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

Primary Purpose

Drug Interaction, Analgesics, Opioid

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Lemborexant

Placebo

Buprenorphine-naloxone

About this trial

This is an interventional treatment trial for Drug Interaction

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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;
Uncontrolled serious psychiatric or major medical disorder, including COPD. Narcolepsy is also considered exclusionary;
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
Current DSM-5 diagnosis of any psychoactive substance use disorder other than opioids, cocaine, marijuana, or nicotine, or mild or moderate alcohol use disorder. Diagnosis of mild to moderate use disorder for alcohol will not be considered exclusionary.
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.

Sites / Locations

Virginia Commonwealth University

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Lemborexant Arm

Placebo Arm

Arm Description

Study Drug Dosage: 5 mg of lemborexant, and 10 mg of lemborexant combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.

Comparative placebo combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.

Outcomes

Primary Outcome Measures

Change in pulse oximetry

A finger pulse oximeter will be used to asses pulse oximetry.

Change in Blood Pressure

Blood Pressure measured with an automatic BP cuff.

Change in patient consciousness

The Richmond Agitation Sedation Scale (RASS) measures level of patient consciousness on a 10 point scale raging from plus 1 (combative/agitated) to minus 5 (unarousable/sedated).

Change in Buprenorphine Plasma Concentration (PK)

Blood will be drawn pre-dose and at specific time points to determine the area under the plasma concentration-time curve for buprenorphine.

Change in Lemborexant PK

Blood will be drawn pre-dose and at specific time points to determine the area under the plasma concentration-time curve for Lemborexant.

Change in respiration

Respiration will be measuring 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

Secondary Outcome Measures

Change in drug effects

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" to "extremely." A higher score indicates greater drug effect.

Change in opioid craving

Opioid craving will be measured by a Brief Substance craving scale (BSCS). The BSCS asks about the drug craving on a 5 point scale. A higher score indicates greater craving

Change in opioid withdrawal effects

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) to 4 (Extremely). A higher score indicates higher opioid withdrawal effects

Change in objective opioid withdrawal

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.

Impulsivity

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 higher impulsivity.

Full Information

NCT ID

NCT04818086

First Posted

March 23, 2021

Last Updated

May 8, 2023

Sponsor

Virginia Commonwealth University

Collaborators

National Institute on Drug Abuse (NIDA)

1. Study Identification

Unique Protocol Identification Number

NCT04818086

Brief Title

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

Official Title

Phase Ib/2a Drug-drug Interaction Study of Lemborexant as an Adjunctive Treatment for Buprenorphine/Naloxone for Opioid Use Disorder

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Completed

Study Start Date

May 3, 2021 (Actual)

Primary Completion Date

April 20, 2023 (Actual)

Study Completion Date

April 20, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Virginia Commonwealth University

Collaborators

National Institute on Drug Abuse (NIDA)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

5. Study Description

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.

Detailed Description

The purpose of this study is to test the effects of lemborexant when used in combination with opioids (including buprenorphine). We are also interested in learning lemborexant might help improve sleep problems and problems related to opioid use (e.g., cravings, withdrawal), in people with opioid use disorder. Study participants will be randomly assigned in a two to one ratio to receive either lemborexant or placebo. Lemborexant (DAYVIGO®) is approved by the U. S. Food and Drug Administration (FDA) for treatment of insomnia. In this study, Participants will be asked to do the following things: Visit the CARI clinic and/or Motivate clinic at Jackson Center to complete study screening. Visit the VCUHS Clinical Research Unit to complete an outpatient blood draw/testing visit. Take either lemborexant or the placebo, depending upon which group subjects are assigned to. Complete two (2) overnight study visits at the VCUHS Clinical Research Unit. Complete 8 outpatient follow-up visits (broken into 2 four day visit groupings) Have an EKG during screening and at each study visit (outpatient and inpatient) Have an IV inserted into your arm for blood draws at the outpatient blood draw visit and each inpatient visit. Record sleep in a sleep diary. Take surveys and answer questions about health, mental health, medications used, drug use, and cravings. Complete tasks on the computer. Complete physical exams during screening, outpatient and inpatient visits. Give permission for the researchers to collect information about opioid treatment, medical status, and other information from your medical record. Participation in this study will last approximately 4 weeks. Approximately 18 people will participate in the drug interaction phase of this study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Drug Interaction, Analgesics, Opioid

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

48 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Lemborexant Arm

Arm Type

Active Comparator

Arm Description

Study Drug Dosage: 5 mg of lemborexant, and 10 mg of lemborexant combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.

Arm Title

Placebo Arm

Arm Type

Placebo Comparator

Arm Description

Comparative placebo combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.

Intervention Type

Drug

Intervention Name(s)

Lemborexant

Other Intervention Name(s)

Dayvigo

Intervention Description

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).

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Buprenorphine-naloxone

Intervention Description

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

Primary Outcome Measure Information:

Title

Change in pulse oximetry

Description

A finger pulse oximeter will be used to asses pulse oximetry.

Time Frame