Cirrhosis, Asthma
Conditions
Keywords
Cirrhosis, Over active bladder, PBPK
Brief summary
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.
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.
Interventions
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.
DRUGMirabegron 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.
DRUGmirabegron 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.
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.
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.
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.
Sponsors
Kafrelsheikh University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Parallel-assignment interventional study to compare dose-modified of mirabegron and montelukast across Child-Pugh classes with standard-dose controls."
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in number of urinary incontinence episodes per 24 hours | 3 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Monitoring of Adverse Effects | 3 months | Adverse effects including headache, dry mouth, abdominal pain, dizziness, hypertension, urinary tract infection will be recorded |
Countries
Egypt
Contacts
STUDY_DIRECTORNoha Mahmoud ELkhodary, Associate Professor
Clinical Pharmacy Department, Faculty of Pharmacy, Kafrelsheikh University
PRINCIPAL_INVESTIGATORAya Emad Fouda, MSc in Clinical Pharmacy
Clinical Pharmacy Department, Faculty of Pharmacy, Kafrelsheikh University
Outcome results
None listed