CLINICAL TRIALS PROFILE FOR PROAMATINE

All Clinical Trials for PROAMATINE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00555880 ↗	Study to Assess the Benefit of Midodrine in the Treatment of Patients With Neurogenic Orthostatic Hypotension	Completed	Shire	Phase 4	2004-09-08	The purpose of this clinical study is to evaluate the clinical effect of midodrine hydrochloride (ProAmatine®) compared to placebo in patients with orthostatic hypotension by measuring the time to onset of near syncopal symptoms and assessing several cardiovascular measurements, such as heart rate, blood pressure, and ECG, using the tilt table test.
NCT00648440 ↗	Food Study of Midodrine HCl Tablets 5 mg and ProAmatine® Tablets 5 mg	Completed	Mylan Pharmaceuticals	Phase 1	2002-10-01	The objective of this study was to investigate the bioequivalence of Mylan's midodrine HCl 5 mg tablets to Roberts ProAmatine® 5 mg tablets following a single, oral 5 mg (1 x 5 mg) dose administration under fed conditions.
NCT00046163 ↗	A Phase IV Study in Subjects With Neurogenic Orthostatic Hypotension	Terminated	Shire	Phase 4	2002-09-05	We are seeking male and female patients to voluntarily take part in a clinical research study. Patients must be aged 18 or older and diagnosed with symptomatic orthostatic hypotension (low blood pressure while in the upright position) due to Parkinson's disease, multiple system atrophy, pure autonomic failure or autonomic neuropathies (i.e. neurogenic orthostatic hypotension). Symptoms of low blood pressure include dizziness, lightheadedness, changes in vision and generalized weakness upon standing. The main effect of the drug being studied is to increase blood pressure in the upright position so symptoms will decrease. The purpose of this clinical study is to further assess the clinical effect of high dose midodrine hydrochloride (ProAmatine®), an approved treatment for orthostatic hypotension. During the course of the study, participants will receive either ProAmatine® or a placebo. Assessments will be made using questionnaires that measure symptom and activity levels. Blood pressure in the lying down, sitting and standing positions will be measured. Patients will also complete standing time assessments. They will be asked to remain standing without moving until they feel sufficiently lightheaded, or dizzy, or feel faint so that they would feel more comfortable sitting down.
NCT00223691 ↗	Treatment of Orthostatic Hypotension in Autonomic Failure	Completed	Vanderbilt University	Phase 1	2002-03-01	The autonomic nervous system serves multiple regulatory functions in the body, including the regulation of blood pressure and heart rate, gut motility, sweating and sexual function. There are several diseases characterized by abnormal function of the autonomic nervous system. Medications can also alter autonomic function. Impairment of the autonomic nervous system by diseases or drugs may lead to several symptoms, including blood pressure problems (e.g., high blood pressure lying down and low blood pressure on standing), sweating abnormalities, constipation or diarrhea and sexual dysfunction. Because treatment options for these patients are limited. We propose to study patients autonomic failure and low blood pressure upon standing and determine the cause of their disease by history and examination and their response to autonomic testing which have already been standardized in our laboratory. Based on their possible cause, we will tests different medications that may alleviate their symptoms.
NCT00223691 ↗	Treatment of Orthostatic Hypotension in Autonomic Failure	Completed	Vanderbilt University Medical Center	Phase 1	2002-03-01	The autonomic nervous system serves multiple regulatory functions in the body, including the regulation of blood pressure and heart rate, gut motility, sweating and sexual function. There are several diseases characterized by abnormal function of the autonomic nervous system. Medications can also alter autonomic function. Impairment of the autonomic nervous system by diseases or drugs may lead to several symptoms, including blood pressure problems (e.g., high blood pressure lying down and low blood pressure on standing), sweating abnormalities, constipation or diarrhea and sexual dysfunction. Because treatment options for these patients are limited. We propose to study patients autonomic failure and low blood pressure upon standing and determine the cause of their disease by history and examination and their response to autonomic testing which have already been standardized in our laboratory. Based on their possible cause, we will tests different medications that may alleviate their symptoms.
NCT00046475 ↗	A Study for Patients With Neurogenic Orthostatic Hypotension	Completed	Shire	Phase 4	1997-12-01	We are seeking male and female patients to voluntarily take part in a clinical research study. Patients must be aged 18 or older and diagnosed with symptomatic orthostatic hypotension (low blood pressure while in the upright position) due to Parkinson's disease, multiple system atrophy, pure autonomic failure or autonomic neuropathies (i.e. neurogenic orthostatic hypotension). Symptoms of low blood pressure include dizziness, lightheadedness, changes in vision and generalized weakness upon standing. The main effect of the drug being studied is to increase blood pressure in the upright position so symptoms will decrease. The purpose of this clinical study is to further assess the clinical benefit of midodrine hydrochloride (ProAmatine®), an approved treatment for orthostatic hypotension. During the course of the study, participants will receive either ProAmatine® or a placebo. Assessments will be made using questionnaires that measure symptom and activity levels. Blood pressure in the lying down and standing positions will be measured at each visit.

Clinical Trial Conditions for PROAMATINE

Condition Name

Condition Name for PROAMATINE
Intervention	Trials
Healthy	3
Hypotension, Orthostatic	3
Orthostatic Hypotension	3
Autonomic Failure	2

Condition MeSH

Condition MeSH for PROAMATINE
Intervention	Trials
Hypotension	7
Hypotension, Orthostatic	6
Cognitive Dysfunction	2
Cognition Disorders	2

Clinical Trial Locations for PROAMATINE

Trials by Country

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−

Trials by Country for PROAMATINE
Location	Trials
United States	35
Egypt	1

Trials by US State

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−

Trials by US State for PROAMATINE
Location	Trials
New York	5
West Virginia	4
Tennessee	3
Texas	3
Ohio	2

Clinical Trial Progress for PROAMATINE

Clinical Trial Phase

Clinical Trial Phase for PROAMATINE
Clinical Trial Phase	Trials
Phase 4	6
Phase 1	5
N/A	2

Clinical Trial Status

Clinical Trial Status for PROAMATINE
Clinical Trial Phase	Trials
Completed	7
Recruiting	2
Terminated	2

Clinical Trial Sponsors for PROAMATINE

Sponsor Name

Sponsor Name for PROAMATINE
Sponsor	Trials
Shire	3
Mylan Pharmaceuticals	3
James J. Peters Veterans Affairs Medical Center	2

Sponsor Type

Sponsor Type for PROAMATINE
Sponsor	Trials
Other	8
Industry	6
U.S. Fed	2

ProAmatine (Midodrine HCl): Clinical Trials Update, Market Analysis, and Projections

Introduction to ProAmatine

ProAmatine, also known as midodrine HCl, is a medication approved in 1996 under the accelerated approval process (Subpart H) by the U.S. Food and Drug Administration (FDA) for the treatment of symptomatic orthostatic hypotension (SOH). Here, we will delve into the recent clinical trials updates, market analysis, and future projections for this drug.

Clinical Trials Update

Initial Approval and Post-Approval Commitments

ProAmatine was initially approved based on its ability to significantly raise blood pressure in patients with SOH. As part of the accelerated approval process, Shire, the original NDA holder, was required to conduct two post-marketing clinical trials to confirm the clinical benefit of midodrine[4].

Disagreement and Additional Trials

Shire completed these trials and submitted the results to the FDA in 2005. However, the FDA deemed these trials inadequate and requested additional clinical trials. Despite Shire's disagreement, citing 15 years of clinical experience and existing trial data, an agreement was reached with the FDA to conduct two more clinical trials[1][4].

Current Status and Future Trials

In 2011, Shire and the FDA agreed on a joint clinical trials proposal, which was submitted for approval by the FDA Commissioner. These trials were expected to begin as soon as possible and be completed by the end of 2014. The agreement ensured that midodrine HCl, including its generic formulations, would remain available to patients while the trials were conducted[1][4].

Market Analysis

Current Market Presence

Midodrine HCl, under the brand name ProAmatine, has been marketed by Shire until 2010. Since 2003, the drug has been manufactured and distributed by generic pharmaceutical companies. Despite Shire no longer having a financial interest in the brand, it continues to invest in regulatory processes to maintain the marketing authorization for generic versions of ProAmatine[4].

Patient Dependence and Clinical Efficacy

The drug remains crucial for patients with SOH, as it significantly improves their ability to manage symptoms. Shire believes that the existing clinical trials and 15 years of clinical experience have established the efficacy of ProAmatine, although the FDA has requested further confirmation[1][4].

Market Projections

Generic Market Impact

The availability of generic midodrine HCl has ensured that the drug remains accessible to patients. However, the ongoing need for additional clinical trials to confirm efficacy could impact market stability. If the trials are successful, it is likely to reinforce the drug's market position and ensure continued availability[1][4].

Competitive Landscape

In the broader context of treatments for orthostatic hypotension, new drugs like ampreloxetine, currently in Phase III trials, may pose future competition. Ampreloxetine, developed by Theravance Biopharma, is projected to have peak sales of $287 million by 2026, although its success depends on demonstrating significant clinical benefits[3].

Safety and Contraindications

Important Safety Information

ProAmatine is contraindicated in patients with severe organic heart disease, acute renal disease, urinary retention, pheochromocytoma, or thyrotoxicosis. It should not be used in patients with persistent and excessive supine hypertension. The drug can cause marked elevation of supine blood pressure, and its use should be carefully considered based on the patient's clinical condition[1][4].

Key Takeaways

• Clinical Trials: Additional trials were agreed upon in 2011 to confirm the clinical benefit of midodrine, with completion anticipated by 2014.
• Market Presence: Midodrine HCl is available in generic formulations, ensuring continued access for patients with SOH.
• Efficacy and Safety: The drug has a established safety profile but requires further trials to fully confirm its clinical benefits.
• Market Projections: The success of ongoing trials will be crucial for maintaining the drug's market position.

FAQs

1. What is ProAmatine used for?

ProAmatine (midodrine HCl) is used for the treatment of symptomatic orthostatic hypotension (SOH).

2. Why were additional clinical trials required for ProAmatine?

The FDA deemed the initial post-marketing trials inadequate and requested additional trials to confirm the clinical benefit of midodrine.

3. Who manufactures and distributes ProAmatine now?

Since 2003, midodrine HCl has been manufactured and distributed by generic pharmaceutical companies, although Shire remains the NDA holder.

4. What are the contraindications for ProAmatine?

ProAmatine is contraindicated in patients with severe organic heart disease, acute renal disease, urinary retention, pheochromocytoma, or thyrotoxicosis, and in those with persistent and excessive supine hypertension.

5. What is the current status of the additional clinical trials for ProAmatine?

The trials were expected to be completed by the end of 2014, but the current status may have evolved since the last public update.

Cited Sources

1. PR Newswire: "ProAmatine® (midodrine HCl) Update: Path Forward Agreed" - December 2, 2011.
2. GlobalData: "NSCLC MARKET - Global Drug Forecast & Market Analysis to 2025".
3. Clinical Trials Arena: "Theravance's ampreloxetine study needs dramatic improvement in neurogenic orthostatic hypotension to spur market uptake but trial success likely" - April 5, 2021.
4. FiercePharma: "ProAmatine® (midodrine HCl) Update: Path Forward Agreed" - December 2, 2011.