Healthy VolunteersPhase 1NCT06840769
A Clinical Trial to Assess Safety and Pharmacokinetics of Fosnetupitant 235 mg and Metabolites in Healthy Volunteers
A Phase 1 study testing Fosnetupitant 235 mg solution and Akynzeo solution in people with Healthy Volunteers, run by Helsinn Healthcare SA at 1 site in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- Fosnetupitant 235 mg solution and Akynzeo solution
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteSwitzerland
- Study dates
- 17 Jun 2023to 23 Oct 2023
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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:
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- Hormonal oral, implantable, transdermal, or injectable contraceptives for at least 2 months before the screening visit.
- A non-hormonal intrauterine device [IUD] for at least 2 months before the screening visit
- A sterile or vasectomized sexual partner
- 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:
- 12 months of spontaneous amenorrhea or
- 6 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL or
- 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:
- A male condom with spermicide
- A sterile sexual partner or a partner in post-menopausal status for at least one year
- 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.
Who cannot join
- 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
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- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I, Open Label, Single Dose, Two Parts Study in Male and Female Healthy Subjects to Assess the Safety and Pharmacokinetics of Fosnetupitant 235 mg Administered as IV Bolus and of Derived Netupitant and Netupitant Metabolites
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
- Healthy Volunteers
- Being tested
- Fosnetupitant 235 mg solution, Akynzeo solution
- Keywords
- Helsinn, PNET-22-08, Fosnetupitant, Netupitant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fosnetupitant 235 mg solutionDrug
Also called Helsinn Fosnetupitant 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
Akynzeo solutionDrug
Also called IV Akynzeo®
235 mg fosnetupitant (corresponding to 260 mg of the chloride hydrochloride salt) / 0.25 mg palonosetron in 20 mL injectable solution
| Study group | Role | What they receive |
|---|---|---|
| Study Part A - cohort 1 | Experimental | Fosnetupitant free base 235 mg administered as single 30 min intravenous infusion or 235 mg fosnetupitant/0.25 mg palonosetron in 20 mL injection solution administered undiluted as a single 30 min intravenous infusion Receives: Drug: Fosnetupitant 235 mg solution; Drug: Akynzeo solution |
| Study Part A - cohort 2 | Experimental | Fosnetupitant free base 235 mg administered as single 15 min intravenous infusion Receives: Drug: Fosnetupitant 235 mg solution |
| Study Part A - cohort 3 | Experimental | Fosnetupitant free base 235 mg administered as single 5 min intravenous infusion Receives: Drug: Fosnetupitant 235 mg solution |
| Study Part A - cohort 4 | Experimental | Fosnetupitant free base 235 mg administered as single 2 min intravenous infusion Receives: Drug: Fosnetupitant 235 mg solution |
What is being measured
The primary outcome is the main question the study is designed to answer.
Study Part A: Number of Treatment-emergent Adverse Events
Number of treatment-emergent adverse events (TEAEs) collected up to 24 h post-dose.
Measured: 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.
Measured: 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.
Measured: 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 (26)
Study Part A: Systolic Blood Pressure
Systolic blood pressure in mmHg measured after 5 min at rest in sitting position
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2025
- Study start17 Jun 2023
- Primary completion18 Oct 2023
- Study completion23 Oct 2023
Why it stopped: Sponsor's decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Health services research
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Open label, single dose, two parts (part A and part B), safety and pharmacokinetic phase I study.
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Helsinn Healthcare SA
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Milko Radicioni, Principal investigator, Cross Research S.A.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06840769
- Sponsor's protocol ID
- PNET-22-08
- Status last verified
- Apr 2025
- First submitted
- 11 Feb 2025
- Last updated
- 4 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: No need to share IPD
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Open Label, Single Dose, Two Parts Study in Male and Female Healthy Subjects to Assess the Safety and Pharmacokinetics of Fosnetupitant 235 mg Administered as IV Bolus and of Derived Netupitant and Netupitant Metabolites
- ClinicalTrials.gov ID
- NCT06840769
- Acronym / sponsor ID
- PNET-22-08
- Conditions
- Healthy Volunteers
- Keywords
- Helsinn, PNET-22-08, Fosnetupitant, Netupitant
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor's decision
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Helsinn Healthcare SAIndustry (pharma, biotech, devices)
- Study start
- 17 Jun 2023 (actual)
- Primary completion
- 18 Oct 2023 (actual)
- Study completion
- 23 Oct 2023 (actual)
- First posted
- 21 Feb 2025 (actual)
- Results
- Posted 4 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Health services research
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- Open label, single dose, two parts (part A and part B), safety and pharmacokinetic phase I study.
| Arm | Type | Receives |
|---|---|---|
| Study Part A - cohort 1 | Experimental | Drug: Fosnetupitant 235 mg solution, Drug: Akynzeo solutionFosnetupitant free base 235 mg administered as single 30 min intravenous infusion or 235 mg fosnetupitant/0.25 mg palonosetron in 20 mL injection solution administered undiluted as a single 30 min intravenous infusion |
| Study Part A - cohort 2 | Experimental | Drug: Fosnetupitant 235 mg solutionFosnetupitant free base 235 mg administered as single 15 min intravenous infusion |
| Study Part A - cohort 3 | Experimental | Drug: Fosnetupitant 235 mg solutionFosnetupitant free base 235 mg administered as single 5 min intravenous infusion |
| Study Part A - cohort 4 | Experimental | Drug: Fosnetupitant 235 mg solutionFosnetupitant free base 235 mg administered as single 2 min intravenous infusion |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (18 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fosnetupitant 235 mg solutionAlso: Helsinn Fosnetupitant solutionFosnetupitant free base 235 mg (corresponding to 260 mg of the chloride hydrochloride salt) in 20 mL ready to use injectable solution for intravenous administration | Drug | Study Part A - cohort 1, Study Part A - cohort 2, Study Part A - cohort 3, Study Part A - cohort 4 |
| Akynzeo solutionAlso: IV Akynzeo®235 mg fosnetupitant (corresponding to 260 mg of the chloride hydrochloride salt) / 0.25 mg palonosetron in 20 mL injectable solution | Drug | Study Part A - cohort 1 |
Primary outcome
Study Part A: Number of Treatment-emergent Adverse Events
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)
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
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)
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
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)
Type of treatment-emergent adverse events (TEAEs) collected up to 24 h post-dose.
26 secondary outcomes
Study Part A: Systolic Blood Pressure
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
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
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
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
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
Time frame: Day 2 (24 h after the end of investigational product administration)
Study Part A: ECGs - Heart Rate
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
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
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
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
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
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
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)
Time frame: Screening visit (day of informed consent signature)/final visit (7 days after the treatment)
Study Part A: Cmax
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
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 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
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 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
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
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
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
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
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
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
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 and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. No need to share IPD
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Milko Radicioni principal investigator
Cross Research S.A.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Fosnetupitant 235 mg solution and Akynzeo solution in people with Healthy Volunteers, run by Helsinn Healthcare SA at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 4 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Study Part A: Number of Treatment-emergent Adverse Events (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)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2025.