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

NCT03203564 | Completed Phase 1 Results DMC

• 1 other identifier: ISO-FF-001
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

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

Conditions

Phase I Study in Healthy Volunteers to Evaluate ECG Effect

Outcome Measures

Primary Outcomes (1)

• Change-from-baseline QTcF (ΔQTcF)

  At each nominal time point specified in the CSP, up to 10 ECG replicates were extracted with TQT Plus methods. TQT Plus ECG extraction technique: Twelve-lead ECGs were extracted from continuous recordings (Holter recordings) prior to and serially after IMP administration at time points as shown in the Schedule of events. Subjects were supinely resting for at least 10 min prior to time points for ECG recordings. The 12-lead Holter and ECG equipment were supplied and supported by iCardiac Technologies, Inc. For all ECG parameters, baseline is defined as the average of the measured ECG intervals from the three pre-dose time points (45, 30, and 15 min pre-dose) on Day 1.

  Pre-dose at following timepoints -2 h, -45 min, -30 min, -15 min. Then at following timepoints; 0, 5 min, 15 min, 30 min, 1 h, 2h, 3h, 4h, 5h, 6h, 8h, 12h and 24h post-dose.

Secondary Outcomes (25)

• Relationship Between ΔΔQTc and Modufolin® (and Metabolites) Plasma Concentrations

  5 minute post-dose time point

• Change-from-baseline Heart Rate (ΔHR)

  Pre-dose at following timepoints -2 h, -45 min, -30 min, -15 min. Then at following timepoints; 0, 5 min, 15 min, 30 min, 1 h, 2h, 3h, 4h, 5h, 6h, 8h, 12h and 24h post-dose.

• Change-from-baseline PR (ΔPR)

  Pre-dose at following timepoints -2 h, -45 min, -30 min, -15 min. Then at following timepoints; 0, 5 min, 15 min, 30 min, 1 h, 2h, 3h, 4h, 5h, 6h, 8h, 12h and 24h post-dose.

• Change-from-baseline QRS (ΔQRS)

  Pre-dose at following timepoints -2 h, -45 min, -30 min, -15 min. Then at following timepoints; 0, 5 min, 15 min, 30 min, 1 h, 2h, 3h, 4h, 5h, 6h, 8h, 12h and 24h post-dose.

• Number of Participants With Categorical QTcF Outliers

  Pre-dose at following timepoints -2 h, -45 min, -30 min, -15 min. Then at following timepoints; 0, 5 min, 15 min, 30 min, 1 h, 2h, 3h, 4h, 5h, 6h, 8h, 12h and 24h post-dose.

Study Arms (2)

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

ACTIVE COMPARATOR

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

Drug: Modufolin (arfolitixorin)

0.9% NaCl sterile solution

PLACEBO COMPARATOR

Three cohorts, 3 subjects will be randomised to placebo

Drug: Modufolin (arfolitixorin)

Interventions

Modufolin (arfolitixorin) 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)

Also known as: arfolitixorin

0.9% NaCl sterile solution; Modufolin® for injection, 200, 350 and 500 mg/m2

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Willing and able to provide a written informed consent for participation in the study.
• Healthy male subject aged 18-60 years inclusive.
• 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
• Clinically normal medical history, physical findings, vital signs, ECG and laboratory values at the time of screening, as judged by the Investigator.
• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Isofol Medical AB: lead

Study Sites (1)

CTC Clinical Trial Consultants

Uppsala, 75185, Sweden

Location

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Isofol Medical AB

karin.ganlov@isofolmedical.com

+46 (0)707646500

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: IMP (Modufolin® for Injection, 100 mg) and Placebo are not identical in appearance and all efforts will be made at the clinic in order to maintain the blind. Both the IMP and the placebo will be masked in such a way that study subjects and study staff will remain blinded during the study. An un-blinded study nurse will prepare the IMP/placebo for injection and will administer the IMP/placebo to the study subject. The un-blinded study nurse performing the dose administration will not be involved in any study-specific assessments or evaluations.
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: An adaptive, randomized, double-blind, single-center, placebo-controlled

Study Record Dates

• First Submitted: June 22, 2017
• First Posted: June 29, 2017
• Study Start: July 4, 2017
• Primary Completion: August 25, 2017
• Study Completion: August 25, 2017
• Last Updated: September 25, 2020
• Results First Posted: March 19, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)