A Study of Safety and Tolerability of Fipamezole in Adult Subjects With Parkinson's Disease Who Are Receiving Levodopa
A Study of Safety and Tolerability of Fipamezole in Adult Subjects With Parkinson's Disease Who Are Receiving Levodopa
The purpose of this clinical trial is to determine the maximum tolerated dose of Fipamezole
 in adult patients with Parkinson's disease who are receiving levodopa.
Parkinson's Disease is the second most common neurodegenerative disorder worldwide. While
 treatment with dopaminergic agents like levodopa, the mainstay of treatment, is effective in
 the early phases of the disease, their benefits decrease with disease progression, and
 problems such as dyskinesia and on-off phenomenon begin to manifest. In this study,
 fipamezole, a new antagonist of an adrenergic receptor, is being investigated to better
 understand the safety and side-effect profile in patients with Parkinson's Disease.

 The sampling method used was simple random sampling.
Inclusion Criteria:

 1. Subject is a man or woman between 30 and 75 years of age, inclusive, with intact oral
 mucosa at Screening (Visit 1) and Randomization (Visit 2).

 2. Subject has a diagnosis of idiopathic Parkinson's disease defined according to the UK
 Parkinson's Disease Society Brain Bank Clinical Diagnosis criteria.

 3. Subject has been receiving a stable regimen of at least three daily administrations of
 levodopa (with a peripheral dopa decarboxylase inhibitor), with no dose changes for at
 least 4 weeks prior to Randomization (Visit 2).

 4. Subject is rated at stage 2 to 4 on the Hoehn and Yahr scale.

 5. If currently taking other medications (other than levodopa), subject must be on a
 stable regimen, defined as no dose changes for at least 1 month prior to Randomization
 (Visit 2).

 6. Subject demonstrates the ability to comprehend the study procedures and provide
 informed consent.

 7. Female subjects must be either postmenopausal for at least 1 year or surgically
 sterilized at least 3 months prior to Randomization (Visit 2). Male subjects must
 either be sterile or willing to use 2 approved methods of contraception when engaged
 in sexual intercourse with a female partner from Randomization (Visit 2) until 30 days
 after the last dose of study drug.

 8. Subject has an upper arm circumference of not less than 24 cm and not more than 42 cm
 for both arms.

 Exclusion Criteria:

 1. Subject participated in an investigational medication study within the 3 months prior
 to Randomization (Visit 2).

 2. Subject has immediate family members who are site Investigators or sponsor employees.

 3. Subject has a history or presence of clinically significant cardiovascular, pulmonary,
 hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic,
 neurologic, or oncologic or any other condition that, in the opinion of the
 Investigator, would jeopardize the safety of the subject or the validity of the study
 results.

 4. Subject has impaired renal function (defined as a creatinine level of ≥ 1.5 times the
 upper limit of normal) at Screening (Visit 1).

 5. Subject has impaired hepatic function (defined as SGOT/AST or SGPT/ALT levels ≥ 1.5
 times the upper limit of normal) at Screening (Visit 1).

 6. Subject has second- or third-degree atrioventricular block or sick sinus syndrome,
 atrial fibrillation, atrial flutter, severe or unstable angina, congestive heart
 failure, or myocardial infarction within 3 months of the screening visit or a
 significant ECG abnormality, including a QRS > 110 msec, a PR interval > 230 msec, a
 QTc ≥ 450 msec for male subjects, or a QTc ≥ 470 msec for female subjects.

 7. Subject has a history of risk factors for Torsades de Pointes, including unexplained
 syncope, known long QT syndrome, or a clinically significant abnormal laboratory
 assessment such as hypokalemia, hypercalcemia, or hypomagnesemia. Subjects with a
 family history of long QT syndrome or Brugada syndrome will also be excluded.

 8. Subject is at immediate risk of requiring hospitalization.

 9. Subject has significant tremor or dyskinesia which, in the opinion of the
 Investigator, might interfere with reliable assessment of continuous Holter ECG and
 ABPM.

 10. Subject has, in the opinion of the Investigator, a clinically important abnormality on
 his/her physical examination, electrocardiography, vital sign measurements, or
 laboratory assessment.

 11. Subject is being treated with a disallowed medication that cannot be discontinued
 prior to Randomization (Visit 2) (See Table 6).

 12. Subject has a current diagnosis of substance abuse or history of alcohol or drug abuse
 in the past 2 years prior to Screening (Visit 1).

 13. Subject has positive findings on urine drug screen at Screening (Visit 1).

 14. Subject has an allergy to fipamezole or its excipients.