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| Name | Class |
|---|---|
| Richmond Pharmacology Limited | INDUSTRY |
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This was a single center, randomized, placebo-controlled study with a sequential i.v. dose escalation cohorts design, to assess safety, tolerability and pharmacokinetics of MOTREM (nangibotide) in healthy volunteers
This was a dose escalation study in healthy volunteers to evaluate the safety and pharmacokinetics of nangibotide in humans
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Matched placebo |
|
| MOTREM 1 | Experimental | nangibotide dose 1 |
|
| MOTREM 2 | Experimental | Nangibotide dose 2 |
|
| MOTREM 3 | Experimental | Nangibotide dose 3 |
|
| MOTREM 4 | Experimental | Nangibotide dose 4 |
|
| MOTREM 5 | Experimental | Nangibotide dose 5 |
|
| MOTREM 6 |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| nangibotide | Drug | Continous i.v. infusion |
|
| Measure | Description | Time Frame |
|---|---|---|
| Safety and Tolerability: the Number of Subjects Experiencing Treatment Emergent Adverse Events | The number of subjects experiencing treatment emergent adverse events was collected to assess the safety and tolerability of MOTREM (LR12) in comparison with placebo. | 30-44 days |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics (Maximum Plasma Concentration) | Plasma concentrations of LR12 were measured by a validated liquid chromatography-mass spectrometry (LC-MS/MS) assay and analyzed using noncompartmental methods to obtain estimates of the pharmacokinetic parameter of Maximum Plasma Concentration (Cmax). | Maximum Plasma Concentration (Cmax) was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min. Cmax is determined over a period of time starting from predose to 10h after start of the loading dose. |
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Inclusion Criteria:
Main Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Valérie Cuvier | Inotrem | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Richmond Pharmacology Ltd. | Croydon | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29885068 | Result | Cuvier V, Lorch U, Witte S, Olivier A, Gibot S, Delor I, Garaud JJ, Derive M, Salcedo-Magguilli M. A first-in-man safety and pharmacokinetics study of nangibotide, a new modulator of innate immune response through TREM-1 receptor inhibition. Br J Clin Pharmacol. 2018 Oct;84(10):2270-2279. doi: 10.1111/bcp.13668. Epub 2018 Jul 20. |
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Subjects were screened within 14 days and screening could be performed over multiple days prior to entering the study on Day -1. A total of 27 subjects were randomized and 26 subjects completed the study (1 subject was lost to follow-up and was prematurely withdrawn).
The study was conducted in the UK. The first subject first visit was on 01 April 2016 and last subject last visit was on 25 August 2016.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Placebo: Placebo |
| FG001 | 1 mg (Loading Dose) Nangibotide | Part A, Cohort 1: 1 mg (loading dose) over 15 minutes i.v. |
| FG002 | 10 mg (Loading Dose) Nangibotide | Part A, Cohort 2: 10 mg (loading dose) over 15 minutes i.v. |
| FG003 | 0.5 mg/kg (Loading Dose) and 0.03 mg/kg/h (Maintenance Dose) Nangibotide | Part B, Cohort 3: 0.5 mg/kg i.v. loading dose and 0.03 mg/kg/h maintenance dose i.v. over 7 hours and 45 min |
| FG004 | 1 mg/kg (Loading Dose) and 0.1 mg/kg/h (Maintenance Dose) Nangibotide | Part B, Cohort 4: 1 mg/kg i.v. loading dose and 0.1 mg/kg/h maintenance dose i.v. over 7 hours and 45 min |
| FG005 | 2 mg/kg (Loading Dose) and 0.3 mg/kg/h (Maintenance Dose) Nangibotide | Part B, Cohort 5: 2 mg/kg i.v. loading dose and 0.3 mg/kg/h maintenance dose i.v. over 7 hours and 45 min |
| FG006 | 5 mg/kg (Loading Dose) and 1 mg/kg/h (Maintenance Dose) Nangibotide | Part B, Cohort 6: 5 mg/kg i.v. loading dose and 1 mg/kg/h maintenance dose i.v. over 7 hours and 45 min |
| FG007 | 5 mg/kg (Loading Dose) and 3 mg/kg/h (Maintenance Dose) Nangibotide | Part B, Cohort 7: 5 mg/kg i.v. loading dose and 3 mg/kg/h maintenance dose i.v. over 7 hours and 45 min |
| FG008 | 5 mg/kg (Loading Dose) and 6 mg/kg/h (Maintenance Dose) Nangibotide | Part B, Cohort 8: 5 mg/kg i.v. loading dose and 6 mg/kg/h maintenance dose i.v. over 7 hours and 45 min |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Baseline characteristics were reported in clinical study report according to the patients enrolled in each cohort, not separately for placebo and investigational medicinal product.
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1 | 1 mg nangibotide over 15 minutes i.v. |
| BG001 | Cohort 2 | 10 mg nangibotide over 15 minutes i.v. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Safety and Tolerability: the Number of Subjects Experiencing Treatment Emergent Adverse Events | The number of subjects experiencing treatment emergent adverse events was collected to assess the safety and tolerability of MOTREM (LR12) in comparison with placebo. | Posted | Count of Participants | Participants | 30-44 days |
|
Adverse events were monitored until day 28 (end of study visit).
All TEAEs were mild in severity, and considered unrelated to the study drug. There was no SAE and no TEAE leading to treatment stop.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Placebo: Placebo | 0 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cerumen removal | Surgical and medical procedures | MedDRA 18.1 | Systematic Assessment |
None reported.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Executive VP Research and Medical Sciences, INOTREM SA | INOTREM SA | 30 62 86 51 | +33 (0)6 | jjg@inotrem.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 22, 2016 | Jan 7, 2025 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| C420324 | nangibotide |
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Nangibotide dose 6 |
|
| MOTREM 7 | Experimental | Nangibotide dose 7 |
|
| MOTREM 8 | Experimental | Nangibotide dose 8 |
|
|
| Placebo | Drug | Placebo |
|
|
| Statistical Analysis of LR12 PK Parameters: Steady State Concentration During the Maintenance Infusion (Cavg30-465) | Plasma concentrations of LR12 were measured by a validated LC-MS/MS assay and analyzed using noncompartmental methods to obtain estimates of the PK parameter of steady state concentration during the maintenance infusion (Cavg30-465). | Cavg30-465 was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min. Cavg30-465 is determined over a period of time starting from predose to 10h after start of the loading dose. |
| Statistical Analysis of LR12 PK Parameters: t1/2 | Plasma concentrations of LR12 were measured by a validated LC-MS/MS assay and analyzed using noncompartmental methods to obtain estimates of the PK parameter of terminal half-life (t1/2). Of note, apparent increase in half-life at increasing doses is explained by the detection of a slow elimination phase, which was below limit of quantification for the lower doses. | t1/2 was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min. t1/2 is determined over a period of time starting from 7 h and 45 min to 10h after start of the loading dose (decaying period). |
| Statistical Analysis of LR12 PK Parameters: AUC0-t | Plasma concentrations of LR12 were measured by a validated LC-MS/MS assay and analyzed using noncompartmental methods to obtain estimates of the PK parameter of the area under the plasma concentration curve (h.ng/mL) from time zero (predose) to the time of last observed concentration (t) measured (which can go up to 10h post loading dose start) using a linear trapezoidal method (AUC0-t). | AUC0-t was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min. AUC0-t is determined over a period of time starting time zero (predose) to the time of last observed concentration (t). |
| Statistical Analysis of LR12 PK Parameters: AUC0-∞ | Plasma concentrations of LR12 were measured by a validated LC-MS/MS assay and analyzed using noncompartmental methods to obtain estimates of the PK parameter of AUC0-∞. AUC0-∞ represents the area under the plasma concentration-time curve (h.ng/mL) from time 0 to infinity (AUC0- ∞= AUC0-t + [Ct/ke], where Ct = the observed concentration of drug for the last sample on the PK profile in which drug was detected, and ke represents the terminal rate constant). The percentage of extrapolation of AUC0-∞ should not exceed 20%. | AUC0-∞ was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min. AUC0-∞ is determined over a period of time starting time zero (predose) to infinity (cf. extrapolation formula in the above section). |
| Statistical Analysis of LR12 PK Parameters: CL | Plasma concentrations of LR12 were measured by a validated LC-MS/MS assay and analyzed using noncompartmental methods to obtain estimates of the PK parameter of systemic clearance (CL). The systemic clearance was estimated using the formula: CL = K0/ Css where K0 is the perfusion rate (ng/kg/h) and Css is the concentration at the end of perfusion (C at 465 min). Of note, this narrow range of the clearance values indicates that the apparent increases in t1/2 and volume of distribution as a function of doses are not due to a non-linearity in the pharmacokinetics, but to the limit of quantification of the bioanalytical assay. | CL was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min (465 min). CL is calculated based on the perfusion rate (ng/kg/h) and the concentration at the end of perfusion (7h45min = 465min). |
| Statistical Analysis of LR12 PK Parameters: Volume of Distribution (V) | The volume of distribution was estimated according to the following equation: V= CL x MRT (mean residence time). However, regarding administration procedures, MRT could not be calculated precisely. Furthermore, in some cases MRT could not be estimated. Thus, the following formula was used V = CL / ke. The terminal rate constant (ke) was estimated by log-linear regression analysis on data points visually assessed to be on the terminal log-linear phase. Of note, it can be said that this apparent increase in V is also explained by the detection of a slow elimination phase, which was below limit of quantification for the lower doses. | V was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min. V is derived from both CL and ke which are calculated from the LR12 concentration time curve from predose to 10h after loading dose start. |
| Statistical Analysis of LR12 PK Parameters: Tmax | Plasma concentrations of LR12 were measured by a validated LC-MS/MS assay and analysed using noncompartmental methods to obtain estimates of the PK parameter of the time at which Cmax is apparent, identified by inspection of the plasma drug concentration vs.time data by WinNonlin (tmax). | tmax was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min. tmax is determined over a period of time starting from predose to 10h after start of the loading dose. |
| Statistical Analysis of LR12 PK Parameters: t Last | This PK parameter was calculated from measured plasma concentrations of LR12 and it represents the time of last observed concentration. | t last was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min. t last is determined as the time of last observed concentration which can go up to 10h after loading dose start. |
| BG002 |
| Cohort 3 |
0.5 mg/kg i.v. and 0.03 mg/kg/h nangibotide i.v. over 7 hours and 45 min or placebo |
| BG003 | Cohort 4 | 1 mg/kg i.v. and 0.1 mg/kg/h i.v. nangibotide over 7 hours and 45 min or placebo |
| BG004 | Cohort 5 | 2 mg/kg i.v. and 0.3 mg/kg/h i.v. nangibotide over 7 hours and 45 min or placebo |
| BG005 | Cohort 6 | 5 mg/kg i.v. and 1 mg/kg/h i.v. nangibotide over 7 hours and 45 min or placebo |
| BG006 | Cohort 7 | 5 mg/kg i.v. and 3 mg/kg/h i.v. nangibotide over 7 hours and 45 min or placebo |
| BG007 | Cohort 8 | 5 mg/kg i.v. and 6 mg/kg/h i.v. nangibotide over 7 hours and 45 min or placebo |
| BG008 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Weight | Median | Full Range | kg |
|
| Height | Median | Full Range | cm |
|
| BMI | Median | Full Range | kg/m² |
|
Part A, Cohort 2: 10 mg (loading dose) over 15 minutes i.v. |
| OG003 | 0.5 mg/kg (Loading Dose) and 0.03 mg/kg/h (Maintenance Dose) Nangibotide | Part B, Cohort 3: 0.5 mg/kg i.v. loading dose and 0.03 mg/kg/h maintenance dose i.v. over 7 hours and 45 min |
| OG004 | 1 mg/kg (Loading Dose) and 0.1 mg/kg/h (Maintenance Dose) Nangibotide | Part B, Cohort 4: 1 mg/kg i.v. loading dose and 0.1 mg/kg/h maintenance dose i.v. over 7 hours and 45 min |
| OG005 | 2 mg/kg (Loading Dose) and 0.3 mg/kg/h (Maintenance Dose) Nangibotide | Part B, Cohort 5: 2 mg/kg i.v. loading dose and 0.3 mg/kg/h maintenance dose i.v. over 7 hours and 45 min |
| OG006 | 5 mg/kg (Loading Dose) and 1 mg/kg/h (Maintenance Dose) Nangibotide | Part B, Cohort 6: 5 mg/kg i.v. loading dose and 1 mg/kg/h maintenance dose i.v. over 7 hours and 45 min |
| OG007 | 5 mg/kg (Loading Dose) and 3 mg/kg/h (Maintenance Dose) Nangibotide | Part B, Cohort 7: 5 mg/kg i.v. loading dose and 3 mg/kg/h maintenance dose i.v. over 7 hours and 45 min |
| OG008 | 5 mg/kg (Loading Dose) and 6 mg/kg/h (Maintenance Dose) | Part B, Cohort 8: 5 mg/kg i.v. loading dose and 6 mg/kg/h maintenance dose i.v. over 7 hours and 45 min |
|
|
| Secondary | Pharmacokinetics (Maximum Plasma Concentration) | Plasma concentrations of LR12 were measured by a validated liquid chromatography-mass spectrometry (LC-MS/MS) assay and analyzed using noncompartmental methods to obtain estimates of the pharmacokinetic parameter of Maximum Plasma Concentration (Cmax). | In cohort 1 and cohort 2, there was 1 subject per cohort and the subjects received only a loading dose. LR12 plasma concentrations were quantifiable only at 15 min post-start of the infusion. For this reason, no PK analysis was performed for these two cohorts and for this reason results were not presented. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Maximum Plasma Concentration (Cmax) was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min. Cmax is determined over a period of time starting from predose to 10h after start of the loading dose. |
|
|
|
| Secondary | Statistical Analysis of LR12 PK Parameters: Steady State Concentration During the Maintenance Infusion (Cavg30-465) | Plasma concentrations of LR12 were measured by a validated LC-MS/MS assay and analyzed using noncompartmental methods to obtain estimates of the PK parameter of steady state concentration during the maintenance infusion (Cavg30-465). | In cohort 1 and cohort 2, there was 1 subject per cohort and the subjects received only a loading dose. LR12 plasma concentrations were quantifiable only at 15 min post-start of the infusion. For this reason, no PK analysis was performed for these two cohorts. For Cohort 3 values for Cavg30-465 were non-calculable. Hence, the results for Cohorts 1,2 and 3 are not presented. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Cavg30-465 was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min. Cavg30-465 is determined over a period of time starting from predose to 10h after start of the loading dose. |
|
|
|
| Secondary | Statistical Analysis of LR12 PK Parameters: t1/2 | Plasma concentrations of LR12 were measured by a validated LC-MS/MS assay and analyzed using noncompartmental methods to obtain estimates of the PK parameter of terminal half-life (t1/2). Of note, apparent increase in half-life at increasing doses is explained by the detection of a slow elimination phase, which was below limit of quantification for the lower doses. | Up to cohort 5, due to paucity of the data, t1/2 could not be determined, hence the results for these cohorts are not presented. | Posted | Geometric Mean | Geometric Coefficient of Variation | minute | t1/2 was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min. t1/2 is determined over a period of time starting from 7 h and 45 min to 10h after start of the loading dose (decaying period). |
|
|
|
| Secondary | Statistical Analysis of LR12 PK Parameters: AUC0-t | Plasma concentrations of LR12 were measured by a validated LC-MS/MS assay and analyzed using noncompartmental methods to obtain estimates of the PK parameter of the area under the plasma concentration curve (h.ng/mL) from time zero (predose) to the time of last observed concentration (t) measured (which can go up to 10h post loading dose start) using a linear trapezoidal method (AUC0-t). | There was 1 subject per cohort in cohort 1 and cohort 2 and the subjects received only a loading dose. LR12 (nangibotide) plasma concentrations were quantifiable only at 15 min post-start of the infusion. For this reason, no PK analysis was planned for these two cohorts and no results were presented. | Posted | Geometric Mean | Geometric Coefficient of Variation | h.ng/ml | AUC0-t was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min. AUC0-t is determined over a period of time starting time zero (predose) to the time of last observed concentration (t). |
|
|
|
| Secondary | Statistical Analysis of LR12 PK Parameters: AUC0-∞ | Plasma concentrations of LR12 were measured by a validated LC-MS/MS assay and analyzed using noncompartmental methods to obtain estimates of the PK parameter of AUC0-∞. AUC0-∞ represents the area under the plasma concentration-time curve (h.ng/mL) from time 0 to infinity (AUC0- ∞= AUC0-t + [Ct/ke], where Ct = the observed concentration of drug for the last sample on the PK profile in which drug was detected, and ke represents the terminal rate constant). The percentage of extrapolation of AUC0-∞ should not exceed 20%. | The percentage of extrapolation of AUC0-∞ was below 1% in subjects up to cohort 5, and due to this it was not determined for these subjects. For this reason, results were not presented for cohorts 1-5. | Posted | Geometric Mean | Geometric Coefficient of Variation | h.ng/ml | AUC0-∞ was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min. AUC0-∞ is determined over a period of time starting time zero (predose) to infinity (cf. extrapolation formula in the above section). |
|
|
|
| Secondary | Statistical Analysis of LR12 PK Parameters: CL | Plasma concentrations of LR12 were measured by a validated LC-MS/MS assay and analyzed using noncompartmental methods to obtain estimates of the PK parameter of systemic clearance (CL). The systemic clearance was estimated using the formula: CL = K0/ Css where K0 is the perfusion rate (ng/kg/h) and Css is the concentration at the end of perfusion (C at 465 min). Of note, this narrow range of the clearance values indicates that the apparent increases in t1/2 and volume of distribution as a function of doses are not due to a non-linearity in the pharmacokinetics, but to the limit of quantification of the bioanalytical assay. | There was 1 subject per cohort and the subjects received only a loading dose in cohort 1 and cohort 2. LR12 (nangibotide) plasma concentrations were quantifiable only at 15 min post-start of the infusion. No PK analysis was planned for these two cohorts. Also, CL values for cohort 3 were non-calculable. For this reason, results for cohorts 1-3 are not presented. | Posted | Geometric Mean | Geometric Coefficient of Variation | L/kg/h | CL was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min (465 min). CL is calculated based on the perfusion rate (ng/kg/h) and the concentration at the end of perfusion (7h45min = 465min). |
|
|
|
| Secondary | Statistical Analysis of LR12 PK Parameters: Volume of Distribution (V) | The volume of distribution was estimated according to the following equation: V= CL x MRT (mean residence time). However, regarding administration procedures, MRT could not be calculated precisely. Furthermore, in some cases MRT could not be estimated. Thus, the following formula was used V = CL / ke. The terminal rate constant (ke) was estimated by log-linear regression analysis on data points visually assessed to be on the terminal log-linear phase. Of note, it can be said that this apparent increase in V is also explained by the detection of a slow elimination phase, which was below limit of quantification for the lower doses. | There was 1 subject per cohort In cohort 1 and cohort 2 and the subjects received only a loading dose. LR12 plasma concentrations were quantifiable only at 15 min post-start of the infusion. No PK analysis was planned for these two cohorts. Also, V values for cohort 3, 4 and 5 were non-calculable. For this reason, no results were presented for cohorts 1-6. | Posted | Geometric Mean | Geometric Coefficient of Variation | L/kg | V was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min. V is derived from both CL and ke which are calculated from the LR12 concentration time curve from predose to 10h after loading dose start. |
|
|
|
| Secondary | Statistical Analysis of LR12 PK Parameters: Tmax | Plasma concentrations of LR12 were measured by a validated LC-MS/MS assay and analysed using noncompartmental methods to obtain estimates of the PK parameter of the time at which Cmax is apparent, identified by inspection of the plasma drug concentration vs.time data by WinNonlin (tmax). | There was 1 subject per cohort in cohort 1 and 2 and the subjects received only a loading dose. LR12 plasma concentrations were quantifiable only at 15 min post-start of the infusion. No PK analysis was planned for these two cohorts. For this reason, results for cohort 1 and 2 were not presented. | Posted | Median | Full Range | minute | tmax was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min. tmax is determined over a period of time starting from predose to 10h after start of the loading dose. |
|
|
|
| Secondary | Statistical Analysis of LR12 PK Parameters: t Last | This PK parameter was calculated from measured plasma concentrations of LR12 and it represents the time of last observed concentration. | There was 1 subject per cohort in cohort 1 and 2 and the subjects received only a loading dose. LR12 plasma concentrations were quantifiable only at 15 min post-start of the infusion. No PK analysis was planned for these two cohorts. For this reason, results for cohort 1 and 2 were not presented. | Posted | Median | Full Range | minute | t last was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min. t last is determined as the time of last observed concentration which can go up to 10h after loading dose start. |
|
|
|
| 6 |
| 0 |
| 6 |
| 1 |
| 6 |
| EG001 | 1 mg (Loading Dose) Nangibotide | Part A, Cohort 1: 1 mg (loading dose) over 15 minutes i.v. | 0 | 1 | 0 | 1 | 0 | 1 |
| EG002 | 10 mg (Loading Dose) Nangibotide | Part A, Cohort 2: 10 mg (loading dose) over 15 minutes i.v. | 0 | 2 | 0 | 2 | 1 | 2 |
| EG003 | 0.5 mg/kg (Loading Dose) and 0.03 mg/kg/h (Maintenance Dose) Nangibotide | Part B, Cohort 3: 0.5 mg/kg i.v. loading dose and 0.03 mg/kg/h maintenance dose i.v. over 7 hours and 45 min | 0 | 3 | 0 | 3 | 1 | 3 |
| EG004 | 1 mg/kg (Loading Dose) and 0.1 mg/kg/h (Maintenance Dose) Nangibotide | Part B, Cohort 4: 1 mg/kg i.v. loading dose and 0.1 mg/kg/h maintenance dose i.v. over 7 hours and 45 min | 0 | 3 | 0 | 3 | 1 | 3 |
| EG005 | 2 mg/kg (Loading Dose) and 0.3 mg/kg/h (Maintenance Dose) Nangibotide | Part B, Cohort 5: 2 mg/kg i.v. loading dose and 0.3 mg/kg/h maintenance dose i.v. over 7 hours and 45 min | 0 | 3 | 0 | 3 | 0 | 3 |
| EG006 | 5 mg/kg (Loading Dose) and 1 mg/kg/h (Maintenance Dose) Nangibotide | Part B, Cohort 6: 5 mg/kg i.v. loading dose and 1 mg/kg/h maintenance dose i.v. over 7 hours and 45 min | 0 | 3 | 0 | 3 | 0 | 3 |
| EG007 | 5 mg/kg (Loading Dose) and 3 mg/kg/h (Maintenance Dose) Nangibotide | Part B, Cohort 7: 5 mg/kg i.v. loading dose and 3 mg/kg/h maintenance dose i.v. over 7 hours and 45 min | 0 | 3 | 0 | 3 | 1 | 3 |
| EG008 | 5 mg/kg (Loading Dose) and 6 mg/kg/h (Maintenance Dose) Nangibotide | Part B, Cohort 8: 5 mg/kg i.v. loading dose and 6 mg/kg/h maintenance dose i.v. over 7 hours and 45 min | 0 | 3 | 0 | 3 | 1 | 3 |
| Haemangioma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.1 | Systematic Assessment |
|
| Viral Pharyngitis | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 18.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 18.1 | Systematic Assessment |
|
| Infusion site reaction | General disorders | MedDRA 18.1 | Systematic Assessment |
|
| Administration site rash | General disorders | MedDRA 18.1 | Systematic Assessment |
|
| Administration site pain | General disorders | MedDRA 18.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 18.1 | Systematic Assessment |
|
| Tooth development disorder | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 18.1 | Systematic Assessment |
|
Not provided
Not provided