A Study to Assess the Effect of a Single Dose of ASP8062... | NCT04447287

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

Name	Class
National Institute on Drug Abuse (NIDA)	NIH

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
ASP8062	Drug	Oral	ASP8062 in combination with buprenorphine/naloxone

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.

Secondary Outcomes

Measure	Description	Time Frame
Pharmacokinetics (PK) of ASP8062 in Plasma: Area Under the Concentration-time Curve From the Time of Dosing Extrapolated to Time Infinity (AUCinf)	AUCinf was recorded from the PK plasma samples collected. Samples for AUCinf were collected for arm 'ASP8062 in combination with buprenorphine/naloxone' at Day 12.	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)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

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.
Subject has a mean corrected QT interval using Fridericia's formula (QTcF) of > 450 msec (for male subjects) and > 470 msec (for female subjects) on day -1. If the mean QTcF exceeds the limits above, 1 additional duplicate ECG may be taken.
Subject has used any prescribed drugs, vitamins and natural or herbal remedies (including, St. John's Wort) in the 2 weeks prior to first IP administration, except for rescue medications, milk of magnesia, acetaminophen, topical dermatological products, including corticosteroid products, hormonal contraceptives and hormone replacement therapy (HRT).
Subject has used any inducer of metabolism (e.g., barbiturates and rifampin) in the 3 months prior to day -1.
Subject has had significant blood loss or 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.
Subject has a positive serology test for antibodies to human immunodeficiency virus type 1 and/or type 2, acute hepatitis B virus infection or acute hepatitis C virus infection, excluding asymptomatic hepatitis C virus infection at screening.
Subject 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.
Subject is an employee of Astellas, the study-related contract research organizations or the clinical unit.
Subject has used any inducer of CYP2C8, 2C9 or 3A4-related metabolism (e.g., barbiturates, rifampin, aprepitant, ritonavir, apalutamide, carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, St. John's wort, bosentan, efavirenz, etravirine, phenobarbital, primidone, armodafinil, modafinil, and rufinamide) in the 3 months prior to day -1.

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

PubMed Identifier	Type	Citation	Retractions
36738100	Derived	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.

Label	URL
Link to results and other applicable study documents on the Astellas Clinical Trials website	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Buprenorphine/Naloxone	Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

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 29, 2020

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title	Denominators	Categories
	ParticipantsBG0005 ParticipantsBG00112 ParticipantsBG0026 ParticipantsBG003

Sex: Female, Male

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG0005 ParticipantsBG00112 ParticipantsBG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG0005 ParticipantsBG00112 ParticipantsBG002

Race (NIH/OMB)

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG0005 ParticipantsBG00112 ParticipantsBG002

Blood Oxygen Saturation (SpO2)

The SpO2 was measured using a pulse oximeter placed on the participant's fingertip. Baseline for SpO2 measurement was the last non-missing observation prior to first administration of Investigational Product (IP).

The analysis population consisted of all participants who received at least 1 dose of IP during Run-in Period; Investigational Period and Down-titration Period.

Mean

Standard Deviation

percentage of oxygen saturation

Title	Denominators	Categories
	ParticipantsBG0005 ParticipantsBG00111

End Tidal Carbon Dioxide (CO2)

End tidal CO2 measurement was obtained per participant utilizing a portable bedside capnography device. The baseline is study Day 11, prior to dosing with ASP8062 or Placebo ASP8062.

The analysis population consisted of all participants who received at least 1 dose of IP during Run-in Period; Investigational Period and Down-titration Period.

Mean

Standard Deviation

millimeter of mercury (mmHg)

Title	Denominators	Categories
	ParticipantsBG0001 ParticipantsBG00112

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

The analysis population was the Safety Analysis Set (SAF), which consisted of all participants who received at least 1 dose of ASP8062.

Posted

Number

Participants

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

ID	Title	Description
OG000	Buprenorphine/Naloxone (Run-in Period)	Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
OG001	ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)	Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
OG002	ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)	Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
OG003	Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)	Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
OG004	Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)	Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.

Units	Counts
Participants	OG00023 OG00112 OG00212 OG003

Title

Denominators

Categories

TEAE

Title	Measurements
	OG00016 OG0016 OG0027 OG003

Primary

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.

The analysis population was the SAF, which consisted of all participants who received at least 1 dose of Investigational Product (IP).

Posted

Count of Participants

Participants

Up to day 27

ID	Title	Description
OG000	Buprenorphine/Naloxone (Run-in Period)	Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
OG001	ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)	Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.

Primary

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.

The analysis population was the SAF, which consisted of all participants who received at least 1 dose of IP and had baseline and post dose measures taken. It was pre-specified to assess only the Run-in Period and Investigational Period Arms/Groups for this Outcome Measure.

Posted

Mean

Standard Deviation

Percentage of oxygen saturation

'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

ID	Title	Description
OG000	Buprenorphine/Naloxone (Run-in Period)	Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
OG001	ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)

Primary

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.

The analysis population was the SAF, which consisted of all participants who received at least 1 dose of IP and had both baseline and post dose measures taken. It was pre-specified to assess only the Run-in Period and Investigational Period Arms/Groups for this Outcome Measure.

Posted

Mean

Standard Deviation

Percentage of oxygen saturation

ID	Title	Description
OG000	Buprenorphine/Naloxone (Run-in Period)	Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
OG001	ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)

Primary

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

Posted

Mean

Standard Deviation

Percentage of oxygen saturation

'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

ID	Title	Description
OG000	Buprenorphine/Naloxone (Run-in Period)	Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
OG001	ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)

Primary

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

Posted

Mean

Standard Deviation

Percentage of oxygen saturation

'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

ID	Title	Description
OG000	Buprenorphine/Naloxone (Run-in Period)	Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
OG001	ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)

Primary

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

Posted

Mean

Standard Deviation

Percentage of oxygen saturation

'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

ID	Title	Description
OG000	Buprenorphine/Naloxone (Run-in Period)	Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
OG001	ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)

Primary

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

Posted

Mean

Standard Deviation

Percentage of oxygen saturation

'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

ID	Title	Description
OG000	Buprenorphine/Naloxone (Run-in Period)	Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
OG001	ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)

Primary

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'.

The analysis population was the Safety Analysis Set (SAF), which consisted of all participants who received at least 1 dose of ASP8062. It was pre-specified to assess only the Investigational Period Arms/Groups for this Outcome Measure.

Posted

Mean

Standard Deviation

mmHg

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

ID	Title	Description
OG000	ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)	Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.
OG001	Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)	Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.

Primary

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'.

Posted

Mean

Standard Deviation

mmHg

ID	Title	Description
OG000	Buprenorphine/Naloxone (Run-in Period)	Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
OG001	ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)	Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.

Primary

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

Posted

Mean

Standard Deviation

mmHg

ID	Title	Description
OG000	Buprenorphine/Naloxone (Run-in Period)	Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
OG001	ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)	Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.

Primary

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

Posted

Mean

Standard Deviation

mmHg

ID	Title	Description
OG000	Buprenorphine/Naloxone (Run-in Period)	Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
OG001	ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)	Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.

Primary

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

Posted

Mean

Standard Deviation

mmHg

ID	Title	Description
OG000	Buprenorphine/Naloxone (Run-in Period)	Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
OG001	ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)	Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.

Secondary

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

AUCinf was recorded from the PK plasma samples collected. Samples for AUCinf were collected for arm 'ASP8062 in combination with buprenorphine/naloxone' at Day 12.

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

Posted

Mean

Standard Deviation

h*ng/mL

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)

ID	Title	Description
OG000	ASP8062 in Combination With Buprenorphine/Naloxone	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.

Units	Counts
Participants

Secondary

Pharmacokinetics (PK) of ASP8062 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. Samples for AUClast were collected for arm 'ASP8062 in combination with buprenorphine/naloxone' at Day 12.

The analysis population was the PKAS, which consisted of all participants who received at least 1 dose of ASP8062 for which concentration data was available to facilitate derivation of at least 1 primary pharmacokinetic parameter.

Posted

Mean

Standard Deviation

h*ng/mL

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)

ID	Title	Description
OG000	ASP8062 in Combination With Buprenorphine/Naloxone	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.

Units	Counts
Participants

Secondary

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

Cmax was recorded from the PK plasma samples collected. Samples for Cmax were collected for arm 'ASP8062 in combination with buprenorphine/naloxone' at Day 12.

Posted

Mean

Standard Deviation

ng/mL

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)

ID	Title	Description
OG000	ASP8062 in Combination With Buprenorphine/Naloxone	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.

Units	Counts
Participants

Secondary

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

AUC24 was recorded from the PK plasma samples collected. Samples for AUC24 were collected for arm 'buprenorphine/naloxone' at Day 11; 'ASP8062 in combination with buprenorphine/naloxone' and 'ASP8062 in combination with Placebo' at Day 12.

The analysis population was the PKAS, which consisted of all participants who received at least 1 dose of buprenorphine (in any applicable period) and for which concentration data were available to facilitate derivation of at least 1 primary pharmacokinetic parameter.

Posted

Mean

Standard Deviation

h*pg/mL

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)

ID	Title	Description
OG000	Buprenorphine/Naloxone	Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
OG001	ASP8062 in Combination With Buprenorphine/Naloxone	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.

Secondary

Pharmacokinetics (PK) of Buprenorphine in Plasma: Cmax

Cmax was recorded from the PK plasma samples collected. Samples for Cmax were collected for arm 'buprenorphine/naloxone' at Day 11; 'ASP8062 in combination with buprenorphine/naloxone' and 'ASP8062 in combination with Placebo' at Day 12.

Posted

Mean

Standard Deviation

pg/mL

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)

ID	Title	Description
OG000	Buprenorphine/Naloxone	Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
OG001	ASP8062 in Combination With Buprenorphine/Naloxone	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.

Secondary

Pharmacokinetics (PK) of Norbuprenorphine (Buprenorphine's Metabolite) in Plasma: AUC24

Posted

Mean

Standard Deviation

h*pg/mL

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)

ID	Title	Description
OG000	Buprenorphine/Naloxone	Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
OG001	ASP8062 in Combination With Buprenorphine/Naloxone	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.

Secondary

Pharmacokinetics (PK) of Norbuprenorphine (Buprenorphine's Metabolite) in Plasma: Cmax

Posted

Mean

Standard Deviation

pg/mL

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)

ID	Title	Description
OG000	Buprenorphine/Naloxone	Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
OG001	ASP8062 in Combination With Buprenorphine/Naloxone	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.

Secondary

Pharmacokinetics (PK) of Naloxone in Plasma: AUC24

The analysis population was the PKAS, which consisted of all participants who received at least 1 dose of naloxone (in any applicable period) and for which concentration data were available to facilitate derivation of at least 1 primary pharmacokinetic parameter.

Posted

Mean

Standard Deviation

h*pg/mL

Predose on day 12 and at the following postdose time points on day 12: 0.25, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 16, 24, 168, 216 and 264 hour(s)

ID	Title	Description
OG000	Buprenorphine/Naloxone	Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
OG001	ASP8062 in Combination With Buprenorphine/Naloxone	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.

Secondary

Pharmacokinetics (PK) of Naloxone in Plasma: Cmax

Posted

Mean

Standard Deviation

pg/mL

Predose on day 12 and at the following postdose time points on day 12: 0.25, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 16, 24, 168, 216 and 264 hour(s)

ID	Title	Description
OG000	Buprenorphine/Naloxone	Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
OG001	ASP8062 in Combination With Buprenorphine/Naloxone	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.

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Buprenorphine/Naloxone	Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.	23	23	16	23
EG001	ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)	Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.	12	12	6	12
EG002	ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)	Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of ASP8062 concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.	12	12	7	12
EG003	Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)	Participants received multiple sublingual doses of buprenorphine/naloxone on days 12 through 18. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12.	6	6	6	6
EG004	Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)	Participants received multiple sublingual doses of buprenorphine/naloxone on days 19 through 26. After randomization on day 12, participants received a single oral dose of Placebo concomitantly with buprenorphine/naloxone and underwent repeat intensive safety assessment on day 12. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.	6	6	2	6

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Constipation	Gastrointestinal disorders	MedDRA v23.	Systematic Assessment	EG0004 events4 affected23 at risk EG0010 events0 affected12 at risk EG0020 events0 affected12 at risk EG0032 events2 affected6 at risk EG0040 events0 affected6 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA v23.	Systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected12 at risk EG0021 events1 affected12 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA v23.	Systematic Assessment	EG0001 events1 affected23 at risk EG0010 events0 affected12 at risk EG0020 events0 affected12 at risk EG003
Salivary hypersecretion	Gastrointestinal disorders	MedDRA v23.	Systematic Assessment	EG0000 events0 affected23 at risk EG0011 events1 affected12 at risk EG0020 events0 affected12 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA v23.	Systematic Assessment	EG0001 events1 affected23 at risk EG0011 events1 affected12 at risk EG0020 events0 affected12 at risk EG003
Asthenia	General disorders	MedDRA v23.	Systematic Assessment	EG0000 events0 affected23 at risk EG0011 events1 affected12 at risk EG0020 events0 affected12 at risk EG003
Drug withdrawal syndrome	General disorders	MedDRA v23.	Systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected12 at risk EG0023 events3 affected12 at risk EG003
Feeling of relaxation	General disorders	MedDRA v23.	Systematic Assessment	EG0000 events0 affected23 at risk EG0011 events1 affected12 at risk EG0020 events0 affected12 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA v23.	Systematic Assessment	EG0004 events4 affected23 at risk EG0010 events0 affected12 at risk EG0020 events0 affected12 at risk EG003
Muscle twitching	Musculoskeletal and connective tissue disorders	MedDRA v23.	Systematic Assessment	EG0000 events0 affected23 at risk EG0011 events1 affected12 at risk EG0020 events0 affected12 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA v23.	Systematic Assessment	EG0002 events2 affected23 at risk EG0010 events0 affected12 at risk EG0020 events0 affected12 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA v23.	Systematic Assessment	EG0002 events2 affected23 at risk EG0011 events1 affected12 at risk EG0020 events0 affected12 at risk EG003
Dizziness	Nervous system disorders	MedDRA v23.	Systematic Assessment	EG0000 events0 affected23 at risk EG0011 events1 affected12 at risk EG0020 events0 affected12 at risk EG003
Headache	Nervous system disorders	MedDRA v23.	Systematic Assessment	EG00013 events8 affected23 at risk EG0015 events4 affected12 at risk EG0023 events2 affected12 at risk EG003
Somnolence	Nervous system disorders	MedDRA v23.	Systematic Assessment	EG0001 events1 affected23 at risk EG0011 events1 affected12 at risk EG0020 events0 affected12 at risk EG003
Anxiety	Psychiatric disorders	MedDRA v23.	Systematic Assessment	EG0003 events3 affected23 at risk EG0010 events0 affected12 at risk EG0020 events0 affected12 at risk EG003
Insomnia	Psychiatric disorders	MedDRA v23.	Systematic Assessment	EG0006 events5 affected23 at risk EG0010 events0 affected12 at risk EG0021 events1 affected12 at risk EG003
Nervousness	Psychiatric disorders	MedDRA v23.	Systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected12 at risk EG0020 events0 affected12 at risk EG003
Dysuria	Renal and urinary disorders	MedDRA v23.	Systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected12 at risk EG0021 events1 affected12 at risk EG003
Pollakiuria	Renal and urinary disorders	MedDRA v23.	Systematic Assessment	EG0000 events0 affected23 at risk EG0011 events1 affected12 at risk EG0020 events0 affected12 at risk EG003
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA v23.	Systematic Assessment	EG0000 events0 affected23 at risk EG0011 events1 affected12 at risk EG0020 events0 affected12 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA v23.	Systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected12 at risk EG0020 events0 affected12 at risk EG003
Phlebitis	Vascular disorders	MedDRA v23.	Systematic Assessment	EG0000 events0 affected23 at risk EG0011 events1 affected12 at risk EG0020 events0 affected12 at risk EG003

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

ID	Term
D002047	Buprenorphine
D009019	Morphinans
D053610	Opiate Alkaloids
D000470	Alkaloids
D006571	Heterocyclic Compounds
D009270	Naloxone
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
D004338	Drug Combinations
D004364	Pharmaceutical Preparations

ID	Title	Description
BG000	Buprenorphine/Naloxone	Participants received multiple sublingual doses of buprenorphine/naloxone on days 1 through 26. Participants were on a stable daily dose of buprenorphine/naloxone on days 5 through 18. The stable dose of buprenorphine/naloxone was down titrated from days 19 through 26.
BG001	ASP8062 in Combination With Buprenorphine/Naloxone	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.
BG002	Placebo ASP8062 in Combination With Buprenorphine/Naloxone	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.
BG003	Total	Total of all reporting groups

ID	Term
C000709210	ASP8062
D000069479	Buprenorphine, Naloxone Drug Combination