A Study to Assess the Effect of a Single Dose of ASP8062 on the Multiple Dose Safety, Tolerability and Pharmacokinetics of Buprenorphine/Naloxone in Participants With Opioid Use Disorder

Sponsor

Astellas Pharma Global Development, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT04447287

Collaborator

National Institute on Drug Abuse (NIDA) (NIH)

Enrollment

Location

Arms

4.9

Actual Duration (Months)

4.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary purpose of this study was to assess the safety and tolerability of multiple doses of buprenorphine/naloxone alone and buprenorphine/naloxone in combination with a single dose of ASP8062.

This study also assessed the potential for pharmacokinetic interaction between ASP8062 and buprenorphine/naloxone.

Condition or Disease	Intervention/Treatment	Phase
Opioid Use Disorder	Drug: ASP8062 Drug: Placebo ASP8062 Drug: buprenorphine/naloxone	Phase 1

Detailed Description

Participants were screened for up to 28 days prior to first investigational product (IP) administration. Eligible participants were admitted to the clinical unit on day -1 and were residential for a single period of 27 days/26 nights.

Participants were discharged from the clinical unit after completion of down-titration on the condition that all required assessments were performed and that there were no medical reasons for a longer stay in the clinical unit; which was the end-of-study visit (ESV). Prior to discharge, participants were provided with local buprenorphine and methadone providers for their reference.

Study Design

Study Type:

Interventional

Actual Enrollment :

23 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

Phase 1b Randomized, Placebo-controlled Study to Assess the Effect of a Single Dose of ASP8062 on the Multiple Dose Safety, Tolerability and Pharmacokinetics of Buprenorphine/Naloxone in Subjects With Opioid Use Disorder

Actual Study Start Date :

Jun 29, 2020

Actual Primary Completion Date :

Nov 25, 2020

Actual Study Completion Date :

Nov 25, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: ASP8062 Oral Drug: buprenorphine/naloxone Sublingual Other Names: Suboxone®
Placebo Comparator: 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.	Drug: Placebo ASP8062 Oral Drug: buprenorphine/naloxone Sublingual Other Names: Suboxone®

Arm

Intervention/Treatment

Experimental: 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.

Drug: ASP8062

Oral

Drug: buprenorphine/naloxone

Sublingual

Other Names:

Suboxone®

Placebo Comparator: 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.

Drug: Placebo ASP8062

Oral

Drug: buprenorphine/naloxone

Sublingual

Other Names:

Suboxone®

Outcome Measures

Primary Outcome Measures

Number of Participants With Adverse Events (AEs) [From first dose of study drug up to end of study visit (up to day 27)]
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.
Number of Participants With Suicidal Ideation and/or Suicidal Behavior as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) [Up to day 27]
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.
Change From Baseline in Blood Oxygen Saturation (SpO2) at Predose ['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]
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.
Change From Baseline in Blood Oxygen Saturation (SpO2) at 1 Hour Postdose ['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]
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.
Change From Baseline in Blood Oxygen Saturation (SpO2) at 2 Hour Postdose ['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]
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.
Change From Baseline in Blood Oxygen Saturation (SpO2) at 4 Hour Postdose ['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]
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.
Change From Baseline in Blood Oxygen Saturation (SpO2) at 8 Hour Postdose ['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]
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.
Change From Baseline in Blood Oxygen Saturation (SpO2) at 12 Hour Postdose ['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]
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.
Change From Baseline in End Tidal Carbon Dioxide (CO2) at Predose ['ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone': Baseline and predose Day 12]
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'.
Change From Baseline in End Tidal Carbon Dioxide (CO2) at 1 Hour Postdose ['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]
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'.
Change From Baseline in End Tidal Carbon Dioxide (CO2) at 2 Hour Postdose ['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]
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'.
Change From Baseline in End Tidal Carbon Dioxide (CO2) at 4 Hour Postdose ['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]
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'.
Change From Baseline in End Tidal Carbon Dioxide (CO2) at 8 Hour Postdose ['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]
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'.

Secondary Outcome Measures

Pharmacokinetics (PK) of ASP8062 in Plasma: Area Under the Concentration-time Curve From the Time of Dosing Extrapolated to Time Infinity (AUCinf) [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)]
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.
Pharmacokinetics (PK) of ASP8062 in Plasma: Area Under the Concentration-time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) [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)]
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.
Pharmacokinetics (PK) of ASP8062 in Plasma: Maximum Concentration (Cmax) [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)]
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.
Pharmacokinetics (PK) of Buprenorphine in Plasma: Area Under the Concentration-time Curve From the Time of Dosing to 24 Hours (AUC24) [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)]
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.
Pharmacokinetics (PK) of Buprenorphine in Plasma: Cmax [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)]
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.
Pharmacokinetics (PK) of Norbuprenorphine (Buprenorphine's Metabolite) in Plasma: AUC24 [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)]
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.
Pharmacokinetics (PK) of Norbuprenorphine (Buprenorphine's Metabolite) in Plasma: Cmax [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)]
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.
Pharmacokinetics (PK) of Naloxone in Plasma: AUC24 [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)]
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.
Pharmacokinetics (PK) of Naloxone in Plasma: Cmax [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)]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Altasciences Clinical Kansas, Inc.	Overland Park	Kansas	United States	66212

Sponsors and Collaborators

Astellas Pharma Global Development, Inc.
National Institute on Drug Abuse (NIDA)

Investigators

Study Director: Executive Medical Director, Astellas Pharma Global Development, Inc.

Study Documents (Full-Text)

Study Protocol and Statistical Analysis Plan - Jul 29, 2020

More Information

Publications

None provided.

Responsible Party:

Astellas Pharma Global Development, Inc.

ClinicalTrials.gov Identifier:

NCT04447287

Other Study ID Numbers:

8062-CL-2003
UG3DA051392

First Posted:

Jun 25, 2020

Last Update Posted:

Jan 12, 2022

Last Verified:

Dec 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Astellas Pharma Global Development, Inc.

Suboxone®

Opioid Use Disorder

buprenorphine/naloxone

ASP8062

pharmacokinetic

Additional relevant MeSH terms:

Disease

Opioid-Related Disorders

Substance-Related Disorders

Buprenorphine

Buprenorphine, Naloxone Drug Combination

ASP8062

Naloxone

Study Results

Participant Flow

Recruitment Details

Participants who had opioid use disorder (OUD) were enrolled in this study. Participants were enrolled in one site in the United States.

Pre-assignment Detail

Participants were randomized using a 2:1 ratio. Eligible participants who met inclusion criteria and none of the exclusion criteria were enrolled. A total of 74 participants entered the screening process and out of which 56 discontinued prior to randomization. Prior to randomization, participants entered a run-in period. A total of 23 participants entered the run-in period and 19 completed, 1 participant completed the run-in period but discontinued before randomization.

Arm/Group Title	Buprenorphine/Naloxone	ASP8062 in Combination With Buprenorphine/Naloxone	Placebo ASP8062 in Combination With Buprenorphine/Naloxone
Arm/Group Description	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.	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.	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.
Period Title: Period 1: Run-in Period
STARTED	23	0	0
COMPLETED	19	0	0
NOT COMPLETED	4	0	0
Period Title: Period 1: Run-in Period
STARTED	1	12	6
COMPLETED	0	12	6
NOT COMPLETED	1	0	0
Period Title: Period 1: Run-in Period
STARTED	0	12	6
COMPLETED	0	12	6
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Buprenorphine/Naloxone	ASP8062 in Combination With Buprenorphine/Naloxone	Placebo ASP8062 in Combination With Buprenorphine/Naloxone	Total
Arm/Group Description	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.	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.	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.	Total of all reporting groups
Overall Participants	5	12	6	23
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	41.4 (5.2)	40.2 (9.2)	43.2 (10.3)	41.2 (8.5)
Sex: Female, Male (Count of Participants)
Female	2 40%	3 25%	2 33.3%	7 30.4%
Male	3 60%	9 75%	4 66.7%	16 69.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	5 100%	12 100%	6 100%	23 100%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	4 80%	7 58.3%	5 83.3%	16 69.6%
White	1 20%	5 41.7%	1 16.7%	7 30.4%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Blood Oxygen Saturation (SpO2) (percentage of oxygen saturation) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of oxygen saturation]	98.2 (0.8)	97.8 (1.9)	97.8 (1.2)	97.9 (1.5)
End Tidal Carbon Dioxide (CO2) (millimeter of mercury (mmHg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [millimeter of mercury (mmHg)]	40 (0)	40.4 (4.1)	38.2 (5.1)	39.7 (4.3)

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events (AEs)
Description	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.
Time Frame	From first dose of study drug up to end of study visit (up to day 27)

Outcome Measure Data

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

Arm/Group Title	Buprenorphine/Naloxone (Run-in Period)	ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)	ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)	Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)	Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	23	12	12	6	6
TEAE	16 320%	6 50%	7 116.7%	6 26.1%	2 NaN
Drug-Related TEAE	12 240%	6 50%	5 83.3%	6 26.1%	1 NaN
Serious TEAE	0 0%	0 0%	0 0%	0 0%	0 NaN
Drug-Related Serious TEAE	0 0%	0 0%	0 0%	0 0%	0 NaN
TEAE Leading to Death	0 0%	0 0%	0 0%	0 0%	0 NaN
Drug-Related TEAE Leading to Death	0 0%	0 0%	0 0%	0 0%	0 NaN
TEAE Leading to Withdrawal of Treatment	0 0%	0 0%	0 0%	0 0%	0 NaN
Drug-Related TEAE Leading to Withdrawal of Treatment	0 0%	0 0%	0 0%	0 0%	0 NaN
Death	0 0%	0 0%	0 0%	0 0%	0 NaN

2. Primary Outcome

Title	Number of Participants With Suicidal Ideation and/or Suicidal Behavior as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)
Description	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.
Time Frame	Up to day 27

Outcome Measure Data

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

Arm/Group Title	Buprenorphine/Naloxone (Run-in Period)	ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)	ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)	Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)	Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	23	12	12	6	6
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%	0 NaN

3. Primary Outcome

Title	Change From Baseline in Blood Oxygen Saturation (SpO2) at Predose
Description	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.
Time Frame	'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

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Buprenorphine/Naloxone (Run-in Period)	ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)	Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
Arm/Group Description	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.	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.	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.
Measure Participants	18	11	6
Mean (Standard Deviation) [Percentage of oxygen saturation]	0.2 (2.1)	-0.4 (2.3)	-0.3 (1.9)

4. Primary Outcome

Title	Change From Baseline in Blood Oxygen Saturation (SpO2) at 1 Hour Postdose
Description	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.
Time Frame	'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

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Buprenorphine/Naloxone (Run-in Period)	ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)	Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
Arm/Group Description	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.	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.	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.
Measure Participants	18	11	6
Mean (Standard Deviation) [Percentage of oxygen saturation]	0.1 (2.5)	-0.6 (2.6)	-0.7 (2.3)

5. Primary Outcome

Title	Change From Baseline in Blood Oxygen Saturation (SpO2) at 2 Hour Postdose
Description	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.
Time Frame	'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

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Buprenorphine/Naloxone (Run-in Period)	ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)	Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
Arm/Group Description	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.	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.	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.
Measure Participants	18	11	6
Mean (Standard Deviation) [Percentage of oxygen saturation]	0.2 (2.2)	-0.8 (2.0)	0.3 (1.8)

6. Primary Outcome

Title	Change From Baseline in Blood Oxygen Saturation (SpO2) at 4 Hour Postdose
Description	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.
Time Frame	'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

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Buprenorphine/Naloxone (Run-in Period)	ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)	Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
Arm/Group Description	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.	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.	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.
Measure Participants	18	11	6
Mean (Standard Deviation) [Percentage of oxygen saturation]	0.3 (1.9)	-0.4 (1.7)	-0.2 (1.2)

7. Primary Outcome

Title	Change From Baseline in Blood Oxygen Saturation (SpO2) at 8 Hour Postdose
Description	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.
Time Frame	'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

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Buprenorphine/Naloxone (Run-in Period)	ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)	Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
Arm/Group Description	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.	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.	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.
Measure Participants	18	11	6
Mean (Standard Deviation) [Percentage of oxygen saturation]	0.1 (2.3)	-0.1 (2.4)	0.7 (1.6)

8. Primary Outcome

Title	Change From Baseline in Blood Oxygen Saturation (SpO2) at 12 Hour Postdose
Description	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.
Time Frame	'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

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Buprenorphine/Naloxone (Run-in Period)	ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)	Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
Arm/Group Description	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.	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.	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.
Measure Participants	18	11	6
Mean (Standard Deviation) [Percentage of oxygen saturation]	-0.6 (1.8)	-0.3 (2.5)	-0.5 (0.8)

9. Primary Outcome

Title	Change From Baseline in End Tidal Carbon Dioxide (CO2) at Predose
Description	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'.
Time Frame	'ASP8062 in combination with buprenorphine/naloxone' and 'Placebo ASP8062 in combination with buprenorphine/naloxone': Baseline and predose Day 12

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)	Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
Arm/Group Description	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.	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.
Measure Participants	12	6
Mean (Standard Deviation) [mmHg]	-1.3 (4.0)	0.5 (6.1)

10. Primary Outcome

Title	Change From Baseline in End Tidal Carbon Dioxide (CO2) at 1 Hour Postdose
Description	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'.
Time Frame	'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

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Buprenorphine/Naloxone (Run-in Period)	ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)	Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
Arm/Group Description	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.	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.	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.
Measure Participants	19	12	6
Mean (Standard Deviation) [mmHg]	1.3 (5.8)	-0.5 (4.0)	3.7 (7.2)

11. Primary Outcome

Title	Change From Baseline in End Tidal Carbon Dioxide (CO2) at 2 Hour Postdose
Description	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'.
Time Frame	'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

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Buprenorphine/Naloxone (Run-in Period)	ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)	Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
Arm/Group Description	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.	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.	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.
Measure Participants	19	12	6
Mean (Standard Deviation) [mmHg]	1.2 (5.1)	0.3 (3.2)	4.2 (5.0)

12. Primary Outcome

Title	Change From Baseline in End Tidal Carbon Dioxide (CO2) at 4 Hour Postdose
Description	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'.
Time Frame	'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

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Buprenorphine/Naloxone (Run-in Period)	ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)	Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
Arm/Group Description	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.	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.	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.
Measure Participants	18	12	6
Mean (Standard Deviation) [mmHg]	0.9 (4.9)	-1.0 (2.3)	5.3 (7.9)

13. Primary Outcome

Title	Change From Baseline in End Tidal Carbon Dioxide (CO2) at 8 Hour Postdose
Description	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'.
Time Frame	'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

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Buprenorphine/Naloxone (Run-in Period)	ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)	Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
Arm/Group Description	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.	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.	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.
Measure Participants	18	12	6
Mean (Standard Deviation) [mmHg]	3.1 (4.1)	1.4 (1.9)	6.0 (5.7)

14. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	ASP8062 in Combination With Buprenorphine/Naloxone
Arm/Group Description	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.
Measure Participants	12
Mean (Standard Deviation) [h*ng/mL]	4450 (1750)

15. Secondary Outcome

Title	Pharmacokinetics (PK) of ASP8062 in Plasma: Area Under the Concentration-time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast)
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	ASP8062 in Combination With Buprenorphine/Naloxone
Arm/Group Description	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.
Measure Participants	12
Mean (Standard Deviation) [h*ng/mL]	4270 (1620)

16. Secondary Outcome

Title	Pharmacokinetics (PK) of ASP8062 in Plasma: Maximum Concentration (Cmax)
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	ASP8062 in Combination With Buprenorphine/Naloxone
Arm/Group Description	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.
Measure Participants	12
Mean (Standard Deviation) [ng/mL]	152 (36.7)

17. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Buprenorphine/Naloxone	ASP8062 in Combination With Buprenorphine/Naloxone	Placebo ASP8062 in Combination With Buprenorphine/Naloxone
Arm/Group Description	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.	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.	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.
Measure Participants	15	12	6
Mean (Standard Deviation) [h*pg/mL]	63800 (20300)	53500 (18300)	67700 (18700)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Buprenorphine/Naloxone (Run-in Period), ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Geometric LS Mean Ratio
	Estimated Value	89.72
	Confidence Interval	(2-Sided) 90% 81.21 to 99.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

18. Secondary Outcome

Title	Pharmacokinetics (PK) of Buprenorphine in Plasma: Cmax
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Buprenorphine/Naloxone	ASP8062 in Combination With Buprenorphine/Naloxone	Placebo ASP8062 in Combination With Buprenorphine/Naloxone
Arm/Group Description	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.	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.	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.
Measure Participants	18	12	6
Mean (Standard Deviation) [pg/mL]	7790 (3280)	6790 (3230)	8440 (2200)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Buprenorphine/Naloxone (Run-in Period), ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Geometric LS Mean Ratio
	Estimated Value	92.15
	Confidence Interval	(2-Sided) 90% 80.22 to 105.86
	Parameter Dispersion	Type: Value:
	Estimation Comments

19. Secondary Outcome

Title	Pharmacokinetics (PK) of Norbuprenorphine (Buprenorphine's Metabolite) in Plasma: AUC24
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Buprenorphine/Naloxone	ASP8062 in Combination With Buprenorphine/Naloxone	Placebo ASP8062 in Combination With Buprenorphine/Naloxone
Arm/Group Description	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.	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.	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.
Measure Participants	15	12	6
Mean (Standard Deviation) [h*pg/mL]	97600 (49200)	96200 (45700)	104000 (43600)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Buprenorphine/Naloxone (Run-in Period), ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Geometric LS Mean Ratio
	Estimated Value	109.09
	Confidence Interval	(2-Sided) 90% 101.10 to 117.71
	Parameter Dispersion	Type: Value:
	Estimation Comments

20. Secondary Outcome

Title	Pharmacokinetics (PK) of Norbuprenorphine (Buprenorphine's Metabolite) in Plasma: Cmax
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Buprenorphine/Naloxone	ASP8062 in Combination With Buprenorphine/Naloxone	Placebo ASP8062 in Combination With Buprenorphine/Naloxone
Arm/Group Description	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.	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.	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.
Measure Participants	18	12	6
Mean (Standard Deviation) [pg/mL]	5260 (2350)	6060 (2870)	5730 (1930)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Buprenorphine/Naloxone (Run-in Period), ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Geometric LS Mean Ratio
	Estimated Value	117.77
	Confidence Interval	(2-Sided) 90% 106.41 to 130.34
	Parameter Dispersion	Type: Value:
	Estimation Comments

21. Secondary Outcome

Title	Pharmacokinetics (PK) of Naloxone in Plasma: AUC24
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Buprenorphine/Naloxone	ASP8062 in Combination With Buprenorphine/Naloxone	Placebo ASP8062 in Combination With Buprenorphine/Naloxone
Arm/Group Description	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.	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.	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.
Measure Participants	16	12	6
Mean (Standard Deviation) [h*pg/mL]	1270 (656)	1060 (624)	1090 (379)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Buprenorphine/Naloxone (Run-in Period), ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Geometric LS Mean Ratio
	Estimated Value	79.39
	Confidence Interval	(2-Sided) 90% 68.10 to 92.55
	Parameter Dispersion	Type: Value:
	Estimation Comments

22. Secondary Outcome

Title	Pharmacokinetics (PK) of Naloxone in Plasma: Cmax
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Buprenorphine/Naloxone	ASP8062 in Combination With Buprenorphine/Naloxone	Placebo ASP8062 in Combination With Buprenorphine/Naloxone
Arm/Group Description	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.	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.	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.
Measure Participants	18	12	6
Mean (Standard Deviation) [pg/mL]	464 (355)	382 (284)	363 (160)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Buprenorphine/Naloxone (Run-in Period), ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Geometric LS Mean Ratio
	Estimated Value	74.45
	Confidence Interval	(2-Sided) 90% 59.28 to 93.50
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

	Buprenorphine/Naloxone		ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)		ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)		Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)		Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
Time Frame	From first dose of study drug up to end of study visit (up to day 27)
Adverse Event Reporting Description

Arm/Group Title	Buprenorphine/Naloxone		ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)		ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)		Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)		Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
Arm/Group Description	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.		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.		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.		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.		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.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/12 (0%)		0/12 (0%)		0/6 (0%)		0/6 (0%)
Serious Adverse Events
	Buprenorphine/Naloxone		ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)		ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)		Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)		Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/12 (0%)		0/12 (0%)		0/6 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Buprenorphine/Naloxone		ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)		ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)		Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Investigational Period)		Placebo ASP8062 in Combination With Buprenorphine/Naloxone (Down-titration Period)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/23 (69.6%)		6/12 (50%)		7/12 (58.3%)		6/6 (100%)		2/6 (33.3%)
Gastrointestinal disorders
Constipation	4/23 (17.4%)	4	0/12 (0%)	0	0/12 (0%)	0	2/6 (33.3%)	2	0/6 (0%)	0
Dyspepsia	0/23 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1	1/6 (16.7%)	1	0/6 (0%)	0
Nausea	1/23 (4.3%)	1	0/12 (0%)	0	0/12 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0
Salivary hypersecretion	0/23 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Vomiting	1/23 (4.3%)	1	1/12 (8.3%)	1	0/12 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
General disorders
Asthenia	0/23 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Drug withdrawal syndrome	0/23 (0%)	0	0/12 (0%)	0	3/12 (25%)	3	0/6 (0%)	0	0/6 (0%)	0
Feeling of relaxation	0/23 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	4/23 (17.4%)	4	0/12 (0%)	0	0/12 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Muscle twitching	0/23 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Musculoskeletal pain	2/23 (8.7%)	2	0/12 (0%)	0	0/12 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0
Neck pain	2/23 (8.7%)	2	1/12 (8.3%)	1	0/12 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Nervous system disorders
Dizziness	0/23 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Headache	8/23 (34.8%)	13	4/12 (33.3%)	5	2/12 (16.7%)	3	3/6 (50%)	4	2/6 (33.3%)	4
Somnolence	1/23 (4.3%)	1	1/12 (8.3%)	1	0/12 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Psychiatric disorders
Anxiety	3/23 (13%)	3	0/12 (0%)	0	0/12 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Insomnia	5/23 (21.7%)	6	0/12 (0%)	0	1/12 (8.3%)	1	0/6 (0%)	0	0/6 (0%)	0
Nervousness	0/23 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0
Renal and urinary disorders
Dysuria	0/23 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1	0/6 (0%)	0	0/6 (0%)	0
Pollakiuria	0/23 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Skin and subcutaneous tissue disorders
Hyperhidrosis	0/23 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Pruritus	0/23 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0
Vascular disorders
Phlebitis	0/23 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0	0/6 (0%)	0	0/6 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Institute and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data. Sponsor must receive a site's manuscript prior to publication for review and comment as specified in the Investigator Agreement.

Results Point of Contact

Name/Title	Clinical Trial Disclosure
Organization	Astellas Pharma Global Development, Inc.
Phone	800-888-7704
Email	astellas.resultsdisclosure@astellas.com

Responsible Party:

Astellas Pharma Global Development, Inc.

ClinicalTrials.gov Identifier:

NCT04447287

Other Study ID Numbers:

8062-CL-2003
UG3DA051392

First Posted:

Jun 25, 2020

Last Update Posted:

Jan 12, 2022

Last Verified:

Dec 1, 2021

A Study to Assess the Effect of a Single Dose of ASP8062 on the Multiple Dose Safety, Tolerability and Pharmacokinetics of Buprenorphine/Naloxone in Participants With Opioid Use Disorder

Study Details

Study Description

Brief Summary

Detailed Description

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Eligibility Criteria

Criteria

Inclusion Criteria:

Exclusion Criteria:

Contacts and Locations

Locations

Sponsors and Collaborators

Investigators

Study Documents (Full-Text)

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Publications

Study Results

Participant Flow

Baseline Characteristics

Outcome Measures

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Adverse Events

All Cause Mortality

Serious Adverse Events

Other (Not Including Serious) Adverse Events

Limitations/Caveats

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Results Point of Contact