Working… Menu

Fipamezole in Neurogenic Orthostatic Hypotension (Foehn)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00758849
Recruitment Status : Unknown
Verified September 2008 by Juvantia Pharma Ltd.
Recruitment status was:  Not yet recruiting
First Posted : September 25, 2008
Last Update Posted : October 1, 2008
Santhera Pharmaceuticals
Information provided by:
Juvantia Pharma Ltd

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.

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

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 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, 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
Study Start Date : September 2008
Estimated Primary Completion Date : May 2009
Estimated Study Completion Date : May 2009

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. 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 Measures :
  1. To compare the efficacy of fipamezole with that of placebo on heart rate (HR) response to orthostatism. [ Time Frame: 28 days ]
  2. To compare the efficacy of fipamezole with that of placebo on clinical symptoms. [ Time Frame: 28 days ]
  3. To explore the relationship between plasma levels of fipamezole and measures of efficacy and safety (pharmacokinetics). [ Time Frame: 28 days ]
  4. To assess safety and tolerability of fipamezole. [ Time Frame: 28 days ]

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   30 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00758849

Layout table for location contacts
Contact: Laurence Negre-Pages 33 5 61 25 34 58

Layout table for location information
Hôpital du Haut Lévêque, CHU de Bordeaux
Bordeaux, France, 33604
Contact: Sandrine Dupouy    +33 6 30 85 95 42   
Principal Investigator: François Tison, MD         
Hôpital de la Cavale Blanche, CHU Brest
Brest, France, 29609
Contact: Anne-Sophie Nedelec    +33 6 30 85 95 42   
Principal Investigator: Anne Pavy-Le Traon, MD         
Hôpital Purpan CIC du CHU de Toulouse
Toulouse, France, 31059
Contact: Pascale Gauteuil    +33 5 61 77 91 14   
Principal Investigator: Olivier Rascol, MD         
Centro de Estudos Egas Moniz, Faculdade de Medicina de Lisboa
Lisbon, Portugal, 1649-028
Contact: Maria Finisterra    +351 21 793 0629   
Principal Investigator: Joaquim Ferreira, MD         
Sponsors and Collaborators
Juvantia Pharma Ltd
Santhera Pharmaceuticals
Layout table for investigator information
Principal Investigator: Olivier Rascol, MD Hôpital Purpan CIC du CHU de Toulouse
Layout table for additonal information
Responsible Party: Juha M. Savola, Director Clinical Development, Santhera Pharmaceuticals Identifier: NCT00758849    
Other Study ID Numbers: SNT-II-005
First Posted: September 25, 2008    Key Record Dates
Last Update Posted: October 1, 2008
Last Verified: September 2008
Keywords provided by Juvantia Pharma Ltd:
Shy-Drager syndrome
Orthostatic hypotension
Olivopontocerebellar atrophy
Striatonigral degeneration
Autonomic Failure
Additional relevant MeSH terms:
Layout table for MeSH terms
Multiple System Atrophy
Shy-Drager Syndrome
Brain Diseases
Parkinson Disease
Hypotension, Orthostatic
Parkinsonian Disorders
Basal Ganglia Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Pathological Conditions, Anatomical
Vascular Diseases
Cardiovascular Diseases
Orthostatic Intolerance
Primary Dysautonomias
Autonomic Nervous System Diseases