Study Evaluating ECG Effects, Safety, Tolerability and Pharmacokinetics of Single Doses of Modufolin (Arfolitixorin) in Healthy Volunteers Tetrahydrofolate in Healthy Male Volunteers
Study Evaluating ECG Effects, Safety, Tolerability and Pharmacokinetics of Single Doses of Modufolin (Arfolitixorin) in Healthy Volunteers Tetrahydrofolate in Healthy Male Volunteers
The purpose of this study is to evaluating ECG effects, safety, tolerability and
 pharmacokinetics of single ascending dose of Modufolin® in healthy male volunteers
An adaptive randomised, double-blind, single-centre, placebo-controlled Phase I study
 evaluating ECG effects, safety, tolerability and PK of single ascending doses of Modufolin®
 for Injection, 100 mg in healthy male volunteers. Thirty-three (33) eligible and consenting
 subjects will be included in 3 cohorts, 11 subjects in each cohort. Within each cohort,
 subjects will be randomised to receive either placebo (3 subjects) or Modufolin® for
 Injection, 100 mg (8 subjects). There will be 3 pre-defined ascending dose-levels. Additional
 dose levels may be considered if recommended by the internal Safety Review cCommittee. There
 will be an interval between each dose level to allow time for safety data to be analyzed and
 evaluated by the iSRC. The iSRC will have the choice to decide to escalate the dose as
 planned, reduce or increase the dose escalation step, repeat the dose, reduce the dose or
 terminate the study. The total study duration for the subjects will be approximately 5 weeks
 and there will be in total 3 visits to the clinic. Subjects will be screened for eligibility
 according to study-specific inclusion/exclusion criteria within 4 weeks prior to start of
 stud treatment (Visit 1; Screening visit). The subjects will be confined to the research
 clinic from the evening before dosing (Day -1) until 24 hrs post dose (Days 1 and 2). The
 subjects should be fasting overnight (8 hrs) before IMP/placebo administration until 4 hrs
 post-dose. A Follow-up Visit will be performed 5 to 10 days after dose administration of for
 each cohort.
Inclusion Criteria:

 1. Willing and able to provide a written informed consent for participation in the study.

 2. Healthy male subject aged 18-60 years inclusive.

 3. Body Mass Index (BMI) ≥ 18 and ≤ 30 kg/m2 and weight at least 50 kg and no more than
 100 kg at screening and body surface area ≤ 2 m2

 4. Clinically normal medical history, physical findings, vital signs, ECG and laboratory
 values at the time of screening, as judged by the Investigator.

 5. Willing to use condom and highly effective contraceptive methods with a failure rate
 of < 1% to prevent pregnancy1 and drug exposure to a partner and refrain from donating
 sperm from the date of dosing until 3 months after dosing of the IMP/placebo.

 Exclusion Criteria:

 -  1. History of any clinically significant disease or disorder which, in the opinion of
 the Investigator, may either put the subject at risk because of participation in the
 study, or influence the results or subject´s ability to participate in the study.

 2. Any clinically significant illness, medical/surgical procedure or trauma within
 four weeks of the first administration of IMP/placebo. 3. Any planned major surgery
 within the duration of the study. 4. Any positive result on screening for serum
 hepatitis B surface antigen, hepatitis C antibody and Human Immunodeficiency Virus
 (HIV). 5. After 10 minutes (min) supine rest at the time of screening, any vital signs
 values outside the following ranges:

 -  Systolic BP > 150 mm Hg

 -  Diastolic BP > 90 mm Hg

 -  Pulse < 40 or > 85 beats per min 6. Prolonged QTcF (>450 ms), cardiac arrhythmias
 or any clinically significant abnormalities in the resting ECG at the time of
 screening, as judged by the Investigator.

 7. History of severe allergy/hypersensitivity or on-going
 allergy/hypersensitivity, as judged by the Investigator, or history of
 hypersensitivity to drugs with a similar chemical structure or class to
 Modufolin® (i.e., folate derivatives). 8. Regular use of any prescribed or
 non-prescribed medication including antacids, analgesics, herbal remedies,
 vitamins and minerals within two weeks prior to the administration of
 IMP/placebo, except occasional intake of paracetamol (maximum 2000 mg/day; and
 not exceeding 3 000 mg/week), at the discretion of the Investigator and nasal
 decongestants without cortisone or antihistamine for a maximum of 10 days, at the
 discretion of the Investigator. 9. Regular use of any prescribed or
 non-prescribed medication which could influence folate and vitamin B12 status
 within 30 days prior to the administration of IMP/placebo.

 10. Administration of another new chemical entity (defined as a compound which
 has not been approved for marketing) or has participated in any other clinical
 study that included drug treatment with less than three months between
 administration of last dose and first dose of IMP/placebo in this study. Subjects
 consented and screened but not dosed in previous phase I studies are not
 excluded. 11. Current smokers or users of nicotine products. Irregular use of
 nicotine (e.g., smoking, snuffing, chewing tobacco) less than three times per
 week is allowed before screening visit. 12. Positive screen for drugs of abuse or
 alcohol at screening or on admission to the unit prior to administration of the
 IMP/placebo. 13. Current or history of alcohol abuse and/or use of anabolic
 steroids or drugs of abuse.

 14. Intake of xanthine and/or taurine containing energy drinks within two days
 prior to screening.

 15. Plasma donation within one month of screening or blood donation (or
 corresponding blood loss) during the three months prior to dosing. 16.
 Investigator considers the subject unlikely to comply with study procedures,
 restrictions and requirements.