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 Droxidopa trial for OH (orthostatic hypotension)- 4 US sites 
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Joined: Fri Aug 11, 2006 1:46 pm
Posts: 4811
Location: SF Bay Area (Northern CA)
Post Droxidopa trial for OH (orthostatic hypotension)- 4 US sites
This will only be of interest to those dealing with OH. (About 40% of LBDers experience orthostatic hypotension.)

There's a drug trial going on at four sites in the US. Patients will be given either droxidopa or placebo in a trial study looking at treatment for OH (orthostatic hypotension).

The main exclusion criteria for this study is if the patient is already taken midodrine but you can discontinue midodrine for 7 days to qualify for this study. The study is at no cost to the patient except for the time to get to one of the research sites and transportation. The five-visit schedule is fairly demanding. FYI - Droxidopa is sometimes called L-DOPS.

I received the following email from the clinical research coordinator at The Parkinson's Institute this morning:

"Droxidopa is a study for people with symptomatic orthostatic hypotension. The drug is approved in Japan for this condition but has never been marketed elsewhere until now. Orthostatic hypotension is defined by the study as a drop in blood pressure by 20 points systolic (high #) or 10 points (low #) diastolic when standing for 3 minutes after lying down. The individual also needs to be symptomatic-(dizziness, eye symptoms, weakness, etc.).

The study is intensive for about 4 weeks. It requires 5 visits minimum.

*Visit 1 is a screening visit whereby we gather medical history, labs, records, EKG, and vital signs.

*Visit 2 occurs generally a week after visit 1. Study drug is administered, labs are drawn, EKG, and vital signs.

*Visit 3 occurs the next day. This is the titration phase where we try and find the best dose according to response. The individual will come back in 1-2 days during this titration phase for approximately 1 week to stabilize the dose to response. This would require a minimum of 2 visits to a maximum of 6 visits. It is based on blood pressure and symptoms. No labs are done.

*Visit 4 occurs a week after the last titration visit. The individual spends the day in our office whereby we administer their dose and monitor their response at intervals. Labs are drawn.

*Visit 5 is the final visit occurring 2 weeks after visit 4 and is similar to visit 4 procedures.

The individual will be eligible to continue active drug at this point in an open label portion of the study. Please note there is a 50% chance the subject will get placebo at visit 4 for the 2 week period until visit 5.

Although this is a quick, intensive trial, it appears it may be very beneficial for the problem. And, it will be available to those who respond for an indefinite time free of charge.

The patient will pay nothing for the study visits or study drug. If transportation is an issue we can discuss options to help the patient. If someone is very interested but lives a distance away, we can discuss alternatives. ...(The) demanding schedule should be considered when looking at the health of the patient. ...

I hope this gives you ample information. My contact information is below. Please do not hesitate to contact me with questions or comments."

Because the info on clinicaltrials.gov does not mention PDD or LBD specifically (though it does mention MSA, one of the other disorders in our local group), I contacted the TPI clinical research coordinator about the possibility of those with PDD or LBD participating. Here's her reply: "Lewy Body Dementia is not excluded. However, the patient needs to be cognitively intact to give informed consent."

You can find the full details of the clinical trial on the government's clinicaltrials.gov website at:
http://clinicaltrials.gov/ct2/show/NCT0 ... ion&rank=5

The remainder of this email is a copy of what appears on that clinicaltrials.gov webpage: (look near the bottom for info on the 4 sites)

Clinical Study of Droxidopa in Patients With
Neurogenic Orthostatic Hypotension (NOH)

This study is currently recruiting participants.

Verified by Chelsea Therapeutics, March 2008
Sponsors and Collaborators: Chelsea Therapeutics; Chiltern
Information provided by: Chelsea Therapeutics

ClinicalTrials.gov Identifier: NCT00633880


Purpose
The purpose of this study is to see whether
Droxidopa is effective in treating symptoms of
neurogenic orthostatic hypotension in patients
with Primary Autonomic Failure (Pure Autonomic
Failure, Multiple System Atrophy, Parkinson's
Disease), Non-diabetic neuropathy, or Beta Hydroxylase deficiency.

Condition
Symptomatic Neurogenic Orthostatic Hypotension (NOH)
Non-Diabetic Neuropathy
Primary Autonomic Failure
Dopamine Beta Hydroxylase Deficiency

Intervention
Drug: Placebo
Drug: Droxidopa

Phase III


Study Type: Interventional
Study Design: Treatment, Randomized, Double
Blind (Subject, Caregiver, Investigator, Outcomes
Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Official Title: Phase III, Multi-Center, Study
to Assess the Clinical Effect of Droxidopa in
Subjects With Primary Autonomic Failure, Dopamine
Beta Hydroxylase Deficiency or Non-Diabetic Neuropathy and Symptomatic NOH

Further study details as provided by Chelsea Therapeutics:

Primary Outcome Measures:
To evaluate the efficacy of droxidopa in patients
with symptomatic NOH as measured by the relative
change in mean score of Item 1 of the (OHSA) 14
days following randomization to continued therapy
with droxidopa or placebo. [ Time Frame: 14 days ]
[ Designated as safety issue: No ]

Secondary Outcome Measures:
Evaluate efficacy of droxidopa as measured by
changes in systolic blood pressure (SBP) and
diastolic blood pressure (DBP) measurements 3
minutes post standing; [ Time Frame: 14 days ]
[Designated as safety issue: No ]

Evaluate efficacy of droxidopa by global
assessment evaluations using the
clinician-recorded and patient-recorded Clinical
Global Impressions-Severity (CGI-S) and Clinical
Global Impressions-Improvement (CGI-I) scales;
[ Time Frame: 14 days ] [ Designated as safety issue: No ]

Evaluate efficacy of droxidopa by symptom and
activity measurements using the composite scores
of OHSA, OHDAS (the two subcomponents of the
Orthostatic Hypotension Questionnaire (OHQ))
[Time Frame: 14 days ] [ Designated as safety issue: No ]

Evaluate the safety of droxidopa based on the
occurence of treatment-emergent adverse events
and specific evaluation of blood pressure, heart
rate, ECG, and laboratory findings across the
study [ Time Frame: up to 5 weeks ] [ Designated as safety issue: Yes ]


Estimated Enrollment: 118
Study Start Date: January 2008
Estimated Study Completion Date: October 2008
Estimated Primary Completion Date: September
2008 (Final data collection date for primary outcome measure)


Arms
Droxidopa: Active Comparator
Double-blind Drug: Droxidopa

Assigned Interventions
100 mg, oral, three times per day 200 mg, oral,
three times per day 300 mg, oral, three times per
day 400 mg, oral, three times per day 500 mg,
oral, three times per day 600 mg, oral, three times per day

Arms
Placebo: Placebo Comparator
Double-blind Drug: Placebo

Assigned Interventions
100 mg, oral, three times per day 200 mg, oral,
three times per day 300 mg, oral, three times per
day 400 mg, oral, three times per day 500 mg,
oral, three times per day 600 mg, oral, three times per day


Detailed Description:
Systolic blood pressure is transiently and
minimally decreased in healthy individuals upon
standing. Normal physiologic feedback mechanisms
work through neurally-mediated pathways to
maintain the standing blood pressure, and thus
maintain adequate cerebral perfusion. The
compensatory mechanisms that regulate blood
pressure upon standing are dysfunctional in
subjects with orthostatic hypotension (OH), a
condition that may lead to inadequate cerebral
perfusion with accompanying symptoms of syncope,
dizziness or lightheadedness, unsteadiness and
blurred or impaired vision, among other symptoms.


The autonomic nervous system has a central role
in the regulation of blood pressure. Primary
Autonomic Failure is manifested in a variety of
syndromes. Orthostatic hypotension is a usual
presenting symptom. Primary Autonomic Failure may
be the primary diagnosis, and classifications
include pure autonomic failure (PAF), also called
idiopathic orthostatic hypotension
(Bradbury-Eggleston syndrome) autonomic failure
with multiple system atrophy (Shy-Drager
syndrome) and also Parkinson's disease.

Regardless of the primary condition, autonomic
dysfunction underlies orthostatic hypotension.

Orthostatic hypotension may be a severely
disabling condition which can seriously interfere
with the quality of life of afflicted subjects.
Currently available therapeutic options provide
some symptomatic relief in a subset of subjects,
but are relatively ineffective and are often
accompanied by severe side effects that limit
their usefulness. Support garments (tight-fitting
leotard) may prove useful in some subjects, but
is difficult to don without family or nursing
assistance, especially for older subjects.

Midodrine, fludrocortisone, methylphenidate,
ephedrine, indomethacin and dihydroergotamine are
among some of the pharmacological interventions
that have been used to treat orthostatic
hypotension, although only midodrine is
specifically approved for this indication. The
limitations of these currently available
therapeutic options, and the incapacitating
nature and often progressive downhill course of
disease, point to the need for an improved therapeutic alternative.

The current withdrawal design study will measure
the efficacy of droxidopa on symptoms of
neurogenic orthostatic hypotension in patients
randomized to continued droxidopa treatment
versus placebo, following 14 days of double-blind treatment.


Droxidopa
Droxidopa [also, known as
L-threo-3,4-dihydroxyphenylserine, L-threo-DOPS,
or L-DOPS] is the International non-proprietary
name (INN) for a synthetic amino acid precursor
of norepinephrine (NE), which was originally
developed by Sumitomo Pharmaceuticals Co.,
Limited, Japan. It has been approved for use in
Japan since 1989. Droxidopa has been shown to
improve symptoms of orthostatic hypotension that
result from a variety of conditions including Shy
Drager syndrome (Multiple System Atrophy), Pure
Autonomic Failure, and Parkinson's disease. There
are four stereoisomers of DOPS; however, only the
L-threo-enantiomer (droxidopa) is biologically active.

The exact mechanism of action of droxidopa in the
treatment of symptomatic NOH has not been
precisely defined; however, its NE replenishing
properties with concomitant recovery of decreased
noradrenergic activity are considered to be of major importance.


Droxidopa has been marketed in Japan since 1989.
Data from clinical studies and post-marketing
surveillance programs conducted in Japan show
that the most commonly reported adverse drug
reactions with droxidopa are increased blood
pressure, nausea, and headache. In clinical
studies, the prevalence and severity of droxidopa
adverse effects appear to be similar to those
reported by the placebo control arm.

Eligibility
Ages Eligible for Study: 18 Years and older
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No

Criteria
PATIENT INCLUSION CRITERIA:
Male or female and aged 18 years or over;
Clinical diagnosis of orthostatic hypotension
associated with Primary Autonomic Failure (PD,
MSA and PAF), Dopamine Beta Hydroxylase
Deficiency or Non-Diabetic Autonomic Neuropathies;
A documented fall in systolic blood pressure of
at least 20 mmHg, or in diastolic blood pressure
of at least 10 mmHg, within 3 minutes after standing;
Provide written informed consent to participate
in the study and understand that they may
withdraw their consent at any time without
prejudice to their future medical care.

MAIN PATIENT EXCLUSION CRITERIA:
Taking ephedrine or midodrine; Patients taking
ephedrine or midodrine may enroll after a minimum 7 day washout period;
Taking anti-hypertensive medication;
Have a history of more than moderate alcohol consumption;
Women who are pregnant or lactating;
Have a history of closed angle glaucoma;
Have pre-existing sustained severe hypertension
(BP > 180/110 mmHg in the sitting position);
Have atrial fibrillation or, in the
investigator's opinion, have any other significant cardiac arrhythmia;
In the investigator's opinion, have any other
significant systemic, hepatic, cardiac or renal illness;
Have diabetes mellitus or insipidus;
Have a known or suspected malignancy;
Have known gastrointestinal illness or other
gastrointestinal disorder that may, in the
investigator's opinion, affect the absorption of study drug;
In the investigator's opinion, have clinically
significant abnormalities on clinical examination or laboratory testing;
Have a serum creatinine level > 130 µmol/L;


Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00633880

Contact: Michelle Anthony (512)
225-0240 michelle.anthony@chiltern.com

Contact: Cynthia Corona (512)
225-0241 cynthia.corona@chiltern.com


Locations
United States, Arizona
Dedicated Clinical Research Recruiting
Litchfield Park, Arizona, United States, 85340
Contact: Jeremy Grove 623-583-2599 jgrove@dedicatedcr.com
Contact: Kelli Bingham (623)
583-2599 kbingham@dedicatedcr.com
Principal Investigator: Troy Anderson, MD


United States, California
The Parkinson's Institute Recruiting
Sunnyvale, California, United States, 94085
Contact: Katherine Smith 408-542-5635 ksmith@thepi.org
Principal Investigator: Grace Liang, MD


United States, Florida
Southeastern Integrated Medical Recruiting
Gainesville, Florida, United States, 32607
Contact: Judy West 352-333-3885 research@simedpl.com
Contact: Tracy Terry (352) 333-3885 research@simedpl.com
Principal Investigator: Anne Rottmann, MD


United States, Indiana
Indiana Medical Research Recruiting
Elkhart, Indiana, United States, 46514
Contact: Sheri Shapner 574-296-3903 shapner@elkhartclinic.com
Contact: Jami Ludington (574)
296-3905 jludingt@elkhartclinic.com
Principal Investigator: Thomas Vidic, MD



Sponsors and Collaborators
Chelsea Therapeutics
Chiltern


Investigators
Principal Investigator: Horacio Kaufmann,
MD New York University Medical Center

Principal Investigator: Christopher J
Mathias, MD Imperial School of Medicine

Principal Investigator: Roy Freeman, MD Harvard Medicine School

Principal Investigator: Phillip A Low, MD Mayo Foundation


Responsible Party: Chelsea Therapeutics ( Cameron Szakacs )


Study ID Numbers: Droxidopa 302

First Received: March 5, 2008

Last Updated: March 11, 2008

ClinicalTrials.gov Identifier: NCT00633880

Health Authority: United States: Food and Drug

Administration; Canada: Health Canada; United

Kingdom: Medicines and Healthcare Products

Regulatory Agency; Poland: Drug Institute


Thu Apr 24, 2008 3:13 pm
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