Symptomatic Neurogenic Orthostatic Hypotension (NOH)Phase 2FoehnNCT00758849
Fipamezole in Neurogenic Orthostatic Hypotension
A Phase 2 study testing Fipamezole in people with Symptomatic Neurogenic Orthostatic Hypotension (NOH) and Parkinson's Disease, run by Juvantia Pharma Ltd at 4 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 30 to 80 years
- Conditions the study is for
- Symptomatic Neurogenic Orthostatic Hypotension (NOH), Parkinson's Disease, Multiple System Atrophy
- What is being tested?
- Fipamezole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 4 sitesin 2 countries
- Study dates
- Sep 2008to May 2009
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
France3 sites
Hôpital du Haut Lévêque, CHU de Bordeaux
Bordeaux, 33604
Sandrine Dupouy, +33 6 30 85 95 42, sandrine.dupouy@chu-bordeaux.fr
François Tison, MD
Hôpital de la Cavale Blanche, CHU Brest
Brest, 29609
Anne-Sophie Nedelec, +33 6 30 85 95 42, anne-sophie.nedelec@chu-brest.fr
Anne Pavy-Le Traon, MD
Hôpital Purpan CIC du CHU de Toulouse
Toulouse, 31059
Pascale Gauteuil, +33 5 61 77 91 14, pascale.gauteul@toulouse.inserm.fr
Olivier Rascol, MD
Portugal1 site
Centro de Estudos Egas Moniz, Faculdade de Medicina de Lisboa
Lisbon, 1649-028
Maria Finisterra, +351 21 793 0629, cicneuro.lisbon@gmail.com
Joaquim Ferreira, MD
About this study
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
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.
Read the 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.
- Conditions
- Symptomatic Neurogenic Orthostatic Hypotension (NOH), Parkinson's Disease, Multiple System Atrophy
- Being tested
- Placebo, Fipamezole
- Keywords
- NOH, Orthostatic hypotension, PAF, MSA, Shy-Drager syndrome, Olivopontocerebellar atrophy, Striatonigral degeneration, Autonomic Failure, Parkinson, Fipamezole, JP-1730
- Medical subject headings
- Parkinson Disease, Multiple System Atrophy, Hypotension, Orthostatic, Shy-Drager Syndrome, Olivopontocerebellar Atrophies, Striatonigral Degeneration, Pure Autonomic Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
One placebo tablet administered tid for 12 days in each of the three crossover treatment blocks, each block separated by 2-days placebo washout
FipamezoleDrug
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 group | Role | What they receive |
|---|---|---|
| 1 | Placebo comparator | Not described Receives: Drug: Placebo |
| 2 | Active comparator | Not described Receives: Drug: Fipamezole |
What is being measured
The primary outcome is the main question the study is designed to answer.
To compare the efficacy of fipamezole with that of placebo on orthostatic hypotension as assessed by blood pressure response to orthostatism.
Measured: 28 days
Secondary outcomes (4)
To compare the efficacy of fipamezole with that of placebo on heart rate (HR) response to orthostatism.
Measured: 28 days
To compare the efficacy of fipamezole with that of placebo on clinical symptoms.
Measured: 28 days
To explore the relationship between plasma levels of fipamezole and measures of efficacy and safety (pharmacokinetics).
Measured: 28 days
To assess safety and tolerability of fipamezole.
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2008 (estimated)
- Study startSep 2008
- Primary completionMay 2009 (estimated)
- Study completionMay 2009 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Symptomatic Neurogenic Orthostatic Hypotension (NOH)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Juvantia Pharma Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Santhera Pharmaceuticals
- Investigators
- Olivier Rascol, MD, Principal investigator, Hôpital Purpan CIC du CHU de Toulouse
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00758849
- Sponsor's protocol ID
- SNT-II-005
- Acronym
- Foehn
- Status last verified
- Sep 2008
- First submitted
- 24 Sep 2008
- Last updated
- 1 Oct 2008
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00758849
- Acronym / sponsor ID
- Foehn / SNT-II-005
- Conditions
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Juvantia Pharma LtdIndustry (pharma, biotech, devices)
- Collaborators
- Santhera Pharmaceuticals
- Study start
- Sep 2008
- Primary completion
- May 2009 (estimated)
- Study completion
- May 2009 (estimated)
- First posted
- 25 Sep 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Placebo comparator | Drug: Placebo |
| 2 | Active comparator | Drug: Fipamezole |
Who may qualify
- Ages
- 30 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboOne placebo tablet administered tid for 12 days in each of the three crossover treatment blocks, each block separated by 2-days placebo washout | Drug | 1 |
| FipamezoleOne 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 | Drug | 2 |
Primary outcome
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
4 secondary outcomes
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2008.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Olivier Rascol, MD principal investigator
Hôpital Purpan CIC du CHU de Toulouse
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Fipamezole in people with Symptomatic Neurogenic Orthostatic Hypotension (NOH) and Parkinson's Disease, run by Juvantia Pharma Ltd at 4 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 1 Oct 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in France, Portugal. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Laurence Negre-Pages (33 5 61 25 34 58, laurence.negres-pages@easyconnect.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2008.