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 - FOEHN

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2007-004890-24-FR
• Date of registration: 09/05/2008
• Prospective Registration: No
• Primary sponsor: Juvantia Pharma Ltd
• Public 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 - FOEHN
• Scientific 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 - FOEHN
• Date of first enrolment: 07/05/2008
• Target sample size: 24
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-004890-24
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: yes Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

France, Portugal

Key inclusion & exclusion 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)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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 (Appendix C), 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 antiinflammatory
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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Neurogenic orthostatic hypotension in patients with multiple system atrophy or Parkinson's disease
MedDRA version: 9.1 Level: LLT Classification code 10013113 Term: Disease Parkinson's
MedDRA version: 9.1 Level: LLT Classification code 10064060 Term: Multiple system atrophy

Intervention(s)

Product Name: Fipamezole hydrochloride 90 mg oral disintegrating tablets
Product Code: JP-1730/F01
Pharmaceutical Form: Orodispersible tablet
INN or Proposed INN: Fipamezole hydrochloride
CAS Number: 150586-72-4
Current Sponsor code: JP-1730
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 90-
Pharmaceutical form of the placebo: Orodispersible tablet
Route of administration of the placebo: Sublingual use

Product Name: Fipamezole hydrochloride 60 mg oral disintegrating tablets
Product Code: JP-1730/F02
Pharmaceutical Form: Orodispersible tablet
INN or Proposed INN: Fipamezole hydrochloride
CAS Number: 150586-72-4
Current Sponsor code: JP-1730
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 60-
Pharmaceutical form of the placebo: Orodispersible tablet
Route of administration of the placebo: Sublingual use

Product Name: Fipamezole hydrochloride 30 mg oral disintegrating tablets
Product Code: JP-1730/F03
Pharmaceutical Form: Orodispersible tablet
INN or Proposed INN: Fipamezole hydrochloride
CAS Number: 150586-72-4
Current Sponsor code: JP-1730
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 30-
Pharmaceutical form of the placebo: Orodispersible tablet
Route of administration of the placebo: Sublingual use

Primary Outcome(s)

Main Objective: To compare the efficacy of fipamezole with that of placebo on orthostatic hypotension as assessed by blood pressure (BP) response to orthostatism

Secondary Objective: - 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.

Primary end point(s): Difference between fipamezole and placebo in maximal fall (standing versus supine) at 1, 2 or 3 hours post-dose in systolic BP (SBP) in response to orthostatism

Secondary ID(s)

SNT-II-005