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Sponsor's decision
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This clinical trial will include two parts, i.e., Part A and Part B.
The goal of the Part A is to define the shortest safe and tolerable duration of an intravenous injection of Fosnetupitant 235 mg solution among 4 durations tested in male and female adult healthy volunteers. In study part A, researchers will compare Fosnetupitant 235 mg solution to Akynzeo® solution.
The duration determined in Part A will be investigated in study Part B.
The Part B of the study was not performed.
The registered product Akynzeo® (235 mg fosnetupitant/0.25 mg palonosetron) solution for intravenous injection, used before chemotherapy, is to be diluted up to a final volume of 50 mL and administered during 30 min infusion. With the aim to facilitate and improve the use of this kind of products, the Sponsor Helsinn focused on the development of a ready to use solution, not requiring additional dilutions, and to be administered as a bolus injection. The product developed by Helsinn is a liquid formulation for infusion, containing exclusively fosnetupitant 235 mg free base.
Aim of the present open label, single dose, two parts (part A and part B) phase I study is to evaluate the safety and the pharmacokinetic profile of this new product, i.e., Fosnetupitant 235 mg ready to use solution for intravenous injection. In addition, the pharmacokinetic profile of fosnetupitant, netupitant (fosnetupitant is rapidly converted in netupitant after intravenous administration) and netupitant metabolites (M1, M2 and M3) will be investigated after a 30-min infusion of the registered Akynzeo® liquid formulation.
Part A of the study:
In cohort 1, 10 healthy volunteers will receive a dose of Fosnetupitant 235 mg solution as a one single 30-min intravenous infusion and additional 10 subjects will receive a single intravenous dose of Akynzeo® solution as a one single 30-min intravenous infusion, according to a parallel group design.
In each of 3 consecutive cohorts (cohorts 2, 3 and 4), 10 healthy volunteers will receive a single intravenous dose of Fosnetupitant 235 mg solution at a predefined infusion duration and will be sequentially treated as 3 subgroups of 3, 3, and 4 subjects, respectively.
A staggered approach with decreasing infusion time duration will be applied, from cohort 1 to cohort 4, to the administration of Fosnetupitant free base 235 mg solution, as follows:
Cohort 1: 30 min Cohort 2: 15 min Cohort 3: 5 min Cohort 4: 2 min
At the end of cohort 1 and of each subgroup of cohorts 2, 3 and 4, safety and tolerability results will be evaluated by the Investigator and the study Sponsor Medical Expert. Predefined stopping rules will be considered for deciding about continuing with the next cohort treatment and a shorter injection duration of Fosnetupitant 235 mg solution. Specifically, after cohort 1, if the injection duration of 30 min proves to be safe and well tolerated, 15 min injection duration will be tested in cohort 2. If the injection duration of 15 min proves to be safe and well-tolerated, 5 min injection duration will be tested in cohort 3. If the injection duration of 5 min proves to be safe and well tolerated, a 2 min injection will be tested in cohort 4.
The selected shortest (safe and tolerable) injection duration determined in Part A will be investigated in study Part B.
The study was prematurely terminated after the end of Part A and study Part B was not performed.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Study Part A - cohort 1 | Experimental | Fosnetupitant free base 235 mg administered as single 30 min intravenous infusion or 235 mg fosnetupitant/0.25 mg palonosetron in 20 mL injection solution administered undiluted as a single 30 min intravenous infusion |
|
| Study Part A - cohort 2 | Experimental | Fosnetupitant free base 235 mg administered as single 15 min intravenous infusion |
|
| Study Part A - cohort 3 | Experimental | Fosnetupitant free base 235 mg administered as single 5 min intravenous infusion |
|
| Study Part A - cohort 4 | Experimental | Fosnetupitant free base 235 mg administered as single 2 min intravenous infusion |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fosnetupitant 235 mg solution | Drug | Fosnetupitant free base 235 mg (corresponding to 260 mg of the chloride hydrochloride salt) in 20 mL ready to use injectable solution for intravenous administration |
| Measure | Description | Time Frame |
|---|---|---|
| Study Part A: Number of Treatment-emergent Adverse Events | Number of treatment-emergent adverse events (TEAEs) collected up to 24 h post-dose. | From screening visit (day of informed consent signature) up to 24 h after the investigational medicinal product administration (a maximum of 21 days) |
| Study Part A: Number of Subjects With Treatment-emergent Adverse Events | Number of subjects with treatment-emergent adverse events (TEAEs) collected up to 24 h post-dose. | From screening visit (day of informed consent signature) up to 24 h after the investigational medicinal product administration (a maximum of 21 days) |
| Study Part A: Type of Treatment-emergent Adverse Events | Type of treatment-emergent adverse events (TEAEs) collected up to 24 h post-dose. | From screening visit (day of informed consent signature) up to 24 h after the investigational medicinal product administration (a maximum of 21 days) |
| Measure | Description | Time Frame |
|---|---|---|
| Study Part A: Systolic Blood Pressure | Systolic blood pressure in mmHg measured after 5 min at rest in sitting position | Screening visit/day -1 (enrolment day)/day 1 (treatment day) at pre-administration, at the end of administration and 1, 2, 4, 24 h after the end of administration/final visit (7 days after the treatment) |
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Inclusion criteria
Informed consent: signed written informed consent before inclusion in the study
Sex and Age: healthy men/women volunteers, 18-55 years old (inclusive)
Body Mass Index (BMI): 18.5-30 kg/m2 inclusive
Vital signs: systolic blood pressure 100-139 mmHg, diastolic blood pressure 50-89 mmHg, pulse rate 50-99 bpm, measured after 5 min at rest in the sitting position
Full comprehension: ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to co-operate with the investigator and to comply with the requirements of the entire study
Contraception and fertility (women only): women of childbearing potential defined as a non-menopausal woman who has not had a bilateral oophorectomy or medically documented ovarian failure and/or at risk for pregnancy must agree, signing the informed consent form, to use a highly effective method of contraception throughout the study and to continue for 14 days after the last dose of the study treatment. Highly effective contraceptive measures include:
Women of non-child-bearing potential or in post-menopausal status defined as such when there is either:
Contraception (men only): men will either be sterile or agree to use one of the following approved methods of contraception from the first study drug administration until at least 14 days after the last administration, also in case their partner is currently pregnant:
Exclusion criteria
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| Name | Affiliation | Role |
|---|---|---|
| Milko Radicioni | Cross Research S.A. | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CROSS Research S.A. | Arzo | Canton Ticino | CH-6864 | Switzerland |
No need to share IPD
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Fifty (50) subjects were included in the study and received the treatment as planned.
Participants were recruited at the Phase I Unit from 12 June 2023 to 14 October 2023 and enrolled in the study from 17 June 2023 to 16 October 2023.
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| ID | Title | Description |
|---|---|---|
| FG000 | Study Part A - Cohort 1 - Akynzeo | 10 subjects were included in the study as planned and received the injection of Akynzeo solution in 30 min. |
| FG001 | Study Part A - Cohort 1 - Fosnetupitant | 10 subjects were included in the study as planned and received the injection of Fosnetupitant 235 mg solution in 30 min. |
| FG002 | Study Part A - Cohort 2 | 10 subjects were included in the study as planned and received the injection of Fosnetupitant 235 mg solution in 15 min. |
| FG003 | Study Part A - Cohort 3 | 10 subjects were included in the study as planned and received the injection of Fosnetupitant 235 mg solution in 5 min. |
| FG004 | Study Part A - Cohort 4 | 10 subjects were included in the study as planned and received the injection of Fosnetupitant 235 mg solution in 2 min. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Study Part A - Cohort 1 - Akynzeo | 10 subjects were included in the study as planned and received the injection of Akynzeo solution in 30 min. |
| BG001 | Study Part A - Cohort 1 - Fosnetupitant |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Study Part A: Number of Treatment-emergent Adverse Events | Number of treatment-emergent adverse events (TEAEs) collected up to 24 h post-dose. | Posted | Number | Number of TEAE | From screening visit (day of informed consent signature) up to 24 h after the investigational medicinal product administration (a maximum of 21 days) |
|
The reporting period for adverse events is the period starting from the time of informed consent signature and lasting until the final visit. Adverse events were collected for each participant for the whole period of the study (i.e., a maximum of 28 days).
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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 | Study Part A - Cohort 1 - Akynzeo | 10 subjects were included in the study as planned and received the injection of Akynzeo solution in 30 min. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Constipation | Gastrointestinal disorders | MedDRA 27.0 | Non-systematic Assessment |
M1 and M3 metabolites on average showed an extent of exposure (AUC) lower than the other analytes. In particular, both metabolites had a significantly longer elimination phase. Indeed, the concentrations of both metabolites were still at a plateau at the end of the sampling period and their elimination kinetics could not be characterized in the present study.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Tulla Spinelli | Helsinn Healthcare SA | +41.91.985.21.21 | Tulla.Spinelli@helsinn.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 24, 2023 | Mar 17, 2025 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 18, 2024 | Mar 17, 2025 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D012996 | Solutions |
| C000595957 | netupitant, palosentron drug combination |
| ID | Term |
|---|---|
| D004364 | Pharmaceutical Preparations |
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Open label, single dose, two parts (part A and part B), safety and pharmacokinetic phase I study.
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|
| Akynzeo solution | Drug | 235 mg fosnetupitant (corresponding to 260 mg of the chloride hydrochloride salt) / 0.25 mg palonosetron in 20 mL injectable solution |
|
|
| Study Part A: Diastolic Blood Pressure |
Diastolic blood pressure in mmHg measured after 5 min at rest in sitting position |
| Screening visit/day -1 (enrolment day)/day 1 (treatment day) at pre-administration, at the end of administration and 1, 2, 4, 24 h after the end of administration/final visit (7 days after the treatment) |
| Study Part A: Pulse Rate | Pulse rate in bpm measured after 5 min at rest in sitting position | Screening visit/day -1 (enrolment day)/day 1 (treatment day) at pre-administration, at the end of administration and 1, 2, 4, 24 h after the end of administration/final visit (7 days after the treatment) |
| Study Part A: Weight | Body weight in kilograms | Screening visit (day of informed consent signature)/final visit (7 days after the treatment) |
| Study Part A: Full Physical Examination Through Apparatus/Systems Check | General appearance, Chest/respiratory, Gastrointestinal, Head, eyes, ears, nose and throat, Heart/cardiovascular, Lymph nodes, Metabolic/endocrine, Musculoskeletal/extremities, Neck (including thyroid), Neurological/psychiatric, Skin/dermatologic systems are checked. Any abnormalities are recorded. | Screening visit (day of informed consent signature)/final visit (7 days after the treatment) |
| Study Part A: Short Physical Examination Through Apparatus/Systems Check | General appearance, Chest/respiratory, Heart/cardiovascular, Lymph nodes, Neurologic/psychiatric, Skin/dermatologic systems are checked. Any abnormalities are recorded. | Day 2 (24 h after the end of investigational product administration) |
| Study Part A: ECGs - Heart Rate | Heart rate in beats/min recorded in supine position after 5 min at rest | Screening visit/ day 1 (treatment day) at pre-administration, at the end of administration and 1, 2, 4, 24 h after the end of administration/final visit (7 days after the treatment) |
| Study Part A: ECGs - PR Interval | PR interval in ms recorded in supine position after 5 min at rest | Screening visit/ day 1 (treatment day) at pre-administration, at the end of administration and 1, 2, 4, 24 h after the end of administration/final visit (7 days after the treatment) |
| Study Part A: ECGs - RR Interval | RR interval in ms recorded in supine position after 5 min at rest | Screening visit/ day 1 (treatment day) at pre-administration, at the end of administration and 1, 2, 4, 24 h after the end of administration/final visit (7 days after the treatment) |
| Study Part A: ECGs - QRS Duration | QRS duration in ms recorded in supine position after 5 min at rest | Screening visit/ day 1 (treatment day) at pre-administration, at the end of administration and 1, 2, 4, 24 h after the end of administration/final visit (7 days after the treatment) |
| Study Part A: ECGs - QT Interval | QT interval in ms recorded in supine position after 5 min at rest | Screening visit/ day 1 (treatment day) at pre-administration, at the end of administration and 1, 2, 4, 24 h after the end of administration/final visit (7 days after the treatment) |
| Study Part A: ECGs - QTcB Interval | QTcB interval in ms recorded in supine position after 5 min at rest | Screening visit/ day 1 (treatment day) at pre-administration, at the end of administration and 1, 2, 4, 24 h after the end of administration/final visit (7 days after the treatment) |
| Study Part A: ECGs - QTcF Interval | QTcF interval in ms recorded in supine position after 5 min at rest | Screening visit/ day 1 (treatment day) at pre-administration, at the end of administration and 1, 2, 4, 24 h after the end of administration/final visit (7 days after the treatment) |
| Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Leukocytes and leukocyte differential count, erythrocytes, haemoglobin, haematocrit, MCV, MCH, MCHC, thrombocytes, electrolytes (sodium, potassium, calcium, chloride, inorganic phosphorus), enzymes (alkaline phosphatase, γ-GT, AST, ALT), substrates/metabolites (total bilirubin, creatinine, glucose, urea, uric acid, total cholesterol, triglycerides), total proteins, urine chemical analysis (pH, specific weight, appearance, color, nitrites, proteins, glucose, urobilinogen, bilirubin, ketones, hematic pigments, leukocytes), urine sediment (analysis performed only if positive: leukocytes, erythrocytes, flat cells, round cells, crystals, cylinders, mucus, bacteria, glomerular erythrocytes). Any abnormalities are recorded. | Screening visit (day of informed consent signature)/final visit (7 days after the treatment) |
| Study Part A: Cmax | Maximum plasma concentration measured for plasma fosnetupitant, netupitant and its main metabolites (M1, M2 and M3) | Day 1 (treatment day) at pre-administration, at 2, 5, 10, 15, 20, 30 and 45 min and at 1, 1.5, 2, 3, 4, 8, 12, 24 h after the administration |
| Study Part A: C0 | Plasma concentration at the end of the administration measured for plasma fosnetupitant, netupitant and its main metabolites (M1, M2 and M3) | Day 1 (treatment day) at pre-administration, at 2, 5, 10, 15, 20, 30 and 45 min and at 1, 1.5, 2, 3, 4, 8, 12, 24 h after the administration |
| Study Part A: Tmax | Time to achieve the maximum plasma concentration measured for plasma fosnetupitant, netupitant and its main metabolites (M1, M2 and M3) | Day 1 (treatment day) at pre-administration, at 2, 5, 10, 15, 20, 30 and 45 min and at 1, 1.5, 2, 3, 4, 8, 12, 24 h after the administration |
| Study Part A: Clast | Last measurable plasma concentration measured for plasma fosnetupitant, netupitant and its main metabolites (M1, M2 and M3) | Day 1 (treatment day) at pre-administration, at 2, 5, 10, 15, 20, 30 and 45 min and at 1, 1.5, 2, 3, 4, 8, 12, 24 h after the administration |
| Study Part A: Tlast | Time of last measurable plasma concentration measured for plasma fosnetupitant, netupitant and its main metabolites (M1, M2 and M3) | Day 1 (treatment day) at pre-administration, at 2, 5, 10, 15, 20, 30 and 45 min and at 1, 1.5, 2, 3, 4, 8, 12, 24 h after the administration |
| Study Part A: AUC0-t | Area under the concentration-time curve from time zero to time of last measurable plasma concentration measured for plasma fosnetupitant, netupitant and its main metabolites (M1, M2 and M3) | Day 1 (treatment day) at pre-administration, at 2, 5, 10, 15, 20, 30 and 45 min and at 1, 1.5, 2, 3, 4, 8, 12, 24 h after the administration |
| Study Part A: AUC0-24 | Area under the plasma concentration-time curve from time zero to 24 h after the administration measured for plasma fosnetupitant, netupitant and its main metabolites (M1, M2 and M3) | Day 1 (treatment day) at pre-administration, at 2, 5, 10, 15, 20, 30 and 45 min and at 1, 1.5, 2, 3, 4, 8, 12, 24 h after the administration |
| Study Part A: Terminal Elimination Rate Constant | Terminal elimination rate constant, calculated, if feasible, by log-linear regression using at least 3 points, C0 and Cmax excluded and measured for plasma fosnetupitant, netupitant and its main metabolites (M1, M2 and M3). Calculation was not feasible for M1 and M3, therefore these analytes are not reported in the Outcome Measure Data Table. | Day 1 (treatment day) at pre-administration, at 2, 5, 10, 15, 20, 30 and 45 min and at 1, 1.5, 2, 3, 4, 8, 12, 24 h after the administration |
| Study Part A: t1/2 | Apparent terminal half-life calculated, if feasible, by as ln2/terminal elimination rate constant and measured for plasma fosnetupitant, netupitant and its main metabolites (M1, M2 and M3). Calculation was not feasible for M1 and M3, therefore these analytes are not reported in the Outcome Measure Data Table. | Day 1 (treatment day) at pre-administration, at 2, 5, 10, 15, 20, 30 and 45 min and at 1, 1.5, 2, 3, 4, 8, 12, 24 h after the administration |
| Study Part A: Systemic Clearance | Systemic clearance measured for plasma fosnetupitant, netupitant and its main metabolites (M1, M2 and M3). Calculation was not feasible for M1 and M3, therefore these analytes are not reported in the Outcome Measure Data Table. | Day 1 (treatment day) at pre-administration, at 2, 5, 10, 15, 20, 30 and 45 min and at 1, 1.5, 2, 3, 4, 8, 12, 24 h after the administration |
| Study Part A: Vz | Apparent volume of distribution in the post-distribution phase measured for plasma fosnetupitant, netupitant and its main metabolites (M1, M2 and M3). Calculation was not feasible for M1 and M3, therefore these analytes are not reported in the Outcome Measure Data Table. | Day 1 (treatment day) at pre-administration, at 2, 5, 10, 15, 20, 30 and 45 min and at 1, 1.5, 2, 3, 4, 8, 12, 24 h after the administration |
| Study Part A: MRT | Mean residence time measured for plasma fosnetupitant, netupitant and its main metabolites (M1, M2 and M3). Calculation was not feasible for M1 and M3, therefore these analytes are not reported in the Outcome Measure Data Table. | Day 1 (treatment day) at pre-administration, at 2, 5, 10, 15, 20, 30 and 45 min and at 1, 1.5, 2, 3, 4, 8, 12, 24 h after the administration |
10 subjects were included in the study as planned and received the injection of Fosnetupitant 235 mg solution in 30 min.
| BG002 | Study Part A - Cohort 2 | 10 subjects were included in the study as planned and received the injection of Fosnetupitant 235 mg solution in 15 min. |
| BG003 | Study Part A - Cohort 3 | 10 subjects were included in the study as planned and received the injection of Fosnetupitant 235 mg solution in 5 min. |
| BG004 | Study Part A - Cohort 4 | 10 subjects were included in the study as planned and received the injection of Fosnetupitant 235 mg solution in 2 min. |
| BG005 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Body weight | Mean | Standard Deviation | kilograms |
|
| Height | Mean | Standard Deviation | centimeters |
|
| Body mass index | Mean | Standard Deviation | kilograms/square meters |
|
| OG002 | Study Part A - Cohort 2 | 10 subjects were included in the study as planned and received the injection of Fosnetupitant 235 mg solution in 15 min. |
| OG003 | Study Part A - Cohort 3 | 10 subjects were included in the study as planned and received the injection of Fosnetupitant 235 mg solution in 5 min. |
| OG004 | Study Part A - Cohort 4 | 10 subjects were included in the study as planned and received the injection of Fosnetupitant 235 mg solution in 2 min. |
|
|
| Primary | Study Part A: Number of Subjects With Treatment-emergent Adverse Events | Number of subjects with treatment-emergent adverse events (TEAEs) collected up to 24 h post-dose. | Posted | Number | Number of subjects with TEAE | From screening visit (day of informed consent signature) up to 24 h after the investigational medicinal product administration (a maximum of 21 days) |
|
|
|
| Primary | Study Part A: Type of Treatment-emergent Adverse Events | Type of treatment-emergent adverse events (TEAEs) collected up to 24 h post-dose. | Posted | Number | Number of TEAE | From screening visit (day of informed consent signature) up to 24 h after the investigational medicinal product administration (a maximum of 21 days) |
|
|
|
| Secondary | Study Part A: Systolic Blood Pressure | Systolic blood pressure in mmHg measured after 5 min at rest in sitting position | Posted | Mean | Standard Deviation | mmHg | Screening visit/day -1 (enrolment day)/day 1 (treatment day) at pre-administration, at the end of administration and 1, 2, 4, 24 h after the end of administration/final visit (7 days after the treatment) |
|
|
|
| Secondary | Study Part A: Diastolic Blood Pressure | Diastolic blood pressure in mmHg measured after 5 min at rest in sitting position | Posted | Mean | Standard Deviation | mmHg | Screening visit/day -1 (enrolment day)/day 1 (treatment day) at pre-administration, at the end of administration and 1, 2, 4, 24 h after the end of administration/final visit (7 days after the treatment) |
|
|
|
| Secondary | Study Part A: Pulse Rate | Pulse rate in bpm measured after 5 min at rest in sitting position | Posted | Mean | Standard Deviation | Beats/min | Screening visit/day -1 (enrolment day)/day 1 (treatment day) at pre-administration, at the end of administration and 1, 2, 4, 24 h after the end of administration/final visit (7 days after the treatment) |
|
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| Secondary | Study Part A: Weight | Body weight in kilograms | Posted | Mean | Standard Deviation | Kilograms | Screening visit (day of informed consent signature)/final visit (7 days after the treatment) |
|
|
|
| Secondary | Study Part A: Full Physical Examination Through Apparatus/Systems Check | General appearance, Chest/respiratory, Gastrointestinal, Head, eyes, ears, nose and throat, Heart/cardiovascular, Lymph nodes, Metabolic/endocrine, Musculoskeletal/extremities, Neck (including thyroid), Neurological/psychiatric, Skin/dermatologic systems are checked. Any abnormalities are recorded. | Posted | Count of Participants | Participants | Screening visit (day of informed consent signature)/final visit (7 days after the treatment) |
|
|
|
| Secondary | Study Part A: Short Physical Examination Through Apparatus/Systems Check | General appearance, Chest/respiratory, Heart/cardiovascular, Lymph nodes, Neurologic/psychiatric, Skin/dermatologic systems are checked. Any abnormalities are recorded. | Posted | Count of Participants | Participants | Day 2 (24 h after the end of investigational product administration) |
|
|
|
| Secondary | Study Part A: ECGs - Heart Rate | Heart rate in beats/min recorded in supine position after 5 min at rest | Posted | Count of Participants | Participants | Screening visit/ day 1 (treatment day) at pre-administration, at the end of administration and 1, 2, 4, 24 h after the end of administration/final visit (7 days after the treatment) |
|
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|
| Secondary | Study Part A: ECGs - PR Interval | PR interval in ms recorded in supine position after 5 min at rest | Posted | Count of Participants | Participants | Screening visit/ day 1 (treatment day) at pre-administration, at the end of administration and 1, 2, 4, 24 h after the end of administration/final visit (7 days after the treatment) |
|
|
|
| Secondary | Study Part A: ECGs - RR Interval | RR interval in ms recorded in supine position after 5 min at rest | Posted | Count of Participants | Participants | Screening visit/ day 1 (treatment day) at pre-administration, at the end of administration and 1, 2, 4, 24 h after the end of administration/final visit (7 days after the treatment) |
|
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|
| Secondary | Study Part A: ECGs - QRS Duration | QRS duration in ms recorded in supine position after 5 min at rest | Posted | Count of Participants | Participants | Screening visit/ day 1 (treatment day) at pre-administration, at the end of administration and 1, 2, 4, 24 h after the end of administration/final visit (7 days after the treatment) |
|
|
|
| Secondary | Study Part A: ECGs - QT Interval | QT interval in ms recorded in supine position after 5 min at rest | Posted | Count of Participants | Participants | Screening visit/ day 1 (treatment day) at pre-administration, at the end of administration and 1, 2, 4, 24 h after the end of administration/final visit (7 days after the treatment) |
|
|
|
| Secondary | Study Part A: ECGs - QTcB Interval | QTcB interval in ms recorded in supine position after 5 min at rest | Posted | Count of Participants | Participants | Screening visit/ day 1 (treatment day) at pre-administration, at the end of administration and 1, 2, 4, 24 h after the end of administration/final visit (7 days after the treatment) |
|
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| Secondary | Study Part A: ECGs - QTcF Interval | QTcF interval in ms recorded in supine position after 5 min at rest | Posted | Count of Participants | Participants | Screening visit/ day 1 (treatment day) at pre-administration, at the end of administration and 1, 2, 4, 24 h after the end of administration/final visit (7 days after the treatment) |
|
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| Secondary | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Leukocytes and leukocyte differential count, erythrocytes, haemoglobin, haematocrit, MCV, MCH, MCHC, thrombocytes, electrolytes (sodium, potassium, calcium, chloride, inorganic phosphorus), enzymes (alkaline phosphatase, γ-GT, AST, ALT), substrates/metabolites (total bilirubin, creatinine, glucose, urea, uric acid, total cholesterol, triglycerides), total proteins, urine chemical analysis (pH, specific weight, appearance, color, nitrites, proteins, glucose, urobilinogen, bilirubin, ketones, hematic pigments, leukocytes), urine sediment (analysis performed only if positive: leukocytes, erythrocytes, flat cells, round cells, crystals, cylinders, mucus, bacteria, glomerular erythrocytes). Any abnormalities are recorded. | Posted | Count of Participants | Participants | Screening visit (day of informed consent signature)/final visit (7 days after the treatment) |
|
|
|
| Secondary | Study Part A: Cmax | Maximum plasma concentration measured for plasma fosnetupitant, netupitant and its main metabolites (M1, M2 and M3) | Posted | Mean | Standard Deviation | ng/mL | Day 1 (treatment day) at pre-administration, at 2, 5, 10, 15, 20, 30 and 45 min and at 1, 1.5, 2, 3, 4, 8, 12, 24 h after the administration |
|
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| Secondary | Study Part A: C0 | Plasma concentration at the end of the administration measured for plasma fosnetupitant, netupitant and its main metabolites (M1, M2 and M3) | Posted | Mean | Standard Deviation | ng/mL | Day 1 (treatment day) at pre-administration, at 2, 5, 10, 15, 20, 30 and 45 min and at 1, 1.5, 2, 3, 4, 8, 12, 24 h after the administration |
|
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| Secondary | Study Part A: Tmax | Time to achieve the maximum plasma concentration measured for plasma fosnetupitant, netupitant and its main metabolites (M1, M2 and M3) | Posted | Median | Full Range | h | Day 1 (treatment day) at pre-administration, at 2, 5, 10, 15, 20, 30 and 45 min and at 1, 1.5, 2, 3, 4, 8, 12, 24 h after the administration |
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| Secondary | Study Part A: Clast | Last measurable plasma concentration measured for plasma fosnetupitant, netupitant and its main metabolites (M1, M2 and M3) | Posted | Mean | Standard Deviation | ng/mL | Day 1 (treatment day) at pre-administration, at 2, 5, 10, 15, 20, 30 and 45 min and at 1, 1.5, 2, 3, 4, 8, 12, 24 h after the administration |
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| Secondary | Study Part A: Tlast | Time of last measurable plasma concentration measured for plasma fosnetupitant, netupitant and its main metabolites (M1, M2 and M3) | Posted | Mean | Standard Deviation | h | Day 1 (treatment day) at pre-administration, at 2, 5, 10, 15, 20, 30 and 45 min and at 1, 1.5, 2, 3, 4, 8, 12, 24 h after the administration |
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| Secondary | Study Part A: AUC0-t | Area under the concentration-time curve from time zero to time of last measurable plasma concentration measured for plasma fosnetupitant, netupitant and its main metabolites (M1, M2 and M3) | Posted | Mean | Standard Deviation | h x ng/mL | Day 1 (treatment day) at pre-administration, at 2, 5, 10, 15, 20, 30 and 45 min and at 1, 1.5, 2, 3, 4, 8, 12, 24 h after the administration |
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| Secondary | Study Part A: AUC0-24 | Area under the plasma concentration-time curve from time zero to 24 h after the administration measured for plasma fosnetupitant, netupitant and its main metabolites (M1, M2 and M3) | Posted | Mean | Standard Deviation | h x ng/mL | Day 1 (treatment day) at pre-administration, at 2, 5, 10, 15, 20, 30 and 45 min and at 1, 1.5, 2, 3, 4, 8, 12, 24 h after the administration |
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| Secondary | Study Part A: Terminal Elimination Rate Constant | Terminal elimination rate constant, calculated, if feasible, by log-linear regression using at least 3 points, C0 and Cmax excluded and measured for plasma fosnetupitant, netupitant and its main metabolites (M1, M2 and M3). Calculation was not feasible for M1 and M3, therefore these analytes are not reported in the Outcome Measure Data Table. | Posted | Mean | Standard Deviation | 1/h | Day 1 (treatment day) at pre-administration, at 2, 5, 10, 15, 20, 30 and 45 min and at 1, 1.5, 2, 3, 4, 8, 12, 24 h after the administration |
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| Secondary | Study Part A: t1/2 | Apparent terminal half-life calculated, if feasible, by as ln2/terminal elimination rate constant and measured for plasma fosnetupitant, netupitant and its main metabolites (M1, M2 and M3). Calculation was not feasible for M1 and M3, therefore these analytes are not reported in the Outcome Measure Data Table. | Posted | Mean | Standard Deviation | h | Day 1 (treatment day) at pre-administration, at 2, 5, 10, 15, 20, 30 and 45 min and at 1, 1.5, 2, 3, 4, 8, 12, 24 h after the administration |
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| Secondary | Study Part A: Systemic Clearance | Systemic clearance measured for plasma fosnetupitant, netupitant and its main metabolites (M1, M2 and M3). Calculation was not feasible for M1 and M3, therefore these analytes are not reported in the Outcome Measure Data Table. | Posted | Mean | Standard Deviation | mL/h | Day 1 (treatment day) at pre-administration, at 2, 5, 10, 15, 20, 30 and 45 min and at 1, 1.5, 2, 3, 4, 8, 12, 24 h after the administration |
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| Secondary | Study Part A: Vz | Apparent volume of distribution in the post-distribution phase measured for plasma fosnetupitant, netupitant and its main metabolites (M1, M2 and M3). Calculation was not feasible for M1 and M3, therefore these analytes are not reported in the Outcome Measure Data Table. | Posted | Mean | Standard Deviation | mL | Day 1 (treatment day) at pre-administration, at 2, 5, 10, 15, 20, 30 and 45 min and at 1, 1.5, 2, 3, 4, 8, 12, 24 h after the administration |
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| Secondary | Study Part A: MRT | Mean residence time measured for plasma fosnetupitant, netupitant and its main metabolites (M1, M2 and M3). Calculation was not feasible for M1 and M3, therefore these analytes are not reported in the Outcome Measure Data Table. | Posted | Mean | Standard Deviation | h | Day 1 (treatment day) at pre-administration, at 2, 5, 10, 15, 20, 30 and 45 min and at 1, 1.5, 2, 3, 4, 8, 12, 24 h after the administration |
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| 0 |
| 10 |
| 0 |
| 10 |
| 5 |
| 10 |
| EG001 | Study Part A - Cohort 1 - Fosnetupitant | 10 subjects were included in the study as planned and received the injection of Fosnetupitant 235 mg solution in 30 min. | 0 | 10 | 0 | 10 | 3 | 10 |
| EG002 | Study Part A - Cohort 2 | 10 subjects were included in the study as planned and received the injection of Fosnetupitant 235 mg solution in 15 min. | 0 | 10 | 0 | 10 | 2 | 10 |
| EG003 | Study Part A - Cohort 3 | 10 subjects were included in the study as planned and received the injection of Fosnetupitant 235 mg solution in 5 min. | 0 | 10 | 0 | 10 | 1 | 10 |
| EG004 | Study Part A - Cohort 4 | 10 subjects were included in the study as planned and received the injection of Fosnetupitant 235 mg solution in 2 min. | 0 | 10 | 0 | 10 | 4 | 10 |
| Nausea | Gastrointestinal disorders | MedDRA 27.0 | Non-systematic Assessment |
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| Fatigue | General disorders | MedDRA 27.0 | Non-systematic Assessment |
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| Infusion site pain | General disorders | MedDRA 27.0 | Non-systematic Assessment |
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| Injection site discomfort | General disorders | MedDRA 27.0 | Non-systematic Assessment |
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| Influenza like illness | General disorders | MedDRA 27.0 | Non-systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 27.0 | Non-systematic Assessment |
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| Presyncope | Nervous system disorders | MedDRA 27.0 | Non-systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 27.0 | Non-systematic Assessment |
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| Dysgeusia | Nervous system disorders | MedDRA 27.0 | Non-systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA 27.0 | Non-systematic Assessment |
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| AST increased | Investigations | MedDRA 27.0 | Non-systematic Assessment |
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Not provided
Not provided
| General disorders and administration site conditions |
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| Nervous system disorders |
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| Psychiatric disorders |
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| Investigations |
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| Day -1 (enrolment day) |
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| Day 1 (treatment day) at pre-administration |
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| Day 1 (treatment day) at the end of administration |
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| Day 1 (treatment day) at 1 h after the end of administration |
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| Day 1 (treatment day) at 2 h after the end of administration |
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| Day 1 (treatment day) at 4 h after the end of administration |
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| Day 1 (treatment day) at 24 h after the end of administration |
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| Final visit (7 days after the treatment) |
|
| Day -1 (enrolment day) |
|
| Day 1 (treatment day) at pre-administration |
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| Day 1 (treatment day) at the end of administration |
|
| Day 1 (treatment day) at 1 h after the end of administration |
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| Day 1 (treatment day) at 2 h after the end of administration |
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| Day 1 (treatment day) at 4 h after the end of administration |
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| Day 1 (treatment day) at 24 h after the end of administration |
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| Final visit (7 days after the treatment) |
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| Day -1 (enrolment day) |
|
| Day 1 (treatment day) at pre-administration |
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| Day 1 (treatment day) at the end of administration |
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| Day 1 (treatment day) at 1 h after the end of administration |
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| Day 1 (treatment day) at 2 h after the end of administration |
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| Day 1 (treatment day) at 4 h after the end of administration |
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| Day 1 (treatment day) at 24 h after the end of administration |
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| Final visit (7 days after the treatment) |
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| Final visit (7 days after the treatment) |
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| Abnormal not clinically significant |
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| Final visit (7 days after the treatment) |
|
| Abnormal not clinically significant |
|
| Abnormal not clinically significant |
|
| Day 1 (treatment day) at pre-administration |
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| Day 1 (treatment day) at the end of administration |
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| Day 1 (treatment day) at 1 h after the end of administration |
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| Day 1 (treatment day) at 2 h after the end of administration |
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| Day 1 (treatment day) at 4 h after the end of administration |
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| Day 1 (treatment day) at 24 h after the end of administration |
|
| Final visit (7 days after the treatment) |
|
| Abnormal, not clinically significant |
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| Day 1 (treatment day) at pre-administration |
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| Day 1 (treatment day) at the end of administration |
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| Day 1 (treatment day) at 1 h after the end of administration |
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| Day 1 (treatment day) at 2 h after the end of administration |
|
| Day 1 (treatment day) at 4 h after the end of administration |
|
| Day 1 (treatment day) at 24 h after the end of administration |
|
| Final visit (7 days after the treatment) |
|
| Abnormal, not clinically significant |
|
| Day 1 (treatment day) at pre-administration |
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| Day 1 (treatment day) at the end of administration |
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| Day 1 (treatment day) at 1 h after the end of administration |
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| Day 1 (treatment day) at 2 h after the end of administration |
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| Day 1 (treatment day) at 4 h after the end of administration |
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| Day 1 (treatment day) at 24 h after the end of administration |
|
| Final visit (7 days after the treatment) |
|
| Abnormal not clinically significant |
|
| Day 1 (treatment day) at pre-administration |
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| Day 1 (treatment day) at the end of administration |
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| Day 1 (treatment day) at 1 h after the end of administration |
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| Day 1 (treatment day) at 2 h after the end of administration |
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| Day 1 (treatment day) at 4 h after the end of administration |
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| Day 1 (treatment day) at 24 h after the end of administration |
|
| Final visit (7 days after the treatment) |
|
| Abnormal, not clinically significant |
|
| Day 1 (treatment day) at pre-administration |
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| Day 1 (treatment day) at the end of administration |
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| Day 1 (treatment day) at 1 h after the end of administration |
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| Day 1 (treatment day) at 2 h after the end of administration |
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| Day 1 (treatment day) at 4 h after the end of administration |
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| Day 1 (treatment day) at 24 h after the end of administration |
|
| Final visit (7 days after the treatment) |
|
| Abnormal not clinically significant |
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| Day 1 (treatment day) at pre-administration |
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| Day 1 (treatment day) at the end of administration |
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| Day 1 (treatment day) at 1 h after the end of administration |
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| Day 1 (treatment day) at 2 h after the end of administration |
|
| Day 1 (treatment day) at 4 h after the end of administration |
|
| Day 1 (treatment day) at 24 h after the end of administration |
|
| Final visit (7 days after the treatment) |
|
| Abnormal not clinically significant |
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| Day 1 (treatment day) at pre-administration |
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| Day 1 (treatment day) at the end of administration |
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| Day 1 (treatment day) at 1 h after the end of administration |
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| Day 1 (treatment day) at 2 h after the end of administration |
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| Day 1 (treatment day) at 4 h after the end of administration |
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| Day 1 (treatment day) at 24 h after the end of administration |
|
| Final visit (7 days after the treatment) |
|
| Abnormal not clinically significant |
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| Abnormal clinically significant |
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| Screening visit - urine |
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| Final visit (7 days after the treatment) - blood |
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| Final visit (7 days after the treatment) - urine |
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| Netupitant |
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| Metabolite M1 |
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| Metabolite M2 |
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| Metabolite M3 |
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| Netupitant |
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| Metabolite M1 |
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| Metabolite M2 |
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| Metabolite M3 |
|
| Netupitant |
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| Metabolite M1 |
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| Metabolite M2 |
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| Metabolite M3 |
|
| Netupitant |
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| Metabolite M1 |
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| Metabolite M2 |
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| Metabolite M3 |
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| Netupitant |
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| Metabolite M1 |
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| Metabolite M2 |
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| Metabolite M3 |
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| Netupitant |
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| Metabolite M1 |
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| Metabolite M2 |
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| Metabolite M3 |
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| Netupitant |
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| Metabolite M1 |
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| Metabolite M2 |
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| Metabolite M3 |
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| Netupitant |
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| Metabolite M2 |
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| Netupitant |
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| Metabolite M2 |
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| Netupitant |
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| Metabolite M2 |
|
| Netupitant |
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| Metabolite M2 |
|
| Netupitant |
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| Metabolite M2 |
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