Clinical Trials/NCT04447287

NCT04447287

Completed

Phase 1

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

Astellas Pharma Global Development, Inc.1 site in 1 country23 target enrollmentJune 29, 2020

ConditionsOpioid Use Disorder

InterventionsASP8062 buprenorphine/naloxone Placebo ASP8062

DrugsASP8062 Placebo ASP8062 buprenorphine/naloxone

Overview

Phase: Phase 1
Intervention: ASP8062
Conditions: Opioid Use Disorder
Sponsor: Astellas Pharma Global Development, Inc.
Enrollment: 23
Locations: 1
Primary Endpoint: Change From Baseline in Blood Oxygen Saturation (SpO2) at Predose
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

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.

Registry

clinicaltrials.gov

Start Date

June 29, 2020

End Date

November 25, 2020

Last Updated

last year

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Astellas Pharma Global Development, Inc.

Responsible Party

Sponsor

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 -
•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.

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 ASP
•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 -
•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.

Arms & Interventions

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.

Intervention: ASP8062

ASP8062 in combination with buprenorphine/naloxone

Intervention: buprenorphine/naloxone

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.

Intervention: Placebo ASP8062

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.

Intervention: buprenorphine/naloxone

Outcomes

Primary Outcomes

Change From Baseline in Blood Oxygen Saturation (SpO2) at Predose

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

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

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

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.

Number of Participants With Suicidal Ideation and/or Suicidal Behavior as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)

Time Frame: Up to day 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 12 Hour Postdose

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

Number of Participants With Adverse Events (AEs)

Time Frame: 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.

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

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

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

Change From Baseline in End Tidal Carbon Dioxide (CO2) at Predose

Time Frame: '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 4 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'.

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

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

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

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

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

Secondary Outcomes

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))
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))
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))
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))
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))
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))
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))
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))
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))