Clinical trial NCT04818086: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Drug Interaction
Analgesics
Opioid Use Disorder
Lead sponsor: Virginia Commonwealth University
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2021-03-26
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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:

1. Visit the CARI clinic and/or Motivate clinic at Jackson Center to complete study screening.
2. Visit the VCUHS Clinical Research Unit to complete an outpatient blood draw/testing visit.
3. Take either lemborexant or the placebo, depending upon which group subjects are assigned to.
4. Complete two (2) overnight study visits at the VCUHS Clinical Research Unit.
5. Complete 8 outpatient follow-up visits (broken into 2 four day visit groupings)
6. Have an EKG during screening and at each study visit (outpatient and inpatient)
7. Have an IV inserted into your arm for blood draws at the outpatient blood draw visit and each inpatient visit.
8. Record sleep in a sleep diary.
9. Take surveys and answer questions about health, mental health, medications used, drug use, and cravings.
10. Complete tasks on the computer.
11. Complete physical exams during screening, outpatient and inpatient visits.
12. 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.

Eligibility criteria: Inclusion Criteria:

1. Males and females between 18 - 65 years-of-age;
2. Understand the study procedures and provide written informed consent in English language;
3. 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;
4. Have a positive urine drug screen for buprenorphine during screening and on admission to the clinical research unit to document buprenorphine use;
5. Have a Pittsburgh Sleep Quality Index (PSQI) Total Score of 6 or higher.

Exclusion Criteria:

1. Contraindications for participation as determined by medical history and physical exam performed by study NP or study physician;
2. Pregnant or nursing women;
3. Baseline ECG with clinically significant abnormal conduction;
4. Uncontrolled serious psychiatric or major medical disorder, including COPD. Narcolepsy is also considered exclusionary;
5. 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);
6. Prescribed medications for insomnia, or unable to discontinue over the counter drugs or dietary supplements used to treat insomnia on study days.
7. Current severe alcohol use disorder or current benzodiazepine use disorder
8. 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.
9. Any previous medically adverse reaction to opioids or lemborexant:
10. 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.
11. Subjects with Suicidal Behaviors Questionnaire-Revised score ≥8 at the screening visit.
12. 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.

Primary outcomes:
measure: Change in Pulse Oximetry During the Baseline Visit
timeFrame: Baseline visit (Safety measure)
measure: Change in Pulse Oximetry During Week 1 Visit
timeFrame: Week 1 visit, safety measure
measure: Change in Pulse Oximetry During Week 2 Visit
timeFrame: Week 2 visit, safety measure
measure: Change in Blood Pressure During Baseline Study Visit
timeFrame: Baseline Visit, safety measure
measure: Change in Blood Pressure During Week 1 Study Visit
timeFrame: Week 1 visit, safety measure
measure: Change in Blood Pressure During Week 2 Study Visit
timeFrame: Week 2 visit, safety measure
measure: Change in Patient Consciousness During the Baseline Visit
timeFrame: Baseline visit, safety measure
measure: Change in Patient Consciousness During the Week 1 Study Visit
timeFrame: Week 1 visit, safety measure
measure: Change in Patient Consciousness
timeFrame: Week 2 visit, safety measure
measure: Change in Buprenorphine Plasma Concentration (PK) During the Baseline Visit
timeFrame: Baseline visit
measure: Change in Buprenorphine Plasma Concentration (PK) During Week 1 Study Visit
timeFrame: Week 1
measure: Change in Buprenorphine Plasma Concentration (PK) During Week 2 Study Visit
timeFrame: Week 2
measure: Change in Lemborexant PK During Baseline Study Visit
timeFrame: Baseline visit
measure: Change in Lemborexant PK During Week 1 Study Visit
timeFrame: Week 1 visit
measure: Change in Lemborexant PK During Week 2 Study Visit
timeFrame: Week 2 visit
measure: Change in Respiration During the Baseline Study Visit (Pre- to Post-dose)
timeFrame: Baseline visit
measure: Change in Respiration During the Week 1 Study Visit (Pre- to Post-dose)
timeFrame: Week 1 visit
measure: Change in Respiration During Week 2 Study Visit (From Pre- to Post-dose)
timeFrame: Week 2 visit
Secondary outcomes:
measure: Change in Drug Effects During Baseline Study Visit (Pre- to Post- Dose)
timeFrame: Baseline visit
measure: Change in Drug Effects During Week 1 Study Visit (Pre- to Post- Dose)
timeFrame: Week 1 visit
measure: Change in Drug Effects During Week 2 Study Visit (Pre- to Post Dose)
timeFrame: Week 2 visit
measure: Change in Opioid Craving During Each Visit (Pre- to Post- Dose)
timeFrame: During each inpatient visit (baseline through week 2) from admission to discharge at each visit, up to 24 hours
measure: Change in Opioid Withdrawal Effects During Baseline Visit (Pre- to Post- Dose)
timeFrame: Baseline visit
measure: Change in Opioid Withdrawal Effects During Week 1 Visit (Pre- to Post- Dose)
timeFrame: Week 1 visit
measure: Change in Opioid Withdrawal Effects During Week 2 Visit (Pre- to Post- Dose)
timeFrame: Week 2 visit
measure: Change in Objective Opioid Withdrawal During Baseline Study Visit (Pre- to Post- Dose)
timeFrame: Baseline visit
measure: Change in Objective Opioid Withdrawal During Week 1 Study Visit (Pre- to Post-dose)
timeFrame: Week 1 visit
measure: Change in Objective Opioid Withdrawal During Week 2 Study Visit (Pre- to Post- Dose)
timeFrame: Week 2 visit
measure: Impulsivity
timeFrame: Baseline visit
measure: Impulsivity
timeFrame: Week 1 visit
measure: Impulsivity
timeFrame: Week 2 visit
Other outcomes:
Locations:
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
Study officials:
affiliation: Virginia Commonwealth University
name: Frederick G Moeller, MD
role: PRINCIPAL_INVESTIGATOR
References: