A Pilot Study of Mirabegron and Montelukast in Cirrhotic Patients

A Pilot Interventional Study to Evaluate the Safety and Tolerability of Mirabegron and Montelukast in Patients With Liver Cirrhosis

This study was a prospective, interventional, pilot clinical study conducted over 3 months on cirrhotic patients with overactive bladder and asthma, evaluating the real-world applicability of selected PBPK-guided dosing regimens. Patients were stratified according to Child-Pugh class (CP-A, CP-B, and CP-C) and administered mirabegron and montelukast at doses corresponding to the closest commercially available strengths to Simcyp®-optimized doses.

Clinical evaluation included number of incontinence episodes, number of micturation, volume voided per micturation, cough, and wheezing. Routine laboratory investigations were conducted to assess efficacy and safety and included liver function tests (serum albumin, total bilirubin, alanine aminotransferase [ALT], and aspartate aminotransferase [AST]), kidney function tests (serum creatinine and blood urea nitrogen [BUN]), and CBC.

Study Overview

• Status: Completed
• Conditions: Asthma; Cirrhosis
• Intervention / Treatment: Drug: Mirabegron 100 mg; Drug: Mirabegron 50mg; Drug: mirabegron 25 mg; Drug: Montelukast 10 mg; Drug: montelukast (5mg QD); Drug: montelukast 4 mg granule

Detailed Description

This study was a prospective, interventional, pilot clinical study conducted over 3 months on Egyptian cirrhotic patients with overactive bladder and asthma. Adult patients aged >18 years with confirmed liver cirrhosis, concomitant overactive bladder and asthma were eligible for inclusion. Patients were experienced acute episodes of disease associated with deterioration of hepatic function within 2 months prior to screening, and received concomitant medications known to strongly interact with the study drugs were excluded. In part 1: Mirabegron dosing was determined based on Simcyp -generated predictions and clinical assessment. 100mg,50 mg, 50 mg, and 25 mg received by control, CP-A, CP-B, and CP-C cirrhosis patients, respectively, orally once daily. In part 2: Montelukast dosing was determined based on Simcyp-generated predictions and clinical assessment. 10mg 5 mg,5 mg, and 4 mg received by control, and CP-A, CP-B, and CP-C cirrhosis patients, respectively, orally once daily. Clinical evaluation included number of incontinence episodes, number of micturation, volume voided per micturation, cough, and wheezing. Routine laboratory investigations were conducted to assess efficacy and safety and included liver function tests (serum albumin, total bilirubin, alanine aminotransferase [ALT],a aspartate aminotransferase [AST]), kidney function tests (serum creatinine and blood urea nitrogen [BUN]),and CBC.

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • Kafr el-Sheikh Governorate
    • Cairo, Kafr el-Sheikh Governorate, Egypt, 33511
      • Kafr El-sheikh University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Clinical diagnosis of hepatic impairment. Diagnosed with overactive bladder. Presence of asthma. Age of patients > 18 years.

Exclusion Criteria:

• Patients with kidney disorder or dialysis
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control -Standard Dose Mirabegron; Mirabegron 100 mg	Drug: Mirabegron 100 mg; Mirabegron is a sympathomimetic beta-3 adrenergic receptor agonist used to relax the smooth muscle of the bladder in the treatment of urinary frequency and incontinence.
Experimental: Mirabegron : Child-Pugh A; Mirabegron 50 mg	Drug: Mirabegron 50mg; Mirabegron is a sympathomimetic beta-3 adrenergic receptor agonist used to relax the smooth muscle of the bladder in the treatment of urinary frequency and incontinence.
Experimental: Mirabegron: Child-Pugh B; Mirabegron 50 mg	Drug: Mirabegron 50mg; Mirabegron is a sympathomimetic beta-3 adrenergic receptor agonist used to relax the smooth muscle of the bladder in the treatment of urinary frequency and incontinence.
Experimental: Mirabegron: Child-Pugh C; Mirabegron 25 mg	Drug: mirabegron 25 mg; Mirabegron is a sympathomimetic beta-3 adrenergic receptor agonist used to relax the smooth muscle of the bladder in the treatment of urinary frequency and incontinence.
Active Comparator: Control -Standard Dose Montelukast; Montelukast 10 mg	Drug: Montelukast 10 mg; Montelukast is a leukotriene receptor antagonist used as part of an asthma therapy regimen, to prevent exercise induced bronchoconstriction, and to treat seasonal allergic rhinitis.
Experimental: Montelukast: Child-Pugh A; Montelukast 5 mg	Drug: montelukast (5mg QD); Montelukast is a leukotriene receptor antagonist used as part of an asthma therapy regimen, to prevent exercise induced bronchoconstriction, and to treat seasonal allergic rhinitis.
Experimental: Montelukast: Child-Pugh B; Montelukast 5 mg	Drug: montelukast (5mg QD); Montelukast is a leukotriene receptor antagonist used as part of an asthma therapy regimen, to prevent exercise induced bronchoconstriction, and to treat seasonal allergic rhinitis.
Experimental: Montelukast: Child-Pugh C; Montelukast 4 mg	Drug: montelukast 4 mg granule; Montelukast is a leukotriene receptor antagonist used as part of an asthma therapy regimen, to prevent exercise induced bronchoconstriction, and to treat seasonal allergic rhinitis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in number of urinary incontinence episodes per 24 hours	The primary outcome will be the change from baseline in the number of urinary incontinence episodes recorded over 24 hours, assessed before and after treatment in the control and treatment groups. Urinary incontinence episodes will be documented using a 24-hour bladder diary.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Monitoring of Adverse Effects	Adverse effects including headache, dry mouth, abdominal pain, dizziness, hypertension, urinary tract infection will be recorded	3 months

Collaborators and Investigators

• Sponsor: Kafrelsheikh University
• Investigators: Principal Investigator: Aya Emad Fouda, MSc in Clinical Pharmacy, Clinical Pharmacy Department, Faculty of Pharmacy, Kafrelsheikh University; Study Director: Noha Mahmoud ELkhodary, Associate Professor, Clinical Pharmacy Department, Faculty of Pharmacy, Kafrelsheikh University

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: April 10, 2026
• First Submitted That Met QC Criteria: April 10, 2026
• First Posted (Actual): April 16, 2026

Study Record Updates

• Last Update Posted (Actual): April 16, 2026
• Last Update Submitted That Met QC Criteria: April 10, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Cirrhosis; PBPK; Over active bladder
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Pathological Conditions, Signs and Symptoms; Asthma; Fibrosis; mirabegron; montelukast
• Other Study ID Numbers: KFSIRB200-211/2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No