3 affected16 at risk EG0013 events2 affected15 at risk EG0022 events2 affected8 at risk EG003
Hypoaesthesia	Nervous system disorders	MedDRA v 23.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected15 at risk EG0020 events0 affected8 at risk EG003
Somnolence	Nervous system disorders	MedDRA v 23.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected15 at risk EG0020 events0 affected8 at risk EG003
Abnormal dreams	Psychiatric disorders	MedDRA v 23.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected15 at risk EG0020 events0 affected8 at risk EG003
Euphoric mood	Psychiatric disorders	MedDRA v 23.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0015 events5 affected15 at risk EG0020 events0 affected8 at risk EG003
Irritability	Psychiatric disorders	MedDRA v 23.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected15 at risk EG0020 events0 affected8 at risk EG003
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA v 23.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0012 events2 affected15 at risk EG0020 events0 affected8 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA v 23.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected15 at risk EG0020 events0 affected8 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA v 23.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0013 events3 affected15 at risk EG0022 events2 affected8 at risk EG003
Flushing	Vascular disorders	MedDRA v 23.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected15 at risk EG0020 events0 affected8 at risk EG003

ID	Term
D009293	Opioid-Related Disorders

ID	Term
D009020	Morphine

Ancestor Terms

ID	Term
D009022	Morphine Derivatives
D009019	Morphinans
D053610	Opiate Alkaloids
D000470	Alkaloids
D006571	Heterocyclic Compounds
D006572	Heterocyclic Compounds, Bridged-Ring
D006576	Heterocyclic Compounds, 4 or More Rings
D000072471	Heterocyclic Compounds, Fused-Ring
D010616	Phenanthrenes
D011084	Polycyclic Aromatic Hydrocarbons
D011083	Polycyclic Compounds

ID	Term
D000079524	Narcotic-Related Disorders
D019966	Substance-Related Disorders
D064419	Chemically-Induced Disorders
D001523	Mental Disorders