Trial Outcomes & Findings for Study Evaluating ECG Effects, Safety, Tolerability and Pharmacokinetics of Single Doses of Modufolin (Arfolitixorin) in Healthy Volunteers Tetrahydrofolate in Healthy Male Volunteers (NCT NCT03203564)
NCT ID: NCT03203564
Last Updated: 2020-09-25
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
33 participants
Primary outcome timeframe
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.
Results posted on
2020-09-25
Participant Flow
Subjects were recruited from a database of healthy volunteers at CTC and from advertising in media, including social media.
Subjects were screened for eligibility according to study-specific inclusion/exclusion criteria within four weeks prior to start of study treatment (Visit 1; Screening Visit).
Participant milestones
| Measure |
200 mg/m2 of Modufolin®
8 subjects were treated with 200 mg/m2 of Modufolin® as an intravenous bolus injection.
|
350 mg/m2 of Modufolin®
8 subjects were treated with 350 mg/m2 of Modufolin® as an intravenous bolus injection.
|
500 mg/m2 of Modufolin®
8 subjects were treated with 500 mg/m2 of Modufolin® as an intravenous bolus injection.
|
Placebo
9 subjects were treated with placebo as an intravenous bolus injection.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
8
|
8
|
8
|
9
|
|
Overall Study
COMPLETED
|
8
|
8
|
8
|
9
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study Evaluating ECG Effects, Safety, Tolerability and Pharmacokinetics of Single Doses of Modufolin (Arfolitixorin) in Healthy Volunteers Tetrahydrofolate in Healthy Male Volunteers
Baseline characteristics by cohort
| Measure |
200 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 200 mg/m2 of Modufolin® as an intravenous bolus injection.
|
350 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 350 mg/m2 of Modufolin® as an intravenous bolus injection.
|
500 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 500 mg/m2 of Modufolin® as an intravenous bolus injection.
|
Placebo
n=9 Participants
9 subjects were treated with placebo as an intravenous bolus injection.
|
Total
n=33 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
8 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
33 Participants
n=21 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
33 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
7 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
31 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Region of Enrollment
Sweden
|
8 participants
n=5 Participants
|
8 participants
n=7 Participants
|
8 participants
n=5 Participants
|
9 participants
n=4 Participants
|
33 participants
n=21 Participants
|
PRIMARY outcome
Timeframe: 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.Population: The QT/QTc Analysis Set includes all subjects in the Safety Analysis Set with measurements at baseline as well as on-treatment with at least one post-dose time point with a valid ΔQTcF (change from baseline QTcF) value.
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.
Outcome measures
| Measure |
200 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 200 mg/m2 of Modufolin® as an intravenous bolus injection.
|
350 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 350 mg/m2 of Modufolin® as an intravenous bolus injection.
|
500 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 500 mg/m2 of Modufolin® as an intravenous bolus injection.
|
Placebo
n=9 Participants
9 subjects were treated with placebo as an intravenous bolus injection.
|
|---|---|---|---|---|
|
Change-from-baseline QTcF (ΔQTcF)
5 min post-dose
|
11.2 msec
Standard Error 2.28
|
9.1 msec
Standard Error 2.28
|
22.4 msec
Standard Error 2.31
|
0.0 msec
Standard Error 2.16
|
|
Change-from-baseline QTcF (ΔQTcF)
15 min post-dose
|
3.1 msec
Standard Error 1.48
|
7.5 msec
Standard Error 1.47
|
12.4 msec
Standard Error 1.51
|
0.2 msec
Standard Error 1.40
|
|
Change-from-baseline QTcF (ΔQTcF)
1 h post-dose
|
-1.2 msec
Standard Error 1.38
|
-0.7 msec
Standard Error 1.38
|
-0.9 msec
Standard Error 1.42
|
1.4 msec
Standard Error 1.32
|
|
Change-from-baseline QTcF (ΔQTcF)
2 h post-dose
|
-3.5 msec
Standard Error 1.97
|
-1.7 msec
Standard Error 1.96
|
1.0 msec
Standard Error 1.99
|
0.7 msec
Standard Error 1.86
|
|
Change-from-baseline QTcF (ΔQTcF)
3 h post-dose
|
-2.8 msec
Standard Error 2.58
|
-0.8 msec
Standard Error 2.58
|
0.9 msec
Standard Error 2.60
|
3.8 msec
Standard Error 2.44
|
|
Change-from-baseline QTcF (ΔQTcF)
End of infusion
|
2.8 msec
Standard Error 2.85
|
9.2 msec
Standard Error 2.84
|
8.5 msec
Standard Error 2.87
|
1.1 msec
Standard Error 2.69
|
|
Change-from-baseline QTcF (ΔQTcF)
30 min post-dose
|
1.2 msec
Standard Error 1.43
|
2.5 msec
Standard Error 1.42
|
4.2 msec
Standard Error 1.47
|
0.8 msec
Standard Error 1.36
|
|
Change-from-baseline QTcF (ΔQTcF)
4 h post-dose
|
-3.3 msec
Standard Error 2.70
|
0.7 msec
Standard Error 2.70
|
0.0 msec
Standard Error 2.72
|
2.6 msec
Standard Error 2.55
|
|
Change-from-baseline QTcF (ΔQTcF)
5 h post-dose
|
5.4 msec
Standard Error 3.25
|
2.6 msec
Standard Error 3.37
|
0.8 msec
Standard Error 3.27
|
11.5 msec
Standard Error 3.07
|
|
Change-from-baseline QTcF (ΔQTcF)
6 h post-dose
|
-0.8 msec
Standard Error 2.73
|
-2.5 msec
Standard Error 2.72
|
-6.7 msec
Standard Error 2.75
|
6.4 msec
Standard Error 2.58
|
|
Change-from-baseline QTcF (ΔQTcF)
8 h post-dose
|
-5.5 msec
Standard Error 2.91
|
-5.5 msec
Standard Error 2.90
|
-7.7 msec
Standard Error 2.93
|
-0.9 msec
Standard Error 2.75
|
|
Change-from-baseline QTcF (ΔQTcF)
12 h post-dose
|
-4.5 msec
Standard Error 2.86
|
-6.6 msec
Standard Error 2.86
|
-4.1 msec
Standard Error 2.95
|
2.8 msec
Standard Error 2.70
|
|
Change-from-baseline QTcF (ΔQTcF)
24 h post-dose
|
-5.9 msec
Standard Error 2.85
|
-8.1 msec
Standard Error 2.84
|
-4.6 msec
Standard Error 3.01
|
-1.3 msec
Standard Error 2.69
|
SECONDARY outcome
Timeframe: 5 minute post-dose time pointPredicted 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.
Outcome measures
| Measure |
200 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 200 mg/m2 of Modufolin® as an intravenous bolus injection.
|
350 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 350 mg/m2 of Modufolin® as an intravenous bolus injection.
|
500 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 500 mg/m2 of Modufolin® as an intravenous bolus injection.
|
Placebo
9 subjects were treated with placebo as an intravenous bolus injection.
|
|---|---|---|---|---|
|
Relationship Between ΔΔQTc and Modufolin® (and Metabolites) Plasma Concentrations
5,10-MTHF
|
24111.78 msec / ng/mL
Interval 19194.04 to 30289.52
|
51566.94 msec / ng/mL
Interval 46351.78 to 57368.87
|
69012.28 msec / ng/mL
Interval 60609.82 to 78579.59
|
—
|
|
Relationship Between ΔΔQTc and Modufolin® (and Metabolites) Plasma Concentrations
THF
|
15995.29 msec / ng/mL
Interval 13750.28 to 18606.83
|
29386.77 msec / ng/mL
Interval 26812.58 to 32208.09
|
44018.37 msec / ng/mL
Interval 40400.31 to 47960.44
|
—
|
|
Relationship Between ΔΔQTc and Modufolin® (and Metabolites) Plasma Concentrations
5-Methyl-THF
|
218.18 msec / ng/mL
Interval 176.04 to 270.4
|
544.01 msec / ng/mL
Interval 435.7 to 679.25
|
333.09 msec / ng/mL
Interval 279.56 to 396.86
|
—
|
|
Relationship Between ΔΔQTc and Modufolin® (and Metabolites) Plasma Concentrations
5-Formyl-THF
|
296.43 msec / ng/mL
Interval 114.76 to 765.71
|
567.17 msec / ng/mL
Interval 414.42 to 776.22
|
379.33 msec / ng/mL
Interval 333.23 to 431.81
|
—
|
|
Relationship Between ΔΔQTc and Modufolin® (and Metabolites) Plasma Concentrations
ΔΔQTcF
|
4.15 msec / ng/mL
Interval 0.97 to 7.33
|
13.25 msec / ng/mL
Interval 9.36 to 17.14
|
19.88 msec / ng/mL
Interval 15.4 to 24.35
|
—
|
SECONDARY outcome
Timeframe: 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.Population: QT/QTc population.
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.
Outcome measures
| Measure |
200 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 200 mg/m2 of Modufolin® as an intravenous bolus injection.
|
350 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 350 mg/m2 of Modufolin® as an intravenous bolus injection.
|
500 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 500 mg/m2 of Modufolin® as an intravenous bolus injection.
|
Placebo
n=9 Participants
9 subjects were treated with placebo as an intravenous bolus injection.
|
|---|---|---|---|---|
|
Change-from-baseline Heart Rate (ΔHR)
1 h post-dose
|
5.0 bpm
Standard Error 1.90
|
0.0 bpm
Standard Error 1.90
|
-0.9 bpm
Standard Error 1.91
|
-1.3 bpm
Standard Error 1.79
|
|
Change-from-baseline Heart Rate (ΔHR)
2 h post-dose
|
3.2 bpm
Standard Error 1.52
|
-0.1 bpm
Standard Error 1.52
|
-2.6 bpm
Standard Error 1.53
|
-1.8 bpm
Standard Error 1.43
|
|
Change-from-baseline Heart Rate (ΔHR)
End of infusion
|
2.6 bpm
Standard Error 1.91
|
2.7 bpm
Standard Error 1.91
|
2.0 bpm
Standard Error 1.92
|
-2.1 bpm
Standard Error 1.80
|
|
Change-from-baseline Heart Rate (ΔHR)
5 min post-dose
|
8.2 bpm
Standard Error 2.56
|
7.4 bpm
Standard Error 2.55
|
13.3 bpm
Standard Error 2.56
|
0.0 bpm
Standard Error 2.41
|
|
Change-from-baseline Heart Rate (ΔHR)
15 min post-dose
|
3.9 bpm
Standard Error 1.63
|
3.6 bpm
Standard Error 1.63
|
2.6 bpm
Standard Error 1.64
|
-1.6 bpm
Standard Error 1.53
|
|
Change-from-baseline Heart Rate (ΔHR)
30 min post-dose
|
3.3 bpm
Standard Error 2.00
|
1.3 bpm
Standard Error 2.00
|
3.0 bpm
Standard Error 2.00
|
-0.7 bpm
Standard Error 1.88
|
|
Change-from-baseline Heart Rate (ΔHR)
3 h post-dose
|
2.2 bpm
Standard Error 1.47
|
0.3 bpm
Standard Error 1.46
|
0.3 bpm
Standard Error 1.47
|
-2.3 bpm
Standard Error 1.38
|
|
Change-from-baseline Heart Rate (ΔHR)
4 h post-dose
|
1.7 bpm
Standard Error 1.82
|
2.0 bpm
Standard Error 1.82
|
0.2 bpm
Standard Error 1.83
|
-3.3 bpm
Standard Error 1.72
|
|
Change-from-baseline Heart Rate (ΔHR)
5 h post-dose
|
11.9 bpm
Standard Error 2.06
|
12.4 bpm
Standard Error 2.12
|
8.9 bpm
Standard Error 2.06
|
9.5 bpm
Standard Error 1.94
|
|
Change-from-baseline Heart Rate (ΔHR)
6 h post-dose
|
8.3 bpm
Standard Error 2.52
|
12.5 bpm
Standard Error 2.52
|
6.2 bpm
Standard Error 2.53
|
5.4 bpm
Standard Error 2.38
|
|
Change-from-baseline Heart Rate (ΔHR)
8 h post-dose
|
8.1 bpm
Standard Error 2.24
|
8.0 bpm
Standard Error 2.23
|
2.5 bpm
Standard Error 2.24
|
2.1 bpm
Standard Error 2.11
|
|
Change-from-baseline Heart Rate (ΔHR)
12 h post-dose
|
7.6 bpm
Standard Error 2.41
|
5.3 bpm
Standard Error 2.41
|
3.6 bpm
Standard Error 2.54
|
0.6 bpm
Standard Error 2.27
|
|
Change-from-baseline Heart Rate (ΔHR)
24 h post-dose
|
6.0 bpm
Standard Error 2.80
|
5.7 bpm
Standard Error 2.80
|
8.0 bpm
Standard Error 3.00
|
8.6 bpm
Standard Error 2.64
|
SECONDARY outcome
Timeframe: 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.Population: QT/QTc population
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.
Outcome measures
| Measure |
200 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 200 mg/m2 of Modufolin® as an intravenous bolus injection.
|
350 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 350 mg/m2 of Modufolin® as an intravenous bolus injection.
|
500 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 500 mg/m2 of Modufolin® as an intravenous bolus injection.
|
Placebo
n=9 Participants
9 subjects were treated with placebo as an intravenous bolus injection.
|
|---|---|---|---|---|
|
Change-from-baseline PR (ΔPR)
5 h post-dose
|
-8.8 msec
Standard Error 2.59
|
-7.1 msec
Standard Error 2.71
|
-7.8 msec
Standard Error 2.59
|
-3.5 msec
Standard Error 2.44
|
|
Change-from-baseline PR (ΔPR)
End of infusion
|
-1.6 msec
Standard Error 2.08
|
-4.4 msec
Standard Error 2.08
|
-2.1 msec
Standard Error 2.08
|
-1.6 msec
Standard Error 1.96
|
|
Change-from-baseline PR (ΔPR)
5 min post-dose
|
-1.5 msec
Standard Error 2.07
|
-4.5 msec
Standard Error 2.07
|
-3.1 msec
Standard Error 2.07
|
-0.1 msec
Standard Error 1.96
|
|
Change-from-baseline PR (ΔPR)
15 min post-dose
|
-2.3 msec
Standard Error 2.61
|
-1.2 msec
Standard Error 2.61
|
0.2 msec
Standard Error 2.61
|
3.8 msec
Standard Error 2.46
|
|
Change-from-baseline PR (ΔPR)
30 min post-dose
|
-1.7 msec
Standard Error 2.11
|
-3.7 msec
Standard Error 2.11
|
1.3 msec
Standard Error 2.11
|
2.9 msec
Standard Error 1.99
|
|
Change-from-baseline PR (ΔPR)
1 h post-dose
|
-5.2 msec
Standard Error 1.89
|
-3.6 msec
Standard Error 1.89
|
-0.3 msec
Standard Error 1.89
|
0.4 msec
Standard Error 1.79
|
|
Change-from-baseline PR (ΔPR)
2 h post-dose
|
-4.1 msec
Standard Error 2.13
|
-4.1 msec
Standard Error 2.13
|
1.1 msec
Standard Error 2.13
|
3.1 msec
Standard Error 2.01
|
|
Change-from-baseline PR (ΔPR)
3 h post-dose
|
-5.3 msec
Standard Error 2.14
|
-4.2 msec
Standard Error 2.14
|
-1.6 msec
Standard Error 2.14
|
1.2 msec
Standard Error 2.02
|
|
Change-from-baseline PR (ΔPR)
4 h post-dose
|
-5.2 msec
Standard Error 1.84
|
-4.6 msec
Standard Error 1.84
|
-2.1 msec
Standard Error 1.84
|
1.4 msec
Standard Error 1.74
|
|
Change-from-baseline PR (ΔPR)
6 h post-dose
|
-9.4 msec
Standard Error 2.04
|
-8.4 msec
Standard Error 2.04
|
-5.8 msec
Standard Error 2.04
|
-3.9 msec
Standard Error 1.93
|
|
Change-from-baseline PR (ΔPR)
8 h post-dose
|
-8.6 msec
Standard Error 2.62
|
-7.2 msec
Standard Error 2.62
|
-4.3 msec
Standard Error 2.62
|
-5.6 msec
Standard Error 2.47
|
|
Change-from-baseline PR (ΔPR)
12 h post-dose
|
-7.9 msec
Standard Error 3.12
|
-1.5 msec
Standard Error 3.12
|
-6.9 msec
Standard Error 3.22
|
-1.7 msec
Standard Error 2.94
|
|
Change-from-baseline PR (ΔPR)
24 h post-dose
|
-5.9 msec
Standard Error 2.77
|
-5.6 msec
Standard Error 2.77
|
-6.4 msec
Standard Error 2.88
|
-6.8 msec
Standard Error 2.61
|
SECONDARY outcome
Timeframe: 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.Population: QT/QTc population
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.
Outcome measures
| Measure |
200 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 200 mg/m2 of Modufolin® as an intravenous bolus injection.
|
350 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 350 mg/m2 of Modufolin® as an intravenous bolus injection.
|
500 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 500 mg/m2 of Modufolin® as an intravenous bolus injection.
|
Placebo
n=9 Participants
9 subjects were treated with placebo as an intravenous bolus injection.
|
|---|---|---|---|---|
|
Change-from-baseline QRS (ΔQRS)
End of infusion
|
-0.1 msec
Standard Error 0.27
|
-0.2 msec
Standard Error 0.27
|
-0.1 msec
Standard Error 0.27
|
0.5 msec
Standard Error 0.25
|
|
Change-from-baseline QRS (ΔQRS)
5 min post-dose
|
-0.7 msec
Standard Error 0.28
|
-0.8 msec
Standard Error 0.28
|
-1.2 msec
Standard Error 0.28
|
0.0 msec
Standard Error 0.26
|
|
Change-from-baseline QRS (ΔQRS)
15 min post-dose
|
-0.2 msec
Standard Error 0.25
|
-0.3 msec
Standard Error 0.25
|
-0.1 msec
Standard Error 0.25
|
0.0 msec
Standard Error 0.24
|
|
Change-from-baseline QRS (ΔQRS)
30 min post-dose
|
-0.7 msec
Standard Error 0.27
|
0.0 msec
Standard Error 0.27
|
-0.5 msec
Standard Error 0.27
|
0.0 msec
Standard Error 0.26
|
|
Change-from-baseline QRS (ΔQRS)
1 h post-dose
|
-0.2 msec
Standard Error 0.26
|
0.1 msec
Standard Error 0.26
|
0.2 msec
Standard Error 0.26
|
0.0 msec
Standard Error 0.24
|
|
Change-from-baseline QRS (ΔQRS)
2 h post-dose
|
-0.2 msec
Standard Error 0.22
|
0.0 msec
Standard Error 0.22
|
-0.1 msec
Standard Error 0.22
|
-0.1 msec
Standard Error 0.21
|
|
Change-from-baseline QRS (ΔQRS)
3 h post-dose
|
0.0 msec
Standard Error 0.30
|
-0.1 msec
Standard Error 0.31
|
-0.4 msec
Standard Error 0.30
|
0.2 msec
Standard Error 0.29
|
|
Change-from-baseline QRS (ΔQRS)
4 h post-dose
|
0.1 msec
Standard Error 0.39
|
-0.5 msec
Standard Error 0.39
|
0.2 msec
Standard Error 0.38
|
0.9 msec
Standard Error 0.36
|
|
Change-from-baseline QRS (ΔQRS)
5 h post-dose
|
0.4 msec
Standard Error 0.47
|
0.4 msec
Standard Error 0.49
|
0.1 msec
Standard Error 0.47
|
0.2 msec
Standard Error 0.45
|
|
Change-from-baseline QRS (ΔQRS)
6 h post-dose
|
-0.3 msec
Standard Error 0.52
|
-0.4 msec
Standard Error 0.52
|
-0.8 msec
Standard Error 0.52
|
-0.7 msec
Standard Error 0.49
|
|
Change-from-baseline QRS (ΔQRS)
8 h post-dose
|
-0.3 msec
Standard Error 0.53
|
-0.3 msec
Standard Error 0.53
|
-0.5 msec
Standard Error 0.53
|
-0.6 msec
Standard Error 0.50
|
|
Change-from-baseline QRS (ΔQRS)
12 h post-dose
|
0.5 msec
Standard Error 0.56
|
0.3 msec
Standard Error 0.56
|
-0.6 msec
Standard Error 0.58
|
-1.0 msec
Standard Error 0.53
|
|
Change-from-baseline QRS (ΔQRS)
24 h post-dose
|
0.0 msec
Standard Error 0.45
|
0.4 msec
Standard Error 0.45
|
-0.9 msec
Standard Error 0.47
|
-0.9 msec
Standard Error 0.42
|
SECONDARY outcome
Timeframe: 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.QTcF outliers per absolute category across treatment groups and QTcF outliers per change-from-baseline category (ΔQTcF)
Outcome measures
| Measure |
200 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 200 mg/m2 of Modufolin® as an intravenous bolus injection.
|
350 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 350 mg/m2 of Modufolin® as an intravenous bolus injection.
|
500 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 500 mg/m2 of Modufolin® as an intravenous bolus injection.
|
Placebo
n=9 Participants
9 subjects were treated with placebo as an intravenous bolus injection.
|
|---|---|---|---|---|
|
Number of Participants With Categorical QTcF Outliers
No. participants with ΔQTcF > 60 msec
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Categorical QTcF Outliers
No. participants with QTcF > 450 and ≤ 480 msec
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Categorical QTcF Outliers
No. participants with QTcF > 480 and ≤ 500 msec
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Categorical QTcF Outliers
No. participants with QTcF > 500 msec
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Categorical QTcF Outliers
No. participants with ΔQTcF of > 30 and ≤ 60 msec
|
0 Participants
|
0 Participants
|
2 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 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 of outliers for HR, PR, and QRS intervals
Outcome measures
| Measure |
200 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 200 mg/m2 of Modufolin® as an intravenous bolus injection.
|
350 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 350 mg/m2 of Modufolin® as an intravenous bolus injection.
|
500 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 500 mg/m2 of Modufolin® as an intravenous bolus injection.
|
Placebo
n=9 Participants
9 subjects were treated with placebo as an intravenous bolus injection.
|
|---|---|---|---|---|
|
Categorical Outliers for HR, PR Interval, QRS Interval
HR changes >25% decrease from baseline to <50 bpm
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Categorical Outliers for HR, PR Interval, QRS Interval
HR changes >25% increase from baseline to >100bpm
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Categorical Outliers for HR, PR Interval, QRS Interval
PR changes > 25% increase from baseline to >200ms
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Categorical Outliers for HR, PR Interval, QRS Interval
QRS changes > 25% increase from baseline to >120ms
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 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 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.
Outcome measures
| Measure |
200 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 200 mg/m2 of Modufolin® as an intravenous bolus injection.
|
350 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 350 mg/m2 of Modufolin® as an intravenous bolus injection.
|
500 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 500 mg/m2 of Modufolin® as an intravenous bolus injection.
|
Placebo
n=9 Participants
9 subjects were treated with placebo as an intravenous bolus injection.
|
|---|---|---|---|---|
|
Categorical Analysis for T Wave Morphology
Flat
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Categorical Analysis for T Wave Morphology
Notched (+)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Categorical Analysis for T Wave Morphology
Biphasic
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Categorical Analysis for T Wave Morphology
Normal (-)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Categorical Analysis for T Wave Morphology
Notched (-)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Categorical Analysis for T Wave Morphology
U wave presence
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: At visit 1 (screening) and follow-upA 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).
Outcome measures
| Measure |
200 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 200 mg/m2 of Modufolin® as an intravenous bolus injection.
|
350 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 350 mg/m2 of Modufolin® as an intravenous bolus injection.
|
500 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 500 mg/m2 of Modufolin® as an intravenous bolus injection.
|
Placebo
n=9 Participants
9 subjects were treated with placebo as an intravenous bolus injection.
|
|---|---|---|---|---|
|
Physical Examination
Abnormal NCS - Visit 1
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Physical Examination
Abnormal CS - Visit 1
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Physical Examination
Abnormal NCS - Follow-up
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Physical Examination
Abnormal CS - Follow-up
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 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).Systolic and diastolic BP and pulse were measured in supine position after 10 min of rest.
Outcome measures
| Measure |
200 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 200 mg/m2 of Modufolin® as an intravenous bolus injection.
|
350 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 350 mg/m2 of Modufolin® as an intravenous bolus injection.
|
500 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 500 mg/m2 of Modufolin® as an intravenous bolus injection.
|
Placebo
n=9 Participants
9 subjects were treated with placebo as an intravenous bolus injection.
|
|---|---|---|---|---|
|
Systolic Blood Pressure
Screening
|
115.50 mmHg
Standard Deviation 7.60
|
121.25 mmHg
Standard Deviation 7.07
|
116.63 mmHg
Standard Deviation 9.56
|
125.56 mmHg
Standard Deviation 14.82
|
|
Systolic Blood Pressure
Visit 2 Day 1 (-00:15)
|
111.38 mmHg
Standard Deviation 10.94
|
109.38 mmHg
Standard Deviation 9.36
|
117.38 mmHg
Standard Deviation 8.11
|
123.67 mmHg
Standard Deviation 24.63
|
|
Systolic Blood Pressure
Visit 2 Day 1 (03:00)
|
108.88 mmHg
Standard Deviation 7.12
|
105.00 mmHg
Standard Deviation 6.89
|
112.50 mmHg
Standard Deviation 9.29
|
111.22 mmHg
Standard Deviation 7.87
|
|
Systolic Blood Pressure
Visit 2 Day 1 (05:00)
|
115.50 mmHg
Standard Deviation 5.61
|
115.00 mmHg
Standard Deviation 8.50
|
120.88 mmHg
Standard Deviation 7.94
|
113.00 mmHg
Standard Deviation 13.32
|
|
Systolic Blood Pressure
Visit 2 Day 1 (08:00)
|
118.50 mmHg
Standard Deviation 9.06
|
113.88 mmHg
Standard Deviation 6.75
|
115.63 mmHg
Standard Deviation 5.83
|
114.89 mmHg
Standard Deviation 10.61
|
|
Systolic Blood Pressure
Visit 2 Day 2
|
117.75 mmHg
Standard Deviation 9.29
|
114.13 mmHg
Standard Deviation 5.77
|
120.88 mmHg
Standard Deviation 8.46
|
119.00 mmHg
Standard Deviation 10.02
|
|
Systolic Blood Pressure
Follow-up
|
121.38 mmHg
Standard Deviation 8.93
|
115.63 mmHg
Standard Deviation 11.03
|
119.38 mmHg
Standard Deviation 10.21
|
122.11 mmHg
Standard Deviation 12.24
|
SECONDARY outcome
Timeframe: 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).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.
Outcome measures
| Measure |
200 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 200 mg/m2 of Modufolin® as an intravenous bolus injection.
|
350 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 350 mg/m2 of Modufolin® as an intravenous bolus injection.
|
500 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 500 mg/m2 of Modufolin® as an intravenous bolus injection.
|
Placebo
n=9 Participants
9 subjects were treated with placebo as an intravenous bolus injection.
|
|---|---|---|---|---|
|
Diastolic Blood Pressure
Screening
|
68.63 mmHg
Standard Deviation 5.21
|
69.75 mmHg
Standard Deviation 8.51
|
72.25 mmHg
Standard Deviation 8.01
|
73.56 mmHg
Standard Deviation 11.75
|
|
Diastolic Blood Pressure
Visit 2 Day 1 (-00:15)
|
69.63 mmHg
Standard Deviation 3.74
|
65.88 mmHg
Standard Deviation 6.42
|
75.38 mmHg
Standard Deviation 2.77
|
69.56 mmHg
Standard Deviation 9.06
|
|
Diastolic Blood Pressure
Visit 2 Day 1 (03:00)
|
69.00 mmHg
Standard Deviation 6.89
|
64.38 mmHg
Standard Deviation 7.37
|
72.63 mmHg
Standard Deviation 5.71
|
65.56 mmHg
Standard Deviation 11.20
|
|
Diastolic Blood Pressure
Visit 2 Day 1 (05:00)
|
65.63 mmHg
Standard Deviation 5.88
|
62.38 mmHg
Standard Deviation 5.04
|
72.25 mmHg
Standard Deviation 7.15
|
67.00 mmHg
Standard Deviation 11.16
|
|
Diastolic Blood Pressure
Visit 2 Day 1 (08:00)
|
69.00 mmHg
Standard Deviation 7.29
|
64.50 mmHg
Standard Deviation 3.89
|
70.25 mmHg
Standard Deviation 6.36
|
66.22 mmHg
Standard Deviation 9.59
|
|
Diastolic Blood Pressure
Visit 2 Day 2
|
71.50 mmHg
Standard Deviation 10.23
|
69.38 mmHg
Standard Deviation 4.50
|
74.25 mmHg
Standard Deviation 5.47
|
71.11 mmHg
Standard Deviation 8.15
|
|
Diastolic Blood Pressure
Follow-up
|
68.25 mmHg
Standard Deviation 4.53
|
70.25 mmHg
Standard Deviation 7.81
|
71.00 mmHg
Standard Deviation 8.07
|
70.11 mmHg
Standard Deviation 7.99
|
SECONDARY outcome
Timeframe: 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).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.
Outcome measures
| Measure |
200 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 200 mg/m2 of Modufolin® as an intravenous bolus injection.
|
350 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 350 mg/m2 of Modufolin® as an intravenous bolus injection.
|
500 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 500 mg/m2 of Modufolin® as an intravenous bolus injection.
|
Placebo
n=9 Participants
9 subjects were treated with placebo as an intravenous bolus injection.
|
|---|---|---|---|---|
|
Vital Signs: Pulse
Visit 2 Day 1 (08:00)
|
60.25 bpm
Standard Deviation 6.82
|
59.00 bpm
Standard Deviation 5.83
|
56.75 bpm
Standard Deviation 7.21
|
55.67 bpm
Standard Deviation 7.23
|
|
Vital Signs: Pulse
Screening
|
59.50 bpm
Standard Deviation 5.21
|
66.50 bpm
Standard Deviation 9.38
|
62.00 bpm
Standard Deviation 11.24
|
63.22 bpm
Standard Deviation 12.88
|
|
Vital Signs: Pulse
Visit 2 Day 1 (-00:15)
|
55.25 bpm
Standard Deviation 5.44
|
52.00 bpm
Standard Deviation 8.60
|
56.38 bpm
Standard Deviation 5.58
|
54.44 bpm
Standard Deviation 11.34
|
|
Vital Signs: Pulse
Visit 2 Day 1 03:00)
|
56.25 bpm
Standard Deviation 5.50
|
53.13 bpm
Standard Deviation 11.01
|
53.75 bpm
Standard Deviation 4.95
|
50.33 bpm
Standard Deviation 6.60
|
|
Vital Signs: Pulse
Visit 2 Day 1 (05:00)
|
65.38 bpm
Standard Deviation 4.00
|
65.25 bpm
Standard Deviation 9.66
|
66.00 bpm
Standard Deviation 11.60
|
61.44 bpm
Standard Deviation 8.92
|
|
Vital Signs: Pulse
Visit 2 Day 2
|
59.38 bpm
Standard Deviation 9.53
|
57.63 bpm
Standard Deviation 8.91
|
61.75 bpm
Standard Deviation 13.48
|
61.22 bpm
Standard Deviation 11.31
|
|
Vital Signs: Pulse
Follow-up
|
66.25 bpm
Standard Deviation 9.04
|
67.88 bpm
Standard Deviation 12.91
|
69.25 bpm
Standard Deviation 16.26
|
67.44 bpm
Standard Deviation 14.47
|
SECONDARY outcome
Timeframe: 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)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.
Outcome measures
| Measure |
200 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 200 mg/m2 of Modufolin® as an intravenous bolus injection.
|
350 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 350 mg/m2 of Modufolin® as an intravenous bolus injection.
|
500 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 500 mg/m2 of Modufolin® as an intravenous bolus injection.
|
Placebo
n=9 Participants
9 subjects were treated with placebo as an intravenous bolus injection.
|
|---|---|---|---|---|
|
Safety Laboratory Measurements
|
0 Clinically relevant changes
|
0 Clinically relevant changes
|
0 Clinically relevant changes
|
0 Clinically relevant changes
|
SECONDARY outcome
Timeframe: From start of IMP administration to follow-up visitPopulation: FAS
An overall summary of AEs occurring after first administration of IMP (TEAE) is presented by treatment
Outcome measures
| Measure |
200 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 200 mg/m2 of Modufolin® as an intravenous bolus injection.
|
350 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 350 mg/m2 of Modufolin® as an intravenous bolus injection.
|
500 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 500 mg/m2 of Modufolin® as an intravenous bolus injection.
|
Placebo
n=9 Participants
9 subjects were treated with placebo as an intravenous bolus injection.
|
|---|---|---|---|---|
|
Frequency, Seriousness and Intensity of AEs
No. of TEAEs
|
8 Adverse events
|
8 Adverse events
|
16 Adverse events
|
2 Adverse events
|
|
Frequency, Seriousness and Intensity of AEs
No. of subject-unique TEAEs
|
8 Adverse events
|
7 Adverse events
|
16 Adverse events
|
2 Adverse events
|
|
Frequency, Seriousness and Intensity of AEs
Subject-unique related TEAEs
|
7 Adverse events
|
4 Adverse events
|
14 Adverse events
|
0 Adverse events
|
|
Frequency, Seriousness and Intensity of AEs
SAEs
|
0 Adverse events
|
0 Adverse events
|
0 Adverse events
|
0 Adverse events
|
SECONDARY outcome
Timeframe: 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-dosePopulation: All samples analysed from the subjects given placebo were below Lower Limit of Quantification.
The mean back-extrapolated concentration at time 0 h (C0) was calculated for MTHF
Outcome measures
| Measure |
200 mg/m2 of Modufolin®
n=7 Participants
8 subjects were treated with 200 mg/m2 of Modufolin® as an intravenous bolus injection.
|
350 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 350 mg/m2 of Modufolin® as an intravenous bolus injection.
|
500 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 500 mg/m2 of Modufolin® as an intravenous bolus injection.
|
Placebo
9 subjects were treated with placebo as an intravenous bolus injection.
|
|---|---|---|---|---|
|
Plasma PK Characteristics: C0
|
34200 ng/mL
Standard Deviation 10300
|
78300 ng/mL
Standard Deviation 12600
|
99000 ng/mL
Standard Deviation 23100
|
—
|
SECONDARY outcome
Timeframe: 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, 24hPopulation: All samples analysed from the subjects given placebo were below Lower Limit of Quantification.
Measured concentration at 5 min post dose (C5min) of MTHF and 5-Formyl-THF
Outcome measures
| Measure |
200 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 200 mg/m2 of Modufolin® as an intravenous bolus injection.
|
350 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 350 mg/m2 of Modufolin® as an intravenous bolus injection.
|
500 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 500 mg/m2 of Modufolin® as an intravenous bolus injection.
|
Placebo
9 subjects were treated with placebo as an intravenous bolus injection.
|
|---|---|---|---|---|
|
Plasma PK Characteristics: C5min
MTHF
|
24600 ng/mL
Standard Deviation 6480
|
52200 ng/mL
Standard Deviation 8530
|
70100 ng/mL
Standard Deviation 13100
|
—
|
|
Plasma PK Characteristics: C5min
5-Formyl-THF
|
443 ng/mL
Standard Deviation 432
|
609 ng/mL
Standard Deviation 240
|
374 ng/mL
Standard Deviation 83.2
|
—
|
SECONDARY outcome
Timeframe: 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.Population: All samples analysed from the subjects given placebo were below Lower Limit of Quantification.
Pharmacokinetic parameters were calculated for test item MTHF, and for the following metabolites: 5-Formyl-THF, 5-Methyl-THF, and THF, if data permitted
Outcome measures
| Measure |
200 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 200 mg/m2 of Modufolin® as an intravenous bolus injection.
|
350 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 350 mg/m2 of Modufolin® as an intravenous bolus injection.
|
500 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 500 mg/m2 of Modufolin® as an intravenous bolus injection.
|
Placebo
9 subjects were treated with placebo as an intravenous bolus injection.
|
|---|---|---|---|---|
|
Plasma PK Characteristics: AUClast
MTHF
|
10900 h*ng/mL
Standard Deviation 1680
|
19700 h*ng/mL
Standard Deviation 1990
|
31100 h*ng/mL
Standard Deviation 3210
|
—
|
|
Plasma PK Characteristics: AUClast
THF
|
31800 h*ng/mL
Standard Deviation 3780
|
53100 h*ng/mL
Standard Deviation 10000
|
90100 h*ng/mL
Standard Deviation 17500
|
—
|
|
Plasma PK Characteristics: AUClast
5-Methyl-THF
|
23400 h*ng/mL
Standard Deviation 4470
|
38500 h*ng/mL
Standard Deviation 6380
|
47400 h*ng/mL
Standard Deviation 7540
|
—
|
SECONDARY outcome
Timeframe: 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.Population: All samples analysed from the subjects given placebo were below Lower Limit of Quantification.
Pharmacokinetic parameters were calculated for test item MTHF, and for the following metabolites: 5-Formyl-THF, 5-Methyl-THF, and THF, if data permitted.
Outcome measures
| Measure |
200 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 200 mg/m2 of Modufolin® as an intravenous bolus injection.
|
350 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 350 mg/m2 of Modufolin® as an intravenous bolus injection.
|
500 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 500 mg/m2 of Modufolin® as an intravenous bolus injection.
|
Placebo
9 subjects were treated with placebo as an intravenous bolus injection.
|
|---|---|---|---|---|
|
Plasma PK Characteristics: AUClast/Dose
MTHF
|
29.2 (h*ng/mL)/mg
Standard Deviation 5.27
|
29.8 (h*ng/mL)/mg
Standard Deviation 2.74
|
32.9 (h*ng/mL)/mg
Standard Deviation 4.93
|
—
|
|
Plasma PK Characteristics: AUClast/Dose
THF
|
85.0 (h*ng/mL)/mg
Standard Deviation 11.8
|
80.1 (h*ng/mL)/mg
Standard Deviation 14.0
|
95.0 (h*ng/mL)/mg
Standard Deviation 19.2
|
—
|
|
Plasma PK Characteristics: AUClast/Dose
5-Methyl-THF
|
62.7 (h*ng/mL)/mg
Standard Deviation 12.5
|
58.3 (h*ng/mL)/mg
Standard Deviation 9.87
|
49.9 (h*ng/mL)/mg
Standard Deviation 7.91
|
—
|
|
Plasma PK Characteristics: AUClast/Dose
5-Formyl-THF
|
2.33 (h*ng/mL)/mg
Standard Deviation 1.97
|
1.24 (h*ng/mL)/mg
Standard Deviation 1.22
|
0.343 (h*ng/mL)/mg
Standard Deviation 0.580
|
—
|
SECONDARY outcome
Timeframe: 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.Population: All samples analysed from the subjects given placebo were below Lower Limit of Quantification (LLOQ).
Pharmacokinetic parameters were calculated for test item MTHF, and for the following metabolites: 5-Formyl-THF, 5-Methyl-THF, and THF, if data permitted.
Outcome measures
| Measure |
200 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 200 mg/m2 of Modufolin® as an intravenous bolus injection.
|
350 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 350 mg/m2 of Modufolin® as an intravenous bolus injection.
|
500 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 500 mg/m2 of Modufolin® as an intravenous bolus injection.
|
Placebo
9 subjects were treated with placebo as an intravenous bolus injection.
|
|---|---|---|---|---|
|
Plasma PK Characteristics: Timepoint for Last Measured Plasma Concentration (Tlast)
MTHF
|
4.38 hour
Standard Deviation 1.95
|
5.37 hour
Standard Deviation 1.30
|
6.75 hour
Standard Deviation 2.31
|
—
|
|
Plasma PK Characteristics: Timepoint for Last Measured Plasma Concentration (Tlast)
THF
|
7.01 hour
Standard Deviation 1.52
|
8.01 hour
Standard Deviation 0.0178
|
8.75 hour
Standard Deviation 2.12
|
—
|
|
Plasma PK Characteristics: Timepoint for Last Measured Plasma Concentration (Tlast)
5-Methyl-THF
|
24.0 hour
Standard Deviation 0.0339
|
24.0 hour
Standard Deviation 0.0980
|
23.8 hour
Standard Deviation 0.135
|
—
|
|
Plasma PK Characteristics: Timepoint for Last Measured Plasma Concentration (Tlast)
5-Formyl-THF
|
3.41 hour
Standard Deviation 2.94
|
3.00 hour
Standard Deviation 2.92
|
1.40 hour
Standard Deviation 2.67
|
—
|
SECONDARY outcome
Timeframe: 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.Population: All samples analysed from the subjects given placebo were below Lower Limit of Quantification
Pharmacokinetic parameters were calculated for test item MTHF, and for the following metabolites: 5-Formyl-THF, 5-Methyl-THF, and THF, if data permitted:
Outcome measures
| Measure |
200 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 200 mg/m2 of Modufolin® as an intravenous bolus injection.
|
350 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 350 mg/m2 of Modufolin® as an intravenous bolus injection.
|
500 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 500 mg/m2 of Modufolin® as an intravenous bolus injection.
|
Placebo
9 subjects were treated with placebo as an intravenous bolus injection.
|
|---|---|---|---|---|
|
Plasma PK Characteristics: t1/2
MTHF
|
0.989 hour
Standard Deviation 0.936
|
1.87 hour
Standard Deviation 0.634
|
2.03 hour
Standard Deviation 0.780
|
—
|
|
Plasma PK Characteristics: t1/2
THF
|
1.35 hour
Standard Deviation 0.211
|
1.51 hour
Standard Deviation 0.267
|
1.59 hour
Standard Deviation 0.370
|
—
|
|
Plasma PK Characteristics: t1/2
5-Methyl-THF
|
5.54 hour
Standard Deviation 0.714
|
5.66 hour
Standard Deviation 0.644
|
5.84 hour
Standard Deviation 0.634
|
—
|
SECONDARY outcome
Timeframe: 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.Population: All samples analysed from the subjects given placebo were below Lower Limit of Quantification.
Pharmacokinetic parameters were calculated for test item MTHF, and for the following metabolites: 5-Formyl-THF, 5-Methyl-THF, and THF, if data permitted.
Outcome measures
| Measure |
200 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 200 mg/m2 of Modufolin® as an intravenous bolus injection.
|
350 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 350 mg/m2 of Modufolin® as an intravenous bolus injection.
|
500 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 500 mg/m2 of Modufolin® as an intravenous bolus injection.
|
Placebo
9 subjects were treated with placebo as an intravenous bolus injection.
|
|---|---|---|---|---|
|
Plasma PK Characteristics: CL
MTHF
|
38.6 L/h
Standard Deviation 1.84
|
35.5 L/h
Standard Deviation 3.05
|
30.6 L/h
Standard Deviation 5.14
|
—
|
|
Plasma PK Characteristics: CL
THF
|
11.6 L/h
Standard Deviation 1.47
|
12.6 L/h
Standard Deviation 2.58
|
10.7 L/h
Standard Deviation 2.37
|
—
|
|
Plasma PK Characteristics: CL
5-Methyl-THF
|
15.6 L/h
Standard Deviation 3.11
|
16.5 L/h
Standard Deviation 2.63
|
19.1 L/h
Standard Deviation 3.49
|
—
|
SECONDARY outcome
Timeframe: 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, 24hPopulation: All samples analysed from the subjects given placebo were below Lower Limit of Quantification.
Pharmacokinetic parameters were calculated for test item MTHF, and for the following metabolites: 5-Formyl-THF, 5-Methyl-THF, and THF, if data permitted
Outcome measures
| Measure |
200 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 200 mg/m2 of Modufolin® as an intravenous bolus injection.
|
350 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 350 mg/m2 of Modufolin® as an intravenous bolus injection.
|
500 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 500 mg/m2 of Modufolin® as an intravenous bolus injection.
|
Placebo
9 subjects were treated with placebo as an intravenous bolus injection.
|
|---|---|---|---|---|
|
Plasma PK Characteristics: Vss
MTHF
|
18.1 litre
Standard Deviation 9.38
|
20.4 litre
Standard Deviation 6.10
|
18.5 litre
Standard Deviation 6.07
|
—
|
|
Plasma PK Characteristics: Vss
THF
|
21.8 litre
Standard Deviation 3.30
|
24.9 litre
Standard Deviation 4.17
|
21.6 litre
Standard Deviation 4.43
|
—
|
|
Plasma PK Characteristics: Vss
5-Methyl-THF
|
138 litre
Standard Deviation 28.4
|
153 litre
Standard Deviation 27.4
|
181 litre
Standard Deviation 27.9
|
—
|
SECONDARY outcome
Timeframe: 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.Population: All samples analysed from the subjects given placebo were below Lower Limit of Quantification.
Pharmacokinetic parameters were calculated for test item MTHF, and for the following metabolites: 5-Formyl-THF, 5-Methyl-THF, and THF, if data permitted
Outcome measures
| Measure |
200 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 200 mg/m2 of Modufolin® as an intravenous bolus injection.
|
350 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 350 mg/m2 of Modufolin® as an intravenous bolus injection.
|
500 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 500 mg/m2 of Modufolin® as an intravenous bolus injection.
|
Placebo
9 subjects were treated with placebo as an intravenous bolus injection.
|
|---|---|---|---|---|
|
Plasma PK Characteristics: Cmax
THF
|
16400 ng/mL
Standard Deviation 3610
|
29600 ng/mL
Standard Deviation 3970
|
44400 ng/mL
Standard Deviation 6090
|
—
|
|
Plasma PK Characteristics: Cmax
5-Methyl-THF
|
2490 ng/mL
Standard Deviation 450
|
3950 ng/mL
Standard Deviation 755
|
4740 ng/mL
Standard Deviation 484
|
—
|
|
Plasma PK Characteristics: Cmax
5-Formyl-THF
|
642 ng/mL
Standard Deviation 474
|
619 ng/mL
Standard Deviation 257
|
386 ng/mL
Standard Deviation 75.3
|
—
|
SECONDARY outcome
Timeframe: 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.Population: All samples analysed from the subjects given placebo were below Lower Limit of Quantification.
Pharmacokinetic parameters were calculated for test item MTHF, and for the following metabolites: 5-Formyl-THF, 5-Methyl-THF, and THF, if data permitted
Outcome measures
| Measure |
200 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 200 mg/m2 of Modufolin® as an intravenous bolus injection.
|
350 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 350 mg/m2 of Modufolin® as an intravenous bolus injection.
|
500 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 500 mg/m2 of Modufolin® as an intravenous bolus injection.
|
Placebo
9 subjects were treated with placebo as an intravenous bolus injection.
|
|---|---|---|---|---|
|
Plasma PK Characteristics: Tmax
THF
|
0.267 hour
Standard Deviation 0.334
|
0.123 hour
Standard Deviation 0.0786
|
0.300 hour
Standard Deviation 0.179
|
—
|
|
Plasma PK Characteristics: Tmax
5-Methyl-THF
|
3.12 hour
Standard Deviation 0.835
|
3.50 hour
Standard Deviation 1.07
|
3.63 hour
Standard Deviation 0.519
|
—
|
|
Plasma PK Characteristics: Tmax
5-Formyl-THF
|
0.0778 hour
Standard Deviation 0.0255
|
0.102 hour
Standard Deviation 0.0601
|
0.142 hour
Standard Deviation 0.145
|
—
|
SECONDARY outcome
Timeframe: 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, 24hPopulation: All samples analysed from the subjects given placebo were below Lower Limit of Quantification.
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.
Outcome measures
| Measure |
200 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 200 mg/m2 of Modufolin® as an intravenous bolus injection.
|
350 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 350 mg/m2 of Modufolin® as an intravenous bolus injection.
|
500 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 500 mg/m2 of Modufolin® as an intravenous bolus injection.
|
Placebo
9 subjects were treated with placebo as an intravenous bolus injection.
|
|---|---|---|---|---|
|
Plasma PK Characteristics: Cmax/Dose for Metabolite 5-Formyl-THF
|
1.73 ng/mL/mg
Standard Deviation 1.33
|
0.934 ng/mL/mg
Standard Deviation 0.379
|
0.407 ng/mL/mg
Standard Deviation 0.0826
|
—
|
SECONDARY outcome
Timeframe: From start of IMP administration to follow-up visitPopulation: FAS
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
Outcome measures
| Measure |
200 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 200 mg/m2 of Modufolin® as an intravenous bolus injection.
|
350 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 350 mg/m2 of Modufolin® as an intravenous bolus injection.
|
500 mg/m2 of Modufolin®
n=8 Participants
8 subjects were treated with 500 mg/m2 of Modufolin® as an intravenous bolus injection.
|
Placebo
n=9 Participants
9 subjects were treated with placebo as an intravenous bolus injection.
|
|---|---|---|---|---|
|
Number of Subjects With AEs
Subjects with at least one related TEAE
|
5 Subjects
|
3 Subjects
|
8 Subjects
|
0 Subjects
|
|
Number of Subjects With AEs
Withdrawals due to TEAE
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With AEs
Subjects with at least one TEAE
|
6 Subjects
|
5 Subjects
|
8 Subjects
|
1 Subjects
|
Adverse Events
200 mg/m2 of Modufolin®
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
350 mg/m2 of Modufolin®
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
500 mg/m2 of Modufolin®
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
200 mg/m2 of Modufolin®
n=8 participants at risk
8 subjects were treated with 200 mg/m2 of Modufolin® as an intravenous bolus injection.
|
350 mg/m2 of Modufolin®
n=8 participants at risk
8 subjects were treated with 350 mg/m2 of Modufolin® as an intravenous bolus injection.
|
500 mg/m2 of Modufolin®
n=8 participants at risk
8 subjects were treated with 500 mg/m2 of Modufolin® as an intravenous bolus injection.
|
Placebo
n=9 participants at risk
9 subjects were treated with placebo as an intravenous bolus injection.
|
|---|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/8 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
12.5%
1/8 • Number of events 1 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
37.5%
3/8 • Number of events 3 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
0.00%
0/9 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
|
Respiratory, thoracic and mediastinal disorders
Sneezing
|
0.00%
0/8 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
0.00%
0/8 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
12.5%
1/8 • Number of events 1 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
0.00%
0/9 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/8 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
0.00%
0/8 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
25.0%
2/8 • Number of events 2 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
0.00%
0/9 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
|
Nervous system disorders
Headache
|
12.5%
1/8 • Number of events 1 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
12.5%
1/8 • Number of events 1 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
12.5%
1/8 • Number of events 1 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
11.1%
1/9 • Number of events 1 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/8 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
12.5%
1/8 • Number of events 1 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
0.00%
0/8 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
0.00%
0/9 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
|
Nervous system disorders
Hypoaesthesia oral
|
0.00%
0/8 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
0.00%
0/8 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
12.5%
1/8 • Number of events 1 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
0.00%
0/9 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
|
Nervous system disorders
Paraesthesia
|
12.5%
1/8 • Number of events 1 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
0.00%
0/8 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
25.0%
2/8 • Number of events 2 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
0.00%
0/9 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
|
Nervous system disorders
Paraesthesia oral
|
25.0%
2/8 • Number of events 2 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
12.5%
1/8 • Number of events 1 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
0.00%
0/8 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
0.00%
0/9 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
|
General disorders
Chills
|
12.5%
1/8 • Number of events 1 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
0.00%
0/8 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
0.00%
0/8 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
0.00%
0/9 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
|
General disorders
Fatigue
|
0.00%
0/8 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
0.00%
0/8 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
0.00%
0/8 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
11.1%
1/9 • Number of events 1 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
|
General disorders
Flushing
|
0.00%
0/8 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
0.00%
0/8 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
12.5%
1/8 • Number of events 1 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
0.00%
0/9 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
|
General disorders
Injection site pain
|
12.5%
1/8 • Number of events 1 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
0.00%
0/8 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
0.00%
0/8 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
0.00%
0/9 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
|
General disorders
Pain
|
0.00%
0/8 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
0.00%
0/8 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
12.5%
1/8 • Number of events 1 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
0.00%
0/9 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
|
Gastrointestinal disorders
Dysgeusia
|
0.00%
0/8 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
12.5%
1/8 • Number of events 1 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
0.00%
0/8 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
0.00%
0/9 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
|
Gastrointestinal disorders
Nausea
|
12.5%
1/8 • Number of events 1 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
25.0%
2/8 • Number of events 2 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
50.0%
4/8 • Number of events 4 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
0.00%
0/9 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
|
Gastrointestinal disorders
Paraesthesia oral
|
12.5%
1/8 • Number of events 1 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
0.00%
0/8 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
0.00%
0/8 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
0.00%
0/9 • Adverse event data was collected from start of IMP administration to last subject last visit, thus during a period of little less than 2 months.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Non-disclosure agreement that prohibits the PI to communicate results without a prior permission from the sponsor.
- Publication restrictions are in place
Restriction type: OTHER