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

NCT04818086 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: HM20021136UG1DA050207
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to test the safety, tolerability, drug interactions with buprenorphine-naloxone, and effectiveness lemborexant when used to treat Opioid Use Disorder.

Conditions

Drug Interaction; Analgesics; Opioid Use Disorder

Outcome Measures

Primary Outcomes (18)

• Change in Pulse Oximetry During the Baseline Visit

  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.

  Baseline visit (Safety measure)

• Change in Pulse Oximetry During Week 1 Visit

  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)

  Week 1 visit, safety measure

• Change in Pulse Oximetry During Week 2 Visit

  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.

  Week 2 visit, safety measure

• Change in Blood Pressure During Baseline Study Visit

  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.

  Baseline Visit, safety measure

• Change in Blood Pressure During Week 1 Study Visit

  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.

  Week 1 visit, safety measure

• Change in Blood Pressure During Week 2 Study Visit

  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.

  Week 2 visit, safety measure

• Change in Patient Consciousness During the Baseline Visit

  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.

  Baseline visit, safety measure

• Change in Patient Consciousness During the Week 1 Study Visit

  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.

  Week 1 visit, safety measure

• Change in Patient Consciousness

  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.

  Week 2 visit, safety measure

• Change in Buprenorphine Plasma Concentration (PK) During the Baseline Visit

  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.

  Baseline visit

• Change in Buprenorphine Plasma Concentration (PK) During Week 1 Study Visit

  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.

  Week 1

• Change in Buprenorphine Plasma Concentration (PK) During Week 2 Study Visit

  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.

  Week 2

• Change in Lemborexant PK During Baseline Study Visit

  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.

  Baseline visit

• Change in Lemborexant PK During Week 1 Study Visit

  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.

  Week 1 visit

• Change in Lemborexant PK During Week 2 Study Visit

  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.

  Week 2 visit

• Change in Respiration During the Baseline Study Visit (Pre- to Post-dose)

  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.

  Baseline visit

• Change in Respiration During the Week 1 Study Visit (Pre- to Post-dose)

  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

  Week 1 visit

• Change in Respiration During Week 2 Study Visit (From Pre- to Post-dose)

  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.

  Week 2 visit

Secondary Outcomes (13)

• Change in Drug Effects During Baseline Study Visit (Pre- to Post- Dose)

  Baseline visit

• Change in Drug Effects During Week 1 Study Visit (Pre- to Post- Dose)

  Week 1 visit

• Change in Drug Effects During Week 2 Study Visit (Pre- to Post Dose)

  Week 2 visit

• Change in Opioid Craving During Each Visit (Pre- to Post- Dose)

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

• Change in Opioid Withdrawal Effects During Baseline Visit (Pre- to Post- Dose)

  Baseline visit

Study Arms (2)

Lemborexant Arm

ACTIVE COMPARATOR

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.

Drug: Lemborexant; Drug: Buprenorphine-naloxone

Placebo Arm

PLACEBO COMPARATOR

Comparative placebo combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film (at both Time 1 and Time 2)

Drug: Placebo; Drug: Buprenorphine-naloxone

Interventions

Lemborexant DRUG

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).

Also known as: Dayvigo

Lemborexant Arm

Placebo DRUG

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 is encapsulated to look the same as the intervention drug.

Placebo Arm

Buprenorphine-naloxone DRUG

Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.

Lemborexant Arm; Placebo Arm

Eligibility Criteria

• Age: 18 Years - 65 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females between 18 - 65 years-of-age;
• Understand the study procedures and provide written informed consent in English language;
• Meet current DSM-5 criteria for opioid use disorder, of at least moderate severity, currently engaged medication assisted treatment at a buprenorphine-naloxone sublingual film daily dose ranging from 8mg/2mg to 24mg/6mg or buprenorphine sublingual tablet 5.7mg/1.4mg to 17.1/4.3 once daily for at least last 2 weeks;
• Have a positive urine drug screen for buprenorphine during screening and on admission to the clinical research unit to document buprenorphine use;
• Have a Pittsburgh Sleep Quality Index (PSQI) Total Score of 6 or higher.

You may not qualify if:

• Contraindications for participation as determined by medical history and physical exam performed by study NP or study physician;
• Pregnant or nursing women;
• Baseline ECG with clinically significant abnormal conduction;
• Taking prescription or over-the counter drugs or dietary supplements known to significantly inhibit CYP3A4 (such as Clarithromycin, telithromycin, nefazodone, itraconazole, ketoconazole, atazanavir, darunavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir), or CYP3A4 inducers (such as phenobarbital, phenytoin, rifampicin, St. John's Wort, and glucocorticoids);
• Prescribed medications for insomnia, or unable to discontinue over the counter drugs or dietary supplements used to treat insomnia on study days.
• Current severe alcohol use disorder or current benzodiazepine use disorder
• Any previous medically adverse reaction to opioids or lemborexant:
• Significant current suicidal or homicidal ideation (C-SSRS "yes" answers on questions 4 or 5) or a history of suicide attempt within the past 6 months.
• Subjects with Suicidal Behaviors Questionnaire-Revised score ≥8 at the screening visit.
• Any other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.

Sponsors & Collaborators

• Virginia Commonwealth University: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

lemborexant; Buprenorphine, Naloxone Drug Combination

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Buprenorphine; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Naloxone; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: Dr. Frederick Gerald Moeller
• Organization: Virginia Commonwealth University

fgmoeller@vcu.edu

804-828-4134

Study Officials

• Frederick G Moeller, MD

  Virginia Commonwealth University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2021
• First Posted: March 26, 2021
• Study Start: May 3, 2021
• Primary Completion: April 20, 2023
• Study Completion: April 20, 2023
• Last Updated: November 13, 2024
• Results First Posted: November 13, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)