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Fipamezole in Neurogenic Orthostatic Hypotension (Foehn)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2008 by Juvantia Pharma Ltd.
Recruitment status was  Not yet recruiting
Sponsor:
Collaborator:
Santhera Pharmaceuticals
Information provided by:
Juvantia Pharma Ltd
ClinicalTrials.gov Identifier:
NCT00758849
First received: September 24, 2008
Last updated: September 30, 2008
Last verified: September 2008
  Purpose

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.


Condition Intervention Phase
Symptomatic Neurogenic Orthostatic Hypotension (NOH)
Parkinson's Disease
Multiple System Atrophy
Drug: Placebo
Drug: Fipamezole
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Juvantia Pharma Ltd:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To compare the efficacy of fipamezole with that of placebo on heart rate (HR) response to orthostatism. [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • To compare the efficacy of fipamezole with that of placebo on clinical symptoms. [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • To explore the relationship between plasma levels of fipamezole and measures of efficacy and safety (pharmacokinetics). [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  • To assess safety and tolerability of fipamezole. [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 24
Study Start Date: September 2008
Estimated Study Completion Date: May 2009
Estimated Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 1 Drug: Placebo
One placebo tablet administered tid for 12 days in each of the three crossover treatment blocks, each block separated by 2-days placebo washout
Active Comparator: 2 Drug: Fipamezole
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

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.

  Eligibility

Ages Eligible for Study:   30 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00758849

Contacts
Contact: Laurence Negre-Pages 33 5 61 25 34 58 laurence.negres-pages@easyconnect.fr

Locations
France
Hôpital du Haut Lévêque, CHU de Bordeaux Not yet recruiting
Bordeaux, France, 33604
Contact: Sandrine Dupouy    +33 6 30 85 95 42    sandrine.dupouy@chu-bordeaux.fr   
Principal Investigator: François Tison, MD         
Hôpital de la Cavale Blanche, CHU Brest Not yet recruiting
Brest, France, 29609
Contact: Anne-Sophie Nedelec    +33 6 30 85 95 42    anne-sophie.nedelec@chu-brest.fr   
Principal Investigator: Anne Pavy-Le Traon, MD         
Hôpital Purpan CIC du CHU de Toulouse Not yet recruiting
Toulouse, France, 31059
Contact: Pascale Gauteuil    +33 5 61 77 91 14    pascale.gauteul@toulouse.inserm.fr   
Principal Investigator: Olivier Rascol, MD         
Portugal
Centro de Estudos Egas Moniz, Faculdade de Medicina de Lisboa Not yet recruiting
Lisbon, Portugal, 1649-028
Contact: Maria Finisterra    +351 21 793 0629    cicneuro.lisbon@gmail.com   
Principal Investigator: Joaquim Ferreira, MD         
Sponsors and Collaborators
Juvantia Pharma Ltd
Santhera Pharmaceuticals
Investigators
Principal Investigator: Olivier Rascol, MD Hôpital Purpan CIC du CHU de Toulouse
  More Information

No publications provided

Responsible Party: Juha M. Savola, Director Clinical Development, Santhera Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00758849     History of Changes
Other Study ID Numbers: SNT-II-005
Study First Received: September 24, 2008
Last Updated: September 30, 2008
Health Authority: United States: Food and Drug Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Portugal: National Pharmacy and Medicines Institute

Keywords provided by Juvantia Pharma Ltd:
Shy-Drager syndrome
NOH
Orthostatic hypotension
PAF
MSA
Olivopontocerebellar atrophy
Striatonigral degeneration
Autonomic Failure
Parkinson
Fipamezole
JP-1730

Additional relevant MeSH terms:
Multiple System Atrophy
Shy-Drager Syndrome
Atrophy
Hypotension
Hypotension, Orthostatic
Parkinson Disease
Autonomic Nervous System Diseases
Basal Ganglia Diseases
Brain Diseases
Cardiovascular Diseases
Central Nervous System Diseases
Movement Disorders
Nervous System Diseases
Neurodegenerative Diseases
Orthostatic Intolerance
Parkinsonian Disorders
Pathological Conditions, Anatomical
Primary Dysautonomias
Vascular Diseases

ClinicalTrials.gov processed this record on November 24, 2014