Study Evaluating ECG Effects, Safety, Tolerability and Pharmacokinetics of Single Doses of Modufolin (Arfolitixorin) in Healthy Volunteers Tetrahydrofolate in Healthy Male Volunteers

NCT ID: NCT03203564

Last Updated: 2020-09-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-07-04
• Study Completion Date: 2017-08-25

Brief Summary

The purpose of this study is to evaluating ECG effects, safety, tolerability and pharmacokinetics of single ascending dose of Modufolin® in healthy male volunteers

Detailed Description

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.

Conditions

Phase I Study in Healthy Volunteers to Evaluate ECG Effect

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: TRIPLE

Study Groups

Modufolin® for injection, 200, 350 and 500 mg/m2

Three cohorts, 8 subjects will be randomised to Modufolin ® for injection 100 mg

Group Type: ACTIVE_COMPARATOR

Modufolin (arfolitixorin)

Intervention Type: DRUG

Thirty-three eligible and consenting subjects will be included in 3 cohorts, 11 subjects in each cohort, Within each cohort, subjects will be randomized to receive either placebo (3 subjects) or Modufolin® for injection, 100mg (8 subjects)

0.9% NaCl sterile solution

Three cohorts, 3 subjects will be randomised to placebo

Group Type: PLACEBO_COMPARATOR

Modufolin (arfolitixorin)

Intervention Type: DRUG

Thirty-three eligible and consenting subjects will be included in 3 cohorts, 11 subjects in each cohort, Within each cohort, subjects will be randomized to receive either placebo (3 subjects) or Modufolin® for injection, 100mg (8 subjects)

Interventions

Modufolin (arfolitixorin)

Thirty-three eligible and consenting subjects will be included in 3 cohorts, 11 subjects in each cohort, Within each cohort, subjects will be randomized to receive either placebo (3 subjects) or Modufolin® for injection, 100mg (8 subjects)

Intervention Type: DRUG

Other Intervention Names

arfolitixorin

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Isofol Medical AB

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

CTC Clinical Trial Consultants

Uppsala, , Sweden

Countries

Sweden

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

ISO-FF-001

Identifier Type: -

Identifier Source: org_study_id