Clinical Efficacy of Midodrine in Symptomatic Orthostatic Hypotension

A Phase 4, Randomized-withdrawal, Double-blind, Placebo Controlled, Parallel-group Study to Investigate the Clinical Benefit of Midodrine Hydrochloride in Male and Female Subjects With Symptomatic Orthostatic Hypotension

To study the effect of midodrine against the symptoms of orthostatic hypotension

Study Overview

• Status: Completed
• Conditions: Symptomatic Orthostatic Hypotension
• Intervention / Treatment: Drug: Placebo; Drug: Midodrine HCl

Detailed Description

The efficacy of midodrine will be assessed in those subjects who have severe symptoms of orthostatic hypotension when not taking midodrine and are controlled when taking midodrine. The study will involve approximately 9 overnight stays.

• Study Type: Interventional
• Enrollment (Actual): 98
• Phase: Phase 4

Contacts and Locations

Study Locations

• Czechia
  • Praha, Czechia, 150 06
    • Fakultní nemocnice v Motole
  • Králové
    • Hradec, Králové, Czechia, 500 05
      • Fakultni Nemocnice Hradec Kralove
  • Poruba
    • Ostrava, Poruba, Czechia, 708 52
      • Fakultni nemocnice Ostrava
• Poland
  • Katowice, Poland, 40-353
    • EMC Silesia Sp. z o.o.; NZOZ Szpital Geriatryczny im. Jana Pawła II w Katowicach
  • Katowice, Poland, 40-588
    • Specjalistyczna Praktyka Lekarska Prof. Grzegorz Opala, + satelite site:NZOZ Szpital Avimed Sp. z o.o.
  • Poznań, Poland, 61-485
    • Centrum Medyczne HCP, Lecznictwo Stacjonarne, Oddział Udarowy
  • Warszawa, Poland, 02-106
    • MTZ Clinical Research Sp. z o.o.
  • Warszawa, Poland, 04-141
    • Wojskowy Instytut Medyczny, Klinika Neurologiczna
• Slovakia
  • Bratislava, Slovakia, 826 06
    • Neurologická klinika SZU a UNB, Univerzitná nemocnica Bratislava
  • Martin, Slovakia, 036 59
    • Neurologická klinika UN Martin, Univerzitná nemocnica Martin
  • Nitra, Slovakia, 949 01
    • Neurologická klinika FN Nitra, Fakultná nemocnica Nitra
  • Spišská Nová Ves, Slovakia, 052 01
    • Neurologické oddelenie, Nemocnica s poliklinikou Spišská Nová Ves, a.s.
  • Trnava, Slovakia, 917 75
    • Neurologické oddelenie FN Trnava, Fakultná nemocnica Trnava
  • Žilina, Slovakia, 012 07
    • Neurologické oddelenie FNsP Žilina, Fakultná nemocnica s poliklinikou Žilina
• United States
  • California
    • Glendale, California, United States, 91206
      • California Clinical Trials Medical Group
    • North Hollywood, California, United States, 91606
      • Pharmaseek-Burbank
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Parkinson's Disease and Movement Disorders Center of Boca Raton
    • New Port Richey, Florida, United States, 34653
      • Advance Research Institute Inc
    • Pinellas Park, Florida, United States, 33782
      • DMI Reasearch Inc
    • Port Charlotte, Florida, United States, 33980
      • Parkinson's Disease Treatment Center of Southwest Florida
  • Illinois
    • North Chicago, Illinois, United States, 60064
      • Chicago Medical VA
  • Kansas
    • Lenexa, Kansas, United States, 66219
      • Analab Clinical Research Inc
  • Maryland
    • Baltimore, Maryland, United States, 21225
      • PAREXEL International - Baltimore EPCU Harbor Hospital
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Frontage Clinical Services
  • New York
    • Buffalo, New York, United States, 14202
      • Buffalo Clinical Research Center (BCRC)
    • New York, New York, United States, 10032
      • Columbia University
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Oregon
    • Roseburg, Oregon, United States, 97471
      • Kidney and Hypertension Center
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • New Orleans Center For Clinical Research - Knoxville
  • Texas
    • Dallas, Texas, United States, 75390
      • UT South West Medical Center
    • McKinney, Texas, United States, 75069
      • The Heartbeat Clinic, PA
  • Utah
    • Orem, Utah, United States, 84058
      • Aspen Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male and female subjects must be 18 years of age or older and ambulatory.
2. Females of child-bearing potential (FOCP) must have a negative serum beta human chorionic gonadotropin (HCG) pregnancy test.
3. A documented history of severe Symptomatic Orthostatic Hypotension (SOH) that, in the judgment of the treating physician, has required treatment with midodrine HCl, and has been at a stable dose for at least 3 months.
4. The subject has manifested at least 1 of the following symptoms while standing or had a medical history of 1 of the following when not treated for orthostatic hypotension (OH): dizziness, lightheadedness, feeling faint, or feeling like they might black out.

Exclusion criteria

1. The subject is a pregnant or lactating female.
2. The subject has pre-existing sustained supine hypertension greater than 180mmHg systolic and 110mmHg diastolic BP or had these measurements at the Screening Visit. Sustained is defined as persistently greater at 2 separate measurements at least 5 minutes apart with the subject supine and at rest for the 5 minutes.
3. Subjects taking concomitant medications of interest are excluded unless those medications are reviewed and discussed with the Medical Monitor or Study Physician and documented prior to enrolling the subject. If agreement is reached between the Investigator and Sponsor for the subject to continue in the study, all allowed medications should be maintained at a constant dose throughout the study.
4. The Principal Investigator deems any clinical laboratory test (at the Screening Visit) abnormality to be clinically significant
5. The subject has participated in other studies of investigational drugs or devices within 30 days prior to enrollment in this study (other than Study SPD426-406).
6. Current or relevant history of physical or psychiatric illness, any medical disorder that may require treatment or make the subject unlikely to fully comply with the requirements of the study or complete the study, or any condition that presents undue risk from the investigational product or study procedures.
7. The subject has a concurrent chronic or acute illness, disability, or other condition (including significant unexpected laboratory or electrocardiogram [ECG] findings) that might confound the results of the tests and/or measurements administered in this study, or that might have increased the risk to the subject.
8. Known or suspected intolerance or hypersensitivity to the investigational product(s), closely-related compounds, or any of the stated ingredients.
9. Prior enrollment failure or randomization in this study.
10. History of alcohol abuse or other substance abuse within the last year.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; single dose of matching placebo
EXPERIMENTAL: Midodrine HCl	Drug: Midodrine HCl; dose at subject's current dose level; Other Names: ProAmatine®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Subjects Who Failed to Maintain a Response	Failure to maintain a response was defined as any randomized subject that met both criterion 1 and criterion 2 below on Day 16: 1. The Orthostatic Hypotension Symptom Assessment (OHSA) Item 1 score increased by >=4 points compared to baseline. OHSA Item 1 is a dizziness scale that is scored on a range from 0 (no dizziness) to 10 (severe dizziness). A lower score indicates less severe symptoms. 2. There was an increase in the number of syncopal/near syncopal events or severity of events within 15 minutes of standing compared to those observed at baseline. Syncope was defined as a loss of consciousness, and near syncope was defined as a feeling (e.g., dizziness, lightheadedness, feeling faint, feeling as though one would black out) that, without intervention, would lead to a loss of consciousness.	30 minutes post-dose on Day 16

Collaborators and Investigators

• Sponsor: Shire

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 23, 2012
• Primary Completion (ACTUAL): November 11, 2013
• Study Completion (ACTUAL): November 11, 2013

Study Registration Dates

• First Submitted: January 18, 2012
• First Submitted That Met QC Criteria: January 18, 2012
• First Posted (ESTIMATE): January 24, 2012

Study Record Updates

• Last Update Posted (ACTUAL): June 9, 2021
• Last Update Submitted That Met QC Criteria: May 25, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Nervous System Diseases; Autonomic Nervous System Diseases; Primary Dysautonomias; Orthostatic Intolerance; Hypotension; Hypotension, Orthostatic; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Sympathomimetics; Vasoconstrictor Agents; Adrenergic alpha-1 Receptor Agonists; Midodrine
• Other Study ID Numbers: SPD426-405; 2012-005760-99 (EUDRACT_NUMBER)