Phase I Study in Healthy Volunteers to Evaluate ECG EffectPhase 1NCT03203564
Study Evaluating ECG Effects, Safety, Tolerability and Pharmacokinetics of Single Doses of Modufolin (Arfolitixorin) in Healthy Volunteers Tetrahydrofolate in Healthy Male Volunteers
A Phase 1 study testing Modufolin (arfolitixorin) in people with Phase I Study in Healthy Volunteers to Evaluate ECG Effect, run by Isofol Medical AB at 1 site in Sweden.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 to 60 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Phase I Study in Healthy Volunteers to Evaluate ECG Effect
- What is being tested?
- Modufolin (arfolitixorin)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 33 participants
- Where
- 1 siteSweden
- Study dates
- 4 Jul 2017to 25 Aug 2017
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 9Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Adaptive, Randomized, Double-blind, Single-center, Placebo-controlled Phase I Study Evaluating ECG Effects, Safety and Pharmacokinetics of Single Ascending Doses of [6R]-5,10-Methylene Tetrahydrofolate (Modufolin® for Injection, 100mg) 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
Read the 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.
- Being tested
- Modufolin (arfolitixorin)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Modufolin (arfolitixorin)Drug
Also called 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)
| Study group | Role | What they receive |
|---|---|---|
| Modufolin® for injection, 200, 350 and 500 mg/m2 | Active comparator | Three cohorts, 8 subjects will be randomised to Modufolin ® for injection 100 mg Receives: Drug: Modufolin (arfolitixorin) |
| 0.9% NaCl sterile solution | Placebo comparator | Three cohorts, 3 subjects will be randomised to placebo Receives: Drug: Modufolin (arfolitixorin) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Predicted ΔΔQTcF interval at geometric mean Cmax for 5,10-MTHF, THF, and 5-Formyl-THF and geometric mean concentration of 5-Methyl-THF observed at 5 minutes post-dose The relationship between plasma concentrations of 5,10-MTHF, THF, 5-Methyl-THF, and 5-Formyl-THF, and change-from-baseline QTcF (ΔQTcF) was quantified using a linear mixed-effects modeling approach with separate analyses for each of the analytes (5,10-MTHF, THF 5-Methyl-THF, and 5-Formyl-THF) initially, with ΔQTcF as the dependent variable, plasma concentration of 5,10-MTHF (or THF, 5-Methyl-THF, or 5-Formyl-THF) as a continuous covariate (i.e., 0 for placebo), centered baseline QTcF as an additional covariate, treatment (active = 1 or placebo = 0) and time (i.e., time point) as categorical factors, and a random intercept and slope per subject. The degrees of freedom estimates were determined by the Kenward-Roger method.
Measured: 5 minute post-dose time point
Change-from-baseline Heart Rate (ΔHR)
The analysis was based on the change-from-baseline post-dosing values. The same (by-time point analysis) model was used as described for QTcF. 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 predose) on Day 1.
Measured: 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)
The analysis was based on the change-from-baseline post-dosing values. The same (by-time point analysis) model was used as described for QTcF. 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 predose) on Day 1.
Measured: 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)
The analysis was based on the change-from-baseline post-dosing values. The same (by-time point analysis) model was used as described for QTcF. 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 predose) on Day 1.
Measured: 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
QTcF outliers per absolute category across treatment groups and QTcF outliers per change-from-baseline category (ΔQTcF)
Measured: 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.
Categorical Outliers for HR, PR Interval, QRS Interval
Categorical Analysis of outliers for HR, PR, and QRS intervals
Measured: 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.
Categorical Analysis for T Wave Morphology
Categorical T-wave morphology analysis and measurement of PR and QRS intervals were fully performed manually in three of the 10 ECG replicates at each time point. Final quality control and diagnostic interpretations were performed by the study cardiologist. When the results for each time point were compiled in the final data set, the comparison was made between ECG parameters from the three manually reviewed ECGs versus the 10 ECG replicates for quality control purposes. No treatment emergent T wave morphology changes were observed. In addition to the T-wave categorical analysis, the presence of abnormal U-waves was noted.
Measured: 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.
Physical Examination
A complete physical examination included assessments of the head, eyes, ears, nose, throat, skin, thyroid, neurological, lungs, cardiovascular, abdomen (liver and spleen), lymph nodes and extremities.
Physical examination findings were categorized as Normal, Abnormal non-clinical significant (NCS), and Abnormal clinical significant (CS).
Measured: At visit 1 (screening) and follow-up
Systolic Blood Pressure
Systolic and diastolic BP and pulse were measured in supine position after 10 min of rest.
Measured: Predose at following timepoints: At screening (visit 1) and at -15 min (visit 2). Postdose at following timepoints: 3h, 5h, 8 h and 24h (visit 2) and at visit 3 (follow-up visit).
Diastolic Blood Pressure
Systolic and diastolic BP and pulse were measured in supine position after 10 min of rest.
There were no clinically relevant mean changes over time or any individual changes assessed as clinically significant with regards to any of the vital signs parameters.
Measured: Predose at following timepoints: At screening (visit 1) and at -15 min (visit 2). Postdose at following timepoints: 3h, 5h, 8 h and 24h (visit 2) and at visit 3 (follow-up visit).
Vital Signs: Pulse
Systolic and diastolic BP and pulse were measured in supine position after 10 min of rest.
There were no clinically relevant mean changes over time or any individual changes assessed as clinically significant with regards to any of the vital signs parameters.
Measured: Predose at following timepoints: At screening (visit 1) and at -15 min (visit 2). Postdose at following timepoints: 3h, 5h, 8 h and 24h (visit 2) and at visit 3 (follow-up visit).
Safety Laboratory Measurements
The following safety laboratory parameters were assessed:
Clinical Chemistry: Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), Albumin, Aspartate aminotransferase (AST), Bilirubin (total and conjugated), Calcium, Chloride, Creatinine, Magnesium, Phosphorous, Potassium, Sodium, Urea nitrogen, Uric acid. Haematology: Haematocrit, Haemoglobin (Hb), Platelet count, Red blood cell (RBC) count, White blood cell (WBC) count with differential count. Urinalysis (dip stick):Glucose, Erythrocytes, Nitrite, Protein, Specific gravity, pH.
Measured: Pre-dose at screening (visit 1) and -2h (visit 2). Post-dose at following timepoints: 24 h (visit 2) and at follow-up (visit 3)
Frequency, Seriousness and Intensity of AEs
An overall summary of AEs occurring after first administration of IMP (TEAE) is presented by treatment
Measured: From start of IMP administration to follow-up visit
Plasma PK Characteristics: C0
The mean back-extrapolated concentration at time 0 h (C0) was calculated for MTHF
Measured: Pre-dose at -15 min and post-dose at following timepoints: 5 min, 15 min, 30 min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 12h, 24h. pre-dose to 24 h post-dose
Plasma PK Characteristics: C5min
Measured concentration at 5 min post dose (C5min) of MTHF and 5-Formyl-THF
Measured: Pre-dose at -15 min and post-dose at following timepoints: 5 min, 15 min, 30 min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 12h, 24h
Plasma PK Characteristics: AUClast
Pharmacokinetic parameters were calculated for test item MTHF, and for the following metabolites: 5-Formyl-THF, 5-Methyl-THF, and THF, if data permitted
Measured: Pre-dose at -15 min and post-dose at following timepoints: 5 min, 15 min, 30 min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 12h, 24h.
Plasma PK Characteristics: AUClast/Dose
Pharmacokinetic parameters were calculated for test item MTHF, and for the following metabolites: 5-Formyl-THF, 5-Methyl-THF, and THF, if data permitted.
Measured: Pre-dose at -15 min and post-dose at following timepoints: 5 min, 15 min, 30 min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 12h, 24h.
Plasma PK Characteristics: Timepoint for Last Measured Plasma Concentration (Tlast)
Pharmacokinetic parameters were calculated for test item MTHF, and for the following metabolites: 5-Formyl-THF, 5-Methyl-THF, and THF, if data permitted.
Measured: Pre-dose at -15 min and post-dose at following timepoints: 5 min, 15 min, 30 min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 12h, 24h.
Plasma PK Characteristics: t1/2
Pharmacokinetic parameters were calculated for test item MTHF, and for the following metabolites: 5-Formyl-THF, 5-Methyl-THF, and THF, if data permitted:
Measured: Pre-dose at -15 min and post-dose at following timepoints: 5 min, 15 min, 30 min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 12h, 24h.
Plasma PK Characteristics: CL
Pharmacokinetic parameters were calculated for test item MTHF, and for the following metabolites: 5-Formyl-THF, 5-Methyl-THF, and THF, if data permitted.
Measured: Pre-dose at -15 min and post-dose at following timepoints: 5 min, 15 min, 30 min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 12h, 24h.
Plasma PK Characteristics: Vss
Pharmacokinetic parameters were calculated for test item MTHF, and for the following metabolites: 5-Formyl-THF, 5-Methyl-THF, and THF, if data permitted
Measured: Pre-dose at -15 min and post-dose at following timepoints: 5 min, 15 min, 30 min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 12h, 24h
Plasma PK Characteristics: Cmax
Pharmacokinetic parameters were calculated for test item MTHF, and for the following metabolites: 5-Formyl-THF, 5-Methyl-THF, and THF, if data permitted
Measured: Pre-dose at -15 min and post-dose at following timepoints: 5 min, 15 min, 30 min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 12h, 24h.
Plasma PK Characteristics: Tmax
Pharmacokinetic parameters were calculated for test item MTHF, and for the following metabolites: 5-Formyl-THF, 5-Methyl-THF, and THF, if data permitted
Measured: Pre-dose at -15 min and post-dose at following timepoints: 5 min, 15 min, 30 min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 12h, 24h.
Plasma PK Characteristics: Cmax/Dose for Metabolite 5-Formyl-THF
Pharmacokinetic parameters were calculated for test item MTHF, and for the following metabolites: 5-Formyl-THF, 5-Methyl-THF, and THF, if data permitted. Only the metabolite 5-Formyl-THF has values above LLOQ and are presented below.
Measured: Pre-dose at -15 min and post-dose at following timepoints: 5 min, 15 min, 30 min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 12h, 24h
Number of Subjects With AEs
An overall summary of subjects with AEs occurring after first administration of IMP (TEAE), number of related TEAEs and number of withdrawals due to TEAEs are presented by treatment
Measured: From start of IMP administration to follow-up visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jun 2017
- Study start4 Jul 2017
- Primary completion25 Aug 2017
- Study completion25 Aug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Phase I Study in Healthy Volunteers to Evaluate ECG EffectStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Single group
- Model description
- An adaptive, randomized, double-blind, single-center, placebo-controlled
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Isofol Medical AB
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03203564
- Sponsor's protocol ID
- ISO-FF-001
- Status last verified
- Sep 2020
- First submitted
- 22 Jun 2017
- Last updated
- 25 Sep 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Adaptive, Randomized, Double-blind, Single-center, Placebo-controlled Phase I Study Evaluating ECG Effects, Safety and Pharmacokinetics of Single Ascending Doses of [6R]-5,10-Methylene Tetrahydrofolate (Modufolin® for Injection, 100mg) in Healthy Male Volunteers
- ClinicalTrials.gov ID
- NCT03203564
- Acronym / sponsor ID
- ISO-FF-001
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Isofol Medical ABIndustry (pharma, biotech, devices)
- Study start
- 4 Jul 2017 (actual)
- Primary completion
- 25 Aug 2017 (actual)
- Study completion
- 25 Aug 2017 (actual)
- First posted
- 29 Jun 2017 (actual)
- Results
- Posted 19 Mar 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- An adaptive, randomized, double-blind, single-center, placebo-controlled
| Arm | Type | Receives |
|---|---|---|
| Modufolin® for injection, 200, 350 and 500 mg/m2 | Active comparator | Drug: Modufolin (arfolitixorin)Three cohorts, 8 subjects will be randomised to Modufolin ® for injection 100 mg |
| 0.9% NaCl sterile solution | Placebo comparator | Drug: Modufolin (arfolitixorin)Three cohorts, 3 subjects will be randomised to placebo |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (9 listed)
- 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:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Modufolin (arfolitixorin)Also: arfolitixorinThirty-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) | Drug | 0.9% NaCl sterile solution, Modufolin® for injection, 200, 350 and 500 mg/m2 |
Primary outcome
Change-from-baseline QTcF (ΔQTcF)
Time frame: 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.
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.
25 secondary outcomes
Relationship Between ΔΔQTc and Modufolin® (and Metabolites) Plasma Concentrations
Time frame: 5 minute post-dose time point
Change-from-baseline Heart Rate (ΔHR)
Time frame: 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)
Time frame: 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)
Time frame: 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
Time frame: 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.
Categorical Outliers for HR, PR Interval, QRS Interval
Time frame: 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.
Categorical Analysis for T Wave Morphology
Time frame: 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.
Physical Examination
Time frame: At visit 1 (screening) and follow-up
Systolic Blood Pressure
Time frame: Predose at following timepoints: At screening (visit 1) and at -15 min (visit 2). Postdose at following timepoints: 3h, 5h, 8 h and 24h (visit 2) and at visit 3 (follow-up visit).
Diastolic Blood Pressure
Time frame: Predose at following timepoints: At screening (visit 1) and at -15 min (visit 2). Postdose at following timepoints: 3h, 5h, 8 h and 24h (visit 2) and at visit 3 (follow-up visit).
Vital Signs: Pulse
Time frame: Predose at following timepoints: At screening (visit 1) and at -15 min (visit 2). Postdose at following timepoints: 3h, 5h, 8 h and 24h (visit 2) and at visit 3 (follow-up visit).
Safety Laboratory Measurements
Time frame: Pre-dose at screening (visit 1) and -2h (visit 2). Post-dose at following timepoints: 24 h (visit 2) and at follow-up (visit 3)
Frequency, Seriousness and Intensity of AEs
Time frame: From start of IMP administration to follow-up visit
Plasma PK Characteristics: C0
Time frame: Pre-dose at -15 min and post-dose at following timepoints: 5 min, 15 min, 30 min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 12h, 24h. pre-dose to 24 h post-dose
Plasma PK Characteristics: C5min
Time frame: Pre-dose at -15 min and post-dose at following timepoints: 5 min, 15 min, 30 min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 12h, 24h
Plasma PK Characteristics: AUClast
Time frame: Pre-dose at -15 min and post-dose at following timepoints: 5 min, 15 min, 30 min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 12h, 24h.
Plasma PK Characteristics: AUClast/Dose
Time frame: Pre-dose at -15 min and post-dose at following timepoints: 5 min, 15 min, 30 min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 12h, 24h.
Plasma PK Characteristics: Timepoint for Last Measured Plasma Concentration (Tlast)
Time frame: Pre-dose at -15 min and post-dose at following timepoints: 5 min, 15 min, 30 min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 12h, 24h.
Plasma PK Characteristics: t1/2
Time frame: Pre-dose at -15 min and post-dose at following timepoints: 5 min, 15 min, 30 min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 12h, 24h.
Plasma PK Characteristics: CL
Time frame: Pre-dose at -15 min and post-dose at following timepoints: 5 min, 15 min, 30 min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 12h, 24h.
Plasma PK Characteristics: Vss
Time frame: Pre-dose at -15 min and post-dose at following timepoints: 5 min, 15 min, 30 min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 12h, 24h
Plasma PK Characteristics: Cmax
Time frame: Pre-dose at -15 min and post-dose at following timepoints: 5 min, 15 min, 30 min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 12h, 24h.
Plasma PK Characteristics: Tmax
Time frame: Pre-dose at -15 min and post-dose at following timepoints: 5 min, 15 min, 30 min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 12h, 24h.
Plasma PK Characteristics: Cmax/Dose for Metabolite 5-Formyl-THF
Time frame: Pre-dose at -15 min and post-dose at following timepoints: 5 min, 15 min, 30 min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 12h, 24h
Number of Subjects With AEs
Time frame: From start of IMP administration to follow-up visit
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Modufolin (arfolitixorin) in people with Phase I Study in Healthy Volunteers to Evaluate ECG Effect, run by Isofol Medical AB at 1 site in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change-from-baseline QTcF (ΔQTcF) (time frame: 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2020.