Fipamezole in Neurogenic Orthostatic Hypotension (Foehn)
Primary Purpose
Symptomatic Neurogenic Orthostatic Hypotension (NOH), Parkinson's Disease, Multiple System Atrophy
Status
Unknown status
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Placebo
Fipamezole
Sponsored by
About this trial
This is an interventional treatment trial for Symptomatic Neurogenic Orthostatic Hypotension (NOH) focused on measuring NOH, Orthostatic hypotension, PAF, MSA, Shy-Drager syndrome, Olivopontocerebellar atrophy, Striatonigral degeneration, Autonomic Failure, Parkinson, Fipamezole, JP-1730
Eligibility Criteria
Inclusion Criteria:
- Male or female patients ≥ 30 and < 80 years of age with an intact oral mucosa at screening
- Diagnosis of MSA or diagnosis of idiopathic PD
- Hoehn and Yahr stages 1 to 4 during 'Off' period
- NOH: reproducible fall in SBP ≥20 mmHg and/or a fall in DBP ≥10 mmHg between 15 min of supine rest and 3 min of standing (or until symptomatic from hypotension after <3 min of standing)
- For patient taking antiparkinsonian medication: stable daily dosing for at least 1 month
- For patient taking fludrocortisone: stable dose for at least 2 months
- Demonstrated ability to comprehend, give informed consent and comply with study procedures (BP self-monitoring, completion of patient diary and self-assessment rating scales)
Exclusion Criteria:
- Other clinically significant conditions apart from those typically associated with MSA or PD
- SBP ≥200 mmHg or DBP ≥120 mmHg after 15 min supine rest in quiet environment
- Clinically significant abnormalities of ECG
- Mini-Mental State Examination (MMSE) score < 24
- Intake of prohibited concomitant medication such as midodrine, intake of medication associated with vasodilatation or induction of liver enzymes; neuroleptics; certain drugs known to be substantially metabolized through the following cytochrome P450 isoenzymes: 1A2, 2B6, 2C19, 2C9, 2D6 and 2E1; or any other drug for the treatment of orthostatic hypotension (including off-label use), such as non-steroidal anti-inflammatory drugs, beta blockers, somatostatin
- Use of St. John's Wort or Ginkgo Biloba within 48 h prior to inclusion and during the course of the study
- Intake of an investigational drug within 30 days prior to screening
Sites / Locations
- Hôpital du Haut Lévêque, CHU de Bordeaux
- Hôpital de la Cavale Blanche, CHU Brest
- Hôpital Purpan CIC du CHU de Toulouse
- Centro de Estudos Egas Moniz, Faculdade de Medicina de Lisboa
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Active Comparator
Arm Label
1
2
Arm Description
Outcomes
Primary Outcome Measures
To compare the efficacy of fipamezole with that of placebo on orthostatic hypotension as assessed by blood pressure response to orthostatism.
Secondary Outcome Measures
To compare the efficacy of fipamezole with that of placebo on heart rate (HR) response to orthostatism.
To compare the efficacy of fipamezole with that of placebo on clinical symptoms.
To explore the relationship between plasma levels of fipamezole and measures of efficacy and safety (pharmacokinetics).
To assess safety and tolerability of fipamezole.
Full Information
NCT ID
NCT00758849
First Posted
September 24, 2008
Last Updated
September 30, 2008
Sponsor
Juvantia Pharma Ltd
Collaborators
Santhera Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT00758849
Brief Title
Fipamezole in Neurogenic Orthostatic Hypotension
Acronym
Foehn
Official Title
A Phase II, Randomised, Placebo-Controlled, Double-Blind, Replicated Crossover, Pilot Study on the Effect of Fipamezole on Neurogenic Orthostatic Hypotension in Patients With Multiple System Atrophy or Parkinson's Disease
Study Type
Interventional
2. Study Status
Record Verification Date
September 2008
Overall Recruitment Status
Unknown status
Study Start Date
September 2008 (undefined)
Primary Completion Date
May 2009 (Anticipated)
Study Completion Date
May 2009 (Anticipated)
3. Sponsor/Collaborators
Name of the Sponsor
Juvantia Pharma Ltd
Collaborators
Santhera Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to determine whether Fipamezole is effective in the treatment of orthostatic hypotension and related symptoms in multiple system atrophy and Parkinson's disease.
Detailed Description
This study will be an exploratory, proof of concept, randomised, placebo-controlled, double-blind, multiple crossover study, with an open-label active run-in phase, in patients with multiple system atrophy (MSA) or Parkinson's disease (PD) who can concomitantly be treated with fludrocortisone and antiparkinsonian medication. Three sites in France and one site in Portugal will participate in this study.
During the open-label active run-in phase, a tolerated dose-escalation regimen (either escalating from 30 to 90 or 60 mg tid, or no escalation but fixed dose of 30 mg tid) will be established for each patient. Once the tolerated treatment regimen has been established, patients will then be randomised to the double-blind crossover treatment. Fipamezole and matched placebo tablets are compared in 3 crossover blocks, each block consisting of a total of 28 days: 12 days fipamezole and 12 days placebo in random order, separated by two days of washout. The patients will be randomly assigned to one of the two possible treatment sequences (fipamezole first followed by placebo or placebo first followed by fipamezole).
For efficacy assessments, the patient blood pressure and heart rate is assessed repeatedly when laying still or standing. Impact of orthostatic hypotension on clinical symptoms is assessed with a subjective scale and questionnaire. To explore potential positive or negative impact of fipamezole on disease characteristics, the MSA and PD patients are assessed with UMSARS and UPDRS scales, respectively. Finally, the study includes investigator and patients assessments of CGI-I and PGI-I scales for clinical condition in general.
Fipamezole
Fipamezole is a new antagonist of the pre-synaptic adrenergic alpha-2 receptors and is being investigated for potential use as an adjunctive therapy for PD. Adrenergic alpha-2 receptors inhibit noradrenaline and some other neurotransmitter release from nerve terminals in a tonic manner, and therefore antagonism of this receptor leads in enhanced neurotransmitter release. Alpha-2 receptors are located widely in the body, both in the central nervous system (CNS) and periphery. Pharmacological studies have suggested that either central or peripheral autonomic nervous system is involved in autonomic failure and orthostatic hypotension in MSA and in PD. Neurogenic orthostatic hypotension in these diseases results from decreased delivery of the sympathetic neurotransmitter noradrenaline (or hormonal adrenaline) to vascular adrenergic receptors, either because of blunted CNS control or impaired function of postganglionic sympathetic neurons. Fipamezole is expected to increase noradrenergic (or adrenergic) turnover in specific areas of the brain or in the periphery in MSA and PD and alleviate symptoms related to fall in BP during orthostatism.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Symptomatic Neurogenic Orthostatic Hypotension (NOH), Parkinson's Disease, Multiple System Atrophy
Keywords
NOH, Orthostatic hypotension, PAF, MSA, Shy-Drager syndrome, Olivopontocerebellar atrophy, Striatonigral degeneration, Autonomic Failure, Parkinson, Fipamezole, JP-1730
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
24 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Placebo Comparator
Arm Title
2
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
One placebo tablet administered tid for 12 days in each of the three crossover treatment blocks, each block separated by 2-days placebo washout
Intervention Type
Drug
Intervention Name(s)
Fipamezole
Intervention Description
One 30-mg tablet of Fipamezole tid from day 1 to 3; one 60-mg tablet of Fipamezole tid from Day 4 to 6; and one 90-mg tablet of Fipamezole tid from Day 7 to 12 in each of the three crossover treatment blocks, each block separated by 2-days placebo washout
Primary Outcome Measure Information:
Title
To compare the efficacy of fipamezole with that of placebo on orthostatic hypotension as assessed by blood pressure response to orthostatism.
Time Frame
28 days
Secondary Outcome Measure Information:
Title
To compare the efficacy of fipamezole with that of placebo on heart rate (HR) response to orthostatism.
Time Frame
28 days
Title
To compare the efficacy of fipamezole with that of placebo on clinical symptoms.
Time Frame
28 days
Title
To explore the relationship between plasma levels of fipamezole and measures of efficacy and safety (pharmacokinetics).
Time Frame
28 days
Title
To assess safety and tolerability of fipamezole.
Time Frame
28 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female patients ≥ 30 and < 80 years of age with an intact oral mucosa at screening
Diagnosis of MSA or diagnosis of idiopathic PD
Hoehn and Yahr stages 1 to 4 during 'Off' period
NOH: reproducible fall in SBP ≥20 mmHg and/or a fall in DBP ≥10 mmHg between 15 min of supine rest and 3 min of standing (or until symptomatic from hypotension after <3 min of standing)
For patient taking antiparkinsonian medication: stable daily dosing for at least 1 month
For patient taking fludrocortisone: stable dose for at least 2 months
Demonstrated ability to comprehend, give informed consent and comply with study procedures (BP self-monitoring, completion of patient diary and self-assessment rating scales)
Exclusion Criteria:
Other clinically significant conditions apart from those typically associated with MSA or PD
SBP ≥200 mmHg or DBP ≥120 mmHg after 15 min supine rest in quiet environment
Clinically significant abnormalities of ECG
Mini-Mental State Examination (MMSE) score < 24
Intake of prohibited concomitant medication such as midodrine, intake of medication associated with vasodilatation or induction of liver enzymes; neuroleptics; certain drugs known to be substantially metabolized through the following cytochrome P450 isoenzymes: 1A2, 2B6, 2C19, 2C9, 2D6 and 2E1; or any other drug for the treatment of orthostatic hypotension (including off-label use), such as non-steroidal anti-inflammatory drugs, beta blockers, somatostatin
Use of St. John's Wort or Ginkgo Biloba within 48 h prior to inclusion and during the course of the study
Intake of an investigational drug within 30 days prior to screening
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Laurence Negre-Pages
Phone
33 5 61 25 34 58
Email
laurence.negres-pages@easyconnect.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Olivier Rascol, MD
Organizational Affiliation
Hôpital Purpan CIC du CHU de Toulouse
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hôpital du Haut Lévêque, CHU de Bordeaux
City
Bordeaux
ZIP/Postal Code
33604
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sandrine Dupouy
Phone
+33 6 30 85 95 42
Email
sandrine.dupouy@chu-bordeaux.fr
First Name & Middle Initial & Last Name & Degree
François Tison, MD
Facility Name
Hôpital de la Cavale Blanche, CHU Brest
City
Brest
ZIP/Postal Code
29609
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anne-Sophie Nedelec
Phone
+33 6 30 85 95 42
Email
anne-sophie.nedelec@chu-brest.fr
First Name & Middle Initial & Last Name & Degree
Anne Pavy-Le Traon, MD
Facility Name
Hôpital Purpan CIC du CHU de Toulouse
City
Toulouse
ZIP/Postal Code
31059
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pascale Gauteuil
Phone
+33 5 61 77 91 14
Email
pascale.gauteul@toulouse.inserm.fr
First Name & Middle Initial & Last Name & Degree
Olivier Rascol, MD
Facility Name
Centro de Estudos Egas Moniz, Faculdade de Medicina de Lisboa
City
Lisbon
ZIP/Postal Code
1649-028
Country
Portugal
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maria Finisterra
Phone
+351 21 793 0629
Email
cicneuro.lisbon@gmail.com
First Name & Middle Initial & Last Name & Degree
Joaquim Ferreira, MD
12. IPD Sharing Statement
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Fipamezole in Neurogenic Orthostatic Hypotension
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