| Primary | Concentration of [6R]-5,10-methylene-THF in Tumor Tissue | Comparison of concentration of the active substance in Modufolin: [6R]-5,10-methylene-THF in tumor tissue after the different treatments. | Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure. | Posted | | Mean | Standard Deviation | pmol/g | | Sample taken Day 1 (Day of surgery) at 0 min (before anesthetics) and 5, 10, 20, 40, 60, 90, 120, 180, 240, 360 min after study drug administration, and 24 h after study drug administration | | | | ID | Title | Description |
|---|
| OG000 | Levoleucovorin 200 mg/m2 | Levoleucovorin: i.v. bolus injection | | OG001 | Levoleucovorin 60 mg/m2 | Levoleucovorin: i.v. bolus injection | | OG002 | Modufolin 200 mg/m2 | [6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection | | OG003 | Modufolin 60 mg/m2 | [6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection |
| | | Title | Denominators | Categories |
|---|
| | | Title | Measurements |
|---|
| - OG0001871± 1159
- OG001959± 417
- OG0024725± 2210
- OG003
|
|
| | Group IDs | Group Description | Statistical Method | Statistical Comment | P-Value | P-Value Comment | Parameter Type | Parameter Value | Dispersion Type | Dispersion Value | Confidence Interval Sides | Confidence Interval % | CI Lower Limit | CI Upper Limit | CI Lower Limit Comment | CI Upper Limit Comment | Estimate Comment | Tested Non-Inferiority | Non-Inferiority Type | Non-Inferiority Comment | Other Analysis Description |
|---|
| The exploratory evaluation of [6R]-5,10-methylene-THF concentration in tumor tissue was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene's test. | Wilcoxon (Mann-Whitney) | | 0.0323 | | | | | | | | | | | | | | Superiority | | | | |
|
| Primary | Concentration of [6R]-5,10-methylene-THF in Adjacent Mucosa Tissue | Comparison of concentration of the active substance in Modufolin: [6R]-5,10-methylene-THF in mucosa adjacent to the tumor after the different treatments. | Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure. | Posted | | Mean | Standard Deviation | pmol/g | | Sample taken Day 1 (Day of surgery) at 0 min (before anesthetics) and 5, 10, 20, 40, 60, 90, 120, 180, 240, 360 min after study drug administration, and 24 h after study drug administration | | | | ID | Title | Description |
|---|
| OG000 | Levoleucovorin 200 mg/m2 | Levoleucovorin: i.v. bolus injection | | OG001 | Levoleucovorin 60 mg/m2 | Levoleucovorin: i.v. bolus injection | | OG002 | Modufolin 200 mg/m2 | [6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection | | OG003 | Modufolin 60 mg/m2 | [6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection |
|
| Primary | Concentration of [6S]-5-THF in Tumor Tissue | Comparison of concentration of the metabolite [6S]-5-THF in tumor after the different treatments. | Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure. | Posted | | Mean | Standard Deviation | pmol/g | | Sample taken Day 1 (Day of surgery) at 0 min (before anesthetics) and 5, 10, 20, 40, 60, 90, 120, 180, 240, 360 min after study drug administration, and 24 h after study drug administration | | | | ID | Title | Description |
|---|
| OG000 | Levoleucovorin 200 mg/m2 | Levoleucovorin: i.v. bolus injection | | OG001 | Levoleucovorin 60 mg/m2 | Levoleucovorin: i.v. bolus injection | | OG002 | Modufolin 200 mg/m2 | [6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection | | OG003 | Modufolin 60 mg/m2 | [6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection |
| |
| Primary | Concentration of [6S]-5-THF in Adjacent Mucosa Tissue | Comparison of concentration of the metabolite [6S]-5-THF in mucosa adjacent to the tumor after the different treatments. | Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure. | Posted | | Mean | Standard Deviation | pmol/g | | Sample taken Day 1 (Day of surgery) at 0 min (before anesthetics) and 5, 10, 20, 40, 60, 90, 120, 180, 240, 360 min after study drug administration, and 24 h after study drug administration | | | | ID | Title | Description |
|---|
| OG000 | Levoleucovorin 200 mg/m2 | Levoleucovorin: i.v. bolus injection | | OG001 | Levoleucovorin 60 mg/m2 | Levoleucovorin: i.v. bolus injection | | OG002 | Modufolin 200 mg/m2 | [6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection | | OG003 | Modufolin 60 mg/m2 | [6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection |
| |
| Primary | Concentration of [6S]-5-methyl-THF in Tumor Tissue | Comparison of concentration of the metabolite [6S]-5-methyl-THF in tumor after the different treatments. | Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure. | Posted | | Mean | Standard Deviation | pmol/g | | Sample taken Day 1 (Day of surgery) at 0 min (before anesthetics) and 5, 10, 20, 40, 60, 90, 120, 180, 240, 360 min after study drug administration, and 24 h after study drug administration | | | | ID | Title | Description |
|---|
| OG000 | Levoleucovorin 200 mg/m2 | Levoleucovorin: i.v. bolus injection | | OG001 | Levoleucovorin 60 mg/m2 | Levoleucovorin: i.v. bolus injection | | OG002 | Modufolin 200 mg/m2 | [6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection | | OG003 | Modufolin 60 mg/m2 | [6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection |
| |
| Primary | Concentration of [6S]-5-methyl-THF in Adjacent Mucosa Tissue | Comparison of concentration of the metabolite [6S]-5-methyl-THF in mucosa adjacent to the tumor after the different treatments. | Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure. | Posted | | Mean | Standard Deviation | pmol/g | | Sample taken Day 1 (Day of surgery) at 0 min (before anesthetics) and 5, 10, 20, 40, 60, 90, 120, 180, 240, 360 min after study drug administration, and 24 h after study drug administration | | | | ID | Title | Description |
|---|
| OG000 | Levoleucovorin 200 mg/m2 | Levoleucovorin: i.v. bolus injection | | OG001 | Levoleucovorin 60 mg/m2 | Levoleucovorin: i.v. bolus injection | | OG002 | Modufolin 200 mg/m2 | [6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection | | OG003 | Modufolin 60 mg/m2 | [6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection |
| |
| Primary | Concentration of [6S]-5-formyl-THF in Tumor Tissue | Comparison of concentration of the metabolite [6S]-5-formyl-THF in tumor after the different treatments. | Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure. | Posted | | Mean | Standard Deviation | pmol/g | | Sample taken Day 1 (Day of surgery) at 0 min (before anesthetics) and 5, 10, 20, 40, 60, 90, 120, 180, 240, 360 min after study drug administration, and 24 h after study drug administration | | | | ID | Title | Description |
|---|
| OG000 | Levoleucovorin 200 mg/m2 | Levoleucovorin: i.v. bolus injection | | OG001 | Levoleucovorin 60 mg/m2 | Levoleucovorin: i.v. bolus injection | | OG002 | Modufolin 200 mg/m2 | [6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection | | OG003 | Modufolin 60 mg/m2 | [6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection |
| |
| Primary | Concentration of [6S]-5-formyl-THF in Adjacent Mucosa Tissue | Comparison of concentration of the metabolite [6S]-5-formyl-THF in mucosa adjacent to the tumor after the different treatments. | Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure. | Posted | | Mean | Standard Deviation | pmol/g | | Sample taken Day 1 (Day of surgery) at 0 min (before anesthetics) and 5, 10, 20, 40, 60, 90, 120, 180, 240, 360 min after study drug administration, and 24 h after study drug administration | | | | ID | Title | Description |
|---|
| OG000 | Levoleucovorin 200 mg/m2 | Levoleucovorin: i.v. bolus injection | | OG001 | Levoleucovorin 60 mg/m2 | Levoleucovorin: i.v. bolus injection | | OG002 | Modufolin 200 mg/m2 | [6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection | | OG003 | Modufolin 60 mg/m2 | [6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection |
| |
| Secondary | AUC(0-2h) of [6R]-5,10-methylene-THF | Area under the plasma concentration versus time curve from time 0 to 2 hours, for the active substance in Modufolin: [6R]-5,10-methylene-THF | Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure. | Posted | | Mean | Standard Deviation | mcg*h/L | | Samples taken Day 1 (Day of surgery) | | | | ID | Title | Description |
|---|
| OG000 | L-LV(200) | | | OG001 | L-LV(60) | | | OG002 | Mod(200) | | | OG003 | Mod(60) | |
| |
| Secondary | AUC(0-2h) of [6S]-5-THF | Area under the plasma concentration versus time curve from time 0 to 2 hours, for the metabolite [6S]-5-THF | Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure. | Posted | | Mean | Standard Deviation | mcg*h/L | | Samples taken Day 1 (Day of surgery) | | | | ID | Title | Description |
|---|
| OG000 | L-LV(200) | | | OG001 | L-LV(60) | | | OG002 | Mod(200) | | | OG003 | Mod(60) | |
| |
| Secondary | AUC(0-2h) of [6S]-5-methyl-THF | Area under the plasma concentration versus time curve from time 0 to 2 hours, for the metabolite: [6S]-5-methyl-THF | Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure. | Posted | | Mean | Standard Deviation | mcg*h/L | | Samples taken Day 1 (Day of surgery) | | | | ID | Title | Description |
|---|
| OG000 | L-LV(200) | | | OG001 | L-LV(60) | | | OG002 | Mod(200) | | | OG003 | Mod(60) | |
| |
| Secondary | AUC(0-2h) of [6SR]-5-formyl-THF | Area under the plasma concentration versus time curve from time 0 to 2 hours, for the metabolite [6S]-5-formyl-THF | Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure. | Posted | | Mean | Standard Deviation | mcg*h/L | | Samples taken Day 1 (Day of surgery) | | | | ID | Title | Description |
|---|
| OG000 | L-LV(200) | | | OG001 | L-LV(60) | | | OG002 | Mod(200) | | | OG003 | Mod(60) | |
| |
| Secondary | AUC(Last) of [6R]-5,10-methylene-THF | Area under the plasma concentration versus time curve, from time 0 to the last time point, for the active substance in Modufolin: [6R]-5,10-methylene-THF | Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure. | Posted | | Mean | Standard Deviation | mcg*h/L | | Samples taken Day 1 (Day of surgery) and Day 2 | | | | ID | Title | Description |
|---|
| OG000 | L-LV(200) | | | OG001 | L-LV(60) | | | OG002 | Mod(200) | | | OG003 | Mod(60) | |
| |
| Secondary | AUC(Last) of [6S]-5-THF | Area under the plasma concentration versus time curve, from time 0 to the last time point, for the metabolite [6S]-5-THF | Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure. | Posted | | Mean | Standard Deviation | mcg*h/L | | Samples taken Day 1 (Day of surgery) and Day 2 | | | | ID | Title | Description |
|---|
| OG000 | L-LV(200) | | | OG001 | L-LV(60) | | | OG002 | Mod(200) | | | OG003 | Mod(60) | |
| |
| Secondary | AUC(Last) of [6S]-5-methyl-THF | Area under the plasma concentration versus time curve, from time 0 to the last time point, for the metabolite [6S]-5-methyl-THF | Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure. | Posted | | Mean | Standard Deviation | mcg*h/L | | Samples taken Day 1 (Day of surgery) and Day 2 | | | | ID | Title | Description |
|---|
| OG000 | L-LV(200) | | | OG001 | L-LV(60) | | | OG002 | Mod(200) | | | OG003 | Mod(60) | |
| |
| Secondary | AUC(Last) of [6S]-5-formyl-THF | Area under the plasma concentration versus time curve, from time 0 to the last time point, for the metabolite [6S]-5-formyl-THF | Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure. | Posted | | Mean | Standard Deviation | mcg*h/L | | Samples taken Day 1 (Day of surgery) and Day 2 | | | | ID | Title | Description |
|---|
| OG000 | L-LV(200) | | | OG001 | L-LV(60) | | | OG002 | Mod(200) | | | OG003 | Mod(60) | |
| |
| Secondary | Cmax of [6R]-5,10-methylene-THF | Maximum concentration (Cmax) in plasma of the active substance in Modufolin: [6R]-5,10-methylene-THF | Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure. | Posted | | Mean | Standard Deviation | µg/L | | Samples taken Day 1 (Day of surgery) and Day 2 | | | | ID | Title | Description |
|---|
| OG000 | L-LV(200) | | | OG001 | L-LV(60) | | | OG002 | Mod(200) | | | OG003 | Mod(60) | |
| |
| Secondary | Cmax of [6S]-5-THF in Plasma | Maximum concentration (Cmax) in plasma of the metabolite [6S]-5-THF | Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure. | Posted | | Mean | Standard Deviation | µg/L | | Samples taken Day 1 (Day of surgery) and Day 2 | | | | ID | Title | Description |
|---|
| OG000 | L-LV(200) | | | OG001 | L-LV(60) | | | OG002 | Mod(200) | | | OG003 | Mod(60) | |
| |
| Secondary | Cmax of [6S]-5-methyl-THF in Plasma | Maximum concentration (Cmax) in plasma of the metabolite [6S]-5-methyl-THF | Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure. | Posted | | Mean | Standard Deviation | µg/L | | Samples taken Day 1 (Day of surgery) and Day 2 | | | | ID | Title | Description |
|---|
| OG000 | L-LV(200) | | | OG001 | L-LV(60) | | | OG002 | Mod(200) | | | OG003 | Mod(60) | |
| |
| Secondary | Cmax of [6S]-5-formyl-THF in Plasma | Maximum concentration (Cmax) in plasma of the active substance in Modufolin: [6R] 5,10- methylene-THF and the metabolites: [6S]-5-THF, [6S]-5-methyl-THF, and [6S]-5-formyl-THF | Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure. | Posted | | Mean | Standard Deviation | µg/L | | Samples taken Day 1 (Day of surgery) and Day 2 | | | | ID | Title | Description |
|---|
| OG000 | L-LV(200) | | | OG001 | L-LV(60) | | | OG002 | Mod(200) | | | OG003 | Mod(60) | |
| |
| Secondary | Tmax of [6R]-5,10-methylene-THF | Timepoint (tmax) when Cmax in plasma occurs of the active substance in Modufolin: [6R]-5,10-methylene-THF | Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure. | Posted | | Mean | Standard Deviation | h | | Samples taken Day 1 (Day of surgery) and Day 2 | | | | ID | Title | Description |
|---|
| OG000 | L-LV(200) | | | OG001 | L-LV(60) | | | OG002 | Mod(200) | | | OG003 | Mod(60) | |
| |
| Secondary | Tmax of [6S]-5-THF | Timepoint (tmax) when Cmax in plasma occurs for the metabolite [6S]-5-THF | Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure. | Posted | | Mean | Standard Deviation | h | | Samples taken Day 1 (Day of surgery) and Day 2 | | | | ID | Title | Description |
|---|
| OG000 | L-LV(200) | | | OG001 | L-LV(60) | | | OG002 | Mod(200) | | | OG003 | Mod(60) | |
| |
| Secondary | Tmax of [6S]-5-methyl-THF | Timepoint (tmax) when Cmax in plasma occurs for the metabolite [6S]-5-methyl-THF | Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure. | Posted | | Mean | Standard Deviation | h | | Samples taken Day 1 (Day of surgery) and Day 2 | | | | ID | Title | Description |
|---|
| OG000 | L-LV(200) | | | OG001 | L-LV(60) | | | OG002 | Mod(200) | | | OG003 | Mod(60) | |
| |
| Secondary | Tmax of [6S]-5-formyl-THF | Timepoint (tmax) when Cmax in plasma occurs for the metabolite [6S]-5-formyl-THF | Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure. | Posted | | Mean | Standard Deviation | h | | Samples taken Day 1 (Day of surgery) and Day 2 | | | | ID | Title | Description |
|---|
| OG000 | L-LV(200) | | | OG001 | L-LV(60) | | | OG002 | Mod(200) | | | OG003 | Mod(60) | |
| |
| Secondary | T(1/2) of [6R]-5,10-methylene-THF | Terminal plasma elimination half-life time for the active substance in Modufolin: [6R]-5,10-methylene-THF | Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure. | Posted | | Mean | Standard Deviation | h | | Samples taken Day 1 (Day of surgery) and Day 2 | | | | ID | Title | Description |
|---|
| OG000 | L-LV(200) | | | OG001 | L-LV(60) | | | OG002 | Mod(200) | | | OG003 | Mod(60) | |
| |
| Secondary | T(1/2) of [6S]-5-THF | Terminal plasma elimination half-life time for the metabolite [6S]-5-THF | Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure. | Posted | | Mean | Standard Deviation | h | | Samples taken Day 1 (Day of surgery) and Day 2 | | | | ID | Title | Description |
|---|
| OG000 | L-LV(200) | | | OG001 | L-LV(60) | | | OG002 | Mod(200) | | | OG003 | Mod(60) | |
| |
| Secondary | T(1/2) of [6S]-5-methyl-THF | Terminal plasma elimination half-life time for the metabolite [6S]-5-methyl-THF | Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure. | Posted | | Mean | Standard Deviation | h | | Samples taken Day 1 (Day of surgery) and Day 2 | | | | ID | Title | Description |
|---|
| OG000 | L-LV(200) | | | OG001 | L-LV(60) | | | OG002 | Mod(200) | | | OG003 | Mod(60) | |
| |
| Secondary | T(1/2) of [6S]-5-formyl-THF | Terminal plasma elimination half-life time for the metabolite [6S]-5-formyl-THF | Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure. | Posted | | Mean | Standard Deviation | h | | Samples taken Day 1 (Day of surgery) and Day 2 | | | | ID | Title | Description |
|---|
| OG000 | L-LV(200) | | | OG001 | L-LV(60) | | | OG002 | Mod(200) | | | OG003 | Mod(60) | |
| |
| Secondary | T(Last) of [6R]-5,10-methylene-THF | The time-point for the last measurable concentration of the active substance in Modufolin: [6R]-5,10-methylene-THF | Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure. | Posted | | Mean | Standard Deviation | h | | Samples taken Day 1 (Day of surgery) and Day 2 | | | | ID | Title | Description |
|---|
| OG000 | L-LV(200) | | | OG001 | L-LV(60) | | | OG002 | Mod(200) | | | OG003 | Mod(60) | |
| |
| Secondary | T(Last) of [6S]-5-THF | The time-point for the last measurable concentration for the metabolite [6S]-5-TH in plasma | Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure. | Posted | | Mean | Standard Deviation | h | | Samples taken Day 1 (Day of surgery) and Day 2 | | | | ID | Title | Description |
|---|
| OG000 | L-LV(200) | | | OG001 | L-LV(60) | | | OG002 | Mod(200) | | | OG003 | Mod(60) | |
| |
| Secondary | T(Last) of [6S]-5-methyl-THF | The time-point for the last measurable concentration for the metabolite [6S]-5-methyl-THF in plasma | Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure. | Posted | | Mean | Standard Deviation | h | | Samples taken Day 1 (Day of surgery) and Day 2 | | | | ID | Title | Description |
|---|
| OG000 | L-LV(200) | | | OG001 | L-LV(60) | | | OG002 | Mod(200) | | | OG003 | Mod(60) | |
| |
| Secondary | T(Last) of [6S]-5-formyl-THF | The time-point for the last measurable concentration for the metabolite [6S]-5-formyl-THF in plasma | Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure. | Posted | | Mean | Standard Deviation | h | | Samples taken Day 1 (Day of surgery) and Day 2 | | | | ID | Title | Description |
|---|
| OG000 | L-LV(200) | | | OG001 | L-LV(60) | | | OG002 | Mod(200) | | | OG003 | Mod(60) | |
| |
| Secondary | Correlation Between Plasma and Tissue Concentration (Tumor and Mucosa) for [6R]-5,10-methylene-THF | Correlation between the exposure of [6R]-5,10-methylene-THF following 2 hours after dosing (AUC[0-2h]) and the concentration of [6R]-5,10-methylene-THF in the tumor or adjacent mucosa at surgery. | The Per Protocol analysis set contained 29 of the 32 enrolled patients. One patient was withdrawn prior to study drug administration and two patients were excluded due to major protocol deviations. | Posted | | Number | | correlation coefficient | | Samples taken Day 1 (Day of surgery) | | | | ID | Title | Description |
|---|
| OG000 | Levoleucovorin 200 mg/m2 | Levoleucovorin: i.v. bolus injection | | OG001 | Levoleucovorin 60 mg/m2 | Levoleucovorin: i.v. bolus injection | | OG002 | Modufolin 200 mg/m2 | [6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection | | OG003 | Modufolin 60 mg/m2 | [6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection |
|
| Secondary | Correlation Between Plasma and Tissue Concentration (Tumor and Mucosa) for [6S]-5-THF | Correlation between the exposure of [6S]-5-THF following 2 hours after dosing (AUC[0-2h]) and the concentration of [6S]-5-THF in the tumor or adjacent mucosa at surgery. | The Per Protocol analysis set contained 29 of the 32 enrolled patients. One patient was withdrawn prior to study drug administration and two patients were excluded due to major protocol deviations. | Posted | | Number | | correlation coefficient | | Samples taken Day 1 (Day of surgery) | | | | ID | Title | Description |
|---|
| OG000 | Levoleucovorin 200 mg/m2 | Levoleucovorin: i.v. bolus injection | | OG001 | Levoleucovorin 60 mg/m2 | Levoleucovorin: i.v. bolus injection | | OG002 | Modufolin 200 mg/m2 | [6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection | | OG003 | Modufolin 60 mg/m2 | [6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection |
|
| Secondary | Correlation Between Plasma and Tissue Concentration (Tumor and Mucosa) for [6S]-5-methyl-THF | Correlation between the exposure of [6S]-5-methyl-THF following 2 hours after dosing (AUC[0-2h]) and the concentration of [6S]-5-methyl-THF in the tumor or adjacent mucosa at surgery. | The Per Protocol analysis set contained 29 of the 32 enrolled patients. One patient was withdrawn prior to study drug administration and two patients were excluded due to major protocol deviations. | Posted | | Number | | correlation coefficient | | Samples taken Day 1 (Day of surgery) | | | | ID | Title | Description |
|---|
| OG000 | Levoleucovorin 200 mg/m2 | Levoleucovorin: i.v. bolus injection | | OG001 | Levoleucovorin 60 mg/m2 | Levoleucovorin: i.v. bolus injection | | OG002 | Modufolin 200 mg/m2 | [6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection | | OG003 | Modufolin 60 mg/m2 | [6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection |
|
| Secondary | Correlation Between Plasma and Tissue Concentration (Tumor and Mucosa) for [6S]-5-formyl-THF | Correlation between the exposure of [6S]-5-formyl-THF following 2 hours after dosing (AUC[0-2h]) and the concentration of [6S]-5-formyl-THF in the tumor or adjacent mucosa at surgery. | The Per Protocol analysis set contained 29 of the 32 enrolled patients. One patient was withdrawn prior to study drug administration and two patients were excluded due to major protocol deviations. | Posted | | Number | | correlation coefficient | | Samples taken Day 1 (Day of surgery) | | | | ID | Title | Description |
|---|
| OG000 | Levoleucovorin 200 mg/m2 | Levoleucovorin: i.v. bolus injection | | OG001 | Levoleucovorin 60 mg/m2 | Levoleucovorin: i.v. bolus injection | | OG002 | Modufolin 200 mg/m2 | [6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection | | OG003 | Modufolin 60 mg/m2 | [6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection |
|
| Secondary | Gene Expression Ratios (Mucosa:Tumor) | Concentration of different genes involved in folate transport and metabolism were analysed in both tumor and adjacent mucosa. The concentration in mucosa was divided by the concentration in tumor. A value above 1 indicate that the gene expression was higher in mucosa than in tumor and a value below 1 that the gene expression was higher in tumor than in mucosa. | The Per Protocol analysis set contained 29 of the 32 enrolled patients. One patient was withdrawn prior to study drug administration and two patients were excluded due to major protocol deviations. | Posted | | Number | | Ratio | | Sample taken Day 1 (Day of Surgery) | | | | ID | Title | Description |
|---|
| OG000 | Modufolin 60 mg/m2 | [6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection | | OG001 | Modufolin 200 mg/m2 | [6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection | | OG002 | Levoleucovorin 60 mg/m2 | Levoleucovorin: i.v. bolus injection | | OG003 | Levoleucovorin 200 mg/m2 | |
|
| Secondary | Correlation of Gene Expression in Tumor and Adjacent Mucosa | Concentration of the gene expression was analysed in both tumor and adjacent mucosa. The presence of any correlation between the results (i.e., concentration of the gene expression in tumor versus adjacent mucosa) was evaluated for each treatment. No evaluation was done between treatments. | The Per Protocol analysis set contained 29 of the 32 enrolled patients. One patient was withdrawn prior to study drug administration and two patients were excluded due to major protocol deviations. | Posted | | Number | | Normalized concentration | | Sample taken Day 1 (Day of Surgery) | | | | ID | Title | Description |
|---|
| OG000 | Levoleucovorin 200 mg/m2 | Levoleucovorin: i.v. bolus injection | | OG001 | Levoleucovorin 60 mg/m2 | Levoleucovorin: i.v. bolus injection | | OG002 | Modufolin 200 mg/m2 | [6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection | | OG003 | Modufolin 60 mg/m2 | [6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection |
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| Secondary | Homocystein Concentration | Blood samples for folate biomarker (homocystein) analysis were collected at Screening, Day 2, and Day 5 (End of study visit). | The Per Protocol analysis set contained 29 of the 32 enrolled patients. One patient was withdrawn prior to study drug administration and two patients were excluded due to major protocol deviations. | Posted | | Mean | Standard Deviation | μmol/L | | Samples taken at Screening visit, Day 2, and End of Study (Day 5) | | | | ID | Title | Description |
|---|
| OG000 | Levoleucovorin 200 mg/m2 | Levoleucovorin: i.v. bolus injection | | OG001 | Levoleucovorin 60 mg/m2 | Levoleucovorin: i.v. bolus injection | | OG002 | Modufolin 200 mg/m2 | [6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection | | OG003 | Modufolin 60 mg/m2 | [6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection |
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| Secondary | S-Folate Concentration | Blood samples for folate biomarker (S-folate) analysis were collected at Screening, Day 2 and Day 5 (End of study visit). | The Per Protocol analysis set contained 29 of the 32 enrolled patients. One patient was withdrawn prior to study drug administration and two patients were excluded due to major protocol deviations. | Posted | | Mean | Standard Deviation | nmol/L | | Samples taken at Screening visit, Day 2 and End of Study (Day 5) | | | | ID | Title | Description |
|---|
| OG000 | Levoleucovorin 200 mg/m2 | Levoleucovorin: i.v. bolus injection | | OG001 | Levoleucovorin 60 mg/m2 | Levoleucovorin: i.v. bolus injection | | OG002 | Modufolin 200 mg/m2 | [6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection | | OG003 | Modufolin 60 mg/m2 | [6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection |
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| Secondary | Change in Homocystein Concentration From Screening | Blood samples for folate biomarker (homocystein) analysis were collected at Screening, Day 2 and Day 5 (End of study visit). Changes from screening to later visits were counted. The criteria for assessment categories "normal", "low" and "high" were based on the reference ranges for plasma-Homocystein as follows: "low" <4,7 mcmol/L; "normal" => 4,7 and <=16 mcmol/L; "high" >16 mcmol/L. Values were applicable for both male and female adults. | The Per Protocol analysis set contained 29 of the 32 enrolled patients. One patient was withdrawn prior to study drug administration and two patients were excluded due to major protocol deviations. | Posted | | Count of Participants | | Participants | | Samples taken at Screening visit, Day 2 and End of Study (Day 5) | | | | ID | Title | Description |
|---|
| OG000 | Modufolin 60 mg/m2 | [6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection | | OG001 | Modufolin 200 mg/m2 | [6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection | | OG002 | Levoleucovorin 60 mg/m2 | Levoleucovorin: i.v. bolus injection | | OG003 |
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| Secondary | Change in S-Folate Concentration From Screening | Blood samples for folate biomarker (S-folate) analysis were collected at Screening, Day 2 and Day 5 (End of study visit). Changes from screening to later visits were counted. | The Per Protocol analysis set contained 29 of the 32 enrolled patients. One patient was withdrawn prior to study drug administration and two patients were excluded due to major protocol deviations. | Posted | | Count of Participants | | Participants | | Samples taken at Screening visit, Day 2 and End of Study (Day 5) | | | | ID | Title | Description |
|---|
| OG000 | Modufolin 60 mg/m2 | [6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection | | OG001 | Modufolin 200 mg/m2 | [6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection | | OG002 | Levoleucovorin 60 mg/m2 | Levoleucovorin: i.v. bolus injection | | OG003 | Levoleucovorin 200 mg/m2 | Levoleucovorin: i.v. bolus injection |
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| Secondary | Number of AEs Per Severity | Number of reported AEs per treatment with respect to severity | The safety population contained 31 of the 32 enrolled patients. One patient randomized to L-LV 60 mg/m2 was withdrawn prior to study drug administration and thus excluded from the safety analysis set. | Posted | | Number | | Events | | Screening visit until end of study, Day 5 | | | | ID | Title | Description |
|---|
| OG000 | Levoleucovorin 200 mg/m2 | Levoleucovorin: i.v. bolus injection | | OG001 | Levoleucovorin 60 mg/m2 | Levoleucovorin: i.v. bolus injection | | OG002 | Modufolin 200 mg/m2 | [6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection | | OG003 | Modufolin mg/m2 | [6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection |
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