Trial Outcomes & Findings for Drug-drug Interaction Study of Lemborexant as an Adjunctive Treatment for Buprenorphine/Naloxone for Opioid Use Disorder (NCT NCT04818086)

Results Overview

A finger pulse oximeter will be used to assess oxygen saturation (%). Change is calculated from the pulse oximetry readings from pre to post medication/placebo dose administered during the baseline study visit, this is a safety measure.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

18 participants

Primary outcome timeframe

Baseline visit (Safety measure)

Results posted on

2024-11-13

Participant Flow

Participant milestones

Participant milestones
Measure	Lemborexant Arm Study Drug Dosage: 5 mg of lemborexant (Time 1) , and 10 mg of lemborexant (Time 2) combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film. Lemborexant: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive 5 mg of lemborexant (first visit) and 10 mg of lemborexant (second visit). Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.	Placebo Arm Comparative placebo combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film (at both Time 1 and Time 2) Placebo: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive a placebo which matches the intervention drug. Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.
Overall Study STARTED	12	6
Overall Study COMPLETED	11	5
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Lemborexant Arm Study Drug Dosage: 5 mg of lemborexant (Time 1) , and 10 mg of lemborexant (Time 2) combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film. Lemborexant: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive 5 mg of lemborexant (first visit) and 10 mg of lemborexant (second visit). Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.	Placebo Arm Comparative placebo combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film (at both Time 1 and Time 2) Placebo: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive a placebo which matches the intervention drug. Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.
Overall Study Physician Decision	1	0
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Drug-drug Interaction Study of Lemborexant as an Adjunctive Treatment for Buprenorphine/Naloxone for Opioid Use Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lemborexant Arm n=12 Participants Study Drug Dosage: 5 mg of lemborexant (Time 1) , and 10 mg of lemborexant (Time 2) combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film. Lemborexant: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive 5 mg of lemborexant (first visit) and 10 mg of lemborexant (second visit). Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.	Placebo Arm n=6 Participants Comparative placebo combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film (at both Time 1 and Time 2) Placebo: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive a placebo which matches the intervention drug. Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.	Total n=18 Participants Total of all reporting groups
Age, Continuous	37.3 years STANDARD_DEVIATION 7.3 • n=5 Participants	44.3 years STANDARD_DEVIATION 14 • n=7 Participants	39.6 years STANDARD_DEVIATION 10.2 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	0 Participants n=7 Participants	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	11 Participants n=5 Participants	6 Participants n=7 Participants	17 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) White	9 Participants n=5 Participants	2 Participants n=7 Participants	11 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	12 participants n=5 Participants	6 participants n=7 Participants	18 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline visit (Safety measure)

Population: Baseline

A finger pulse oximeter will be used to assess oxygen saturation (%). Change is calculated from the pulse oximetry readings from pre to post medication/placebo dose administered during the baseline study visit, this is a safety measure.

Outcome measures

Outcome measures
Measure	Lemborexant Arm n=12 Participants Study Drug Dosage: 5 mg of lemborexant (Time 1) , and 10 mg of lemborexant (Time 2) combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film. Lemborexant: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive 5 mg of lemborexant (first visit) and 10 mg of lemborexant (second visit). Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.	Placebo Arm n=6 Participants Comparative placebo combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film (at both Time 1 and Time 2) Placebo: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive a placebo which matches the intervention drug. Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.
Change in Pulse Oximetry During the Baseline Visit	-0.17 percentage of oxygen saturation Standard Deviation .94	-0.33 percentage of oxygen saturation Standard Deviation .82

PRIMARY outcome

Timeframe: Week 1 visit, safety measure

Population: Week 1

A finger pulse oximeter will be used to asses pulse oximetry. Change is calculated from the pulse oximetry readings from pre to post medication/placebo dose administered during the study visit (safety measure)

Outcome measures

Outcome measures
Measure	Lemborexant Arm n=12 Participants Study Drug Dosage: 5 mg of lemborexant (Time 1) , and 10 mg of lemborexant (Time 2) combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film. Lemborexant: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive 5 mg of lemborexant (first visit) and 10 mg of lemborexant (second visit). Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.	Placebo Arm n=6 Participants Comparative placebo combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film (at both Time 1 and Time 2) Placebo: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive a placebo which matches the intervention drug. Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.
Change in Pulse Oximetry During Week 1 Visit	-0.17 percentage of oxygen saturation Standard Deviation 1.94	-0.50 percentage of oxygen saturation Standard Deviation 1.05

PRIMARY outcome

Timeframe: Week 2 visit, safety measure

Population: Week 2

A finger pulse oximeter will be used to assess pulse oximetry. Change is calculated from the pulse oximetry readings from pre to post medication/placebo dose administered during the study visit. This is a safety measure.

Outcome measures

Outcome measures
Measure	Lemborexant Arm n=11 Participants Study Drug Dosage: 5 mg of lemborexant (Time 1) , and 10 mg of lemborexant (Time 2) combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film. Lemborexant: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive 5 mg of lemborexant (first visit) and 10 mg of lemborexant (second visit). Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.	Placebo Arm n=5 Participants Comparative placebo combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film (at both Time 1 and Time 2) Placebo: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive a placebo which matches the intervention drug. Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.
Change in Pulse Oximetry During Week 2 Visit	-0.27 percentage of oxygen saturation Standard Deviation 1.49	-0.20 percentage of oxygen saturation Standard Deviation 0.84

PRIMARY outcome

Timeframe: Baseline Visit, safety measure

Population: Baseline

Blood Pressure measured with an automatic BP cuff. Change is calculated from the blood pressure readings from pre to post medication/placebo dose administered during the study visit. This is a safety measure.

Outcome measures

Outcome measures
Measure	Lemborexant Arm n=12 Participants Study Drug Dosage: 5 mg of lemborexant (Time 1) , and 10 mg of lemborexant (Time 2) combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film. Lemborexant: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive 5 mg of lemborexant (first visit) and 10 mg of lemborexant (second visit). Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.	Placebo Arm n=6 Participants Comparative placebo combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film (at both Time 1 and Time 2) Placebo: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive a placebo which matches the intervention drug. Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.
Change in Blood Pressure During Baseline Study Visit	-9.42 mmHg (millimeters of mercury) Standard Deviation 10.40	-2.50 mmHg (millimeters of mercury) Standard Deviation 12.29

PRIMARY outcome

Timeframe: Week 1 visit, safety measure

Population: Week 1

Blood Pressure measured with an automatic BP cuff. Change is calculated from the blood pressure readings from pre to post medication/placebo dose administered during the study visit. This is a safety measure.

Outcome measures

Outcome measures
Measure	Lemborexant Arm n=12 Participants Study Drug Dosage: 5 mg of lemborexant (Time 1) , and 10 mg of lemborexant (Time 2) combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film. Lemborexant: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive 5 mg of lemborexant (first visit) and 10 mg of lemborexant (second visit). Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.	Placebo Arm n=6 Participants Comparative placebo combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film (at both Time 1 and Time 2) Placebo: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive a placebo which matches the intervention drug. Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.
Change in Blood Pressure During Week 1 Study Visit	-6.58 mmHg (millimeters of mercury) Standard Deviation 6.64	-4.50 mmHg (millimeters of mercury) Standard Deviation 5.68

PRIMARY outcome

Timeframe: Week 2 visit, safety measure

Population: Week 2

Blood Pressure measured with an automatic BP cuff. Change is calculated from the blood pressure readings from pre to post medication/placebo dose administered during the study visit. This is a safety measure.

Outcome measures

Outcome measures
Measure	Lemborexant Arm n=11 Participants Study Drug Dosage: 5 mg of lemborexant (Time 1) , and 10 mg of lemborexant (Time 2) combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film. Lemborexant: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive 5 mg of lemborexant (first visit) and 10 mg of lemborexant (second visit). Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.	Placebo Arm n=5 Participants Comparative placebo combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film (at both Time 1 and Time 2) Placebo: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive a placebo which matches the intervention drug. Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.
Change in Blood Pressure During Week 2 Study Visit	1.09 mmHg (millimeters of mercury) Standard Deviation 12.85	-3.60 mmHg (millimeters of mercury) Standard Deviation 8.53

PRIMARY outcome

Timeframe: Baseline visit, safety measure

Population: Baseline

The Richmond Agitation Sedation Scale (RASS) measures level of patient consciousness on a 10 point scale ranging from plus +4 (combative/agitated) to minus 5 (unarousable/sedated). Change is calculated from the RASS assessment scores obtained from pre to post medication/placebo dose administered during the study visit. This is a safety measure. RASS is one of the most commonly used scales to determine the sedation level, and it measures the severity of agitation and sedation with a score of +4 to -5: +4: combative, +3: very agitated, +2: agitated, +1: restless, 0: alert and calm, -1: drowsy, -2: light sedation, -3: moderate sedation, -4: deep sedation, and -5 unarousable. A positive score is preferable to a negative score.

Outcome measures

Outcome measures
Measure	Lemborexant Arm n=12 Participants Study Drug Dosage: 5 mg of lemborexant (Time 1) , and 10 mg of lemborexant (Time 2) combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film. Lemborexant: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive 5 mg of lemborexant (first visit) and 10 mg of lemborexant (second visit). Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.	Placebo Arm n=6 Participants Comparative placebo combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film (at both Time 1 and Time 2) Placebo: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive a placebo which matches the intervention drug. Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.
Change in Patient Consciousness During the Baseline Visit	-0.17 score on a scale Standard Deviation 0.39	0 score on a scale Standard Deviation .63

PRIMARY outcome

Timeframe: Week 1 visit, safety measure

Population: week 1

The Richmond Agitation Sedation Scale (RASS) measures level of patient consciousness on a 10 point scale ranging from plus 4 (combative/agitated) to minus 5 (unarousable/sedated).Change is calculated from the RASS assessment scores obtained from pre to post medication/placebo dose administered during the study visit. This is a safety measure. RASS is one of the most commonly used scales to determine the sedation level, and it measures the severity of agitation and sedation with a score of +4 to -5: +4: combative, +3: very agitated, +2: agitated, +1: restless, 0: alert and calm, -1: drowsy, -2: light sedation, -3: moderate sedation, -4: deep sedation, and -5 unarousable. A positive score is preferable to a negative score.

Outcome measures

Outcome measures
Measure	Lemborexant Arm n=12 Participants Study Drug Dosage: 5 mg of lemborexant (Time 1) , and 10 mg of lemborexant (Time 2) combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film. Lemborexant: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive 5 mg of lemborexant (first visit) and 10 mg of lemborexant (second visit). Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.	Placebo Arm n=6 Participants Comparative placebo combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film (at both Time 1 and Time 2) Placebo: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive a placebo which matches the intervention drug. Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.
Change in Patient Consciousness During the Week 1 Study Visit	0.00 score on a scale Standard Deviation 0.60	0.33 score on a scale Standard Deviation 0.52

PRIMARY outcome

Timeframe: Week 2 visit, safety measure

Population: week 2

The Richmond Agitation Sedation Scale (RASS) measures level of patient consciousness on a 10 point scale ranging from plus 4 (combative/agitated) to minus 5 (unarousable/sedated). Change is calculated from the RASS assessment scores obtained from pre to post medication/placebo dose administered during the study visit. This is a safety measure. RASS is one of the most commonly used scales to determine the sedation level, and it measures the severity of agitation and sedation with a score of +4 to -5: +4: combative, +3: very agitated, +2: agitated, +1: restless, 0: alert and calm, -1: drowsy, -2: light sedation, -3: moderate sedation, -4: deep sedation, and -5 unarousable. A positive score is preferable to a negative score.

Outcome measures

Outcome measures
Measure	Lemborexant Arm n=11 Participants Study Drug Dosage: 5 mg of lemborexant (Time 1) , and 10 mg of lemborexant (Time 2) combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film. Lemborexant: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive 5 mg of lemborexant (first visit) and 10 mg of lemborexant (second visit). Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.	Placebo Arm n=5 Participants Comparative placebo combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film (at both Time 1 and Time 2) Placebo: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive a placebo which matches the intervention drug. Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.
Change in Patient Consciousness	-0.18 score on a scale Standard Deviation 0.87	-0.20 score on a scale Standard Deviation 0.45

PRIMARY outcome

Timeframe: Baseline visit

Population: Baseline

Blood will be drawn pre-dose and at specific time points (8, 8:30, 10, 12 and 4pm) to determine the area under the plasma concentration-time curve for buprenorphine.

Outcome measures

Outcome measures
Measure	Lemborexant Arm n=12 Participants Study Drug Dosage: 5 mg of lemborexant (Time 1) , and 10 mg of lemborexant (Time 2) combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film. Lemborexant: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive 5 mg of lemborexant (first visit) and 10 mg of lemborexant (second visit). Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.	Placebo Arm Comparative placebo combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film (at both Time 1 and Time 2) Placebo: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive a placebo which matches the intervention drug. Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.
Change in Buprenorphine Plasma Concentration (PK) During the Baseline Visit	0.26 Nanograms/milliliter (ng/mL) Standard Deviation 0.29	—

PRIMARY outcome

Timeframe: Week 1

Population: Week 1

Blood will be drawn pre-dose and at specific time points (8, 8:30, 10, 12 and 4pm) to determine the area under the plasma concentration-time curve for buprenorphine.

Outcome measures

Outcome measures
Measure	Lemborexant Arm n=12 Participants Study Drug Dosage: 5 mg of lemborexant (Time 1) , and 10 mg of lemborexant (Time 2) combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film. Lemborexant: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive 5 mg of lemborexant (first visit) and 10 mg of lemborexant (second visit). Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.	Placebo Arm Comparative placebo combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film (at both Time 1 and Time 2) Placebo: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive a placebo which matches the intervention drug. Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.
Change in Buprenorphine Plasma Concentration (PK) During Week 1 Study Visit	0.15 Nanograms/milliliter (ng/mL) Standard Deviation 0.18	—

PRIMARY outcome

Timeframe: Week 2

Population: Week 2

Blood will be drawn pre-dose and at specific time points (8, 8:30, 10, 12 and 4pm) to determine the area under the plasma concentration-time curve for buprenorphine.

Outcome measures

Outcome measures
Measure	Lemborexant Arm n=11 Participants Study Drug Dosage: 5 mg of lemborexant (Time 1) , and 10 mg of lemborexant (Time 2) combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film. Lemborexant: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive 5 mg of lemborexant (first visit) and 10 mg of lemborexant (second visit). Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.	Placebo Arm Comparative placebo combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film (at both Time 1 and Time 2) Placebo: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive a placebo which matches the intervention drug. Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.
Change in Buprenorphine Plasma Concentration (PK) During Week 2 Study Visit	0.12 Nanograms/milliliter (ng/mL) Standard Deviation 0.18	—

PRIMARY outcome

Timeframe: Baseline visit

Population: Lemborexant serum levels are not provided as the detailed methods for lemborexant level determination are proprietary and we do not have access to those methods. Hence, we are not able to provide the lemborexant levels. Currently, we have no pathway to obtain the lorcaserin PK results. The reason for that is the methods used for the original lorcaserin human PK testing are proprietary and we would have to re-do all of that research ourselves, which is outside the scope of what we are able to do.

Blood will be drawn pre-dose and at specific time points (8, 8:30, 10, 12 and 4pm) to determine the peak plasma concentration for Lemborexant. Currently, we have no pathway to obtain the lorcaserin PK results. The reason for that is the methods used for the original lorcaserin human PK testing are proprietary and we would have to re-do all of that research ourselves, which is outside the scope of what we are able to do.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Week 1 visit

Population: Lemborexant serum levels are not provided as the detailed methods for lemborexant level determination are proprietary and we do not have access to those methods. Hence, we are not able to provide the lemborexant levels. Currently, we have no pathway to obtain the lorcaserin PK results. The reason for that is the methods used for the original lorcaserin human PK testing are proprietary and we would have to re-do all of that research ourselves, which is outside the scope of what we are able to do.

Blood will be drawn pre-dose and at specific time points (8, 8:30, 10, 12 and 4pm) to determine the area under the plasma concentration-time curve for Lemborexant. Currently, we have no pathway to obtain the lorcaserin PK results. The reason for that is the methods used for the original lorcaserin human PK testing are proprietary and we would have to re-do all of that research ourselves, which is outside the scope of what we are able to do.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Week 2 visit

Population: Lemborexant serum levels are not provided as the detailed methods for lemborexant level determination are proprietary and we do not have access to those methods. Hence, we are not able to provide the lemborexant levels. Currently, we have no pathway to obtain the lorcaserin PK results. The reason for that is the methods used for the original lorcaserin human PK testing are proprietary and we would have to re-do all of that research ourselves, which is outside the scope of what we are able to do.

Blood will be drawn pre-dose and at specific time points (8, 8:30, 10, 12 and 4pm) to determine the peak plasma concentration for Lemborexant. Currently, we have no pathway to obtain the lorcaserin PK results. The reason for that is the methods used for the original lorcaserin human PK testing are proprietary and we would have to re-do all of that research ourselves, which is outside the scope of what we are able to do.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Baseline visit

Population: Baseline

Respiration will be measured with End Title CO2( EtC02) which is a measure of CO2 (measured in millimeters of mercury, "mmHg") plotted against time. Participants will wear a mask which will be connected to a Capnographer. End Title CO2 should be between 35-45 mmHg with box wave form.

Outcome measures

Outcome measures
Measure	Lemborexant Arm n=12 Participants Study Drug Dosage: 5 mg of lemborexant (Time 1) , and 10 mg of lemborexant (Time 2) combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film. Lemborexant: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive 5 mg of lemborexant (first visit) and 10 mg of lemborexant (second visit). Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.	Placebo Arm n=6 Participants Comparative placebo combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film (at both Time 1 and Time 2) Placebo: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive a placebo which matches the intervention drug. Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.
Change in Respiration During the Baseline Study Visit (Pre- to Post-dose)	1.0 mmHg (millimeters of mercury) Standard Deviation 4.18	1.40 mmHg (millimeters of mercury) Standard Deviation 3.65

PRIMARY outcome

Timeframe: Week 1 visit

Population: Week 1

Respiration will be measured with End Title CO2( EtC02) which is a measure of CO2 (measured in millimeters of mercury, "mmHg") plotted against time. Participants will wear a mask which will be connected to a Capnographer. End Title CO2 should be between 35-45 mmHg with box wave form

Outcome measures

Outcome measures
Measure	Lemborexant Arm n=12 Participants Study Drug Dosage: 5 mg of lemborexant (Time 1) , and 10 mg of lemborexant (Time 2) combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film. Lemborexant: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive 5 mg of lemborexant (first visit) and 10 mg of lemborexant (second visit). Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.	Placebo Arm n=6 Participants Comparative placebo combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film (at both Time 1 and Time 2) Placebo: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive a placebo which matches the intervention drug. Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.
Change in Respiration During the Week 1 Study Visit (Pre- to Post-dose)	1.67 millimeters of mercury (mmHg) Standard Deviation 2.46	0.50 millimeters of mercury (mmHg) Standard Deviation 8.80

PRIMARY outcome

Timeframe: Week 2 visit

Population: Week 2

Respiration will be measured with End Title CO2( EtC02) which is a measure of CO2 (measured in millimeters of mercury, "mmHg") plotted against time. Participants will wear a mask which will be connected to a Capnographer. End Title CO2 should be between 35-45 mmHg with box wave form.

Outcome measures

Outcome measures
Measure	Lemborexant Arm n=11 Participants Study Drug Dosage: 5 mg of lemborexant (Time 1) , and 10 mg of lemborexant (Time 2) combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film. Lemborexant: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive 5 mg of lemborexant (first visit) and 10 mg of lemborexant (second visit). Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.	Placebo Arm n=5 Participants Comparative placebo combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film (at both Time 1 and Time 2) Placebo: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive a placebo which matches the intervention drug. Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.
Change in Respiration During Week 2 Study Visit (From Pre- to Post-dose)	2.18 mmHg (millimeters of mercury) Standard Deviation 3.28	1.60 mmHg (millimeters of mercury) Standard Deviation 1.52

SECONDARY outcome

Timeframe: Baseline visit

Population: Baseline

Drug effects will be assessed using the Drug Effects Questionnaire (DEQ). The DEQ is comprised of 11 items which assess physical effects of the drug. Participants rate each physical effect on a visual analog scale from "not at all" (0) to "extremely" (100). A higher score indicates greater drug effect. The Drug Effects Questionnaire (DEQ) is widely used in studies of acute subjective response (SR) to a variety of substances and assesses the extent to which participants (1) feel any substance effect(s), (2) feel high, (3) like the effects, (4) dislike the effects, and (5) want more of the substance using 100mm Visual Analog Scales.

Outcome measures

Outcome measures
Measure	Lemborexant Arm n=12 Participants Study Drug Dosage: 5 mg of lemborexant (Time 1) , and 10 mg of lemborexant (Time 2) combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film. Lemborexant: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive 5 mg of lemborexant (first visit) and 10 mg of lemborexant (second visit). Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.	Placebo Arm n=6 Participants Comparative placebo combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film (at both Time 1 and Time 2) Placebo: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive a placebo which matches the intervention drug. Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.
Change in Drug Effects During Baseline Study Visit (Pre- to Post- Dose)	21.0 score on a scale Standard Deviation 39.95	7.33 score on a scale Standard Deviation 8.91

SECONDARY outcome

Timeframe: Week 1 visit

Population: Week 1

Drug effects will be assessed using the Drug Effects Questionnaire (DEQ). The DEQ is comprised of 11 items which assess physical effects of the drug. Participants rate each physical effect on a visual analog scale from "not at all" (0) to "extremely" (100). A higher score indicates greater drug effect. The Drug Effects Questionnaire (DEQ) is widely used in studies of acute subjective response (SR) to a variety of substances and assesses the extent to which participants (1) feel any substance effect(s), (2) feel high, (3) like the effects, (4) dislike the effects, and (5) want more of the substance using 100mm Visual Analog Scales.

Outcome measures

Outcome measures
Measure	Lemborexant Arm n=12 Participants Study Drug Dosage: 5 mg of lemborexant (Time 1) , and 10 mg of lemborexant (Time 2) combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film. Lemborexant: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive 5 mg of lemborexant (first visit) and 10 mg of lemborexant (second visit). Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.	Placebo Arm n=6 Participants Comparative placebo combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film (at both Time 1 and Time 2) Placebo: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive a placebo which matches the intervention drug. Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.
Change in Drug Effects During Week 1 Study Visit (Pre- to Post- Dose)	14.50 score on a scale Standard Deviation 21.72	5.33 score on a scale Standard Deviation 35.83

SECONDARY outcome

Timeframe: Week 2 visit

Population: Week 2

Drug effects will be assessed using the Drug Effects Questionnaire (DEQ). The DEQ is comprised of 11 items which assess physical effects of the drug. Participants rate each physical effect on a visual analog scale from "not at all" (0) to "extremely" (100). A higher score indicates greater drug effect. The Drug Effects Questionnaire (DEQ) is widely used in studies of acute subjective response (SR) to a variety of substances and assesses the extent to which participants (1) feel any substance effect(s), (2) feel high, (3) like the effects, (4) dislike the effects, and (5) want more of the substance using 100mm Visual Analog Scales.

Outcome measures

Outcome measures
Measure	Lemborexant Arm n=11 Participants Study Drug Dosage: 5 mg of lemborexant (Time 1) , and 10 mg of lemborexant (Time 2) combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film. Lemborexant: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive 5 mg of lemborexant (first visit) and 10 mg of lemborexant (second visit). Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.	Placebo Arm n=5 Participants Comparative placebo combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film (at both Time 1 and Time 2) Placebo: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive a placebo which matches the intervention drug. Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.
Change in Drug Effects During Week 2 Study Visit (Pre- to Post Dose)	5.45 score on a scale Standard Deviation 41.31	18.00 score on a scale Standard Deviation 32.27

SECONDARY outcome

Timeframe: During each inpatient visit (baseline through week 2) from admission to discharge at each visit, up to 24 hours

Population: During each inpatient visit from admission to discharge, up to 24 hours (Baseline through week 2)

Opioid craving will be measured by a Brief Substance craving scale (BSCS). The BSCS is a 16 item, self-report instrument assesses craving for substances of abuse over a 24 hour period. Intensity and frequency of craving are recorded on a five-point Likert scale, with higher scores indicating greater craving. 0-none at all, 1- slight, 2-moderate, 3-considerable, 4-extreme.

Outcome measures

Outcome measures
Measure	Lemborexant Arm n=12 Participants Study Drug Dosage: 5 mg of lemborexant (Time 1) , and 10 mg of lemborexant (Time 2) combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film. Lemborexant: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive 5 mg of lemborexant (first visit) and 10 mg of lemborexant (second visit). Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.	Placebo Arm n=6 Participants Comparative placebo combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film (at both Time 1 and Time 2) Placebo: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive a placebo which matches the intervention drug. Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.
Change in Opioid Craving During Each Visit (Pre- to Post- Dose)	-025 score on a scale Standard Deviation 2.09	3.0 score on a scale Standard Deviation 8.0

SECONDARY outcome

Timeframe: Baseline visit

Population: Baseline

Opioid withdrawal symptoms will be measured with the Subjective Opioid Withdrawal Scale (SOWS). The SOWS contains 16 likert scaled items with participant rate from 0 (not at all), 1(slight), 2 (moderate), 3 (considerable) to 4 (Extreme). A higher score indicates higher opioid withdrawal effects (Range 0-64).

Outcome measures

Outcome measures
Measure	Lemborexant Arm n=12 Participants Study Drug Dosage: 5 mg of lemborexant (Time 1) , and 10 mg of lemborexant (Time 2) combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film. Lemborexant: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive 5 mg of lemborexant (first visit) and 10 mg of lemborexant (second visit). Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.	Placebo Arm n=6 Participants Comparative placebo combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film (at both Time 1 and Time 2) Placebo: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive a placebo which matches the intervention drug. Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.
Change in Opioid Withdrawal Effects During Baseline Visit (Pre- to Post- Dose)	-1.92 score on a scale Standard Deviation 2.39	-.033 score on a scale Standard Deviation 0.52

SECONDARY outcome

Timeframe: Week 1 visit

Population: Week 1

Opioid withdrawal symptoms will be measured with the Subjective Opioid Withdrawal Scale (SOWS). The SOWS contains 16 likert scaled items with participant rate from 0 (not at all), 1(slight), 2 (moderate), 3 (considerable) to 4 (Extremely). A higher score indicates higher opioid withdrawal effects(Range 0-64).

Outcome measures

Outcome measures
Measure	Lemborexant Arm n=12 Participants Study Drug Dosage: 5 mg of lemborexant (Time 1) , and 10 mg of lemborexant (Time 2) combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film. Lemborexant: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive 5 mg of lemborexant (first visit) and 10 mg of lemborexant (second visit). Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.	Placebo Arm n=6 Participants Comparative placebo combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film (at both Time 1 and Time 2) Placebo: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive a placebo which matches the intervention drug. Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.
Change in Opioid Withdrawal Effects During Week 1 Visit (Pre- to Post- Dose)	-0.25 score on a scale Standard Deviation 0.97	-0.17 score on a scale Standard Deviation 0.41

SECONDARY outcome

Timeframe: Week 2 visit

Population: Week 2

Opioid withdrawal symptoms will be measured with the Subjective Opioid Withdrawal Scale (SOWS). The SOWS contains 16 likert scaled items with participant rate from 0 (not at all), 1(slight), 2 (moderate), 3 (considerable) to 4 (Extremely). A higher score indicates higher opioid withdrawal effects (Range 0-64).

Outcome measures

Outcome measures
Measure	Lemborexant Arm n=11 Participants Study Drug Dosage: 5 mg of lemborexant (Time 1) , and 10 mg of lemborexant (Time 2) combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film. Lemborexant: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive 5 mg of lemborexant (first visit) and 10 mg of lemborexant (second visit). Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.	Placebo Arm n=5 Participants Comparative placebo combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film (at both Time 1 and Time 2) Placebo: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive a placebo which matches the intervention drug. Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.
Change in Opioid Withdrawal Effects During Week 2 Visit (Pre- to Post- Dose)	-0.45 score on a scale Standard Deviation 0.93	0 score on a scale Standard Deviation 0

SECONDARY outcome

Timeframe: Baseline visit

Population: Baseline

Participants will be assessed by research staff using the Clinical Opioid Withdrawal Scale (COWS) which consists of 11 items. A higher score indicates greater withdrawal effects. (COWS, range 0-48). 5-12=mild, 13-24=moderate, 25-36=moderate severe, and more than 36=severe withdrawal.

Outcome measures

Outcome measures
Measure	Lemborexant Arm n=12 Participants Study Drug Dosage: 5 mg of lemborexant (Time 1) , and 10 mg of lemborexant (Time 2) combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film. Lemborexant: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive 5 mg of lemborexant (first visit) and 10 mg of lemborexant (second visit). Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.	Placebo Arm n=6 Participants Comparative placebo combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film (at both Time 1 and Time 2) Placebo: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive a placebo which matches the intervention drug. Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.
Change in Objective Opioid Withdrawal During Baseline Study Visit (Pre- to Post- Dose)	-0.83 score on a scale Standard Deviation 1.19	-0.17 score on a scale Standard Deviation 0.98

SECONDARY outcome

Timeframe: Week 1 visit

Population: Week 1

Participants will be assessed by research staff using the Clinical Opioid Withdrawal Scale (COWS) which consists of 11 items. A higher score indicates greater withdrawal effects(COWS, range 0-48). 5-12=mild, 13-24=moderate, 25-36=moderate severe, and more than 36=severe withdrawal.

Outcome measures

Outcome measures
Measure	Lemborexant Arm n=12 Participants Study Drug Dosage: 5 mg of lemborexant (Time 1) , and 10 mg of lemborexant (Time 2) combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film. Lemborexant: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive 5 mg of lemborexant (first visit) and 10 mg of lemborexant (second visit). Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.	Placebo Arm n=6 Participants Comparative placebo combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film (at both Time 1 and Time 2) Placebo: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive a placebo which matches the intervention drug. Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.
Change in Objective Opioid Withdrawal During Week 1 Study Visit (Pre- to Post-dose)	-0.50 score on a scale Standard Deviation 1.09	-0.17 score on a scale Standard Deviation 0.41

SECONDARY outcome

Timeframe: Week 2 visit

Population: Week 2

Participants will be assessed by research staff using the Clinical Opioid Withdrawal Scale (COWS) which consists of 11 items. A higher score indicates greater withdrawal effects (COWS, range 0-48). 5-12=mild, 13-24=moderate, 25-36=moderate severe, and more than 36=severe withdrawal.

Outcome measures

Outcome measures
Measure	Lemborexant Arm n=11 Participants Study Drug Dosage: 5 mg of lemborexant (Time 1) , and 10 mg of lemborexant (Time 2) combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film. Lemborexant: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive 5 mg of lemborexant (first visit) and 10 mg of lemborexant (second visit). Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.	Placebo Arm n=5 Participants Comparative placebo combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film (at both Time 1 and Time 2) Placebo: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive a placebo which matches the intervention drug. Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.
Change in Objective Opioid Withdrawal During Week 2 Study Visit (Pre- to Post- Dose)	-0.27 score on a scale Standard Deviation 1.27	0 score on a scale Standard Deviation 0

SECONDARY outcome

Timeframe: Baseline visit

Population: Baseline

Impulsivity is measured by a delayed discounting task (DDT). Participants are presented with a series of choices and will choose to receive pretend money now or after a delay. The task yields a discounting rate. Higher discounting rates indicate greater impulsivity. Delay discounting, the tendency to choose small, immediate rewards over larger, delayed rewards is robustly associated with substance use. The longer the timeframe that the subject delays the rewards, the larger the reward.

Outcome measures

Outcome measures
Measure	Lemborexant Arm n=12 Participants Study Drug Dosage: 5 mg of lemborexant (Time 1) , and 10 mg of lemborexant (Time 2) combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film. Lemborexant: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive 5 mg of lemborexant (first visit) and 10 mg of lemborexant (second visit). Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.	Placebo Arm n=6 Participants Comparative placebo combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film (at both Time 1 and Time 2) Placebo: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive a placebo which matches the intervention drug. Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.
Impulsivity	55.73 score on a scale Standard Deviation 90.25	74.74 score on a scale Standard Deviation 51.31

SECONDARY outcome

Timeframe: Week 1 visit

Population: Week 1

Impulsivity is measured by a delayed discounting task (DDT). Participants are presented with a series of choices and will choose to receive pretend money now or after a delay. The task yields a discounting rate. Higher discounting rates indicate greater impulsivity. Delay discounting, the tendency to choose small, immediate rewards over larger, delayed rewards is robustly associated with substance use. The longer the timeframe that the subject delays the rewards, the larger the reward.

Outcome measures

Outcome measures
Measure	Lemborexant Arm n=12 Participants Study Drug Dosage: 5 mg of lemborexant (Time 1) , and 10 mg of lemborexant (Time 2) combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film. Lemborexant: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive 5 mg of lemborexant (first visit) and 10 mg of lemborexant (second visit). Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.	Placebo Arm n=6 Participants Comparative placebo combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film (at both Time 1 and Time 2) Placebo: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive a placebo which matches the intervention drug. Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.
Impulsivity	6.51 score on a scale Standard Deviation 76.73	22.92 score on a scale Standard Deviation 23.96

SECONDARY outcome

Timeframe: Week 2 visit

Population: Week 2

Impulsivity is measured by a delayed discounting task (DDT). Participants are presented with a series of choices and will choose to receive pretend money now or after a delay. The task yields a discounting rate. Higher discounting rates indicate greater impulsivity. Delay discounting, the tendency to choose small, immediate rewards over larger, delayed rewards is robustly associated with substance use. The longer the timeframe that the subject delays the rewards, the larger the reward.

Outcome measures

Outcome measures
Measure	Lemborexant Arm n=11 Participants Study Drug Dosage: 5 mg of lemborexant (Time 1) , and 10 mg of lemborexant (Time 2) combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film. Lemborexant: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive 5 mg of lemborexant (first visit) and 10 mg of lemborexant (second visit). Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.	Placebo Arm n=5 Participants Comparative placebo combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film (at both Time 1 and Time 2) Placebo: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive a placebo which matches the intervention drug. Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.
Impulsivity	-40.63 score on a scale Standard Deviation 126.27	-1.25 score on a scale Standard Deviation 9.47

Adverse Events

Lemborexant Arm

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Placebo Arm

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Lemborexant Arm n=12 participants at risk Study Drug Dosage: 5 mg of lemborexant (Time 1) , and 10 mg of lemborexant (Time 2) combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film. Lemborexant: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive 5 mg of lemborexant (first visit) and 10 mg of lemborexant (second visit). Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.	Placebo Arm n=6 participants at risk Comparative placebo combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film (at both Time 1 and Time 2) Placebo: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive a placebo which matches the intervention drug. Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.
Injury, poisoning and procedural complications Assaulted	0.00% 0/12 • Baseline to the end of the second week scheduled visit.	16.7% 1/6 • Number of events 1 • Baseline to the end of the second week scheduled visit.
Nervous system disorders tongue numbness	0.00% 0/12 • Baseline to the end of the second week scheduled visit.	16.7% 1/6 • Number of events 1 • Baseline to the end of the second week scheduled visit.
Gastrointestinal disorders Nausea/vomiting/diarrhea	8.3% 1/12 • Number of events 1 • Baseline to the end of the second week scheduled visit.	0.00% 0/6 • Baseline to the end of the second week scheduled visit.
Skin and subcutaneous tissue disorders Sweating	8.3% 1/12 • Number of events 1 • Baseline to the end of the second week scheduled visit.	0.00% 0/6 • Baseline to the end of the second week scheduled visit.
Psychiatric disorders Anxiety	8.3% 1/12 • Number of events 1 • Baseline to the end of the second week scheduled visit.	0.00% 0/6 • Baseline to the end of the second week scheduled visit.
Nervous system disorders sleep paralysis	8.3% 1/12 • Number of events 1 • Baseline to the end of the second week scheduled visit.	0.00% 0/6 • Baseline to the end of the second week scheduled visit.
Musculoskeletal and connective tissue disorders back/shoulder pain	8.3% 1/12 • Number of events 1 • Baseline to the end of the second week scheduled visit.	16.7% 1/6 • Number of events 1 • Baseline to the end of the second week scheduled visit.
Skin and subcutaneous tissue disorders skin/soft tissue irriatation	16.7% 2/12 • Number of events 2 • Baseline to the end of the second week scheduled visit.	16.7% 1/6 • Number of events 2 • Baseline to the end of the second week scheduled visit.
Musculoskeletal and connective tissue disorders arthritis flare	0.00% 0/12 • Baseline to the end of the second week scheduled visit.	16.7% 1/6 • Number of events 2 • Baseline to the end of the second week scheduled visit.

Additional Information

Dr. Frederick Gerald Moeller

Virginia Commonwealth University

Phone: 804-828-4134

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place