| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| This postmarketing Phase I study is performed in healthy volunteers. The IMP rasagiline 1mg is indicated for the treatment of Parkinson's Disease (PD). |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10061536 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To assess tyramine sensitivity when administered with rasagiline, and the selectivity of rasagiline for monoamine oxidase type B (MAO-B) |
|
| E.2.2 | Secondary objectives of the trial |
| To investigate orthostatic blood pressure and pulse timed to rasagiline dosing |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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.
|
|
| E.4 | Principal 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 reactions associated with ingestion of tyramine-containing food.
25.Clinically significant or unstable vascular disease such as arrhythmia or valvular heart disease, congestive heart failure, ischemic heart or cerebrovascular disease.
26.Clinically significant history of syncope associated with hypotension within the last 2 years.
27.History of orthostatic hypotension (and/or SBP decrease of ≥20 mmHg 2 minutes after standing, compared to supine SBP).
28.History of liver disease or abnormal liver function tests.
29.Use of tricyclic antidepressants, SSRIs and selective-norepinephrine reuptake inhibitors (SNRI’s) within 14 days preceding the first administration of tyramine, MAO inhibitors within 90 days preceding the first administration of tyramine, and fluoxetine within 5 weeks preceding the first administration of tyramine.
30.Requirement for any medication contraindicated for use with a MAO-inhibitor.
31.Breast-feeding.
32.Positive urine pregnancy test at screening.
33.Female subjects of childbearing potential having unprotected sexual intercourse with any non-sterile male partner within 14 days prior to the first tyramine administration. |
|
| E.5 End points |
| E.5.1 | 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. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Information not present in EudraCT |
| E.6.2 | Prophylaxis | Information not present in EudraCT |
| E.6.3 | Therapy | Information not present in EudraCT |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Information not present in EudraCT |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | Information not present in EudraCT |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Information not present in EudraCT |
| E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| Interaction study between rasagiline and tyramine |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | Yes |
| E.7.1.3.1 | Other trial type description |
| Phase I Interaction study |
|
| E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
| E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Information not present in EudraCT |
| E.8.1.3 | Single blind | Information not present in EudraCT |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| One arm-active comparator is administed as open-label |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
|
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.5.1 | Number of sites anticipated in the EEA | 1 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 5 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
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