Efficacy and Safety of Lemborexant for Patients With Cirrhosis and Sleep Problems

Safety and Efficacy of Lemborexant for Patients With Cirrhosis and Sleep Problems: a Randomized Clinical Trial

Sleep disturbance poses significant in patients with liver cirrhosis and is associated with impaired quality of life and worsening clinical status. Current pharmacological options remain limited and often have safety concerns due to altered hepatic metabolism. Lemborexant, a dual orexin receptor antagonist, promotes physiological sleep by inhibiting orexin-mediated wakefulness pathways. This study aims to evaluate the efficacy and safety of lemborexant for improving sleep in patients with liver cirrhosis.

Study Overview

• Status: Completed
• Conditions: Liver Cirrhosis; Hepatic Encephalopathy; Insomnia; Cirrhosis; Sleep Quality
• Intervention / Treatment: Drug: Lemborexant; Drug: Placebo

Detailed Description

Patients with liver cirrhosis frequently experience sleep-wake disturbances such as insomnia, delayed sleep onset, or fragmented sleep. These disturbances may contribute to neurocognitive dysfunction and precipitate hepatic encephalopathy. However, conventional hypnotics such as benzodiazepines may worsen encephalopathy and are generally avoided.

Lemborexant selectively antagonizes orexin receptors OX1R and OX2R, modulating sleep without profound respiratory suppression or GABAergic effects. This randomized, three-armed, double-blind placebo-controlled trial aims to determine whether lemborexant improves sleep quality in patients with cirrhosis while maintaining acceptable neurocognitive and safety outcomes.

• Study Type: Interventional
• Enrollment (Actual): 82
• Phase: Phase 2

Contacts and Locations

Study Locations

• Indonesia
  • DKI Jakarta
    • Jakarta, DKI Jakarta, Indonesia, 10430
      • Hepatobiliary Division, Internal Medicine Department, Dr Cipto Mangunkusumo National General Hospital, Faculty of Medicine Universitas Indonesia, Jakarta

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• adults aged 18 years or older;
• willingness to participate in the clinical trial as evidenced by written informed consent; documented diagnosis of liver cirrhosis in the medical record, with disease severity assessed using the Child-Pugh score and supported by imaging findings consistent with cirrhosis on FibroScan or ultrasonography;
• presence of sleep disturbance defined by a Pittsburgh Sleep Quality Index (PSQI) score greater than 5;
• patients receiving inpatient or outpatient care at Cipto Mangunkusumo National General Hospital;
• ability to take oral medication;
• willingness of the patient or caregiver to maintain a sleep diary throughout the study period;
• ability of the patient or caregiver to comply with the clinical trial protocol and complete scheduled serial assessments.

Exclusion Criteria:

• advanced liver cirrhosis defined as Child-Pugh class C;
• current use of medications with significant interactions affecting the metabolism of Lemborexant, including itraconazole, clarithromycin, fluconazole, verapamil, tramadol, rifampicin, carbamazepine, bosentan, efavirenz, etravirine, and modafinil;
• ongoing alcohol consumption or intake of grapefruit juice during the study period;
• pregnancy, breastfeeding, or plans to become pregnant during the study;
• presence of significant comorbid conditions such as autoimmune disease,
• stage V chronic kidney disease, HIV/AIDS, or known or suspected hypersensitivity to the investigational drug;
• concurrent participation in another clinical trial at the time of screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 5 mg lemborexant; Lemborexant 5 mg orally once nightly before bedtime	Drug: Lemborexant; Lemborexant 5 mg orally once nightly before bedtime/ Lemborexant 10 mg orally once nightly before bedtime,
Experimental: 10 mg lemborexant; Lemborexant 10 mg orally once nightly before bedtime	Drug: Lemborexant; Lemborexant 5 mg orally once nightly before bedtime/ Lemborexant 10 mg orally once nightly before bedtime,
Placebo Comparator: Placebo; Placebo orally once nightly before bedtime	Drug: Placebo; Matching placebo taken orally once nightly before bedtime.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sleep quality	PSQI score	From enrollment to the end of treatment at 2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hepatic Encephalopathy - Stroop Test	Stroop Test Score	From enrollment to the end of treatment at 2 weeks
Liver function tests	Liver function tests including ALT, AST, and total bilirubin levels	From enrollment to the end of treatment at 2 weeks
Persistence of effects (sleep quality)	PSQI score	PSQI changes post-crossover at week 2 - week 4

Collaborators and Investigators

• Sponsor: Indonesia University
• Investigators: Principal Investigator: Rino Alvani Gani, Professor, Internist, MD, Hepatobiliary Division, Internal Medicine Department, Dr Cipto Mangunkusumo National General Hospital, Faculty of Medicine Universitas Indonesia, Jakarta; Study Director: Pitt Akbar, MD, Internist, Hepatobiliary Division, Internal Medicine Department, Dr Cipto Mangunkusumo National General Hospital, Faculty of Medicine Universitas Indonesia, Jakarta

Publications and helpful links

General Publications

• Marjot T, Ray DW, Williams FR, Tomlinson JW, Armstrong MJ. Sleep and liver disease: a bidirectional relationship. Lancet Gastroenterol Hepatol. 2021 Oct;6(10):850-863. doi: 10.1016/S2468-1253(21)00169-2. Epub 2021 Jul 15.
• Karppa M, Yardley J, Pinner K, Filippov G, Zammit G, Moline M, Perdomo C, Inoue Y, Ishikawa K, Kubota N. Long-term efficacy and tolerability of lemborexant compared with placebo in adults with insomnia disorder: results from the phase 3 randomized clinical trial SUNRISE 2. Sleep. 2020 Sep 14;43(9):zsaa123. doi: 10.1093/sleep/zsaa123.
• Rosenberg R, Murphy P, Zammit G, Mayleben D, Kumar D, Dhadda S, Filippov G, LoPresti A, Moline M. Comparison of Lemborexant With Placebo and Zolpidem Tartrate Extended Release for the Treatment of Older Adults With Insomnia Disorder: A Phase 3 Randomized Clinical Trial. JAMA Netw Open. 2019 Dec 2;2(12):e1918254. doi: 10.1001/jamanetworkopen.2019.18254.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2024
• Primary Completion (Actual): October 30, 2025
• Study Completion (Actual): October 30, 2025

Study Registration Dates

• First Submitted: March 13, 2026
• First Submitted That Met QC Criteria: March 13, 2026
• First Posted (Actual): March 18, 2026

Study Record Updates

• Last Update Posted (Actual): March 18, 2026
• Last Update Submitted That Met QC Criteria: March 13, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: safety; sleep; insomnia; efficacy; cirrhosis; liver; sleep quality; orexin; lemborexant
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Pathologic Processes; Metabolic Diseases; Digestive System Diseases; Liver Diseases; Sleep Wake Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Brain Diseases, Metabolic; Liver Failure; Hepatic Insufficiency; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Fibrosis; Sleep Initiation and Maintenance Disorders; Liver Cirrhosis; Hepatic Encephalopathy; lemborexant
• Other Study ID Numbers: 24-11-1690

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data underlying the results reported in the publication, including baseline characteristics, as well as efficacy and safety outcome measures.
• IPD Sharing Time Frame: Beginning 6 months after publication and ending 5 years after publication.
• IPD Sharing Access Criteria: Data will be available to investigators whose proposed use of the data has been approved by the study investigators following submission of a methodologically sound research proposal and completion of a data-sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No