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Trial record 11 of 11 for:    neurogenic orthostatic hypotension phase 3

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

Tracking Information
First Submitted Date  ICMJE September 24, 2008
First Posted Date  ICMJE September 25, 2008
Last Update Posted Date October 1, 2008
Study Start Date  ICMJE September 2008
Estimated Primary Completion Date May 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 24, 2008)
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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT00758849 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 24, 2008)
  • To compare the efficacy of fipamezole with that of placebo on heart rate (HR) response to orthostatism. [ Time Frame: 28 days ]
  • To compare the efficacy of fipamezole with that of placebo on clinical symptoms. [ Time Frame: 28 days ]
  • To explore the relationship between plasma levels of fipamezole and measures of efficacy and safety (pharmacokinetics). [ Time Frame: 28 days ]
  • To assess safety and tolerability of fipamezole. [ Time Frame: 28 days ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Fipamezole in Neurogenic Orthostatic Hypotension
Official Title  ICMJE 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
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 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Symptomatic Neurogenic Orthostatic Hypotension (NOH)
  • Parkinson's Disease
  • Multiple System Atrophy
Intervention  ICMJE
  • 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
  • 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
Study Arms  ICMJE
  • Placebo Comparator: 1
    Intervention: Drug: Placebo
  • Active Comparator: 2
    Intervention: Drug: Fipamezole
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: September 24, 2008)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2009
Estimated Primary Completion Date May 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 30 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   Portugal
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT00758849
Other Study ID Numbers  ICMJE SNT-II-005
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Juha M. Savola, Director Clinical Development, Santhera Pharmaceuticals
Study Sponsor  ICMJE Juvantia Pharma Ltd
Collaborators  ICMJE Santhera Pharmaceuticals
Investigators  ICMJE
Principal Investigator: Olivier Rascol, MD Hôpital Purpan CIC du CHU de Toulouse
PRS Account Juvantia Pharma Ltd
Verification Date September 2008

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP