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A PHASE I, DOUBLE BLIND, PLACEBO CONTROLLED, RANDOMIZED (WITHIN EACH GROUP) STUDY TO EVALUATE THE INTERACTION BETWEEN ORALLY ADMINISTERED TYRAMINE HYDROCHLORIDE AND RASAGILINE MESILATE IN HEALTHY SUBJECTS - Tyramine challenge study

Phase 1
Conditions
MedDRA version: 9.1Level: PTClassification code 10061536
This postmarketing Phase I study is performed in healthy volunteers. The IMP rasagiline 1mg is indicated for the treatment of Parkinson's Disease (PD).
Registration Number
EUCTR2006-005140-89-NL
Lead Sponsor
TEVA Pharmaceuticals Industries Ltd
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
All
Target Recruitment
160
Inclusion Criteria

1.Gender: male or female;
2.Age: between 40 and 70 years of age, inclusive;
3.BMI:19.0 – 30.0 kg/m2 [Body Mass Index (BMI) (kg/m2) = Body weight (kg) ? Height2 (m2)];
4.Willingness to sign the written Informed Consent Form (ICF);
5.Willing to inpatient stay for the full length required by the protocol.

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

1.Clinically significant illnessess, as judged by the Medical Investigator, within 8 weeks prior to the first administration of tyramine.
2.Clinically significant surgery, as judged by the Medical Investigator, within 8 weeks prior to the first administration of tyramine.
3.Any clinically significant abnormality found during medical screening.
4.Any reason which, in the opinion of the Medical Investigator, would preclude safe and complete study participation.
5.Abnormal laboratory tests judged clinically significant.
6.Positive testing for hepatitis B, hepatitis C, or HIV at screening.
7.The mean of 3 consecutive supine systolic and diastolic BP readings taken within 10 minutes exceeds 140 mm Hg and 90 mmHg, respectively, and/or is not stable (supine SBP exceeds a maximum range of 10 mmHg between the lowest and highest values)
8.Clinically significant ECG, vital signs abnormalities or cardiovascular symptomatology observed during the bicycle exercise test at screening, as judged by the Medical Investigator, or positive suggestion of any cardiovascular symptomatology underline disease.
9.History of significant alcohol abuse or drug abuse within 1 year prior to the screening visit.
10.Regular use of alcohol within 6 months prior to the screening visit
11.Use of soft drugs (such as marijuana) within 3 months prior to the screening visit or hard drugs within 1 year prior to the screening visit or positive urine drug or alcohol screen at screening.
12.History of allergic reactions to rasagiline, phenelzine, tyramine or other related drugs.
13.Use of any drugs known to induce or inhibit hepatic drug metabolism within 30 days prior to the first administration of tyramine.
14.Use of an investigational drug with unknown mechanism of action/unknown half-life or participation in an investigational first-in-man study within 90 days prior to the first administration of tyramine, or participation in any other investigational study within 60 days or 5 half-lives of the investigational study drug, which ever is longer, prior to the first administration of tyramine.
15.Clinically significant history or presence of any clinically significant gastrointestinal pathology, unresolved gastrointestinal symptoms, kidney disease, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of the drug.
16.Any clinically significant history or presence of clinically significant neurological, endocrinal, pulmonary, hematologic, immunologic, psychiatric, or metabolic disease.
17.Use of prescription medication within 14 days prior to the first administration of tyramine or over-the-counter products within 7 days prior to the first administration of tyramine, especially sympathomimetics and except for topical products without systemic absorption or hormonal contraceptives.
18.Use of grapefruit products within 7 days prior to Period 1.
19.Difficulty to swallow study medication.
20.Any food allergy, intolerance, restriction or special diet that, in the opinion of the Medical Investigator, could contraindicate the subject‘s participation in this study.
21.A depot injection or an implant of any drug (other than hormonal contraceptive) within 3 months prior to the first administration of tyramine.
22.Donation of more than 50 mL blood within 3 months prior to the first administration of tyramine.
23.History or known presence of intracranial or systemic aneurysm, intracranial hemorrhage or pheochromocytoma.
24.Known adverse r

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: To assess tyramine sensitivity when administered with rasagiline, and the selectivity of rasagiline for monoamine oxidase type B (MAO-B);Secondary Objective: To investigate orthostatic blood pressure and pulse timed to rasagiline dosing;Primary end point(s): TYR30 ratio, calculated as the tyramine dose associated with 3 consecutive increases from baseline in SBP = 30 mmHg (over 10 minutes) in Period 1, divided by the dose associated with the same change in SBP in Period 3.
Secondary Outcome Measures
NameTimeMethod
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