Mirabegron in Achalasia: A Clinical and Manometric Proof of Concept Pilot Study

NCT03411252 | Terminated Early Phase 1 DMC FDA Drug

• 1 other identifier: 17P.054
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluates whether a medication called mirabegron is better than placebo (sugar pill) in helping patients with achalasia swallow better. Each patient will receive either mirabegron or the placebo for 4 weeks followed by the opposite medication. Each patient will complete several surveys and undergo several tests to determine if the mirabegron is helping reduce the pressures in the esophagus (swallowing tube).

Conditions

Achalasia

Outcome Measures

Primary Outcomes (1)

• Changes in lower esophageal sphincter pressures

  Evaluation of changes in lower esophageal sphincter pressures using high resolution manometry

  Change in lower esophageal sphincter pressure from baseline after 4 weeks of placebo or Mirabegron

Secondary Outcomes (1)

• Eckardt Achalasia Score (EAS)

  Patients will complete the EAS on study day -14, 0, 7, 28, 42, 49, 70, 84. We will evaluate changes in patient's EAS between day 0 and all of these time points.

Study Arms (2)

Mirabegron

EXPERIMENTAL

Patients will receive 50 mg of oral Mirabegron daily for 4 weeks and then switch to placebo by mouth daily for an additional 4 weeks.

Drug: Mirabegron 50 MG; Drug: Placebo

Placebo

PLACEBO COMPARATOR

Patients will receive placebo by mouth daily for 4 weeks and then switch to oral Mirabegron 50 mg daily for an additional 4 weeks.

Drug: Mirabegron 50 MG; Drug: Placebo

Interventions

Mirabegron 50 MG DRUG

Myrbetriq (Mirabegron) tablet

Also known as: Myrbetriq

Mirabegron; Placebo

Placebo DRUG

Sugar pill manufactured to mimic Mirabegron

Also known as: Placebo (for Mirabegron)

Mirabegron; Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years old \< Age \< 75 years old with prior diagnosis of achalasia via manometry and/or radiographically

You may not qualify if:

• \< 18 years old or \> 75 years old
• History of hypertension not controlled on oral medications (blood pressure \> 160/100 mm Hg)
• No prior history of hypertension with a blood pressure \> 160/100 mm Hg
• History of bladder outlet obstruction
• History of angioedema
• Pregnant or breast-feeding women: Women between 18 and 40 years old who are enrolled in the study will be required to use a form of birth control during the study
• Patients currently receiving certain medications (digoxin, warfarin, any overactive bladder medications, thioridazine, flecainide, propafenone, phosphodiesterase inhibitors)
• Patients with prolonged QTc interval or risk factors to develop it:
• Baseline QTc on EKG of \> 450 milliseconds
• History of additional risk factors for Torsades de Pointes (heart failure, family history of long QT syndrome)
• Concomitant medications that prolong the QTc interval: ranolazine, sotalol, dofetilide, procainamide, disopyramide, propafenone, azole antifungals, fluoroquinolones, macrolide antibiotics, HIV antiretrovirals, chemotherapy, beta-2 agonists, tricyclic antidepressants, selective serotonin reuptake inhibitors
• Prior surgeries for achalasia
• \< 2 months since last endoscopic botulinum toxin injection into LES or endoscopic dilation
• Stage 4 Chronic kidney disease (severe renal impairment with GFR 15-29 ml/min), Stage 5 Chronic Kidney disease (GFR \< 15 ml/min or on dialysis)
• Childs Pugh B (moderate) or C (severe) Cirrhotic (hepatic impairment)

Sponsors & Collaborators

• Thomas Jefferson University: lead
• Astellas Pharma Inc: collaborator

Study Sites (1)

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

MeSH Terms

Conditions

Esophageal Achalasia

Interventions

mirabegron

Condition Hierarchy (Ancestors)

Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr Anthony J DiMarino, Chair, Division of Gastroenterology

Study Record Dates

• First Submitted: December 11, 2017
• First Posted: January 26, 2018
• Study Start: February 15, 2018
• Primary Completion: December 15, 2019
• Study Completion: December 15, 2019
• Last Updated: March 24, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)