A Single and Multiple Dose Study to Assess How the Drug Enters, Moves Through and Exits the Body, Safety and Tolerability of Safinamide in Healthy Adult Chinese Volunteers
Condition: Healthy
Intervention: Safinamide 50 mg; Safinamide 100mg
Intervention description: Safinamide 50mg film-coated tablets will be administered to subjects in Cohort 1. The subjects will receive the tablets orally in the morning, at 8:00±1hour, under fasting conditions, with 240 mL (total volume) of still mineral water. A mouth-and-hand check will be performed immediately after dosing to ensure treatment compliance.; Safinamide 100mg film-coated tablets will be administered to subjects in Cohort 2. The subjects will receive the tablets orally in the morning, at 8:00±1hour, under fasting conditions, with 240 mL (total volume) of still mineral water. A mouth-and-hand check will be performed immediately after dosing to ensure treatment compliance.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: There will be 2 treatment groups. A total of 24 subjects will be randomized to receive 50mg or 100 mg Safinamide in Period 1 (Day 1) and Period 2 (Days 8 to 14) separated by a 7 days washout period.
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Pharmacokinetic; Safety; Tolerability; Healthy Chinese subjects

Summary:

      This is a Phase I, single center, single and multiple-dose, open-label, randomised,
      parallel-group, pharmacokinetics, safety and tolerability study. The subjects will be
      randomised into two study cohorts to receive single and multiple doses of 50 mg safinamide
      (cohort 1), or single and multiple doses of 100 mg safinamide (cohort 2) as follows:

      Cohort 1: One safinamide 50 mg film-coated tablet will be administered on day 1 followed by 7
      safinamide 50 mg film-coated tablets in total from day 8 to day 14 and hence administered 1
      tablet orally from day 8 to day 14.

      Cohort 2: One safinamide 100 mg film-coated tablet will be administered on day 1 followed by
      7 safinamide 100 mg film-coated tablets in total from day 8 to day 14 and hence administered
      1 tablet orally from day 8 to day 14.

      The investigational products will be administered in the morning, at 8:00±1hour, under
      fasting conditions, with 240 mL (total volume) of still mineral water. A mouth-and-hand check
      will be performed immediately after dosing to ensure treatment compliance.

      The primary endpoint will assess the pharmacokinetic parameters after single and multiple
      dose administration of the study drug. The secondary endpoint will provide the safety and
      tolerability data after single and multiple dose administration of the study drug.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Informed consent: signed written informed consent before inclusion in the study

          2. Sex and Age: males and females, 18-45-year old inclusive

          3. Ethnicity: Chinese

          4. Weight: body weight ≥ 50 kg;

          5. Body Mass Index: 19-26 kg/m2 inclusive

          6. Vital signs: systolic blood pressure 100-139 mmHg, diastolic blood pressure 50-89
             mmHg, heart rate 50-90 bpm, measured after 5 min at rest in the sitting/supine
             position

          7. Full comprehension: ability to comprehend the full nature and purpose of the study,
             including possible risks and side effects; ability to co-operate with the investigator
             and to comply with the requirements of the entire study

          8. No nicotine addiction (smoker subjects only): ability to abstain for smoking for the
             duration of the clinical study

          9. Contraception and fertility (women only): women of child-bearing potential must be
             using at least one of the following reliable methods of contraception during the study
             and two weeks post-dose:

               1. Hormonal oral, implantable, transdermal, or injectable contraceptives for at
                  least 2 months before the screening visit

               2. A non-hormonal intrauterine device or female condom with spermicide or
                  contraceptive sponge with spermicide or diaphragm with spermicide or cervical cap
                  with spermicide for at least 2 months before the screening visit

               3. A male sexual partner who agrees to use a male condom with spermicide

               4. A sterile sexual partner

        Women of non-child-bearing potential or in post-menopausal status for at least 1 year will
        be admitted.

        For all women, pregnancy test result must be negative at screening and day -1.

        Exclusion Criteria:

          1. Electrocardiogram (12-lead ECG in supine position): clinically significant
             abnormalities

          2. Physical findings: clinically significant abnormal physical findings which could
             interfere with the objectives of the study

          3. Laboratory analyses: clinically significant abnormal laboratory values indicative of
             physical illness

          4. Allergy: ascertained or presumptive hypersensitivity to the active principle and/or
             formulations' ingredients; history of anaphylaxis to drugs or allergic reactions in
             general, which the investigator considers may affect the outcome of the study

          5. Diseases: significant history of renal, hepatic, gastrointestinal, cardiovascular,
             respiratory, skin, haematological, endocrine or neurological diseases that may
             interfere with the aim of the study; positive result on HIV, hepatitis B (HBV) (except
             for vaccination), hepatitis C (HCV). Retinal degeneration, uveitis, inherited
             retinopathy or severe progressive diabetic retinopathy.

          6. Medications: medications, including over the counter medications, herbal remedies and
             traditional Chinese remedies for 2 weeks before the start of the study. In particular
             statins and β-Hydroxy β-methylglutaryl-CoA (HMG-CoA)reductase inhibitors in the 2
             weeks before the screening visit; medicinal products that are Breast Cancer Resistance
             Protein (BCRP) substrates; treatment with morphine or other similar opioids, whose
             concomitant use with Monoamine oxidase B (MAO-B) inhibitors is contraindicated,
             Selective serotonin reuptake inhibitors (SSRIs), Serotonin-norepinephrine reuptake
             inhibitors (SNRIs), tri- or tetracyclic antidepressant, tramadol, pethidine,
             dextromethorphan, Monoamino oxidase (MAO) inhibitors (e.g. selegiline), meperidine
             derivatives and antiepileptic drugs in the 4 weeks before the screening visit;
             treatment with any known enzyme inhibiting or inducing agent within 4 weeks preceding
             the screening visit. Hormonal contraceptives for women will be allowed

          7. Investigative drug studies: participation in the evaluation of any investigational
             product for 3 months before this study

          8. Blood donation: blood donations or blood components transfusion for 3 months before
             this study

          9. Abuse drug, alcohol, caffeine, tobacco: history of drug, alcohol [>1 drink/day for
             females and >2 drinks/day for males, defined according to the USDA Dietary Guidelines
             2015-2020], caffeine (>5 cups coffee/tea/day) or tobacco abuse (≥10 cigarettes or
             equivalent amount of tobacco per day within 3 months prior to day-1)

         10. Abuse drug test: positive result at urine drug test at screening or day-1

         11. Alcohol test: positive alcohol breath test at day -1

         12. Diet: abnormal diets (<1600 or >3500 kcal/day) or substantial changes in eating habits
             in the 4 weeks before this study; vegetarians; consumption of grapefruit or products
             containing grapefruit within 48 hours prior to the enrolment; consumption of beverages
             containing xanthines (e.g. coffee, tea, soda, coffee, milk, energy drinks) within 48
             hours prior to the enrolment

         13. Pregnancy (females only): positive or missing pregnancy test at screening or day -1,
             pregnant or lactating women.