Healthy Volunteers
Conditions
Keywords
Helsinn, PNET-22-08, Fosnetupitant, Netupitant
Brief summary
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.
Detailed description
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.
Interventions
DRUGAkynzeo solution
235 mg fosnetupitant (corresponding to 260 mg of the chloride hydrochloride salt) / 0.25 mg palonosetron in 20 mL injectable solution
DRUGFosnetupitant 235 mg solution
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
Sponsors
Helsinn Healthcare SA
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
NONE
Intervention model description
Open label, single dose, two parts (part A and part B), safety and pharmacokinetic phase I study.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Informed consent: signed written informed consent before inclusion in the study 2. Sex and Age: healthy men/women volunteers, 18-55 years old (inclusive) 3. Body Mass Index (BMI): 18.5-30 kg/m2 inclusive 4. 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 5. 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 6. 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: 1. Hormonal oral, implantable, transdermal, or injectable contraceptives for at least 2 months before the screening visit. 2. A non-hormonal intrauterine device \[IUD\] for at least 2 months before the screening visit 3. A sterile or vasectomized sexual partner 4. True (long-term) heterosexual abstinence, defined as refraining from heterosexual intercourse when this is in line with the preferred and usual lifestyle of the subject, while periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), lactational amenorrhea and withdrawal are not acceptable. Women of non-child-bearing potential or in post-menopausal status defined as such when there is either: 1. 12 months of spontaneous amenorrhea or 2. 6 months of spontaneous amenorrhea with serum FSH levels \> 40 mIU/mL or 3. 6 weeks documented postsurgical bilateral oophorectomy with or without hysterectomy will be admitted. For all women, pregnancy test result must be negative at screening and admission (Day -1). 7. 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: 1. A male condom with spermicide 2. A sterile sexual partner or a partner in post-menopausal status for at least one year 3. Use by the female sexual partner of an IUD, a female condom with spermicide, a contraceptive sponge with spermicide, a diaphragm with spermicide, a cervical cap with spermicide, or hormonal oral, implantable, transdermal, or injectable contraceptives for at least 2 months before the screening visit Men must accept to inform their partners of the participation in the clinical study. Furthermore, they will not donate sperm from the date of the informed consent form's signature, throughout the study, and for at least 14 days after the last dose of the study treatment. These requirements are based upon the availability and results of reproductive toxicity data.
Exclusion criteria
1. 12-leads Electrocardiogram (ECG) (supine position): clinically significant abnormalities at screening. With regards to QTc, the following will be considered as exclusion criterion: mean corrected QT (QTcF) \> 450 ms. HR \< 50 or \> 99 bpm. PR \< 100 or \>220 ms. QRS \> 120 ms. Relevantly abnormal T-wave patterns 2. Physical examination findings: clinically significant abnormal physical findings which could interfere with the objectives of the study 3. Laboratory analyses: clinically significant abnormal laboratory values at screening, indicative of physical illness or suggesting the subject's exclusion, in his/her best interest 4. Allergy: ascertained or presumptive hypersensitivity to the active principle and/or formulations' ingredients; history of anaphylaxis to drugs or allergic reactions in general, which the investigator considers may affect the outcome of the study 5. Diseases: significant history, in the opinion of the Investigator, of renal, hepatic, gastrointestinal, cardiovascular (in particular, heart failure, hypokalemia, family history of Long QT Syndrome, history of superficial thrombophlebitis or deep vein thrombosis), respiratory, skin, hematological, endocrine or neurological diseases that may interfere with the aim of the study 6. Medications: medications, including over the counter (OTC) medications and herbal remedies in the 2 weeks before the first visit of the study. Hormonal contraceptives for women are allowed 7. CYP3A4 inducers and inhibitors: use of any inducer or inhibitor of CYP3A4 enzymes (drugs, food, herbal remedies) in the 28 days or in the 7 days, respectively, before the planned first study drug administration and during the whole study 8. Investigative drug studies: participation in the evaluation of any investigational product for 3 months before this study. The 3-month interval is calculated as the time between the first calendar day of the month that follows the last visit of the previous study and the first day of the present study 9. Blood donation or significant blood loss: blood donations or significant blood loss in the 3 months before the first visit of this study 10. Drug, alcohol, caffeine, tobacco: history of drug, alcohol \[\>1 drink/day for women and \>2 drinks/day for men, defined according to the USDA Dietary Guidelines 2020-2025 (11)\], caffeine (\>5 cups coffee/tea/day) or tobacco abuse (≥10 cigarettes/day) 11. Drug test: positive result at the urine drug screening test at screening or Day -1 12. Alcohol test: positive salivary alcohol test at Day -1 13. Diet: abnormal diets (\<1600 or \>3500 kcal/day) or substantial changes in eating habits in the 4 weeks before screening; vegetarians 14. Pregnancy (women only): positive or missing pregnancy test at screening or Day -1, pregnant or lactating women 15. Netupitant studies: enrolment in a previous study of netupitant or fosnetupitant (alone or in combination with palonosetron)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Study Part A: Number of Treatment-emergent Adverse Events | From screening visit (day of informed consent signature) up to 24 h after the investigational medicinal product administration (a maximum of 21 days) | Number of treatment-emergent adverse events (TEAEs) collected up to 24 h post-dose. |
| Study Part A: Number of Subjects With Treatment-emergent Adverse Events | From screening visit (day of informed consent signature) up to 24 h after the investigational medicinal product administration (a maximum of 21 days) | Number of subjects with treatment-emergent adverse events (TEAEs) collected up to 24 h post-dose. |
| Study Part A: Type of Treatment-emergent Adverse Events | From screening visit (day of informed consent signature) up to 24 h after the investigational medicinal product administration (a maximum of 21 days) | Type of treatment-emergent adverse events (TEAEs) collected up to 24 h post-dose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Study Part A: Pulse Rate | 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) | Pulse rate in bpm measured after 5 min at rest in sitting position |
| Study Part A: Weight | Screening visit (day of informed consent signature)/final visit (7 days after the treatment) | Body weight in kilograms |
| Study Part A: Full Physical Examination Through Apparatus/Systems Check | Screening visit (day of informed consent signature)/final visit (7 days after the treatment) | 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. |
| Study Part A: Short Physical Examination Through Apparatus/Systems Check | Day 2 (24 h after the end of investigational product administration) | General appearance, Chest/respiratory, Heart/cardiovascular, Lymph nodes, Neurologic/psychiatric, Skin/dermatologic systems are checked. Any abnormalities are recorded. |
| Study Part A: ECGs - Heart Rate | 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) | Heart rate in beats/min recorded in supine position after 5 min at rest |
| Study Part A: ECGs - PR Interval | 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) | PR interval in ms recorded in supine position after 5 min at rest |
| Study Part A: ECGs - RR Interval | 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) | RR interval in ms recorded in supine position after 5 min at rest |
| Study Part A: ECGs - QRS Duration | 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) | QRS duration in ms recorded in supine position after 5 min at rest |
| Study Part A: ECGs - QT Interval | 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) | QT interval in ms recorded in supine position after 5 min at rest |
| Study Part A: ECGs - QTcF Interval | 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) | QTcF interval in ms recorded in supine position after 5 min at rest |
| Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Screening visit (day of informed consent signature)/final visit (7 days after the treatment) | 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. |
| Study Part A: ECGs - QTcB Interval | 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) | QTcB interval in ms recorded in supine position after 5 min at rest |
| Study Part A: C0 | 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 | Plasma concentration at the end of the administration measured for plasma fosnetupitant, netupitant and its main metabolites (M1, M2 and M3) |
| Study Part A: Tmax | 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 | Time to achieve the maximum plasma concentration measured for plasma fosnetupitant, netupitant and its main metabolites (M1, M2 and M3) |
| Study Part A: Clast | 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 | Last measurable plasma concentration measured for plasma fosnetupitant, netupitant and its main metabolites (M1, M2 and M3) |
| Study Part A: Tlast | 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 | Time of last measurable plasma concentration measured for plasma fosnetupitant, netupitant and its main metabolites (M1, M2 and M3) |
| Study Part A: AUC0-t | 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 | 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) |
| Study Part A: AUC0-24 | 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 | 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) |
| Study Part A: Terminal Elimination Rate Constant | 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 | 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. |
| Study Part A: t1/2 | 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 | 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. |
| Study Part A: Systemic Clearance | 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 | 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. |
| Study Part A: Vz | 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 | 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. |
| Study Part A: MRT | 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 | 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. |
| Study Part A: Cmax | 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 | Maximum plasma concentration measured for plasma fosnetupitant, netupitant and its main metabolites (M1, M2 and M3) |
| Study Part A: Systolic Blood Pressure | 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) | Systolic blood pressure in mmHg measured after 5 min at rest in sitting position |
| Study Part A: Diastolic Blood Pressure | 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) | Diastolic blood pressure in mmHg measured after 5 min at rest in sitting position |
Countries
Switzerland
Participant flow
Recruitment details
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.
Pre-assignment details
Fifty (50) subjects were included in the study and received the treatment as planned.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 10 |
| 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. | 10 |
| 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. | 10 |
| 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. | 10 |
| 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. | 10 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Study Part A - Cohort 4 | Total | Study Part A - Cohort 2 | Study Part A - Cohort 1 - Fosnetupitant | Study Part A - Cohort 1 - Akynzeo | Study Part A - Cohort 3 |
|---|---|---|---|---|---|---|
| Age, Continuous | 38.1 years STANDARD_DEVIATION 13.5 | 37.5 years STANDARD_DEVIATION 11.1 | 38.9 years STANDARD_DEVIATION 13.2 | 40.7 years STANDARD_DEVIATION 8.2 | 31.7 years STANDARD_DEVIATION 8.9 | 37.9 years STANDARD_DEVIATION 10.8 |
| Body mass index | 24.83 kilograms/square meters STANDARD_DEVIATION 3.42 | 24.24 kilograms/square meters STANDARD_DEVIATION 2.86 | 24.69 kilograms/square meters STANDARD_DEVIATION 2.65 | 24.49 kilograms/square meters STANDARD_DEVIATION 3.36 | 22.46 kilograms/square meters STANDARD_DEVIATION 2.2 | 24.74 kilograms/square meters STANDARD_DEVIATION 2.26 |
| Body weight | 71.30 kilograms STANDARD_DEVIATION 11.66 | 70.85 kilograms STANDARD_DEVIATION 12.16 | 71.98 kilograms STANDARD_DEVIATION 13.16 | 69.83 kilograms STANDARD_DEVIATION 15.15 | 65.94 kilograms STANDARD_DEVIATION 9.5 | 75.20 kilograms STANDARD_DEVIATION 11.24 |
| Height | 169.4 centimeters STANDARD_DEVIATION 9.1 | 170.5 centimeters STANDARD_DEVIATION 9 | 170.1 centimeters STANDARD_DEVIATION 8.4 | 168.0 centimeters STANDARD_DEVIATION 9.3 | 171.0 centimeters STANDARD_DEVIATION 8.1 | 174.0 centimeters STANDARD_DEVIATION 10.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 46 Participants | 9 Participants | 10 Participants | 10 Participants | 8 Participants |
| Region of Enrollment Switzerland | 10 participants | 10 participants | 10 participants | 10 participants | 10 participants | 10 participants |
| Sex: Female, Male Female | 4 Participants | 20 Participants | 3 Participants | 6 Participants | 4 Participants | 3 Participants |
| Sex: Female, Male Male | 6 Participants | 30 Participants | 7 Participants | 4 Participants | 6 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 5 / 10 | 3 / 10 | 2 / 10 | 1 / 10 | 4 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 10 |
Outcome results
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.
Time frame: From screening visit (day of informed consent signature) up to 24 h after the investigational medicinal product administration (a maximum of 21 days)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Number of Subjects With Treatment-emergent Adverse Events | 5 Number of subjects with TEAE |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Number of Subjects With Treatment-emergent Adverse Events | 3 Number of subjects with TEAE |
| Study Part A - Cohort 2 | Study Part A: Number of Subjects With Treatment-emergent Adverse Events | 2 Number of subjects with TEAE |
| Study Part A - Cohort 3 | Study Part A: Number of Subjects With Treatment-emergent Adverse Events | 1 Number of subjects with TEAE |
| Study Part A - Cohort 4 | Study Part A: Number of Subjects With Treatment-emergent Adverse Events | 4 Number of subjects with TEAE |
Primary
Study Part A: Number of Treatment-emergent Adverse Events
Number of treatment-emergent adverse events (TEAEs) collected up to 24 h post-dose.
Time frame: From screening visit (day of informed consent signature) up to 24 h after the investigational medicinal product administration (a maximum of 21 days)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Number of Treatment-emergent Adverse Events | 7 Number of TEAE |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Number of Treatment-emergent Adverse Events | 4 Number of TEAE |
| Study Part A - Cohort 2 | Study Part A: Number of Treatment-emergent Adverse Events | 3 Number of TEAE |
| Study Part A - Cohort 3 | Study Part A: Number of Treatment-emergent Adverse Events | 1 Number of TEAE |
| Study Part A - Cohort 4 | Study Part A: Number of Treatment-emergent Adverse Events | 4 Number of TEAE |
Primary
Study Part A: Type of Treatment-emergent Adverse Events
Type of treatment-emergent adverse events (TEAEs) collected up to 24 h post-dose.
Time frame: From screening visit (day of informed consent signature) up to 24 h after the investigational medicinal product administration (a maximum of 21 days)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Type of Treatment-emergent Adverse Events | Psychiatric disorders | 1 Number of TEAE |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Type of Treatment-emergent Adverse Events | Gastrointestinal disorders | 2 Number of TEAE |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Type of Treatment-emergent Adverse Events | Investigations | 0 Number of TEAE |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Type of Treatment-emergent Adverse Events | General disorders and administration site conditions | 2 Number of TEAE |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Type of Treatment-emergent Adverse Events | Nervous system disorders | 2 Number of TEAE |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Type of Treatment-emergent Adverse Events | Psychiatric disorders | 0 Number of TEAE |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Type of Treatment-emergent Adverse Events | Nervous system disorders | 1 Number of TEAE |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Type of Treatment-emergent Adverse Events | General disorders and administration site conditions | 2 Number of TEAE |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Type of Treatment-emergent Adverse Events | Investigations | 0 Number of TEAE |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Type of Treatment-emergent Adverse Events | Gastrointestinal disorders | 1 Number of TEAE |
| Study Part A - Cohort 2 | Study Part A: Type of Treatment-emergent Adverse Events | Nervous system disorders | 2 Number of TEAE |
| Study Part A - Cohort 2 | Study Part A: Type of Treatment-emergent Adverse Events | Gastrointestinal disorders | 0 Number of TEAE |
| Study Part A - Cohort 2 | Study Part A: Type of Treatment-emergent Adverse Events | General disorders and administration site conditions | 0 Number of TEAE |
| Study Part A - Cohort 2 | Study Part A: Type of Treatment-emergent Adverse Events | Psychiatric disorders | 0 Number of TEAE |
| Study Part A - Cohort 2 | Study Part A: Type of Treatment-emergent Adverse Events | Investigations | 1 Number of TEAE |
| Study Part A - Cohort 3 | Study Part A: Type of Treatment-emergent Adverse Events | Investigations | 0 Number of TEAE |
| Study Part A - Cohort 3 | Study Part A: Type of Treatment-emergent Adverse Events | Gastrointestinal disorders | 0 Number of TEAE |
| Study Part A - Cohort 3 | Study Part A: Type of Treatment-emergent Adverse Events | Psychiatric disorders | 0 Number of TEAE |
| Study Part A - Cohort 3 | Study Part A: Type of Treatment-emergent Adverse Events | Nervous system disorders | 0 Number of TEAE |
| Study Part A - Cohort 3 | Study Part A: Type of Treatment-emergent Adverse Events | General disorders and administration site conditions | 1 Number of TEAE |
| Study Part A - Cohort 4 | Study Part A: Type of Treatment-emergent Adverse Events | Nervous system disorders | 4 Number of TEAE |
| Study Part A - Cohort 4 | Study Part A: Type of Treatment-emergent Adverse Events | Psychiatric disorders | 0 Number of TEAE |
| Study Part A - Cohort 4 | Study Part A: Type of Treatment-emergent Adverse Events | Gastrointestinal disorders | 0 Number of TEAE |
| Study Part A - Cohort 4 | Study Part A: Type of Treatment-emergent Adverse Events | Investigations | 0 Number of TEAE |
| Study Part A - Cohort 4 | Study Part A: Type of Treatment-emergent Adverse Events | General disorders and administration site conditions | 0 Number of TEAE |
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)
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Study Part A - Cohort 1 - Akynzeo | Study Part A: AUC0-24 | Metabolite M2 | 1234.204 h x ng/mL | Standard Deviation 767.496 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: AUC0-24 | Fosnetupitant | 3228.246 h x ng/mL | Standard Deviation 781.172 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: AUC0-24 | Metabolite M3 | 833.606 h x ng/mL | Standard Deviation 164.142 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: AUC0-24 | Netupitant | 5404.315 h x ng/mL | Standard Deviation 1227.399 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: AUC0-24 | Metabolite M1 | 468.997 h x ng/mL | Standard Deviation 113.819 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: AUC0-24 | Metabolite M2 | 1260.320 h x ng/mL | Standard Deviation 477.244 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: AUC0-24 | Metabolite M1 | 456.214 h x ng/mL | Standard Deviation 173.046 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: AUC0-24 | Netupitant | 5232.178 h x ng/mL | Standard Deviation 1119.31 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: AUC0-24 | Metabolite M3 | 895.624 h x ng/mL | Standard Deviation 304.534 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: AUC0-24 | Fosnetupitant | 3382.473 h x ng/mL | Standard Deviation 657.505 |
| Study Part A - Cohort 2 | Study Part A: AUC0-24 | Metabolite M1 | 436.089 h x ng/mL | Standard Deviation 142.089 |
| Study Part A - Cohort 2 | Study Part A: AUC0-24 | Fosnetupitant | 4833.636 h x ng/mL | Standard Deviation 4577.777 |
| Study Part A - Cohort 2 | Study Part A: AUC0-24 | Netupitant | 5792.056 h x ng/mL | Standard Deviation 1520.649 |
| Study Part A - Cohort 2 | Study Part A: AUC0-24 | Metabolite M2 | 959.756 h x ng/mL | Standard Deviation 382.755 |
| Study Part A - Cohort 2 | Study Part A: AUC0-24 | Metabolite M3 | 831.375 h x ng/mL | Standard Deviation 306.679 |
| Study Part A - Cohort 3 | Study Part A: AUC0-24 | Metabolite M3 | 826.377 h x ng/mL | Standard Deviation 156.114 |
| Study Part A - Cohort 3 | Study Part A: AUC0-24 | Fosnetupitant | 3668.069 h x ng/mL | Standard Deviation 631.004 |
| Study Part A - Cohort 3 | Study Part A: AUC0-24 | Metabolite M2 | 1137.332 h x ng/mL | Standard Deviation 331.659 |
| Study Part A - Cohort 3 | Study Part A: AUC0-24 | Metabolite M1 | 426.440 h x ng/mL | Standard Deviation 122.749 |
| Study Part A - Cohort 3 | Study Part A: AUC0-24 | Netupitant | 5344.307 h x ng/mL | Standard Deviation 1385.625 |
| Study Part A - Cohort 4 | Study Part A: AUC0-24 | Metabolite M1 | 447.497 h x ng/mL | Standard Deviation 143.611 |
| Study Part A - Cohort 4 | Study Part A: AUC0-24 | Metabolite M2 | 1182.642 h x ng/mL | Standard Deviation 560.829 |
| Study Part A - Cohort 4 | Study Part A: AUC0-24 | Fosnetupitant | 3844.251 h x ng/mL | Standard Deviation 859.498 |
| Study Part A - Cohort 4 | Study Part A: AUC0-24 | Metabolite M3 | 935.410 h x ng/mL | Standard Deviation 441.878 |
| Study Part A - Cohort 4 | Study Part A: AUC0-24 | Netupitant | 5656.305 h x ng/mL | Standard Deviation 1998.286 |
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)
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Study Part A - Cohort 1 - Akynzeo | Study Part A: AUC0-t | Metabolite M2 | 1234.204 h x ng/mL | Standard Deviation 767.496 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: AUC0-t | Fosnetupitant | 3217.286 h x ng/mL | Standard Deviation 780.235 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: AUC0-t | Metabolite M3 | 833.606 h x ng/mL | Standard Deviation 164.142 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: AUC0-t | Netupitant | 5404.315 h x ng/mL | Standard Deviation 1227.399 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: AUC0-t | Metabolite M1 | 468.997 h x ng/mL | Standard Deviation 113.819 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: AUC0-t | Metabolite M2 | 1260.320 h x ng/mL | Standard Deviation 477.244 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: AUC0-t | Metabolite M1 | 456.214 h x ng/mL | Standard Deviation 173.046 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: AUC0-t | Netupitant | 5232.178 h x ng/mL | Standard Deviation 1119.31 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: AUC0-t | Metabolite M3 | 895.624 h x ng/mL | Standard Deviation 304.534 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: AUC0-t | Fosnetupitant | 3374.275 h x ng/mL | Standard Deviation 658.088 |
| Study Part A - Cohort 2 | Study Part A: AUC0-t | Metabolite M1 | 436.089 h x ng/mL | Standard Deviation 142.089 |
| Study Part A - Cohort 2 | Study Part A: AUC0-t | Fosnetupitant | 4807.383 h x ng/mL | Standard Deviation 4537.62 |
| Study Part A - Cohort 2 | Study Part A: AUC0-t | Netupitant | 5792.056 h x ng/mL | Standard Deviation 1520.649 |
| Study Part A - Cohort 2 | Study Part A: AUC0-t | Metabolite M2 | 959.756 h x ng/mL | Standard Deviation 382.755 |
| Study Part A - Cohort 2 | Study Part A: AUC0-t | Metabolite M3 | 831.375 h x ng/mL | Standard Deviation 306.679 |
| Study Part A - Cohort 3 | Study Part A: AUC0-t | Metabolite M3 | 826.377 h x ng/mL | Standard Deviation 156.114 |
| Study Part A - Cohort 3 | Study Part A: AUC0-t | Fosnetupitant | 3662.088 h x ng/mL | Standard Deviation 630.455 |
| Study Part A - Cohort 3 | Study Part A: AUC0-t | Metabolite M2 | 1137.332 h x ng/mL | Standard Deviation 331.659 |
| Study Part A - Cohort 3 | Study Part A: AUC0-t | Metabolite M1 | 426.440 h x ng/mL | Standard Deviation 122.749 |
| Study Part A - Cohort 3 | Study Part A: AUC0-t | Netupitant | 5344.307 h x ng/mL | Standard Deviation 1385.625 |
| Study Part A - Cohort 4 | Study Part A: AUC0-t | Metabolite M1 | 447.497 h x ng/mL | Standard Deviation 143.611 |
| Study Part A - Cohort 4 | Study Part A: AUC0-t | Metabolite M2 | 1182.642 h x ng/mL | Standard Deviation 560.829 |
| Study Part A - Cohort 4 | Study Part A: AUC0-t | Fosnetupitant | 3839.681 h x ng/mL | Standard Deviation 859.368 |
| Study Part A - Cohort 4 | Study Part A: AUC0-t | Metabolite M3 | 935.410 h x ng/mL | Standard Deviation 441.878 |
| Study Part A - Cohort 4 | Study Part A: AUC0-t | Netupitant | 5656.305 h x ng/mL | Standard Deviation 1998.286 |
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)
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Study Part A - Cohort 1 - Akynzeo | Study Part A: C0 | Metabolite M2 | 28.150 ng/mL | Standard Deviation 10.059 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: C0 | Fosnetupitant | 8486.000 ng/mL | Standard Deviation 2095.382 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: C0 | Metabolite M3 | 6.214 ng/mL | Standard Deviation 4.144 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: C0 | Netupitant | 743.100 ng/mL | Standard Deviation 173.921 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: C0 | Metabolite M1 | 1.714 ng/mL | Standard Deviation 2.229 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: C0 | Metabolite M2 | 49.121 ng/mL | Standard Deviation 34.243 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: C0 | Metabolite M1 | 1.753 ng/mL | Standard Deviation 1.969 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: C0 | Netupitant | 893.400 ng/mL | Standard Deviation 283.232 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: C0 | Metabolite M3 | 6.799 ng/mL | Standard Deviation 2.989 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: C0 | Fosnetupitant | 8920.000 ng/mL | Standard Deviation 1722.892 |
| Study Part A - Cohort 2 | Study Part A: C0 | Metabolite M1 | 0.337 ng/mL | Standard Deviation 1.066 |
| Study Part A - Cohort 2 | Study Part A: C0 | Fosnetupitant | 23650.000 ng/mL | Standard Deviation 20971.899 |
| Study Part A - Cohort 2 | Study Part A: C0 | Netupitant | 946.100 ng/mL | Standard Deviation 419.234 |
| Study Part A - Cohort 2 | Study Part A: C0 | Metabolite M2 | 32.300 ng/mL | Standard Deviation 22.563 |
| Study Part A - Cohort 2 | Study Part A: C0 | Metabolite M3 | 0.727 ng/mL | Standard Deviation 1.711 |
| Study Part A - Cohort 3 | Study Part A: C0 | Metabolite M3 | 0.000 ng/mL | Standard Deviation 0 |
| Study Part A - Cohort 3 | Study Part A: C0 | Fosnetupitant | 32540.000 ng/mL | Standard Deviation 6607.437 |
| Study Part A - Cohort 3 | Study Part A: C0 | Metabolite M2 | 25.680 ng/mL | Standard Deviation 11.219 |
| Study Part A - Cohort 3 | Study Part A: C0 | Metabolite M1 | 0.000 ng/mL | Standard Deviation 0 |
| Study Part A - Cohort 3 | Study Part A: C0 | Netupitant | 1019.400 ng/mL | Standard Deviation 319.82 |
| Study Part A - Cohort 4 | Study Part A: C0 | Metabolite M1 | 0.000 ng/mL | Standard Deviation 0 |
| Study Part A - Cohort 4 | Study Part A: C0 | Metabolite M2 | 12.706 ng/mL | Standard Deviation 6.689 |
| Study Part A - Cohort 4 | Study Part A: C0 | Fosnetupitant | 33557.000 ng/mL | Standard Deviation 15972.519 |
| Study Part A - Cohort 4 | Study Part A: C0 | Metabolite M3 | 0.000 ng/mL | Standard Deviation 0 |
| Study Part A - Cohort 4 | Study Part A: C0 | Netupitant | 596.810 ng/mL | Standard Deviation 383.903 |
Secondary
Study Part A: Clast
Last measurable plasma concentration measured for plasma fosnetupitant, netupitant and its main metabolites (M1, M2 and M3)
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Clast | Metabolite M2 | 20.090 ng/mL | Standard Deviation 10.519 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Clast | Fosnetupitant | 79.780 ng/mL | Standard Deviation 71.819 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Clast | Metabolite M3 | 46.370 ng/mL | Standard Deviation 12.315 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Clast | Netupitant | 149.150 ng/mL | Standard Deviation 111.842 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Clast | Metabolite M1 | 21.150 ng/mL | Standard Deviation 3.876 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Clast | Metabolite M2 | 18.850 ng/mL | Standard Deviation 7.89 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Clast | Metabolite M1 | 20.380 ng/mL | Standard Deviation 7.875 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Clast | Netupitant | 122.490 ng/mL | Standard Deviation 40.233 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Clast | Metabolite M3 | 48.020 ng/mL | Standard Deviation 17.273 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Clast | Fosnetupitant | 49.410 ng/mL | Standard Deviation 35.149 |
| Study Part A - Cohort 2 | Study Part A: Clast | Metabolite M1 | 20.532 ng/mL | Standard Deviation 6.667 |
| Study Part A - Cohort 2 | Study Part A: Clast | Fosnetupitant | 97.140 ng/mL | Standard Deviation 122.226 |
| Study Part A - Cohort 2 | Study Part A: Clast | Netupitant | 136.340 ng/mL | Standard Deviation 39.724 |
| Study Part A - Cohort 2 | Study Part A: Clast | Metabolite M2 | 14.534 ng/mL | Standard Deviation 4.789 |
| Study Part A - Cohort 2 | Study Part A: Clast | Metabolite M3 | 44.960 ng/mL | Standard Deviation 15.634 |
| Study Part A - Cohort 3 | Study Part A: Clast | Metabolite M3 | 47.080 ng/mL | Standard Deviation 14.763 |
| Study Part A - Cohort 3 | Study Part A: Clast | Fosnetupitant | 45.620 ng/mL | Standard Deviation 28.083 |
| Study Part A - Cohort 3 | Study Part A: Clast | Metabolite M2 | 18.770 ng/mL | Standard Deviation 5.515 |
| Study Part A - Cohort 3 | Study Part A: Clast | Metabolite M1 | 19.990 ng/mL | Standard Deviation 5.977 |
| Study Part A - Cohort 3 | Study Part A: Clast | Netupitant | 123.740 ng/mL | Standard Deviation 28.843 |
| Study Part A - Cohort 4 | Study Part A: Clast | Metabolite M1 | 21.440 ng/mL | Standard Deviation 7.826 |
| Study Part A - Cohort 4 | Study Part A: Clast | Metabolite M2 | 17.067 ng/mL | Standard Deviation 7.953 |
| Study Part A - Cohort 4 | Study Part A: Clast | Fosnetupitant | 34.330 ng/mL | Standard Deviation 16.176 |
| Study Part A - Cohort 4 | Study Part A: Clast | Metabolite M3 | 52.060 ng/mL | Standard Deviation 27.374 |
| Study Part A - Cohort 4 | Study Part A: Clast | Netupitant | 137.270 ng/mL | Standard Deviation 66.827 |
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.
Time frame: Screening visit (day of informed consent signature)/final visit (7 days after the treatment)
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Final visit (7 days after the treatment) - blood | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Final visit (7 days after the treatment) - urine | Abnormal not clinically significant | 7 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Screening visit - blood | Normal | 5 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Screening visit - urine | Normal | 3 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Screening visit - urine | Abnormal clinically significant | 0 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Final visit (7 days after the treatment) - urine | Abnormal clinically significant | 0 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Final visit (7 days after the treatment) - urine | Normal | 3 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Screening visit - blood | Abnormal clinically significant | 0 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Screening visit - urine | Abnormal not clinically significant | 7 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Final visit (7 days after the treatment) - blood | Normal | 2 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Screening visit - blood | Abnormal not clinically significant | 5 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Final visit (7 days after the treatment) - blood | Abnormal clinically significant | 0 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Final visit (7 days after the treatment) - urine | Abnormal clinically significant | 0 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Screening visit - urine | Abnormal clinically significant | 0 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Screening visit - blood | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Final visit (7 days after the treatment) - blood | Normal | 4 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Screening visit - blood | Normal | 2 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Final visit (7 days after the treatment) - urine | Abnormal not clinically significant | 7 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Screening visit - blood | Abnormal clinically significant | 0 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Final visit (7 days after the treatment) - blood | Abnormal not clinically significant | 6 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Final visit (7 days after the treatment) - urine | Normal | 3 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Screening visit - urine | Normal | 3 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Final visit (7 days after the treatment) - blood | Abnormal clinically significant | 0 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Screening visit - urine | Abnormal not clinically significant | 7 Participants |
| Study Part A - Cohort 2 | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Final visit (7 days after the treatment) - urine | Abnormal not clinically significant | 7 Participants |
| Study Part A - Cohort 2 | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Screening visit - blood | Normal | 2 Participants |
| Study Part A - Cohort 2 | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Screening visit - blood | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Screening visit - blood | Abnormal clinically significant | 0 Participants |
| Study Part A - Cohort 2 | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Screening visit - urine | Normal | 4 Participants |
| Study Part A - Cohort 2 | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Screening visit - urine | Abnormal not clinically significant | 6 Participants |
| Study Part A - Cohort 2 | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Screening visit - urine | Abnormal clinically significant | 0 Participants |
| Study Part A - Cohort 2 | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Final visit (7 days after the treatment) - blood | Normal | 1 Participants |
| Study Part A - Cohort 2 | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Final visit (7 days after the treatment) - blood | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Final visit (7 days after the treatment) - blood | Abnormal clinically significant | 1 Participants |
| Study Part A - Cohort 2 | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Final visit (7 days after the treatment) - urine | Normal | 3 Participants |
| Study Part A - Cohort 2 | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Final visit (7 days after the treatment) - urine | Abnormal clinically significant | 0 Participants |
| Study Part A - Cohort 3 | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Screening visit - urine | Abnormal clinically significant | 0 Participants |
| Study Part A - Cohort 3 | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Screening visit - blood | Normal | 3 Participants |
| Study Part A - Cohort 3 | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Final visit (7 days after the treatment) - blood | Abnormal not clinically significant | 9 Participants |
| Study Part A - Cohort 3 | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Screening visit - urine | Abnormal not clinically significant | 7 Participants |
| Study Part A - Cohort 3 | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Final visit (7 days after the treatment) - blood | Abnormal clinically significant | 0 Participants |
| Study Part A - Cohort 3 | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Screening visit - urine | Normal | 3 Participants |
| Study Part A - Cohort 3 | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Final visit (7 days after the treatment) - urine | Abnormal clinically significant | 0 Participants |
| Study Part A - Cohort 3 | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Final visit (7 days after the treatment) - urine | Normal | 4 Participants |
| Study Part A - Cohort 3 | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Screening visit - blood | Abnormal clinically significant | 0 Participants |
| Study Part A - Cohort 3 | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Screening visit - blood | Abnormal not clinically significant | 7 Participants |
| Study Part A - Cohort 3 | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Final visit (7 days after the treatment) - urine | Abnormal not clinically significant | 6 Participants |
| Study Part A - Cohort 3 | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Final visit (7 days after the treatment) - blood | Normal | 1 Participants |
| Study Part A - Cohort 4 | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Screening visit - urine | Abnormal clinically significant | 0 Participants |
| Study Part A - Cohort 4 | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Final visit (7 days after the treatment) - urine | Normal | 3 Participants |
| Study Part A - Cohort 4 | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Screening visit - blood | Normal | 1 Participants |
| Study Part A - Cohort 4 | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Final visit (7 days after the treatment) - blood | Abnormal not clinically significant | 10 Participants |
| Study Part A - Cohort 4 | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Screening visit - blood | Abnormal not clinically significant | 9 Participants |
| Study Part A - Cohort 4 | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Screening visit - urine | Normal | 2 Participants |
| Study Part A - Cohort 4 | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Final visit (7 days after the treatment) - urine | Abnormal clinically significant | 0 Participants |
| Study Part A - Cohort 4 | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Screening visit - urine | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 4 | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Final visit (7 days after the treatment) - blood | Abnormal clinically significant | 0 Participants |
| Study Part A - Cohort 4 | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Final visit (7 days after the treatment) - blood | Normal | 0 Participants |
| Study Part A - Cohort 4 | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Screening visit - blood | Abnormal clinically significant | 0 Participants |
| Study Part A - Cohort 4 | Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis) | Final visit (7 days after the treatment) - urine | Abnormal not clinically significant | 7 Participants |
Secondary
Study Part A: Cmax
Maximum plasma concentration measured for plasma fosnetupitant, netupitant and its main metabolites (M1, M2 and M3)
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Cmax | Metabolite M1 | 23.910 ng/mL | Standard Deviation 5.324 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Cmax | Fosnetupitant | 8486.000 ng/mL | Standard Deviation 2095.382 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Cmax | Metabolite M3 | 46.880 ng/mL | Standard Deviation 11.936 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Cmax | Netupitant | 767.400 ng/mL | Standard Deviation 136.572 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Cmax | Metabolite M2 | 135.730 ng/mL | Standard Deviation 58.257 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Cmax | Metabolite M3 | 48.450 ng/mL | Standard Deviation 17.019 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Cmax | Metabolite M1 | 22.380 ng/mL | Standard Deviation 8.433 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Cmax | Netupitant | 893.400 ng/mL | Standard Deviation 283.232 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Cmax | Metabolite M2 | 150.110 ng/mL | Standard Deviation 72.607 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Cmax | Fosnetupitant | 8920.000 ng/mL | Standard Deviation 1722.892 |
| Study Part A - Cohort 2 | Study Part A: Cmax | Metabolite M1 | 22.012 ng/mL | Standard Deviation 6.687 |
| Study Part A - Cohort 2 | Study Part A: Cmax | Fosnetupitant | 23650.000 ng/mL | Standard Deviation 20971.899 |
| Study Part A - Cohort 2 | Study Part A: Cmax | Netupitant | 1050.100 ng/mL | Standard Deviation 260.591 |
| Study Part A - Cohort 2 | Study Part A: Cmax | Metabolite M2 | 102.450 ng/mL | Standard Deviation 44.216 |
| Study Part A - Cohort 2 | Study Part A: Cmax | Metabolite M3 | 46.570 ng/mL | Standard Deviation 16.137 |
| Study Part A - Cohort 3 | Study Part A: Cmax | Fosnetupitant | 32540.000 ng/mL | Standard Deviation 6607.437 |
| Study Part A - Cohort 3 | Study Part A: Cmax | Metabolite M3 | 47.680 ng/mL | Standard Deviation 14.446 |
| Study Part A - Cohort 3 | Study Part A: Cmax | Metabolite M2 | 118.160 ng/mL | Standard Deviation 49.015 |
| Study Part A - Cohort 3 | Study Part A: Cmax | Metabolite M1 | 21.930 ng/mL | Standard Deviation 6.958 |
| Study Part A - Cohort 3 | Study Part A: Cmax | Netupitant | 1170.700 ng/mL | Standard Deviation 276.31 |
| Study Part A - Cohort 4 | Study Part A: Cmax | Metabolite M1 | 22.910 ng/mL | Standard Deviation 7.61 |
| Study Part A - Cohort 4 | Study Part A: Cmax | Metabolite M2 | 146.490 ng/mL | Standard Deviation 88.541 |
| Study Part A - Cohort 4 | Study Part A: Cmax | Fosnetupitant | 37500.000 ng/mL | Standard Deviation 11243.27 |
| Study Part A - Cohort 4 | Study Part A: Cmax | Metabolite M3 | 52.100 ng/mL | Standard Deviation 27.347 |
| Study Part A - Cohort 4 | Study Part A: Cmax | Netupitant | 1382.700 ng/mL | Standard Deviation 315.816 |
Secondary
Study Part A: Diastolic Blood Pressure
Diastolic blood pressure in mmHg measured after 5 min at rest in sitting position
Time frame: 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)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Diastolic Blood Pressure | Final visit (7 days after the treatment) | 70.1 mmHg | Standard Deviation 7.2 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Diastolic Blood Pressure | Day 1 (treatment day) at 2 h after the end of administration | 64.5 mmHg | Standard Deviation 8.5 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Diastolic Blood Pressure | Day 1 (treatment day) at 1 h after the end of administration | 63.9 mmHg | Standard Deviation 6.4 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Diastolic Blood Pressure | Screening visit | 72.3 mmHg | Standard Deviation 6.5 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Diastolic Blood Pressure | Day -1 (enrolment day) | 68.9 mmHg | Standard Deviation 8.6 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Diastolic Blood Pressure | Day 1 (treatment day) at 24 h after the end of administration | 67.0 mmHg | Standard Deviation 9.4 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Diastolic Blood Pressure | Day 1 (treatment day) at pre-administration | 72.1 mmHg | Standard Deviation 9 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Diastolic Blood Pressure | Day 1 (treatment day) at 4 h after the end of administration | 65.9 mmHg | Standard Deviation 6.6 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Diastolic Blood Pressure | Day 1 (treatment day) at the end of administration | 62.4 mmHg | Standard Deviation 11.1 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Diastolic Blood Pressure | Day 1 (treatment day) at the end of administration | 71.7 mmHg | Standard Deviation 8.3 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Diastolic Blood Pressure | Day 1 (treatment day) at 2 h after the end of administration | 72.8 mmHg | Standard Deviation 7.3 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Diastolic Blood Pressure | Day 1 (treatment day) at pre-administration | 74.9 mmHg | Standard Deviation 9.2 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Diastolic Blood Pressure | Day 1 (treatment day) at 1 h after the end of administration | 73.4 mmHg | Standard Deviation 8.3 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Diastolic Blood Pressure | Final visit (7 days after the treatment) | 74.4 mmHg | Standard Deviation 7.5 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Diastolic Blood Pressure | Day 1 (treatment day) at 4 h after the end of administration | 68.9 mmHg | Standard Deviation 8.8 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Diastolic Blood Pressure | Day -1 (enrolment day) | 77.7 mmHg | Standard Deviation 5.8 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Diastolic Blood Pressure | Screening visit | 76.8 mmHg | Standard Deviation 6.9 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Diastolic Blood Pressure | Day 1 (treatment day) at 24 h after the end of administration | 72.7 mmHg | Standard Deviation 7.9 |
| Study Part A - Cohort 2 | Study Part A: Diastolic Blood Pressure | Day 1 (treatment day) at 1 h after the end of administration | 76.7 mmHg | Standard Deviation 8.8 |
| Study Part A - Cohort 2 | Study Part A: Diastolic Blood Pressure | Screening visit | 80.4 mmHg | Standard Deviation 8 |
| Study Part A - Cohort 2 | Study Part A: Diastolic Blood Pressure | Day -1 (enrolment day) | 76.1 mmHg | Standard Deviation 7 |
| Study Part A - Cohort 2 | Study Part A: Diastolic Blood Pressure | Day 1 (treatment day) at pre-administration | 76.0 mmHg | Standard Deviation 10.1 |
| Study Part A - Cohort 2 | Study Part A: Diastolic Blood Pressure | Day 1 (treatment day) at the end of administration | 75.2 mmHg | Standard Deviation 10.1 |
| Study Part A - Cohort 2 | Study Part A: Diastolic Blood Pressure | Day 1 (treatment day) at 2 h after the end of administration | 74.8 mmHg | Standard Deviation 11.2 |
| Study Part A - Cohort 2 | Study Part A: Diastolic Blood Pressure | Day 1 (treatment day) at 4 h after the end of administration | 76.6 mmHg | Standard Deviation 9.8 |
| Study Part A - Cohort 2 | Study Part A: Diastolic Blood Pressure | Day 1 (treatment day) at 24 h after the end of administration | 77.5 mmHg | Standard Deviation 8.8 |
| Study Part A - Cohort 2 | Study Part A: Diastolic Blood Pressure | Final visit (7 days after the treatment) | 77.7 mmHg | Standard Deviation 7.1 |
| Study Part A - Cohort 3 | Study Part A: Diastolic Blood Pressure | Day 1 (treatment day) at the end of administration | 75.2 mmHg | Standard Deviation 10.1 |
| Study Part A - Cohort 3 | Study Part A: Diastolic Blood Pressure | Screening visit | 80.4 mmHg | Standard Deviation 8 |
| Study Part A - Cohort 3 | Study Part A: Diastolic Blood Pressure | Day 1 (treatment day) at 2 h after the end of administration | 74.8 mmHg | Standard Deviation 11.2 |
| Study Part A - Cohort 3 | Study Part A: Diastolic Blood Pressure | Day 1 (treatment day) at pre-administration | 76.0 mmHg | Standard Deviation 10.1 |
| Study Part A - Cohort 3 | Study Part A: Diastolic Blood Pressure | Day 1 (treatment day) at 4 h after the end of administration | 76.6 mmHg | Standard Deviation 9.8 |
| Study Part A - Cohort 3 | Study Part A: Diastolic Blood Pressure | Day -1 (enrolment day) | 76.1 mmHg | Standard Deviation 7 |
| Study Part A - Cohort 3 | Study Part A: Diastolic Blood Pressure | Final visit (7 days after the treatment) | 77.7 mmHg | Standard Deviation 7.1 |
| Study Part A - Cohort 3 | Study Part A: Diastolic Blood Pressure | Day 1 (treatment day) at 24 h after the end of administration | 77.5 mmHg | Standard Deviation 8.8 |
| Study Part A - Cohort 3 | Study Part A: Diastolic Blood Pressure | Day 1 (treatment day) at 1 h after the end of administration | 76.7 mmHg | Standard Deviation 8.8 |
| Study Part A - Cohort 4 | Study Part A: Diastolic Blood Pressure | Day 1 (treatment day) at 2 h after the end of administration | 71.5 mmHg | Standard Deviation 9.2 |
| Study Part A - Cohort 4 | Study Part A: Diastolic Blood Pressure | Day 1 (treatment day) at the end of administration | 70.1 mmHg | Standard Deviation 9.3 |
| Study Part A - Cohort 4 | Study Part A: Diastolic Blood Pressure | Day 1 (treatment day) at 1 h after the end of administration | 72.5 mmHg | Standard Deviation 7.2 |
| Study Part A - Cohort 4 | Study Part A: Diastolic Blood Pressure | Day 1 (treatment day) at pre-administration | 71.9 mmHg | Standard Deviation 10.5 |
| Study Part A - Cohort 4 | Study Part A: Diastolic Blood Pressure | Day 1 (treatment day) at 24 h after the end of administration | 73.2 mmHg | Standard Deviation 7.7 |
| Study Part A - Cohort 4 | Study Part A: Diastolic Blood Pressure | Final visit (7 days after the treatment) | 77.4 mmHg | Standard Deviation 6.4 |
| Study Part A - Cohort 4 | Study Part A: Diastolic Blood Pressure | Screening visit | 76.7 mmHg | Standard Deviation 7.5 |
| Study Part A - Cohort 4 | Study Part A: Diastolic Blood Pressure | Day 1 (treatment day) at 4 h after the end of administration | 70.7 mmHg | Standard Deviation 8.5 |
| Study Part A - Cohort 4 | Study Part A: Diastolic Blood Pressure | Day -1 (enrolment day) | 74.8 mmHg | Standard Deviation 6.9 |
Secondary
Study Part A: ECGs - Heart Rate
Heart rate in beats/min recorded in supine position after 5 min at rest
Time frame: 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)
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - Heart Rate | Screening visit | Abnormal not clinically significant | 7 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at pre-administration | Normal | 1 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at pre-administration | Abnormal not clinically significant | 9 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - Heart Rate | Screening visit | Normal | 3 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at 1 h after the end of administration | Abnormal not clinically significant | 9 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at 2 h after the end of administration | Normal | 0 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at 2 h after the end of administration | Abnormal not clinically significant | 10 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at 4 h after the end of administration | Normal | 1 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at 4 h after the end of administration | Abnormal not clinically significant | 9 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at 24 h after the end of administration | Normal | 0 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at 24 h after the end of administration | Abnormal not clinically significant | 10 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - Heart Rate | Final visit (7 days after the treatment) | Normal | 2 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - Heart Rate | Final visit (7 days after the treatment) | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at 1 h after the end of administration | Normal | 1 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at pre-administration | Abnormal not clinically significant | 6 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - Heart Rate | Screening visit | Normal | 4 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at 4 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at the end of administration | Abnormal not clinically significant | 7 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at 4 h after the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at 24 h after the end of administration | Normal | 4 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - Heart Rate | Final visit (7 days after the treatment) | Abnormal not clinically significant | 3 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at 1 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at the end of administration | Normal | 3 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - Heart Rate | Final visit (7 days after the treatment) | Normal | 7 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at 1 h after the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - Heart Rate | Screening visit | Abnormal not clinically significant | 6 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at 2 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at 24 h after the end of administration | Abnormal not clinically significant | 6 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at pre-administration | Normal | 4 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at 2 h after the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at 2 h after the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - Heart Rate | Screening visit | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at 2 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at 4 h after the end of administration | Normal | 1 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at pre-administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - Heart Rate | Final visit (7 days after the treatment) | Abnormal not clinically significant | 7 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at 24 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at 1 h after the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at 4 h after the end of administration | Abnormal not clinically significant | 9 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - Heart Rate | Screening visit | Normal | 2 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at pre-administration | Normal | 2 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at 24 h after the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - Heart Rate | Final visit (7 days after the treatment) | Normal | 3 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at 1 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at 24 h after the end of administration | Abnormal not clinically significant | 7 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at pre-administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - Heart Rate | Final visit (7 days after the treatment) | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at 1 h after the end of administration | Normal | 1 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at 1 h after the end of administration | Abnormal not clinically significant | 9 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at 2 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - Heart Rate | Final visit (7 days after the treatment) | Normal | 2 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at 2 h after the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at 4 h after the end of administration | Normal | 1 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at 4 h after the end of administration | Abnormal not clinically significant | 9 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at 24 h after the end of administration | Normal | 3 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - Heart Rate | Screening visit | Normal | 3 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - Heart Rate | Screening visit | Abnormal not clinically significant | 7 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at pre-administration | Normal | 2 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at 4 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - Heart Rate | Final visit (7 days after the treatment) | Normal | 4 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at 2 h after the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at pre-administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - Heart Rate | Screening visit | Normal | 5 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at 2 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at 1 h after the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at 1 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at pre-administration | Normal | 2 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - Heart Rate | Screening visit | Abnormal not clinically significant | 5 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at 4 h after the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - Heart Rate | Final visit (7 days after the treatment) | Abnormal not clinically significant | 6 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at 24 h after the end of administration | Abnormal not clinically significant | 5 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - Heart Rate | Day 1 (treatment day) at 24 h after the end of administration | Normal | 5 Participants |
Secondary
Study Part A: ECGs - PR Interval
PR interval in ms recorded in supine position after 5 min at rest
Time frame: 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)
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - PR Interval | Screening visit | Abnormal, not clinically significant | 7 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at pre-administration | Normal | 1 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at pre-administration | Abnormal, not clinically significant | 9 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - PR Interval | Screening visit | Normal | 3 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at the end of administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at 1 h after the end of administration | Normal | 1 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at 1 h after the end of administration | Abnormal, not clinically significant | 9 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at 2 h after the end of administration | Normal | 0 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at 2 h after the end of administration | Abnormal, not clinically significant | 10 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at 4 h after the end of administration | Normal | 1 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at 4 h after the end of administration | Abnormal, not clinically significant | 9 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at 24 h after the end of administration | Normal | 0 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at 24 h after the end of administration | Abnormal, not clinically significant | 10 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - PR Interval | Final visit (7 days after the treatment) | Normal | 2 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - PR Interval | Final visit (7 days after the treatment) | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at 24 h after the end of administration | Abnormal, not clinically significant | 6 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at 2 h after the end of administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at 2 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - PR Interval | Final visit (7 days after the treatment) | Normal | 7 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at 1 h after the end of administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at the end of administration | Normal | 3 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at pre-administration | Abnormal, not clinically significant | 6 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - PR Interval | Screening visit | Abnormal, not clinically significant | 6 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - PR Interval | Screening visit | Normal | 4 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at 24 h after the end of administration | Normal | 4 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at the end of administration | Abnormal, not clinically significant | 7 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at pre-administration | Normal | 4 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - PR Interval | Final visit (7 days after the treatment) | Abnormal, not clinically significant | 3 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at 4 h after the end of administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at 4 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at 1 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at 24 h after the end of administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at pre-administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at the end of administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at 1 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at 1 h after the end of administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - PR Interval | Final visit (7 days after the treatment) | Normal | 3 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at 2 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at 2 h after the end of administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at 4 h after the end of administration | Normal | 1 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at 4 h after the end of administration | Abnormal, not clinically significant | 9 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at 24 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - PR Interval | Screening visit | Normal | 2 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - PR Interval | Final visit (7 days after the treatment) | Abnormal, not clinically significant | 7 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - PR Interval | Screening visit | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at pre-administration | Normal | 2 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at 2 h after the end of administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - PR Interval | Final visit (7 days after the treatment) | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at 4 h after the end of administration | Normal | 1 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at 24 h after the end of administration | Abnormal, not clinically significant | 7 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at 4 h after the end of administration | Abnormal, not clinically significant | 9 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at the end of administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at 24 h after the end of administration | Normal | 3 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at pre-administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - PR Interval | Screening visit | Normal | 3 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at pre-administration | Normal | 2 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at 1 h after the end of administration | Abnormal, not clinically significant | 9 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at 2 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - PR Interval | Final visit (7 days after the treatment) | Normal | 2 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at 1 h after the end of administration | Normal | 1 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - PR Interval | Screening visit | Abnormal, not clinically significant | 7 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at 24 h after the end of administration | Normal | 5 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at 2 h after the end of administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - PR Interval | Final visit (7 days after the treatment) | Normal | 4 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - PR Interval | Screening visit | Abnormal, not clinically significant | 5 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at 1 h after the end of administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at 4 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - PR Interval | Final visit (7 days after the treatment) | Abnormal, not clinically significant | 6 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at the end of administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at 2 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - PR Interval | Screening visit | Normal | 5 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at 4 h after the end of administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at 1 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at 24 h after the end of administration | Abnormal, not clinically significant | 5 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at pre-administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - PR Interval | Day 1 (treatment day) at pre-administration | Normal | 2 Participants |
Secondary
Study Part A: ECGs - QRS Duration
QRS duration in ms recorded in supine position after 5 min at rest
Time frame: 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)
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QRS Duration | Screening visit | Abnormal not clinically significant | 7 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at pre-administration | Normal | 1 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at pre-administration | Abnormal not clinically significant | 9 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QRS Duration | Screening visit | Normal | 3 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at 1 h after the end of administration | Normal | 1 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at 1 h after the end of administration | Abnormal not clinically significant | 9 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at 2 h after the end of administration | Normal | 0 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at 2 h after the end of administration | Abnormal not clinically significant | 10 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at 4 h after the end of administration | Normal | 1 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at 4 h after the end of administration | Abnormal not clinically significant | 9 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at 24 h after the end of administration | Normal | 0 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at 24 h after the end of administration | Abnormal not clinically significant | 10 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QRS Duration | Final visit (7 days after the treatment) | Normal | 2 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QRS Duration | Final visit (7 days after the treatment) | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at 24 h after the end of administration | Abnormal not clinically significant | 6 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at 2 h after the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at 2 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QRS Duration | Final visit (7 days after the treatment) | Normal | 7 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at 1 h after the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at the end of administration | Normal | 3 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at pre-administration | Abnormal not clinically significant | 6 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QRS Duration | Screening visit | Abnormal not clinically significant | 6 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QRS Duration | Screening visit | Normal | 4 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at 24 h after the end of administration | Normal | 4 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at the end of administration | Abnormal not clinically significant | 7 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at pre-administration | Normal | 4 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QRS Duration | Final visit (7 days after the treatment) | Abnormal not clinically significant | 3 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at 4 h after the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at 4 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at 1 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at 24 h after the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at pre-administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at 1 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at 1 h after the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QRS Duration | Final visit (7 days after the treatment) | Normal | 3 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at 2 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at 2 h after the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at 4 h after the end of administration | Normal | 1 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at 4 h after the end of administration | Abnormal not clinically significant | 9 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at 24 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QRS Duration | Screening visit | Normal | 2 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QRS Duration | Final visit (7 days after the treatment) | Abnormal not clinically significant | 7 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QRS Duration | Screening visit | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at pre-administration | Normal | 2 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at 2 h after the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QRS Duration | Final visit (7 days after the treatment) | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at 4 h after the end of administration | Normal | 1 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at 24 h after the end of administration | Abnormal not clinically significant | 7 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at 4 h after the end of administration | Abnormal not clinically significant | 9 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at 24 h after the end of administration | Normal | 3 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at pre-administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QRS Duration | Screening visit | Normal | 3 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at pre-administration | Normal | 2 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at 1 h after the end of administration | Abnormal not clinically significant | 9 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at 2 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QRS Duration | Final visit (7 days after the treatment) | Normal | 2 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at 1 h after the end of administration | Normal | 1 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QRS Duration | Screening visit | Abnormal not clinically significant | 7 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at 24 h after the end of administration | Normal | 5 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at 2 h after the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QRS Duration | Final visit (7 days after the treatment) | Normal | 4 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QRS Duration | Screening visit | Abnormal not clinically significant | 5 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at 1 h after the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at 4 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QRS Duration | Final visit (7 days after the treatment) | Abnormal not clinically significant | 6 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at 2 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QRS Duration | Screening visit | Normal | 5 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at 4 h after the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at 1 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at 24 h after the end of administration | Abnormal not clinically significant | 5 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at pre-administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QRS Duration | Day 1 (treatment day) at pre-administration | Normal | 2 Participants |
Secondary
Study Part A: ECGs - QTcB Interval
QTcB interval in ms recorded in supine position after 5 min at rest
Time frame: 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)
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QTcB Interval | Screening visit | Abnormal not clinically significant | 7 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at pre-administration | Normal | 1 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at pre-administration | Abnormal not clinically significant | 9 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QTcB Interval | Screening visit | Normal | 3 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at 1 h after the end of administration | Normal | 1 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at 1 h after the end of administration | Abnormal not clinically significant | 9 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at 2 h after the end of administration | Normal | 0 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at 2 h after the end of administration | Abnormal not clinically significant | 10 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at 4 h after the end of administration | Normal | 1 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at 4 h after the end of administration | Abnormal not clinically significant | 9 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at 24 h after the end of administration | Normal | 0 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at 24 h after the end of administration | Abnormal not clinically significant | 10 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QTcB Interval | Final visit (7 days after the treatment) | Normal | 2 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QTcB Interval | Final visit (7 days after the treatment) | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at 24 h after the end of administration | Abnormal not clinically significant | 6 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at 2 h after the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at 2 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QTcB Interval | Final visit (7 days after the treatment) | Normal | 7 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at 1 h after the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at the end of administration | Normal | 3 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at pre-administration | Abnormal not clinically significant | 6 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QTcB Interval | Screening visit | Abnormal not clinically significant | 6 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QTcB Interval | Screening visit | Normal | 4 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at 24 h after the end of administration | Normal | 4 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at the end of administration | Abnormal not clinically significant | 7 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at pre-administration | Normal | 4 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QTcB Interval | Final visit (7 days after the treatment) | Abnormal not clinically significant | 3 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at 4 h after the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at 4 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at 1 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at 24 h after the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at pre-administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at 1 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at 1 h after the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QTcB Interval | Final visit (7 days after the treatment) | Normal | 3 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at 2 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at 2 h after the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at 4 h after the end of administration | Normal | 1 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at 4 h after the end of administration | Abnormal not clinically significant | 9 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at 24 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QTcB Interval | Screening visit | Normal | 2 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QTcB Interval | Final visit (7 days after the treatment) | Abnormal not clinically significant | 7 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QTcB Interval | Screening visit | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at pre-administration | Normal | 2 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at 2 h after the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QTcB Interval | Final visit (7 days after the treatment) | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at 4 h after the end of administration | Normal | 1 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at 24 h after the end of administration | Abnormal not clinically significant | 7 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at 4 h after the end of administration | Abnormal not clinically significant | 9 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at 24 h after the end of administration | Normal | 3 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at pre-administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QTcB Interval | Screening visit | Normal | 3 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at pre-administration | Normal | 2 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at 1 h after the end of administration | Abnormal not clinically significant | 9 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at 2 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QTcB Interval | Final visit (7 days after the treatment) | Normal | 2 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at 1 h after the end of administration | Normal | 1 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QTcB Interval | Screening visit | Abnormal not clinically significant | 7 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at 24 h after the end of administration | Normal | 5 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at 2 h after the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QTcB Interval | Final visit (7 days after the treatment) | Normal | 4 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QTcB Interval | Screening visit | Abnormal not clinically significant | 5 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at 1 h after the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at 4 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QTcB Interval | Final visit (7 days after the treatment) | Abnormal not clinically significant | 6 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at 2 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QTcB Interval | Screening visit | Normal | 5 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at 4 h after the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at 1 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at 24 h after the end of administration | Abnormal not clinically significant | 5 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at pre-administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QTcB Interval | Day 1 (treatment day) at pre-administration | Normal | 2 Participants |
Secondary
Study Part A: ECGs - QTcF Interval
QTcF interval in ms recorded in supine position after 5 min at rest
Time frame: 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)
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QTcF Interval | Screening visit | Abnormal not clinically significant | 7 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at pre-administration | Normal | 1 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at pre-administration | Abnormal not clinically significant | 9 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QTcF Interval | Screening visit | Normal | 3 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at 1 h after the end of administration | Normal | 1 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at 1 h after the end of administration | Abnormal not clinically significant | 9 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at 2 h after the end of administration | Normal | 0 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at 2 h after the end of administration | Abnormal not clinically significant | 10 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at 4 h after the end of administration | Normal | 1 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at 4 h after the end of administration | Abnormal not clinically significant | 9 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at 24 h after the end of administration | Normal | 0 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at 24 h after the end of administration | Abnormal not clinically significant | 10 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QTcF Interval | Final visit (7 days after the treatment) | Normal | 2 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QTcF Interval | Final visit (7 days after the treatment) | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at 24 h after the end of administration | Abnormal not clinically significant | 6 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at 2 h after the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at 2 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QTcF Interval | Final visit (7 days after the treatment) | Normal | 7 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at 1 h after the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at the end of administration | Normal | 3 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at pre-administration | Abnormal not clinically significant | 6 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QTcF Interval | Screening visit | Abnormal not clinically significant | 6 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QTcF Interval | Screening visit | Normal | 4 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at 24 h after the end of administration | Normal | 4 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at the end of administration | Abnormal not clinically significant | 7 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at pre-administration | Normal | 4 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QTcF Interval | Final visit (7 days after the treatment) | Abnormal not clinically significant | 3 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at 4 h after the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at 4 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at 1 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at 24 h after the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at pre-administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at 1 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at 1 h after the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QTcF Interval | Final visit (7 days after the treatment) | Normal | 3 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at 2 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at 2 h after the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at 4 h after the end of administration | Normal | 1 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at 4 h after the end of administration | Abnormal not clinically significant | 9 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at 24 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QTcF Interval | Screening visit | Normal | 2 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QTcF Interval | Final visit (7 days after the treatment) | Abnormal not clinically significant | 7 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QTcF Interval | Screening visit | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at pre-administration | Normal | 2 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at 2 h after the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QTcF Interval | Final visit (7 days after the treatment) | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at 4 h after the end of administration | Normal | 1 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at 24 h after the end of administration | Abnormal not clinically significant | 7 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at 4 h after the end of administration | Abnormal not clinically significant | 9 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at 24 h after the end of administration | Normal | 3 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at pre-administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QTcF Interval | Screening visit | Normal | 3 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at pre-administration | Normal | 2 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at 1 h after the end of administration | Abnormal not clinically significant | 9 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at 2 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QTcF Interval | Final visit (7 days after the treatment) | Normal | 2 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at 1 h after the end of administration | Normal | 1 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QTcF Interval | Screening visit | Abnormal not clinically significant | 7 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at 24 h after the end of administration | Normal | 5 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at 2 h after the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QTcF Interval | Final visit (7 days after the treatment) | Normal | 4 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QTcF Interval | Screening visit | Abnormal not clinically significant | 5 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at 1 h after the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at 4 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QTcF Interval | Final visit (7 days after the treatment) | Abnormal not clinically significant | 6 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at 2 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QTcF Interval | Screening visit | Normal | 5 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at 4 h after the end of administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at 1 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at 24 h after the end of administration | Abnormal not clinically significant | 5 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at pre-administration | Abnormal not clinically significant | 8 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QTcF Interval | Day 1 (treatment day) at pre-administration | Normal | 2 Participants |
Secondary
Study Part A: ECGs - QT Interval
QT interval in ms recorded in supine position after 5 min at rest
Time frame: 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)
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QT Interval | Screening visit | Abnormal, not clinically significant | 7 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at pre-administration | Normal | 1 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at pre-administration | Abnormal, not clinically significant | 9 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QT Interval | Screening visit | Normal | 3 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at the end of administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at 1 h after the end of administration | Normal | 1 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at 1 h after the end of administration | Abnormal, not clinically significant | 9 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at 2 h after the end of administration | Normal | 0 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at 2 h after the end of administration | Abnormal, not clinically significant | 10 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at 4 h after the end of administration | Normal | 1 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at 4 h after the end of administration | Abnormal, not clinically significant | 9 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at 24 h after the end of administration | Normal | 0 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at 24 h after the end of administration | Abnormal, not clinically significant | 10 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QT Interval | Final visit (7 days after the treatment) | Normal | 2 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - QT Interval | Final visit (7 days after the treatment) | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at 24 h after the end of administration | Abnormal, not clinically significant | 6 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at 2 h after the end of administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at 2 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QT Interval | Final visit (7 days after the treatment) | Normal | 7 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at 1 h after the end of administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at the end of administration | Normal | 3 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at pre-administration | Abnormal, not clinically significant | 6 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QT Interval | Screening visit | Abnormal, not clinically significant | 6 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QT Interval | Screening visit | Normal | 4 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at 24 h after the end of administration | Normal | 4 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at the end of administration | Abnormal, not clinically significant | 7 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at pre-administration | Normal | 4 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QT Interval | Final visit (7 days after the treatment) | Abnormal, not clinically significant | 3 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at 4 h after the end of administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at 4 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at 1 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at 24 h after the end of administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at pre-administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at the end of administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at 1 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at 1 h after the end of administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QT Interval | Final visit (7 days after the treatment) | Normal | 3 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at 2 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at 2 h after the end of administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at 4 h after the end of administration | Normal | 1 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at 4 h after the end of administration | Abnormal, not clinically significant | 9 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at 24 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QT Interval | Screening visit | Normal | 2 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QT Interval | Final visit (7 days after the treatment) | Abnormal, not clinically significant | 7 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QT Interval | Screening visit | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at pre-administration | Normal | 2 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at 2 h after the end of administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QT Interval | Final visit (7 days after the treatment) | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at 4 h after the end of administration | Normal | 1 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at 24 h after the end of administration | Abnormal, not clinically significant | 7 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at 4 h after the end of administration | Abnormal, not clinically significant | 9 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at the end of administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at 24 h after the end of administration | Normal | 3 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at pre-administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QT Interval | Screening visit | Normal | 3 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at pre-administration | Normal | 2 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at 1 h after the end of administration | Abnormal, not clinically significant | 9 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at 2 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QT Interval | Final visit (7 days after the treatment) | Normal | 2 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at 1 h after the end of administration | Normal | 1 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - QT Interval | Screening visit | Abnormal, not clinically significant | 7 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at 24 h after the end of administration | Normal | 5 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at 2 h after the end of administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QT Interval | Final visit (7 days after the treatment) | Normal | 4 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QT Interval | Screening visit | Abnormal, not clinically significant | 5 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at 1 h after the end of administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at 4 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QT Interval | Final visit (7 days after the treatment) | Abnormal, not clinically significant | 6 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at the end of administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at 2 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QT Interval | Screening visit | Normal | 5 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at 4 h after the end of administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at 1 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at 24 h after the end of administration | Abnormal, not clinically significant | 5 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at pre-administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - QT Interval | Day 1 (treatment day) at pre-administration | Normal | 2 Participants |
Secondary
Study Part A: ECGs - RR Interval
RR interval in ms recorded in supine position after 5 min at rest
Time frame: 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)
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - RR Interval | Screening visit | Abnormal, not clinically significant | 7 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at pre-administration | Normal | 1 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at pre-administration | Abnormal, not clinically significant | 9 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - RR Interval | Screening visit | Normal | 3 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at the end of administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at 1 h after the end of administration | Normal | 1 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at 1 h after the end of administration | Abnormal, not clinically significant | 9 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at 2 h after the end of administration | Normal | 0 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at 2 h after the end of administration | Abnormal, not clinically significant | 10 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at 4 h after the end of administration | Normal | 1 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at 4 h after the end of administration | Abnormal, not clinically significant | 9 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at 24 h after the end of administration | Normal | 0 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at 24 h after the end of administration | Abnormal, not clinically significant | 10 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - RR Interval | Final visit (7 days after the treatment) | Normal | 2 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: ECGs - RR Interval | Final visit (7 days after the treatment) | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at 24 h after the end of administration | Abnormal, not clinically significant | 6 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at 2 h after the end of administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at 2 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - RR Interval | Final visit (7 days after the treatment) | Normal | 7 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at 1 h after the end of administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at the end of administration | Normal | 3 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at pre-administration | Abnormal, not clinically significant | 6 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - RR Interval | Screening visit | Abnormal, not clinically significant | 6 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - RR Interval | Screening visit | Normal | 4 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at 24 h after the end of administration | Normal | 4 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at the end of administration | Abnormal, not clinically significant | 7 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at pre-administration | Normal | 4 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - RR Interval | Final visit (7 days after the treatment) | Abnormal, not clinically significant | 3 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at 4 h after the end of administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at 4 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at 1 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at 24 h after the end of administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at pre-administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at the end of administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at 1 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at 1 h after the end of administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - RR Interval | Final visit (7 days after the treatment) | Normal | 3 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at 2 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at 2 h after the end of administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at 4 h after the end of administration | Normal | 1 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at 4 h after the end of administration | Abnormal, not clinically significant | 9 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at 24 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - RR Interval | Screening visit | Normal | 2 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - RR Interval | Final visit (7 days after the treatment) | Abnormal, not clinically significant | 7 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - RR Interval | Screening visit | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 2 | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at pre-administration | Normal | 2 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at 2 h after the end of administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - RR Interval | Final visit (7 days after the treatment) | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at 4 h after the end of administration | Normal | 1 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at 24 h after the end of administration | Abnormal, not clinically significant | 7 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at 4 h after the end of administration | Abnormal, not clinically significant | 9 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at the end of administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at 24 h after the end of administration | Normal | 3 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at pre-administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - RR Interval | Screening visit | Normal | 3 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at pre-administration | Normal | 2 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at 1 h after the end of administration | Abnormal, not clinically significant | 9 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at 2 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - RR Interval | Final visit (7 days after the treatment) | Normal | 2 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at 1 h after the end of administration | Normal | 1 Participants |
| Study Part A - Cohort 3 | Study Part A: ECGs - RR Interval | Screening visit | Abnormal, not clinically significant | 7 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at 24 h after the end of administration | Normal | 5 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at 2 h after the end of administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - RR Interval | Final visit (7 days after the treatment) | Normal | 4 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - RR Interval | Screening visit | Abnormal, not clinically significant | 5 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at 1 h after the end of administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at 4 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - RR Interval | Final visit (7 days after the treatment) | Abnormal, not clinically significant | 6 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at the end of administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at 2 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - RR Interval | Screening visit | Normal | 5 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at 4 h after the end of administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at 1 h after the end of administration | Normal | 2 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at 24 h after the end of administration | Abnormal, not clinically significant | 5 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at pre-administration | Abnormal, not clinically significant | 8 Participants |
| Study Part A - Cohort 4 | Study Part A: ECGs - RR Interval | Day 1 (treatment day) at pre-administration | Normal | 2 Participants |
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.
Time frame: Screening visit (day of informed consent signature)/final visit (7 days after the treatment)
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Full Physical Examination Through Apparatus/Systems Check | Screening visit | Normal | 10 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Full Physical Examination Through Apparatus/Systems Check | Screening visit | Abnormal not clinically significant | 0 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Full Physical Examination Through Apparatus/Systems Check | Final visit (7 days after the treatment) | Normal | 10 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Full Physical Examination Through Apparatus/Systems Check | Final visit (7 days after the treatment) | Abnormal not clinically significant | 0 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Full Physical Examination Through Apparatus/Systems Check | Screening visit | Normal | 7 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Full Physical Examination Through Apparatus/Systems Check | Final visit (7 days after the treatment) | Abnormal not clinically significant | 3 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Full Physical Examination Through Apparatus/Systems Check | Screening visit | Abnormal not clinically significant | 3 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Full Physical Examination Through Apparatus/Systems Check | Final visit (7 days after the treatment) | Normal | 7 Participants |
| Study Part A - Cohort 2 | Study Part A: Full Physical Examination Through Apparatus/Systems Check | Final visit (7 days after the treatment) | Abnormal not clinically significant | 0 Participants |
| Study Part A - Cohort 2 | Study Part A: Full Physical Examination Through Apparatus/Systems Check | Screening visit | Abnormal not clinically significant | 1 Participants |
| Study Part A - Cohort 2 | Study Part A: Full Physical Examination Through Apparatus/Systems Check | Final visit (7 days after the treatment) | Normal | 10 Participants |
| Study Part A - Cohort 2 | Study Part A: Full Physical Examination Through Apparatus/Systems Check | Screening visit | Normal | 9 Participants |
| Study Part A - Cohort 3 | Study Part A: Full Physical Examination Through Apparatus/Systems Check | Screening visit | Normal | 10 Participants |
| Study Part A - Cohort 3 | Study Part A: Full Physical Examination Through Apparatus/Systems Check | Screening visit | Abnormal not clinically significant | 0 Participants |
| Study Part A - Cohort 3 | Study Part A: Full Physical Examination Through Apparatus/Systems Check | Final visit (7 days after the treatment) | Abnormal not clinically significant | 0 Participants |
| Study Part A - Cohort 3 | Study Part A: Full Physical Examination Through Apparatus/Systems Check | Final visit (7 days after the treatment) | Normal | 10 Participants |
| Study Part A - Cohort 4 | Study Part A: Full Physical Examination Through Apparatus/Systems Check | Final visit (7 days after the treatment) | Abnormal not clinically significant | 0 Participants |
| Study Part A - Cohort 4 | Study Part A: Full Physical Examination Through Apparatus/Systems Check | Final visit (7 days after the treatment) | Normal | 10 Participants |
| Study Part A - Cohort 4 | Study Part A: Full Physical Examination Through Apparatus/Systems Check | Screening visit | Abnormal not clinically significant | 1 Participants |
| Study Part A - Cohort 4 | Study Part A: Full Physical Examination Through Apparatus/Systems Check | Screening visit | Normal | 9 Participants |
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.
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Study Part A - Cohort 1 - Akynzeo | Study Part A: MRT | Fosnetupitant | 0.253 h | Standard Deviation 0.001 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: MRT | Metabolite M2 | 14.343 h | Standard Deviation 2.22 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: MRT | Netupitant | 28.529 h | Standard Deviation 9.761 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: MRT | Netupitant | 26.760 h | Standard Deviation 5.78 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: MRT | Fosnetupitant | 0.254 h | Standard Deviation 0.002 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: MRT | Metabolite M2 | 15.895 h | Standard Deviation 7.651 |
| Study Part A - Cohort 2 | Study Part A: MRT | Netupitant | 33.752 h | Standard Deviation 21.148 |
| Study Part A - Cohort 2 | Study Part A: MRT | Fosnetupitant | 0.275 h | Standard Deviation 0.038 |
| Study Part A - Cohort 2 | Study Part A: MRT | Metabolite M2 | 16.347 h | Standard Deviation 5.492 |
| Study Part A - Cohort 3 | Study Part A: MRT | Fosnetupitant | 0.109 h | Standard Deviation 0.014 |
| Study Part A - Cohort 3 | Study Part A: MRT | Metabolite M2 | 16.299 h | Standard Deviation 3.936 |
| Study Part A - Cohort 3 | Study Part A: MRT | Netupitant | 24.493 h | Standard Deviation 3.866 |
| Study Part A - Cohort 4 | Study Part A: MRT | Netupitant | 40.753 h | Standard Deviation 34.769 |
| Study Part A - Cohort 4 | Study Part A: MRT | Fosnetupitant | 0.086 h | Standard Deviation 0.014 |
| Study Part A - Cohort 4 | Study Part A: MRT | Metabolite M2 | 14.975 h | Standard Deviation 4.858 |
Secondary
Study Part A: Pulse Rate
Pulse rate in bpm measured after 5 min at rest in sitting position
Time frame: 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)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Pulse Rate | Final visit (7 days after the treatment) | 56.8 Beats/min | Standard Deviation 8.1 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Pulse Rate | Day 1 (treatment day) at 1 h after the end of administration | 59.3 Beats/min | Standard Deviation 10.4 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Pulse Rate | Day -1 (enrolment day) | 68.4 Beats/min | Standard Deviation 8.9 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Pulse Rate | Day 1 (treatment day) at 2 h after the end of administration | 56.4 Beats/min | Standard Deviation 6.8 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Pulse Rate | Day 1 (treatment day) at 24 h after the end of administration | 58.8 Beats/min | Standard Deviation 9.8 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Pulse Rate | Day 1 (treatment day) at pre-administration | 60.0 Beats/min | Standard Deviation 5.6 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Pulse Rate | Day 1 (treatment day) at 4 h after the end of administration | 56.8 Beats/min | Standard Deviation 7.2 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Pulse Rate | Day 1 (treatment day) at the end of administration | 58.3 Beats/min | Standard Deviation 7.5 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Pulse Rate | Screening visit | 60.9 Beats/min | Standard Deviation 7.3 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Pulse Rate | Day 1 (treatment day) at 4 h after the end of administration | 62.7 Beats/min | Standard Deviation 7.5 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Pulse Rate | Day 1 (treatment day) at 2 h after the end of administration | 61.4 Beats/min | Standard Deviation 6.8 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Pulse Rate | Day 1 (treatment day) at the end of administration | 64.2 Beats/min | Standard Deviation 8.6 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Pulse Rate | Day 1 (treatment day) at 1 h after the end of administration | 62.8 Beats/min | Standard Deviation 5.4 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Pulse Rate | Day 1 (treatment day) at pre-administration | 62.4 Beats/min | Standard Deviation 8.6 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Pulse Rate | Final visit (7 days after the treatment) | 62.9 Beats/min | Standard Deviation 6.8 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Pulse Rate | Day -1 (enrolment day) | 74.9 Beats/min | Standard Deviation 8.6 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Pulse Rate | Screening visit | 65.3 Beats/min | Standard Deviation 7.8 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Pulse Rate | Day 1 (treatment day) at 24 h after the end of administration | 65.5 Beats/min | Standard Deviation 7.9 |
| Study Part A - Cohort 2 | Study Part A: Pulse Rate | Day 1 (treatment day) at 2 h after the end of administration | 58.5 Beats/min | Standard Deviation 7.8 |
| Study Part A - Cohort 2 | Study Part A: Pulse Rate | Screening visit | 61.0 Beats/min | Standard Deviation 10.5 |
| Study Part A - Cohort 2 | Study Part A: Pulse Rate | Day -1 (enrolment day) | 75.6 Beats/min | Standard Deviation 11.7 |
| Study Part A - Cohort 2 | Study Part A: Pulse Rate | Day 1 (treatment day) at pre-administration | 59.0 Beats/min | Standard Deviation 9.4 |
| Study Part A - Cohort 2 | Study Part A: Pulse Rate | Day 1 (treatment day) at the end of administration | 59.5 Beats/min | Standard Deviation 7.7 |
| Study Part A - Cohort 2 | Study Part A: Pulse Rate | Day 1 (treatment day) at 1 h after the end of administration | 59.3 Beats/min | Standard Deviation 7.8 |
| Study Part A - Cohort 2 | Study Part A: Pulse Rate | Day 1 (treatment day) at 4 h after the end of administration | 56.4 Beats/min | Standard Deviation 7.2 |
| Study Part A - Cohort 2 | Study Part A: Pulse Rate | Day 1 (treatment day) at 24 h after the end of administration | 60.9 Beats/min | Standard Deviation 9 |
| Study Part A - Cohort 2 | Study Part A: Pulse Rate | Final visit (7 days after the treatment) | 61.5 Beats/min | Standard Deviation 7.4 |
| Study Part A - Cohort 3 | Study Part A: Pulse Rate | Day 1 (treatment day) at the end of administration | 59.5 Beats/min | Standard Deviation 7.7 |
| Study Part A - Cohort 3 | Study Part A: Pulse Rate | Day 1 (treatment day) at 2 h after the end of administration | 58.5 Beats/min | Standard Deviation 7.8 |
| Study Part A - Cohort 3 | Study Part A: Pulse Rate | Day 1 (treatment day) at pre-administration | 59.0 Beats/min | Standard Deviation 9.4 |
| Study Part A - Cohort 3 | Study Part A: Pulse Rate | Day 1 (treatment day) at 4 h after the end of administration | 56.4 Beats/min | Standard Deviation 7.2 |
| Study Part A - Cohort 3 | Study Part A: Pulse Rate | Day -1 (enrolment day) | 75.6 Beats/min | Standard Deviation 11.7 |
| Study Part A - Cohort 3 | Study Part A: Pulse Rate | Final visit (7 days after the treatment) | 61.5 Beats/min | Standard Deviation 7.4 |
| Study Part A - Cohort 3 | Study Part A: Pulse Rate | Day 1 (treatment day) at 24 h after the end of administration | 60.9 Beats/min | Standard Deviation 9 |
| Study Part A - Cohort 3 | Study Part A: Pulse Rate | Screening visit | 61.0 Beats/min | Standard Deviation 10.5 |
| Study Part A - Cohort 3 | Study Part A: Pulse Rate | Day 1 (treatment day) at 1 h after the end of administration | 59.3 Beats/min | Standard Deviation 7.8 |
| Study Part A - Cohort 4 | Study Part A: Pulse Rate | Screening visit | 68.3 Beats/min | Standard Deviation 7.3 |
| Study Part A - Cohort 4 | Study Part A: Pulse Rate | Day 1 (treatment day) at the end of administration | 62.0 Beats/min | Standard Deviation 10.1 |
| Study Part A - Cohort 4 | Study Part A: Pulse Rate | Day 1 (treatment day) at 2 h after the end of administration | 62.1 Beats/min | Standard Deviation 9.2 |
| Study Part A - Cohort 4 | Study Part A: Pulse Rate | Day 1 (treatment day) at pre-administration | 65.2 Beats/min | Standard Deviation 7.2 |
| Study Part A - Cohort 4 | Study Part A: Pulse Rate | Day 1 (treatment day) at 1 h after the end of administration | 62.4 Beats/min | Standard Deviation 8.9 |
| Study Part A - Cohort 4 | Study Part A: Pulse Rate | Final visit (7 days after the treatment) | 72.3 Beats/min | Standard Deviation 10.5 |
| Study Part A - Cohort 4 | Study Part A: Pulse Rate | Day 1 (treatment day) at 24 h after the end of administration | 67.8 Beats/min | Standard Deviation 6.5 |
| Study Part A - Cohort 4 | Study Part A: Pulse Rate | Day 1 (treatment day) at 4 h after the end of administration | 62.8 Beats/min | Standard Deviation 7.9 |
| Study Part A - Cohort 4 | Study Part A: Pulse Rate | Day -1 (enrolment day) | 77.7 Beats/min | Standard Deviation 8.8 |
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.
Time frame: Day 2 (24 h after the end of investigational product administration)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Short Physical Examination Through Apparatus/Systems Check | Normal | 9 Participants |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Short Physical Examination Through Apparatus/Systems Check | Abnormal not clinically significant | 1 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Short Physical Examination Through Apparatus/Systems Check | Normal | 7 Participants |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Short Physical Examination Through Apparatus/Systems Check | Abnormal not clinically significant | 3 Participants |
| Study Part A - Cohort 2 | Study Part A: Short Physical Examination Through Apparatus/Systems Check | Normal | 10 Participants |
| Study Part A - Cohort 2 | Study Part A: Short Physical Examination Through Apparatus/Systems Check | Abnormal not clinically significant | 0 Participants |
| Study Part A - Cohort 3 | Study Part A: Short Physical Examination Through Apparatus/Systems Check | Abnormal not clinically significant | 0 Participants |
| Study Part A - Cohort 3 | Study Part A: Short Physical Examination Through Apparatus/Systems Check | Normal | 10 Participants |
| Study Part A - Cohort 4 | Study Part A: Short Physical Examination Through Apparatus/Systems Check | Normal | 10 Participants |
| Study Part A - Cohort 4 | Study Part A: Short Physical Examination Through Apparatus/Systems Check | Abnormal not clinically significant | 0 Participants |
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.
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Systemic Clearance | Fosnetupitant | 61821.940 mL/h | Standard Deviation 16436.343 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Systemic Clearance | Metabolite M2 | 172324.405 mL/h | Standard Deviation 50962.753 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Systemic Clearance | Netupitant | 27219.010 mL/h | Standard Deviation 3356.654 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Systemic Clearance | Netupitant | 28693.446 mL/h | Standard Deviation 7660.44 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Systemic Clearance | Fosnetupitant | 66942.974 mL/h | Standard Deviation 12370.822 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Systemic Clearance | Metabolite M2 | 162039.804 mL/h | Standard Deviation 57537.646 |
| Study Part A - Cohort 2 | Study Part A: Systemic Clearance | Netupitant | 24200.268 mL/h | Standard Deviation 6832.625 |
| Study Part A - Cohort 2 | Study Part A: Systemic Clearance | Fosnetupitant | 65171.229 mL/h | Standard Deviation 21219.721 |
| Study Part A - Cohort 2 | Study Part A: Systemic Clearance | Metabolite M2 | 211825.621 mL/h | Standard Deviation 68310.261 |
| Study Part A - Cohort 3 | Study Part A: Systemic Clearance | Fosnetupitant | 65651.064 mL/h | Standard Deviation 9975.506 |
| Study Part A - Cohort 3 | Study Part A: Systemic Clearance | Metabolite M2 | 174034.336 mL/h | Standard Deviation 64374.511 |
| Study Part A - Cohort 3 | Study Part A: Systemic Clearance | Netupitant | 27596.213 mL/h | Standard Deviation 6404.903 |
| Study Part A - Cohort 4 | Study Part A: Systemic Clearance | Netupitant | 26994.542 mL/h | Standard Deviation 10531.874 |
| Study Part A - Cohort 4 | Study Part A: Systemic Clearance | Fosnetupitant | 63748.966 mL/h | Standard Deviation 13353.411 |
| Study Part A - Cohort 4 | Study Part A: Systemic Clearance | Metabolite M2 | 182468.624 mL/h | Standard Deviation 68658.409 |
Secondary
Study Part A: Systolic Blood Pressure
Systolic blood pressure in mmHg measured after 5 min at rest in sitting position
Time frame: 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)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Systolic Blood Pressure | Final visit (7 days after the treatment) | 114.4 mmHg | Standard Deviation 9.3 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Systolic Blood Pressure | Day 1 (treatment day) at 1 h after the end of administration | 110.4 mmHg | Standard Deviation 8.2 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Systolic Blood Pressure | Day -1 (enrolment day) | 113.1 mmHg | Standard Deviation 6.2 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Systolic Blood Pressure | Day 1 (treatment day) at 2 h after the end of administration | 106.6 mmHg | Standard Deviation 6.9 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Systolic Blood Pressure | Day 1 (treatment day) at 24 h after the end of administration | 108.5 mmHg | Standard Deviation 8.2 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Systolic Blood Pressure | Day 1 (treatment day) at pre-administration | 112.5 mmHg | Standard Deviation 8.2 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Systolic Blood Pressure | Day 1 (treatment day) at 4 h after the end of administration | 108.3 mmHg | Standard Deviation 10.5 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Systolic Blood Pressure | Day 1 (treatment day) at the end of administration | 107.7 mmHg | Standard Deviation 12.3 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Systolic Blood Pressure | Screening visit | 119.7 mmHg | Standard Deviation 9.4 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Systolic Blood Pressure | Day 1 (treatment day) at 4 h after the end of administration | 107.6 mmHg | Standard Deviation 9.5 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Systolic Blood Pressure | Day 1 (treatment day) at 2 h after the end of administration | 109.8 mmHg | Standard Deviation 11.6 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Systolic Blood Pressure | Day 1 (treatment day) at the end of administration | 111.5 mmHg | Standard Deviation 8.5 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Systolic Blood Pressure | Day 1 (treatment day) at 1 h after the end of administration | 111.7 mmHg | Standard Deviation 10.6 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Systolic Blood Pressure | Day 1 (treatment day) at pre-administration | 112.8 mmHg | Standard Deviation 12.9 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Systolic Blood Pressure | Final visit (7 days after the treatment) | 111.1 mmHg | Standard Deviation 11.8 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Systolic Blood Pressure | Day -1 (enrolment day) | 116.7 mmHg | Standard Deviation 6.6 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Systolic Blood Pressure | Screening visit | 118.8 mmHg | Standard Deviation 9.7 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Systolic Blood Pressure | Day 1 (treatment day) at 24 h after the end of administration | 112.9 mmHg | Standard Deviation 11.7 |
| Study Part A - Cohort 2 | Study Part A: Systolic Blood Pressure | Day 1 (treatment day) at 2 h after the end of administration | 114.1 mmHg | Standard Deviation 10.8 |
| Study Part A - Cohort 2 | Study Part A: Systolic Blood Pressure | Screening visit | 122.6 mmHg | Standard Deviation 12.5 |
| Study Part A - Cohort 2 | Study Part A: Systolic Blood Pressure | Day -1 (enrolment day) | 122.0 mmHg | Standard Deviation 12.5 |
| Study Part A - Cohort 2 | Study Part A: Systolic Blood Pressure | Day 1 (treatment day) at pre-administration | 114.2 mmHg | Standard Deviation 12.2 |
| Study Part A - Cohort 2 | Study Part A: Systolic Blood Pressure | Day 1 (treatment day) at the end of administration | 113.6 mmHg | Standard Deviation 10.6 |
| Study Part A - Cohort 2 | Study Part A: Systolic Blood Pressure | Day 1 (treatment day) at 1 h after the end of administration | 113.4 mmHg | Standard Deviation 11.9 |
| Study Part A - Cohort 2 | Study Part A: Systolic Blood Pressure | Day 1 (treatment day) at 4 h after the end of administration | 113.8 mmHg | Standard Deviation 12.7 |
| Study Part A - Cohort 2 | Study Part A: Systolic Blood Pressure | Day 1 (treatment day) at 24 h after the end of administration | 116.7 mmHg | Standard Deviation 10.8 |
| Study Part A - Cohort 2 | Study Part A: Systolic Blood Pressure | Final visit (7 days after the treatment) | 116.2 mmHg | Standard Deviation 8.7 |
| Study Part A - Cohort 3 | Study Part A: Systolic Blood Pressure | Day 1 (treatment day) at the end of administration | 113.6 mmHg | Standard Deviation 10.6 |
| Study Part A - Cohort 3 | Study Part A: Systolic Blood Pressure | Day 1 (treatment day) at 2 h after the end of administration | 114.1 mmHg | Standard Deviation 10.8 |
| Study Part A - Cohort 3 | Study Part A: Systolic Blood Pressure | Day 1 (treatment day) at pre-administration | 114.2 mmHg | Standard Deviation 12.2 |
| Study Part A - Cohort 3 | Study Part A: Systolic Blood Pressure | Day 1 (treatment day) at 4 h after the end of administration | 113.8 mmHg | Standard Deviation 12.7 |
| Study Part A - Cohort 3 | Study Part A: Systolic Blood Pressure | Day -1 (enrolment day) | 122.0 mmHg | Standard Deviation 12.5 |
| Study Part A - Cohort 3 | Study Part A: Systolic Blood Pressure | Final visit (7 days after the treatment) | 116.2 mmHg | Standard Deviation 8.7 |
| Study Part A - Cohort 3 | Study Part A: Systolic Blood Pressure | Day 1 (treatment day) at 24 h after the end of administration | 116.7 mmHg | Standard Deviation 10.8 |
| Study Part A - Cohort 3 | Study Part A: Systolic Blood Pressure | Screening visit | 122.6 mmHg | Standard Deviation 12.5 |
| Study Part A - Cohort 3 | Study Part A: Systolic Blood Pressure | Day 1 (treatment day) at 1 h after the end of administration | 113.4 mmHg | Standard Deviation 11.9 |
| Study Part A - Cohort 4 | Study Part A: Systolic Blood Pressure | Screening visit | 119.1 mmHg | Standard Deviation 8.9 |
| Study Part A - Cohort 4 | Study Part A: Systolic Blood Pressure | Day 1 (treatment day) at the end of administration | 113.2 mmHg | Standard Deviation 13.5 |
| Study Part A - Cohort 4 | Study Part A: Systolic Blood Pressure | Day 1 (treatment day) at 2 h after the end of administration | 112.4 mmHg | Standard Deviation 7.6 |
| Study Part A - Cohort 4 | Study Part A: Systolic Blood Pressure | Day 1 (treatment day) at pre-administration | 115.6 mmHg | Standard Deviation 10.7 |
| Study Part A - Cohort 4 | Study Part A: Systolic Blood Pressure | Day 1 (treatment day) at 1 h after the end of administration | 112.3 mmHg | Standard Deviation 10.2 |
| Study Part A - Cohort 4 | Study Part A: Systolic Blood Pressure | Final visit (7 days after the treatment) | 120.5 mmHg | Standard Deviation 10.9 |
| Study Part A - Cohort 4 | Study Part A: Systolic Blood Pressure | Day 1 (treatment day) at 24 h after the end of administration | 115.8 mmHg | Standard Deviation 10.6 |
| Study Part A - Cohort 4 | Study Part A: Systolic Blood Pressure | Day 1 (treatment day) at 4 h after the end of administration | 109.8 mmHg | Standard Deviation 9.6 |
| Study Part A - Cohort 4 | Study Part A: Systolic Blood Pressure | Day -1 (enrolment day) | 118.8 mmHg | Standard Deviation 9.7 |
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.
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Study Part A - Cohort 1 - Akynzeo | Study Part A: t1/2 | Fosnetupitant | 0.057 h | Standard Deviation 0.003 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: t1/2 | Metabolite M2 | 11.538 h | Standard Deviation 2.49 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: t1/2 | Netupitant | 22.104 h | Standard Deviation 7.005 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: t1/2 | Netupitant | 21.356 h | Standard Deviation 4.151 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: t1/2 | Fosnetupitant | 0.059 h | Standard Deviation 0.004 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: t1/2 | Metabolite M2 | 12.855 h | Standard Deviation 5.985 |
| Study Part A - Cohort 2 | Study Part A: t1/2 | Netupitant | 25.176 h | Standard Deviation 14.727 |
| Study Part A - Cohort 2 | Study Part A: t1/2 | Fosnetupitant | 0.080 h | Standard Deviation 0.115 |
| Study Part A - Cohort 2 | Study Part A: t1/2 | Metabolite M2 | 12.918 h | Standard Deviation 4.023 |
| Study Part A - Cohort 3 | Study Part A: t1/2 | Fosnetupitant | 0.039 h | Standard Deviation 0.011 |
| Study Part A - Cohort 3 | Study Part A: t1/2 | Metabolite M2 | 12.468 h | Standard Deviation 3.215 |
| Study Part A - Cohort 3 | Study Part A: t1/2 | Netupitant | 18.017 h | Standard Deviation 2.747 |
| Study Part A - Cohort 4 | Study Part A: t1/2 | Netupitant | 30.061 h | Standard Deviation 24.561 |
| Study Part A - Cohort 4 | Study Part A: t1/2 | Fosnetupitant | 0.040 h | Standard Deviation 0.017 |
| Study Part A - Cohort 4 | Study Part A: t1/2 | Metabolite M2 | 12.248 h | Standard Deviation 3.863 |
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.
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Terminal Elimination Rate Constant | Fosnetupitant | 12.157 1/h | Standard Deviation 0.662 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Terminal Elimination Rate Constant | Metabolite M2 | 0.063 1/h | Standard Deviation 0.014 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Terminal Elimination Rate Constant | Netupitant | 0.034 1/h | Standard Deviation 0.012 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Terminal Elimination Rate Constant | Netupitant | 0.034 1/h | Standard Deviation 0.007 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Terminal Elimination Rate Constant | Fosnetupitant | 11.734 1/h | Standard Deviation 0.754 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Terminal Elimination Rate Constant | Metabolite M2 | 0.061 1/h | Standard Deviation 0.018 |
| Study Part A - Cohort 2 | Study Part A: Terminal Elimination Rate Constant | Netupitant | 0.033 1/h | Standard Deviation 0.012 |
| Study Part A - Cohort 2 | Study Part A: Terminal Elimination Rate Constant | Fosnetupitant | 14.979 1/h | Standard Deviation 5.582 |
| Study Part A - Cohort 2 | Study Part A: Terminal Elimination Rate Constant | Metabolite M2 | 0.058 1/h | Standard Deviation 0.017 |
| Study Part A - Cohort 3 | Study Part A: Terminal Elimination Rate Constant | Fosnetupitant | 18.613 1/h | Standard Deviation 3.868 |
| Study Part A - Cohort 3 | Study Part A: Terminal Elimination Rate Constant | Metabolite M2 | 0.059 1/h | Standard Deviation 0.013 |
| Study Part A - Cohort 3 | Study Part A: Terminal Elimination Rate Constant | Netupitant | 0.039 1/h | Standard Deviation 0.005 |
| Study Part A - Cohort 4 | Study Part A: Terminal Elimination Rate Constant | Netupitant | 0.032 1/h | Standard Deviation 0.014 |
| Study Part A - Cohort 4 | Study Part A: Terminal Elimination Rate Constant | Fosnetupitant | 19.141 1/h | Standard Deviation 5.429 |
| Study Part A - Cohort 4 | Study Part A: Terminal Elimination Rate Constant | Metabolite M2 | 0.061 1/h | Standard Deviation 0.015 |
Secondary
Study Part A: Tlast
Time of last measurable plasma concentration measured for plasma fosnetupitant, netupitant and its main metabolites (M1, M2 and M3)
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Tlast | Fosnetupitant | 0.83 h | Standard Deviation 0.118 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Tlast | Metabolite M1 | 24 h | Standard Deviation 0 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Tlast | Metabolite M3 | 24 h | Standard Deviation 0 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Tlast | Metabolite M2 | 24 h | Standard Deviation 0 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Tlast | Netupitant | 24 h | Standard Deviation 0 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Tlast | Fosnetupitant | 0.95 h | Standard Deviation 0.23 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Tlast | Netupitant | 24 h | Standard Deviation 0 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Tlast | Metabolite M1 | 24 h | Standard Deviation 0 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Tlast | Metabolite M2 | 24 h | Standard Deviation 0 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Tlast | Metabolite M3 | 24 h | Standard Deviation 0 |
| Study Part A - Cohort 2 | Study Part A: Tlast | Fosnetupitant | 1.075 h | Standard Deviation 1.048 |
| Study Part A - Cohort 2 | Study Part A: Tlast | Metabolite M2 | 24 h | Standard Deviation 0 |
| Study Part A - Cohort 2 | Study Part A: Tlast | Metabolite M1 | 24 h | Standard Deviation 0 |
| Study Part A - Cohort 2 | Study Part A: Tlast | Netupitant | 24 h | Standard Deviation 0 |
| Study Part A - Cohort 2 | Study Part A: Tlast | Metabolite M3 | 24 h | Standard Deviation 0 |
| Study Part A - Cohort 3 | Study Part A: Tlast | Metabolite M2 | 24 h | Standard Deviation 0 |
| Study Part A - Cohort 3 | Study Part A: Tlast | Metabolite M1 | 24 h | Standard Deviation 0 |
| Study Part A - Cohort 3 | Study Part A: Tlast | Metabolite M3 | 24 h | Standard Deviation 0 |
| Study Part A - Cohort 3 | Study Part A: Tlast | Fosnetupitant | 0.6 h | Standard Deviation 0.316 |
| Study Part A - Cohort 3 | Study Part A: Tlast | Netupitant | 24 h | Standard Deviation 0 |
| Study Part A - Cohort 4 | Study Part A: Tlast | Metabolite M3 | 24 h | Standard Deviation 0 |
| Study Part A - Cohort 4 | Study Part A: Tlast | Fosnetupitant | 0.633 h | Standard Deviation 0.35 |
| Study Part A - Cohort 4 | Study Part A: Tlast | Metabolite M1 | 24 h | Standard Deviation 0 |
| Study Part A - Cohort 4 | Study Part A: Tlast | Metabolite M2 | 24 h | Standard Deviation 0 |
| Study Part A - Cohort 4 | Study Part A: Tlast | Netupitant | 24 h | Standard Deviation 0 |
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)
Time frame: 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
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Tmax | Metabolite M2 | 2 h |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Tmax | Fosnetupitant | 0.5 h |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Tmax | Metabolite M3 | 24 h |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Tmax | Netupitant | 0.5 h |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Tmax | Metabolite M1 | 12 h |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Tmax | Metabolite M2 | 2 h |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Tmax | Metabolite M1 | 10 h |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Tmax | Netupitant | 0.5 h |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Tmax | Metabolite M3 | 24 h |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Tmax | Fosnetupitant | 0.5 h |
| Study Part A - Cohort 2 | Study Part A: Tmax | Metabolite M1 | 12 h |
| Study Part A - Cohort 2 | Study Part A: Tmax | Fosnetupitant | 0.25 h |
| Study Part A - Cohort 2 | Study Part A: Tmax | Netupitant | 0.25 h |
| Study Part A - Cohort 2 | Study Part A: Tmax | Metabolite M2 | 2.5 h |
| Study Part A - Cohort 2 | Study Part A: Tmax | Metabolite M3 | 24 h |
| Study Part A - Cohort 3 | Study Part A: Tmax | Metabolite M3 | 24 h |
| Study Part A - Cohort 3 | Study Part A: Tmax | Fosnetupitant | 0.08 h |
| Study Part A - Cohort 3 | Study Part A: Tmax | Metabolite M2 | 2 h |
| Study Part A - Cohort 3 | Study Part A: Tmax | Metabolite M1 | 12 h |
| Study Part A - Cohort 3 | Study Part A: Tmax | Netupitant | 0.125 h |
| Study Part A - Cohort 4 | Study Part A: Tmax | Metabolite M1 | 12 h |
| Study Part A - Cohort 4 | Study Part A: Tmax | Metabolite M2 | 1.75 h |
| Study Part A - Cohort 4 | Study Part A: Tmax | Fosnetupitant | 0.05 h |
| Study Part A - Cohort 4 | Study Part A: Tmax | Metabolite M3 | 24 h |
| Study Part A - Cohort 4 | Study Part A: Tmax | Netupitant | 0.08 h |
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.
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Vz | Fosnetupitant | 5129.653 mL | Standard Deviation 1631.449 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Vz | Metabolite M2 | 2895427.080 mL | Standard Deviation 954908.605 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Vz | Netupitant | 848022.360 mL | Standard Deviation 215723.734 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Vz | Netupitant | 872978.816 mL | Standard Deviation 264673.002 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Vz | Fosnetupitant | 5765.916 mL | Standard Deviation 1352.379 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Vz | Metabolite M2 | 2820832.784 mL | Standard Deviation 1000428.13 |
| Study Part A - Cohort 2 | Study Part A: Vz | Netupitant | 772482.708 mL | Standard Deviation 205893.262 |
| Study Part A - Cohort 2 | Study Part A: Vz | Fosnetupitant | 4796.595 mL | Standard Deviation 1491.027 |
| Study Part A - Cohort 2 | Study Part A: Vz | Metabolite M2 | 4109459.426 mL | Standard Deviation 2374558.032 |
| Study Part A - Cohort 3 | Study Part A: Vz | Fosnetupitant | 3728.124 mL | Standard Deviation 1263.039 |
| Study Part A - Cohort 3 | Study Part A: Vz | Metabolite M2 | 3083100.830 mL | Standard Deviation 1154481.625 |
| Study Part A - Cohort 3 | Study Part A: Vz | Netupitant | 719627.108 mL | Standard Deviation 219903.292 |
| Study Part A - Cohort 4 | Study Part A: Vz | Netupitant | 944544.565 mL | Standard Deviation 311425.672 |
| Study Part A - Cohort 4 | Study Part A: Vz | Fosnetupitant | 3572.355 mL | Standard Deviation 1199.382 |
| Study Part A - Cohort 4 | Study Part A: Vz | Metabolite M2 | 3122087.067 mL | Standard Deviation 1170365.896 |
Secondary
Study Part A: Weight
Body weight in kilograms
Time frame: Screening visit (day of informed consent signature)/final visit (7 days after the treatment)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Weight | Screening visit | 65.94 Kilograms | Standard Deviation 9.5 |
| Study Part A - Cohort 1 - Akynzeo | Study Part A: Weight | Final visit (7 days after the treatment) | 66.68 Kilograms | Standard Deviation 9.49 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Weight | Screening visit | 69.83 Kilograms | Standard Deviation 15.15 |
| Study Part A - Cohort 1 - Fosnetupitant | Study Part A: Weight | Final visit (7 days after the treatment) | 70.08 Kilograms | Standard Deviation 14.67 |
| Study Part A - Cohort 2 | Study Part A: Weight | Screening visit | 71.98 Kilograms | Standard Deviation 13.16 |
| Study Part A - Cohort 2 | Study Part A: Weight | Final visit (7 days after the treatment) | 72.44 Kilograms | Standard Deviation 13.72 |
| Study Part A - Cohort 3 | Study Part A: Weight | Final visit (7 days after the treatment) | 72.44 Kilograms | Standard Deviation 13.72 |
| Study Part A - Cohort 3 | Study Part A: Weight | Screening visit | 71.98 Kilograms | Standard Deviation 13.16 |
| Study Part A - Cohort 4 | Study Part A: Weight | Screening visit | 71.30 Kilograms | Standard Deviation 11.66 |
| Study Part A - Cohort 4 | Study Part A: Weight | Final visit (7 days after the treatment) | 71.40 Kilograms | Standard Deviation 11.48 |