TerminatedNCT06840769Updated May 4, 2025Results posted

A Clinical Trial to Assess Safety and Pharmacokinetics of Fosnetupitant 235 mg and Metabolites in Healthy Volunteers

A Phase 1 interventional study of Fosnetupitant 235 mg solution and Akynzeo solution in Healthy Volunteers, sponsored by Helsinn Healthcare SA. Terminated at 1 site in Switzerland. Open to participants aged 18 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-05-04.

Sponsored by Helsinn Healthcare SA · Phase 1, Interventional, and Health services research

Why this study was terminated

Sponsor's decision

Phase: Phase 1
Study type: Interventional
Enrollment: 50
Allocation: Non-randomized
Ages: 18 Years to 55 Years
Sex: All

Study 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.

Read the 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.

Conditions studied

Healthy Volunteers

Keywords

Helsinn
PNET-22-08
Fosnetupitant
Netupitant

Who can participate

Ages eligible: 18 Years to 55 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

Inclusion criteria

Informed consent: signed written informed consent before inclusion in the study
Sex and Age: healthy men/women volunteers, 18-55 years old (inclusive)
Body Mass Index (BMI): 18.5-30 kg/m2 inclusive
Vital signs: systolic blood pressure 100-139 mmHg, diastolic blood pressure 50-89 mmHg, pulse rate 50-99 bpm, measured after 5 min at rest in the sitting position
Full comprehension: ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to co-operate with the investigator and to comply with the requirements of the entire study
Contraception and fertility (women only): women of childbearing potential defined as a non-menopausal woman who has not had a bilateral oophorectomy or medically documented ovarian failure and/or at risk for pregnancy must agree, signing the informed consent form, to use a highly effective method of contraception throughout the study and to continue for 14 days after the last dose of the study treatment. Highly effective contraceptive measures include:
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).
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

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
Physical examination findings: clinically significant abnormal physical findings which could interfere with the objectives of the study
Laboratory analyses: clinically significant abnormal laboratory values at screening, indicative of physical illness or suggesting the subject's exclusion, in his/her best interest
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
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
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
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
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
Blood donation or significant blood loss: blood donations or significant blood loss in the 3 months before the first visit of this study
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)
Drug test: positive result at the urine drug screening test at screening or Day -1
Alcohol test: positive salivary alcohol test at Day -1
Diet: abnormal diets (\<1600 or >3500 kcal/day) or substantial changes in eating habits in the 4 weeks before screening; vegetarians
Pregnancy (women only): positive or missing pregnancy test at screening or Day -1, pregnant or lactating women
Netupitant studies: enrolment in a previous study of netupitant or fosnetupitant (alone or in combination with palonosetron)

Study design

Phase: Phase 1
Primary purpose: Health services research
Allocation: Non-randomized
Intervention model: Sequential assignment
Masking: None (open label)
Enrollment: 50 participants (actual)

Study arms

Experimental
Study Part A - cohort 1
Fosnetupitant free base 235 mg administered as single 30 min intravenous infusion or 235 mg fosnetupitant/0.25 mg palonosetron in 20 mL injection solution administered undiluted as a single 30 min intravenous infusion
Drug: Fosnetupitant 235 mg solution · Drug: Akynzeo solution
Experimental
Study Part A - cohort 2
Fosnetupitant free base 235 mg administered as single 15 min intravenous infusion
Drug: Fosnetupitant 235 mg solution
Experimental
Study Part A - cohort 3
Fosnetupitant free base 235 mg administered as single 5 min intravenous infusion
Drug: Fosnetupitant 235 mg solution
Experimental
Study Part A - cohort 4
Fosnetupitant free base 235 mg administered as single 2 min intravenous infusion
Drug: Fosnetupitant 235 mg solution

Interventions

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
Also known as: Helsinn Fosnetupitant solution
DrugAkynzeo solution
235 mg fosnetupitant (corresponding to 260 mg of the chloride hydrochloride salt) / 0.25 mg palonosetron in 20 mL injectable solution
Also known as: IV Akynzeo®

What researchers measure

Primary outcomes

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)
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)
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)

Secondary outcomes

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)
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)
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)
Study Part A: Weight
Body weight in kilograms
Time frame: Screening visit (day of informed consent signature)/final visit (7 days after the treatment)
Study Part A: Full Physical Examination Through Apparatus/Systems Check
General appearance, Chest/respiratory, Gastrointestinal, Head, eyes, ears, nose and throat, Heart/cardiovascular, Lymph nodes, Metabolic/endocrine, Musculoskeletal/extremities, Neck (including thyroid), Neurological/psychiatric, Skin/dermatologic systems are checked. Any abnormalities are recorded.
Time frame: Screening visit (day of informed consent signature)/final visit (7 days after the treatment)
Study Part A: Short Physical Examination Through Apparatus/Systems Check
General appearance, Chest/respiratory, Heart/cardiovascular, Lymph nodes, Neurologic/psychiatric, Skin/dermatologic systems are checked. Any abnormalities are recorded.
Time frame: Day 2 (24 h after the end of investigational product administration)
Study Part A: ECGs - Heart Rate
Heart rate in beats/min recorded in supine position after 5 min at rest
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)
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)
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)
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)
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)
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)
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)
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)
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
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
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
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
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
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
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
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
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
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
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
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

Results

Posted May 4, 2025

Limitations and caveats

M1 and M3 metabolites on average showed an extent of exposure (AUC) lower than the other analytes. In particular, both metabolites had a significantly longer elimination phase. Indeed, the concentrations of both metabolites were still at a plateau at the end of the sampling period and their elimination kinetics could not be characterized in the present study.

Participant flow

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.

Participant flow — Overall Study
Milestone	Study Part A - Cohort 1 - Akynzeo	Study Part A - Cohort 1 - Fosnetupitant	Study Part A - Cohort 2	Study Part A - Cohort 3	Study Part A - Cohort 4
Started	10	10	10	10	10
Completed	9	10	10	10	10
Not completed	1	0	0	0	0
Withdrew: Withdrawal by subject	1	0	0	0	0

Outcome measures

PrimaryStudy 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)
Reported as:: Number · Number of TEAE

Study Part A: Number of Treatment-emergent Adverse Events
Number of TEAE	Study Part A - Cohort 1 - Akynzeo	Study Part A - Cohort 1 - Fosnetupitant	Study Part A - Cohort 2	Study Part A - Cohort 3	Study Part A - Cohort 4
Study Part A: Number of Treatment-emergent Adverse Events	7	4	3	1	4

PrimaryStudy 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)
Reported as:: Number · Number of subjects with TEAE

Study Part A: Number of Subjects With Treatment-emergent Adverse Events
Number of subjects with TEAE	Study Part A - Cohort 1 - Akynzeo	Study Part A - Cohort 1 - Fosnetupitant	Study Part A - Cohort 2	Study Part A - Cohort 3	Study Part A - Cohort 4
Study Part A: Number of Subjects With Treatment-emergent Adverse Events	5	3	2	1	4

PrimaryStudy 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)
Reported as:: Number · Number of TEAE

Study Part A: Type of Treatment-emergent Adverse Events
Number of TEAE	Study Part A - Cohort 1 - Akynzeo	Study Part A - Cohort 1 - Fosnetupitant	Study Part A - Cohort 2	Study Part A - Cohort 3	Study Part A - Cohort 4
Gastrointestinal disorders	2	1	0	0	0
General disorders and administration site conditions	2	2	0	1	0
Nervous system disorders	2	1	2	0	4
Psychiatric disorders	1	0	0	0	0
Investigations	0	0	1	0	0

SecondaryStudy 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)
Reported as:: Mean · mmHg

Study Part A: Systolic Blood Pressure
mmHg	Study Part A - Cohort 1 - Akynzeo	Study Part A - Cohort 1 - Fosnetupitant	Study Part A - Cohort 2	Study Part A - Cohort 3	Study Part A - Cohort 4
Screening visit	119.7 ± 9.4	118.8 ± 9.7	122.6 ± 12.5	122.6 ± 12.5	119.1 ± 8.9
Day -1 (enrolment day)	113.1 ± 6.2	116.7 ± 6.6	122.0 ± 12.5	122.0 ± 12.5	118.8 ± 9.7
Day 1 (treatment day) at pre-administration	112.5 ± 8.2	112.8 ± 12.9	114.2 ± 12.2	114.2 ± 12.2	115.6 ± 10.7
Day 1 (treatment day) at the end of administration	107.7 ± 12.3	111.5 ± 8.5	113.6 ± 10.6	113.6 ± 10.6	113.2 ± 13.5
Day 1 (treatment day) at 1 h after the end of administration	110.4 ± 8.2	111.7 ± 10.6	113.4 ± 11.9	113.4 ± 11.9	112.3 ± 10.2
Day 1 (treatment day) at 2 h after the end of administration	106.6 ± 6.9	109.8 ± 11.6	114.1 ± 10.8	114.1 ± 10.8	112.4 ± 7.6
Day 1 (treatment day) at 4 h after the end of administration	108.3 ± 10.5	107.6 ± 9.5	113.8 ± 12.7	113.8 ± 12.7	109.8 ± 9.6
Day 1 (treatment day) at 24 h after the end of administration	108.5 ± 8.2	112.9 ± 11.7	116.7 ± 10.8	116.7 ± 10.8	115.8 ± 10.6
Final visit (7 days after the treatment)	114.4 ± 9.3	111.1 ± 11.8	116.2 ± 8.7	116.2 ± 8.7	120.5 ± 10.9

SecondaryStudy 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)
Reported as:: Mean · mmHg

Study Part A: Diastolic Blood Pressure
mmHg	Study Part A - Cohort 1 - Akynzeo	Study Part A - Cohort 1 - Fosnetupitant	Study Part A - Cohort 2	Study Part A - Cohort 3	Study Part A - Cohort 4
Screening visit	72.3 ± 6.5	76.8 ± 6.9	80.4 ± 8.0	80.4 ± 8.0	76.7 ± 7.5
Day -1 (enrolment day)	68.9 ± 8.6	77.7 ± 5.8	76.1 ± 7.0	76.1 ± 7.0	74.8 ± 6.9
Day 1 (treatment day) at pre-administration	72.1 ± 9.0	74.9 ± 9.2	76.0 ± 10.1	76.0 ± 10.1	71.9 ± 10.5
Day 1 (treatment day) at the end of administration	62.4 ± 11.1	71.7 ± 8.3	75.2 ± 10.1	75.2 ± 10.1	70.1 ± 9.3
Day 1 (treatment day) at 1 h after the end of administration	63.9 ± 6.4	73.4 ± 8.3	76.7 ± 8.8	76.7 ± 8.8	72.5 ± 7.2
Day 1 (treatment day) at 2 h after the end of administration	64.5 ± 8.5	72.8 ± 7.3	74.8 ± 11.2	74.8 ± 11.2	71.5 ± 9.2
Day 1 (treatment day) at 4 h after the end of administration	65.9 ± 6.6	68.9 ± 8.8	76.6 ± 9.8	76.6 ± 9.8	70.7 ± 8.5
Day 1 (treatment day) at 24 h after the end of administration	67.0 ± 9.4	72.7 ± 7.9	77.5 ± 8.8	77.5 ± 8.8	73.2 ± 7.7
Final visit (7 days after the treatment)	70.1 ± 7.2	74.4 ± 7.5	77.7 ± 7.1	77.7 ± 7.1	77.4 ± 6.4

SecondaryStudy 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)
Reported as:: Mean · Beats/min

Study Part A: Pulse Rate
Beats/min	Study Part A - Cohort 1 - Akynzeo	Study Part A - Cohort 1 - Fosnetupitant	Study Part A - Cohort 2	Study Part A - Cohort 3	Study Part A - Cohort 4
Screening visit	60.9 ± 7.3	65.3 ± 7.8	61.0 ± 10.5	61.0 ± 10.5	68.3 ± 7.3
Day -1 (enrolment day)	68.4 ± 8.9	74.9 ± 8.6	75.6 ± 11.7	75.6 ± 11.7	77.7 ± 8.8
Day 1 (treatment day) at pre-administration	60.0 ± 5.6	62.4 ± 8.6	59.0 ± 9.4	59.0 ± 9.4	65.2 ± 7.2
Day 1 (treatment day) at the end of administration	58.3 ± 7.5	64.2 ± 8.6	59.5 ± 7.7	59.5 ± 7.7	62.0 ± 10.1
Day 1 (treatment day) at 1 h after the end of administration	59.3 ± 10.4	62.8 ± 5.4	59.3 ± 7.8	59.3 ± 7.8	62.4 ± 8.9
Day 1 (treatment day) at 2 h after the end of administration	56.4 ± 6.8	61.4 ± 6.8	58.5 ± 7.8	58.5 ± 7.8	62.1 ± 9.2
Day 1 (treatment day) at 4 h after the end of administration	56.8 ± 7.2	62.7 ± 7.5	56.4 ± 7.2	56.4 ± 7.2	62.8 ± 7.9
Day 1 (treatment day) at 24 h after the end of administration	58.8 ± 9.8	65.5 ± 7.9	60.9 ± 9.0	60.9 ± 9.0	67.8 ± 6.5
Final visit (7 days after the treatment)	56.8 ± 8.1	62.9 ± 6.8	61.5 ± 7.4	61.5 ± 7.4	72.3 ± 10.5

SecondaryStudy Part A: Weight

Body weight in kilograms

Time frame:: Screening visit (day of informed consent signature)/final visit (7 days after the treatment)
Reported as:: Mean · Kilograms

Study Part A: Weight
Kilograms	Study Part A - Cohort 1 - Akynzeo	Study Part A - Cohort 1 - Fosnetupitant	Study Part A - Cohort 2	Study Part A - Cohort 3	Study Part A - Cohort 4
Screening visit	65.94 ± 9.50	69.83 ± 15.15	71.98 ± 13.16	71.98 ± 13.16	71.30 ± 11.66
Final visit (7 days after the treatment)	66.68 ± 9.49	70.08 ± 14.67	72.44 ± 13.72	72.44 ± 13.72	71.40 ± 11.48

SecondaryStudy 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)
Reported as:: Count of participants · Participants

Study Part A: Full Physical Examination Through Apparatus/Systems Check
Participants	Study Part A - Cohort 1 - Akynzeo	Study Part A - Cohort 1 - Fosnetupitant	Study Part A - Cohort 2	Study Part A - Cohort 3	Study Part A - Cohort 4
Screening visit — Normal	10	7	9	10	9
Screening visit — Abnormal not clinically significant	0	3	1	0	1
Final visit (7 days after the treatment) — Normal	10	7	10	10	10
Final visit (7 days after the treatment) — Abnormal not clinically significant	0	3	0	0	0

SecondaryStudy 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)
Reported as:: Count of participants · Participants

Study Part A: Short Physical Examination Through Apparatus/Systems Check
Participants	Study Part A - Cohort 1 - Akynzeo	Study Part A - Cohort 1 - Fosnetupitant	Study Part A - Cohort 2	Study Part A - Cohort 3	Study Part A - Cohort 4
Normal	9	7	10	10	10
Abnormal not clinically significant	1	3	0	0	0

SecondaryStudy 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)
Reported as:: Count of participants · Participants

Study Part A: ECGs - Heart Rate
Participants	Study Part A - Cohort 1 - Akynzeo	Study Part A - Cohort 1 - Fosnetupitant	Study Part A - Cohort 2	Study Part A - Cohort 3	Study Part A - Cohort 4
Screening visit — Normal	3	4	2	3	5
Screening visit — Abnormal not clinically significant	7	6	8	7	5
Day 1 (treatment day) at pre-administration — Normal	1	4	2	2	2
Day 1 (treatment day) at pre-administration — Abnormal not clinically significant	9	6	8	8	8
Day 1 (treatment day) at the end of administration — Normal	2	3	2	2	2
Day 1 (treatment day) at the end of administration — Abnormal not clinically significant	8	7	8	8	8
Day 1 (treatment day) at 1 h after the end of administration — Normal	1	2	2	1	2
Day 1 (treatment day) at 1 h after the end of administration — Abnormal not clinically significant	9	8	8	9	8
Day 1 (treatment day) at 2 h after the end of administration — Normal	0	2	2	2	2
Day 1 (treatment day) at 2 h after the end of administration — Abnormal not clinically significant	10	8	8	8	8
Day 1 (treatment day) at 4 h after the end of administration — Normal	1	2	1	1	2
Day 1 (treatment day) at 4 h after the end of administration — Abnormal not clinically significant	9	8	9	9	8
Day 1 (treatment day) at 24 h after the end of administration — Normal	0	4	2	3	5
Day 1 (treatment day) at 24 h after the end of administration — Abnormal not clinically significant	10	6	8	7	5
Final visit (7 days after the treatment) — Normal	2	7	3	2	4
Final visit (7 days after the treatment) — Abnormal not clinically significant	8	3	7	8	6

SecondaryStudy 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)
Reported as:: Count of participants · Participants

Study Part A: ECGs - PR Interval
Participants	Study Part A - Cohort 1 - Akynzeo	Study Part A - Cohort 1 - Fosnetupitant	Study Part A - Cohort 2	Study Part A - Cohort 3	Study Part A - Cohort 4
Screening visit — Normal	3	4	2	3	5
Screening visit — Abnormal, not clinically significant	7	6	8	7	5
Day 1 (treatment day) at pre-administration — Normal	1	4	2	2	2
Day 1 (treatment day) at pre-administration — Abnormal, not clinically significant	9	6	8	8	8
Day 1 (treatment day) at the end of administration — Normal	2	3	2	2	2
Day 1 (treatment day) at the end of administration — Abnormal, not clinically significant	8	7	8	8	8
Day 1 (treatment day) at 1 h after the end of administration — Normal	1	2	2	1	2
Day 1 (treatment day) at 1 h after the end of administration — Abnormal, not clinically significant	9	8	8	9	8
Day 1 (treatment day) at 2 h after the end of administration — Normal	0	2	2	2	2
Day 1 (treatment day) at 2 h after the end of administration — Abnormal, not clinically significant	10	8	8	8	8
Day 1 (treatment day) at 4 h after the end of administration — Normal	1	2	1	1	2
Day 1 (treatment day) at 4 h after the end of administration — Abnormal, not clinically significant	9	8	9	9	8
Day 1 (treatment day) at 24 h after the end of administration — Normal	0	4	2	3	5
Day 1 (treatment day) at 24 h after the end of administration — Abnormal, not clinically significant	10	6	8	7	5
Final visit (7 days after the treatment) — Normal	2	7	3	2	4
Final visit (7 days after the treatment) — Abnormal, not clinically significant	8	3	7	8	6

SecondaryStudy 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)
Reported as:: Count of participants · Participants

Study Part A: ECGs - RR Interval
Participants	Study Part A - Cohort 1 - Akynzeo	Study Part A - Cohort 1 - Fosnetupitant	Study Part A - Cohort 2	Study Part A - Cohort 3	Study Part A - Cohort 4
Screening visit — Normal	3	4	2	3	5
Screening visit — Abnormal, not clinically significant	7	6	8	7	5
Day 1 (treatment day) at pre-administration — Normal	1	4	2	2	2
Day 1 (treatment day) at pre-administration — Abnormal, not clinically significant	9	6	8	8	8
Day 1 (treatment day) at the end of administration — Normal	2	3	2	2	2
Day 1 (treatment day) at the end of administration — Abnormal, not clinically significant	8	7	8	8	8
Day 1 (treatment day) at 1 h after the end of administration — Normal	1	2	2	1	2
Day 1 (treatment day) at 1 h after the end of administration — Abnormal, not clinically significant	9	8	8	9	8
Day 1 (treatment day) at 2 h after the end of administration — Normal	0	2	2	2	2
Day 1 (treatment day) at 2 h after the end of administration — Abnormal, not clinically significant	10	8	8	8	8
Day 1 (treatment day) at 4 h after the end of administration — Normal	1	2	1	1	2
Day 1 (treatment day) at 4 h after the end of administration — Abnormal, not clinically significant	9	8	9	9	8
Day 1 (treatment day) at 24 h after the end of administration — Normal	0	4	2	3	5
Day 1 (treatment day) at 24 h after the end of administration — Abnormal, not clinically significant	10	6	8	7	5
Final visit (7 days after the treatment) — Normal	2	7	3	2	4
Final visit (7 days after the treatment) — Abnormal, not clinically significant	8	3	7	8	6

SecondaryStudy 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)
Reported as:: Count of participants · Participants

Study Part A: ECGs - QRS Duration
Participants	Study Part A - Cohort 1 - Akynzeo	Study Part A - Cohort 1 - Fosnetupitant	Study Part A - Cohort 2	Study Part A - Cohort 3	Study Part A - Cohort 4
Screening visit — Normal	3	4	2	3	5
Screening visit — Abnormal not clinically significant	7	6	8	7	5
Day 1 (treatment day) at pre-administration — Normal	1	4	2	2	2
Day 1 (treatment day) at pre-administration — Abnormal not clinically significant	9	6	8	8	8
Day 1 (treatment day) at the end of administration — Normal	2	3	2	2	2
Day 1 (treatment day) at the end of administration — Abnormal not clinically significant	8	7	8	8	8
Day 1 (treatment day) at 1 h after the end of administration — Normal	1	2	2	1	2
Day 1 (treatment day) at 1 h after the end of administration — Abnormal not clinically significant	9	8	8	9	8
Day 1 (treatment day) at 2 h after the end of administration — Normal	0	2	2	2	2
Day 1 (treatment day) at 2 h after the end of administration — Abnormal not clinically significant	10	8	8	8	8
Day 1 (treatment day) at 4 h after the end of administration — Normal	1	2	1	1	2
Day 1 (treatment day) at 4 h after the end of administration — Abnormal not clinically significant	9	8	9	9	8
Day 1 (treatment day) at 24 h after the end of administration — Normal	0	4	2	3	5
Day 1 (treatment day) at 24 h after the end of administration — Abnormal not clinically significant	10	6	8	7	5
Final visit (7 days after the treatment) — Normal	2	7	3	2	4
Final visit (7 days after the treatment) — Abnormal not clinically significant	8	3	7	8	6

SecondaryStudy 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)
Reported as:: Count of participants · Participants

Study Part A: ECGs - QT Interval
Participants	Study Part A - Cohort 1 - Akynzeo	Study Part A - Cohort 1 - Fosnetupitant	Study Part A - Cohort 2	Study Part A - Cohort 3	Study Part A - Cohort 4
Screening visit — Normal	3	4	2	3	5
Screening visit — Abnormal, not clinically significant	7	6	8	7	5
Day 1 (treatment day) at pre-administration — Normal	1	4	2	2	2
Day 1 (treatment day) at pre-administration — Abnormal, not clinically significant	9	6	8	8	8
Day 1 (treatment day) at the end of administration — Normal	2	3	2	2	2
Day 1 (treatment day) at the end of administration — Abnormal, not clinically significant	8	7	8	8	8
Day 1 (treatment day) at 1 h after the end of administration — Normal	1	2	2	1	2
Day 1 (treatment day) at 1 h after the end of administration — Abnormal, not clinically significant	9	8	8	9	8
Day 1 (treatment day) at 2 h after the end of administration — Normal	0	2	2	2	2
Day 1 (treatment day) at 2 h after the end of administration — Abnormal, not clinically significant	10	8	8	8	8
Day 1 (treatment day) at 4 h after the end of administration — Normal	1	2	1	1	2
Day 1 (treatment day) at 4 h after the end of administration — Abnormal, not clinically significant	9	8	9	9	8
Day 1 (treatment day) at 24 h after the end of administration — Normal	0	4	2	3	5
Day 1 (treatment day) at 24 h after the end of administration — Abnormal, not clinically significant	10	6	8	7	5
Final visit (7 days after the treatment) — Normal	2	7	3	2	4
Final visit (7 days after the treatment) — Abnormal, not clinically significant	8	3	7	8	6

SecondaryStudy 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)
Reported as:: Count of participants · Participants

Study Part A: ECGs - QTcB Interval
Participants	Study Part A - Cohort 1 - Akynzeo	Study Part A - Cohort 1 - Fosnetupitant	Study Part A - Cohort 2	Study Part A - Cohort 3	Study Part A - Cohort 4
Screening visit — Normal	3	4	2	3	5
Screening visit — Abnormal not clinically significant	7	6	8	7	5
Day 1 (treatment day) at pre-administration — Normal	1	4	2	2	2
Day 1 (treatment day) at pre-administration — Abnormal not clinically significant	9	6	8	8	8
Day 1 (treatment day) at the end of administration — Normal	2	3	2	2	2
Day 1 (treatment day) at the end of administration — Abnormal not clinically significant	8	7	8	8	8
Day 1 (treatment day) at 1 h after the end of administration — Normal	1	2	2	1	2
Day 1 (treatment day) at 1 h after the end of administration — Abnormal not clinically significant	9	8	8	9	8
Day 1 (treatment day) at 2 h after the end of administration — Normal	0	2	2	2	2
Day 1 (treatment day) at 2 h after the end of administration — Abnormal not clinically significant	10	8	8	8	8
Day 1 (treatment day) at 4 h after the end of administration — Normal	1	2	1	1	2
Day 1 (treatment day) at 4 h after the end of administration — Abnormal not clinically significant	9	8	9	9	8
Day 1 (treatment day) at 24 h after the end of administration — Normal	0	4	2	3	5
Day 1 (treatment day) at 24 h after the end of administration — Abnormal not clinically significant	10	6	8	7	5
Final visit (7 days after the treatment) — Normal	2	7	3	2	4
Final visit (7 days after the treatment) — Abnormal not clinically significant	8	3	7	8	6

SecondaryStudy 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)
Reported as:: Count of participants · Participants

Study Part A: ECGs - QTcF Interval
Participants	Study Part A - Cohort 1 - Akynzeo	Study Part A - Cohort 1 - Fosnetupitant	Study Part A - Cohort 2	Study Part A - Cohort 3	Study Part A - Cohort 4
Screening visit — Normal	3	4	2	3	5
Screening visit — Abnormal not clinically significant	7	6	8	7	5
Day 1 (treatment day) at pre-administration — Normal	1	4	2	2	2
Day 1 (treatment day) at pre-administration — Abnormal not clinically significant	9	6	8	8	8
Day 1 (treatment day) at the end of administration — Normal	2	3	2	2	2
Day 1 (treatment day) at the end of administration — Abnormal not clinically significant	8	7	8	8	8
Day 1 (treatment day) at 1 h after the end of administration — Normal	1	2	2	1	2
Day 1 (treatment day) at 1 h after the end of administration — Abnormal not clinically significant	9	8	8	9	8
Day 1 (treatment day) at 2 h after the end of administration — Normal	0	2	2	2	2
Day 1 (treatment day) at 2 h after the end of administration — Abnormal not clinically significant	10	8	8	8	8
Day 1 (treatment day) at 4 h after the end of administration — Normal	1	2	1	1	2
Day 1 (treatment day) at 4 h after the end of administration — Abnormal not clinically significant	9	8	9	9	8
Day 1 (treatment day) at 24 h after the end of administration — Normal	0	4	2	3	5
Day 1 (treatment day) at 24 h after the end of administration — Abnormal not clinically significant	10	6	8	7	5
Final visit (7 days after the treatment) — Normal	2	7	3	2	4
Final visit (7 days after the treatment) — Abnormal not clinically significant	8	3	7	8	6

SecondaryStudy 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)
Reported as:: Count of participants · Participants

Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis)
Participants	Study Part A - Cohort 1 - Akynzeo	Study Part A - Cohort 1 - Fosnetupitant	Study Part A - Cohort 2	Study Part A - Cohort 3	Study Part A - Cohort 4
Screening visit - blood — Normal	5	2	2	3	1
Screening visit - blood — Abnormal not clinically significant	5	8	8	7	9
Screening visit - blood — Abnormal clinically significant	0	0	0	0	0
Screening visit - urine — Normal	3	3	4	3	2
Screening visit - urine — Abnormal not clinically significant	7	7	6	7	8
Screening visit - urine — Abnormal clinically significant	0	0	0	0	0
Final visit (7 days after the treatment) - blood — Normal	2	4	1	1	0
Final visit (7 days after the treatment) - blood — Abnormal not clinically significant	8	6	8	9	10
Final visit (7 days after the treatment) - blood — Abnormal clinically significant	0	0	1	0	0
Final visit (7 days after the treatment) - urine — Normal	3	3	3	4	3
Final visit (7 days after the treatment) - urine — Abnormal not clinically significant	7	7	7	6	7
Final visit (7 days after the treatment) - urine — Abnormal clinically significant	0	0	0	0	0

SecondaryStudy 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
Reported as:: Mean · ng/mL

Study Part A: Cmax
ng/mL	Study Part A - Cohort 1 - Akynzeo	Study Part A - Cohort 1 - Fosnetupitant	Study Part A - Cohort 2	Study Part A - Cohort 3	Study Part A - Cohort 4
Fosnetupitant	8486.000 ± 2095.382	8920.000 ± 1722.892	23650.000 ± 20971.899	32540.000 ± 6607.437	37500.000 ± 11243.270
Netupitant	767.400 ± 136.572	893.400 ± 283.232	1050.100 ± 260.591	1170.700 ± 276.310	1382.700 ± 315.816
Metabolite M1	23.910 ± 5.324	22.380 ± 8.433	22.012 ± 6.687	21.930 ± 6.958	22.910 ± 7.610
Metabolite M2	135.730 ± 58.257	150.110 ± 72.607	102.450 ± 44.216	118.160 ± 49.015	146.490 ± 88.541
Metabolite M3	46.880 ± 11.936	48.450 ± 17.019	46.570 ± 16.137	47.680 ± 14.446	52.100 ± 27.347

SecondaryStudy 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
Reported as:: Mean · ng/mL

Study Part A: C0
ng/mL	Study Part A - Cohort 1 - Akynzeo	Study Part A - Cohort 1 - Fosnetupitant	Study Part A - Cohort 2	Study Part A - Cohort 3	Study Part A - Cohort 4
Fosnetupitant	8486.000 ± 2095.382	8920.000 ± 1722.892	23650.000 ± 20971.899	32540.000 ± 6607.437	33557.000 ± 15972.519
Netupitant	743.100 ± 173.921	893.400 ± 283.232	946.100 ± 419.234	1019.400 ± 319.820	596.810 ± 383.903
Metabolite M1	1.714 ± 2.229	1.753 ± 1.969	0.337 ± 1.066	0.000 ± 0.000	0.000 ± 0.000
Metabolite M2	28.150 ± 10.059	49.121 ± 34.243	32.300 ± 22.563	25.680 ± 11.219	12.706 ± 6.689
Metabolite M3	6.214 ± 4.144	6.799 ± 2.989	0.727 ± 1.711	0.000 ± 0.000	0.000 ± 0.000

SecondaryStudy 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
Reported as:: Median · h

Study Part A: Tmax
h	Study Part A - Cohort 1 - Akynzeo	Study Part A - Cohort 1 - Fosnetupitant	Study Part A - Cohort 2	Study Part A - Cohort 3	Study Part A - Cohort 4
Fosnetupitant	0.5 (0.5 to 0.5)	0.5 (0.5 to 0.5)	0.25 (0.25 to 0.3)	0.08 (0.08 to 0.08)	0.05 (0.033 to 0.08)
Netupitant	0.5 (0.5 to 2)	0.5 (0.5 to 0.5)	0.25 (0.25 to 0.33)	0.125 (0.08 to 0.17)	0.08 (0.08 to 0.17)
Metabolite M1	12 (2 to 24)	10 (2 to 24)	12 (1.5 to 24)	12 (4 to 24)	12 (8 to 24)
Metabolite M2	2 (2 to 4)	2 (1.5 to 3)	2.5 (0.33 to 3)	2 (1.5 to 3)	1.75 (1.5 to 4)
Metabolite M3	24 (12 to 24)	24 (2 to 24)	24 (12 to 24)	24 (12 to 24)	24 (12 to 24)

SecondaryStudy 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
Reported as:: Mean · ng/mL

Study Part A: Clast
ng/mL	Study Part A - Cohort 1 - Akynzeo	Study Part A - Cohort 1 - Fosnetupitant	Study Part A - Cohort 2	Study Part A - Cohort 3	Study Part A - Cohort 4
Fosnetupitant	79.780 ± 71.819	49.410 ± 35.149	97.140 ± 122.226	45.620 ± 28.083	34.330 ± 16.176
Netupitant	149.150 ± 111.842	122.490 ± 40.233	136.340 ± 39.724	123.740 ± 28.843	137.270 ± 66.827
Metabolite M1	21.150 ± 3.876	20.380 ± 7.875	20.532 ± 6.667	19.990 ± 5.977	21.440 ± 7.826
Metabolite M2	20.090 ± 10.519	18.850 ± 7.890	14.534 ± 4.789	18.770 ± 5.515	17.067 ± 7.953
Metabolite M3	46.370 ± 12.315	48.020 ± 17.273	44.960 ± 15.634	47.080 ± 14.763	52.060 ± 27.374

SecondaryStudy 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
Reported as:: Mean · h

Study Part A: Tlast
h	Study Part A - Cohort 1 - Akynzeo	Study Part A - Cohort 1 - Fosnetupitant	Study Part A - Cohort 2	Study Part A - Cohort 3	Study Part A - Cohort 4
Fosnetupitant	0.83 ± 0.118	0.95 ± 0.23	1.075 ± 1.048	0.6 ± 0.316	0.633 ± 0.35
Netupitant	24 ± 0	24 ± 0	24 ± 0	24 ± 0	24 ± 0
Metabolite M1	24 ± 0	24 ± 0	24 ± 0	24 ± 0	24 ± 0
Metabolite M2	24 ± 0	24 ± 0	24 ± 0	24 ± 0	24 ± 0
Metabolite M3	24 ± 0	24 ± 0	24 ± 0	24 ± 0	24 ± 0

SecondaryStudy 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
Reported as:: Mean · h x ng/mL

Study Part A: AUC0-t
h x ng/mL	Study Part A - Cohort 1 - Akynzeo	Study Part A - Cohort 1 - Fosnetupitant	Study Part A - Cohort 2	Study Part A - Cohort 3	Study Part A - Cohort 4
Fosnetupitant	3217.286 ± 780.235	3374.275 ± 658.088	4807.383 ± 4537.620	3662.088 ± 630.455	3839.681 ± 859.368
Netupitant	5404.315 ± 1227.399	5232.178 ± 1119.310	5792.056 ± 1520.649	5344.307 ± 1385.625	5656.305 ± 1998.286
Metabolite M1	468.997 ± 113.819	456.214 ± 173.046	436.089 ± 142.089	426.440 ± 122.749	447.497 ± 143.611
Metabolite M2	1234.204 ± 767.496	1260.320 ± 477.244	959.756 ± 382.755	1137.332 ± 331.659	1182.642 ± 560.829
Metabolite M3	833.606 ± 164.142	895.624 ± 304.534	831.375 ± 306.679	826.377 ± 156.114	935.410 ± 441.878

SecondaryStudy 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
Reported as:: Mean · h x ng/mL

Study Part A: AUC0-24
h x ng/mL	Study Part A - Cohort 1 - Akynzeo	Study Part A - Cohort 1 - Fosnetupitant	Study Part A - Cohort 2	Study Part A - Cohort 3	Study Part A - Cohort 4
Fosnetupitant	3228.246 ± 781.172	3382.473 ± 657.505	4833.636 ± 4577.777	3668.069 ± 631.004	3844.251 ± 859.498
Netupitant	5404.315 ± 1227.399	5232.178 ± 1119.310	5792.056 ± 1520.649	5344.307 ± 1385.625	5656.305 ± 1998.286
Metabolite M1	468.997 ± 113.819	456.214 ± 173.046	436.089 ± 142.089	426.440 ± 122.749	447.497 ± 143.611
Metabolite M2	1234.204 ± 767.496	1260.320 ± 477.244	959.756 ± 382.755	1137.332 ± 331.659	1182.642 ± 560.829
Metabolite M3	833.606 ± 164.142	895.624 ± 304.534	831.375 ± 306.679	826.377 ± 156.114	935.410 ± 441.878

SecondaryStudy 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
Reported as:: Mean · 1/h

Study Part A: Terminal Elimination Rate Constant
1/h	Study Part A - Cohort 1 - Akynzeo	Study Part A - Cohort 1 - Fosnetupitant	Study Part A - Cohort 2	Study Part A - Cohort 3	Study Part A - Cohort 4
Fosnetupitant	12.157 ± 0.662	11.734 ± 0.754	14.979 ± 5.582	18.613 ± 3.868	19.141 ± 5.429
Netupitant	0.034 ± 0.012	0.034 ± 0.007	0.033 ± 0.012	0.039 ± 0.005	0.032 ± 0.014
Metabolite M2	0.063 ± 0.014	0.061 ± 0.018	0.058 ± 0.017	0.059 ± 0.013	0.061 ± 0.015

SecondaryStudy 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
Reported as:: Mean · h

Study Part A: t1/2
h	Study Part A - Cohort 1 - Akynzeo	Study Part A - Cohort 1 - Fosnetupitant	Study Part A - Cohort 2	Study Part A - Cohort 3	Study Part A - Cohort 4
Fosnetupitant	0.057 ± 0.003	0.059 ± 0.004	0.080 ± 0.115	0.039 ± 0.011	0.040 ± 0.017
Netupitant	22.104 ± 7.005	21.356 ± 4.151	25.176 ± 14.727	18.017 ± 2.747	30.061 ± 24.561
Metabolite M2	11.538 ± 2.490	12.855 ± 5.985	12.918 ± 4.023	12.468 ± 3.215	12.248 ± 3.863

SecondaryStudy 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
Reported as:: Mean · mL/h

Study Part A: Systemic Clearance
mL/h	Study Part A - Cohort 1 - Akynzeo	Study Part A - Cohort 1 - Fosnetupitant	Study Part A - Cohort 2	Study Part A - Cohort 3	Study Part A - Cohort 4
Fosnetupitant	61821.940 ± 16436.343	66942.974 ± 12370.822	65171.229 ± 21219.721	65651.064 ± 9975.506	63748.966 ± 13353.411
Netupitant	27219.010 ± 3356.654	28693.446 ± 7660.440	24200.268 ± 6832.625	27596.213 ± 6404.903	26994.542 ± 10531.874
Metabolite M2	172324.405 ± 50962.753	162039.804 ± 57537.646	211825.621 ± 68310.261	174034.336 ± 64374.511	182468.624 ± 68658.409

SecondaryStudy 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
Reported as:: Mean · mL

Study Part A: Vz
mL	Study Part A - Cohort 1 - Akynzeo	Study Part A - Cohort 1 - Fosnetupitant	Study Part A - Cohort 2	Study Part A - Cohort 3	Study Part A - Cohort 4
Fosnetupitant	5129.653 ± 1631.449	5765.916 ± 1352.379	4796.595 ± 1491.027	3728.124 ± 1263.039	3572.355 ± 1199.382
Netupitant	848022.360 ± 215723.734	872978.816 ± 264673.002	772482.708 ± 205893.262	719627.108 ± 219903.292	944544.565 ± 311425.672
Metabolite M2	2895427.080 ± 954908.605	2820832.784 ± 1000428.130	4109459.426 ± 2374558.032	3083100.830 ± 1154481.625	3122087.067 ± 1170365.896

SecondaryStudy 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
Reported as:: Mean · h

Study Part A: MRT
h	Study Part A - Cohort 1 - Akynzeo	Study Part A - Cohort 1 - Fosnetupitant	Study Part A - Cohort 2	Study Part A - Cohort 3	Study Part A - Cohort 4
Fosnetupitant	0.253 ± 0.001	0.254 ± 0.002	0.275 ± 0.038	0.109 ± 0.014	0.086 ± 0.014
Netupitant	28.529 ± 9.761	26.760 ± 5.780	33.752 ± 21.148	24.493 ± 3.866	40.753 ± 34.769
Metabolite M2	14.343 ± 2.220	15.895 ± 7.651	16.347 ± 5.492	16.299 ± 3.936	14.975 ± 4.858

Adverse events

Collected over The reporting period for adverse events is the period starting from the time of informed consent signature and lasting until the final visit. Adverse events were collected for each participant for the whole period of the study (i.e., a maximum of 28 days).. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Study Part A - Cohort 1 - Akynzeo	0/10 (0%)	0/10 (0%)	5/10 (50%)
Study Part A - Cohort 1 - Fosnetupitant	0/10 (0%)	0/10 (0%)	3/10 (30%)
Study Part A - Cohort 2	0/10 (0%)	0/10 (0%)	2/10 (20%)
Study Part A - Cohort 3	0/10 (0%)	0/10 (0%)	1/10 (10%)
Study Part A - Cohort 4	0/10 (0%)	0/10 (0%)	4/10 (40%)

Most frequent other events

Showing 10 of 12

Most frequent other events
Event	Study Part A - Cohort 1 - Akynzeo	Study Part A - Cohort 1 - Fosnetupitant	Study Part A - Cohort 2	Study Part A - Cohort 3	Study Part A - Cohort 4
ConstipationGastrointestinal disorders	2/10	0/10	0/10	0/10	0/10
FatigueGeneral disorders	2/10	0/10	0/10	0/10	0/10
HeadacheNervous system disorders	0/10	1/10	1/10	0/10	2/10
NauseaGastrointestinal disorders	0/10	1/10	0/10	0/10	0/10
Infusion site painGeneral disorders	0/10	1/10	0/10	0/10	0/10
Injection site discomfortGeneral disorders	0/10	1/10	0/10	0/10	0/10
Influenza like illnessGeneral disorders	0/10	0/10	0/10	1/10	0/10
DizzinessNervous system disorders	1/10	0/10	1/10	0/10	1/10
PresyncopeNervous system disorders	1/10	0/10	0/10	0/10	0/10
DysgeusiaNervous system disorders	0/10	0/10	0/10	0/10	1/10

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Study Part A - Cohort 1 - Akynzeo	Study Part A - Cohort 1 - Fosnetupitant	Study Part A - Cohort 2	Study Part A - Cohort 3	Study Part A - Cohort 4	Total
Mean	31.7 ± 8.9	40.7 ± 8.2	38.9 ± 13.2	37.9 ± 10.8	38.1 ± 13.5	37.5 ± 11.1

Sex: Female, Male
Sex: Female, Male(Participants)	Study Part A - Cohort 1 - Akynzeo	Study Part A - Cohort 1 - Fosnetupitant	Study Part A - Cohort 2	Study Part A - Cohort 3	Study Part A - Cohort 4	Total
Female	4	6	3	3	4	20
Male	6	4	7	7	6	30

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Study Part A - Cohort 1 - Akynzeo	Study Part A - Cohort 1 - Fosnetupitant	Study Part A - Cohort 2	Study Part A - Cohort 3	Study Part A - Cohort 4	Total
American Indian or Alaska Native	0	0	0	0	0	0
Asian	0	0	0	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0
Black or African American	0	0	1	0	0	1
White	10	10	9	8	9	46
More than one race	0	0	0	2	1	3
Unknown or Not Reported	0	0	0	0	0	0

Region of Enrollment
Region of Enrollment(participants)	Study Part A - Cohort 1 - Akynzeo	Study Part A - Cohort 1 - Fosnetupitant	Study Part A - Cohort 2	Study Part A - Cohort 3	Study Part A - Cohort 4	Total
Switzerland	10	10	10	10	10	10

Body weight
Body weight(kilograms)	Study Part A - Cohort 1 - Akynzeo	Study Part A - Cohort 1 - Fosnetupitant	Study Part A - Cohort 2	Study Part A - Cohort 3	Study Part A - Cohort 4	Total
Mean	65.94 ± 9.50	69.83 ± 15.15	71.98 ± 13.16	75.20 ± 11.24	71.30 ± 11.66	70.85 ± 12.16

Height
Height(centimeters)	Study Part A - Cohort 1 - Akynzeo	Study Part A - Cohort 1 - Fosnetupitant	Study Part A - Cohort 2	Study Part A - Cohort 3	Study Part A - Cohort 4	Total
Mean	171.0 ± 8.1	168.0 ± 9.3	170.1 ± 8.4	174.0 ± 10.4	169.4 ± 9.1	170.5 ± 9.0

Body mass index
Body mass index(kilograms/square meters)	Study Part A - Cohort 1 - Akynzeo	Study Part A - Cohort 1 - Fosnetupitant	Study Part A - Cohort 2	Study Part A - Cohort 3	Study Part A - Cohort 4	Total
Mean	22.46 ± 2.20	24.49 ± 3.36	24.69 ± 2.65	24.74 ± 2.26	24.83 ± 3.42	24.24 ± 2.86

Study locations

1 site

CROSS Research S.A.
Arzo, Canton Ticino CH-6864, Switzerland

References and documents

Study documents

Study protocol · May 24, 2023
Statistical analysis plan · Jun 18, 2024

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No — No need to share IPD

Registry details

Key details

Study ID: NCT06840769
Lead sponsor: Helsinn Healthcare SA
Responsible party: Sponsor
First posted: Feb 21, 2025
Start date: Jun 17, 2023
Primary completion: Oct 18, 2023
Completion: Oct 23, 2023
Results posted: May 4, 2025
Last update: May 4, 2025

Study contacts

Milko Radicioni

principal investigator · Cross Research S.A.

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

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