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

NCT06840769 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: PNET-22-08
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial will include two parts, i.e., Part A and Part B. The goal of the Part A is to define the shortest safe and tolerable duration of an intravenous injection of Fosnetupitant 235 mg solution among 4 durations tested in male and female adult healthy volunteers. In study part A, researchers will compare Fosnetupitant 235 mg solution to Akynzeo® solution. The duration determined in Part A will be investigated in study Part B. The Part B of the study was not performed.

Conditions

Healthy Volunteers

Keywords

Helsinn; PNET-22-08; Fosnetupitant; Netupitant

Outcome Measures

Primary Outcomes (3)

• Study Part A: Number of Treatment-emergent Adverse Events

  Number of treatment-emergent adverse events (TEAEs) collected up to 24 h post-dose.

  From screening visit (day of informed consent signature) up to 24 h after the investigational medicinal product administration (a maximum of 21 days)

• Study Part A: Number of Subjects With Treatment-emergent Adverse Events

  Number of subjects with treatment-emergent adverse events (TEAEs) collected up to 24 h post-dose.

  From screening visit (day of informed consent signature) up to 24 h after the investigational medicinal product administration (a maximum of 21 days)

• Study Part A: Type of Treatment-emergent Adverse Events

  Type of treatment-emergent adverse events (TEAEs) collected up to 24 h post-dose.

  From screening visit (day of informed consent signature) up to 24 h after the investigational medicinal product administration (a maximum of 21 days)

Secondary Outcomes (26)

• Study Part A: Systolic Blood Pressure

  Screening visit/day -1 (enrolment day)/day 1 (treatment day) at pre-administration, at the end of administration and 1, 2, 4, 24 h after the end of administration/final visit (7 days after the treatment)

• Study Part A: Diastolic Blood Pressure

  Screening visit/day -1 (enrolment day)/day 1 (treatment day) at pre-administration, at the end of administration and 1, 2, 4, 24 h after the end of administration/final visit (7 days after the treatment)

• Study Part A: Pulse Rate

  Screening visit/day -1 (enrolment day)/day 1 (treatment day) at pre-administration, at the end of administration and 1, 2, 4, 24 h after the end of administration/final visit (7 days after the treatment)

• Study Part A: Weight

  Screening visit (day of informed consent signature)/final visit (7 days after the treatment)

• Study Part A: Full Physical Examination Through Apparatus/Systems Check

  Screening visit (day of informed consent signature)/final visit (7 days after the treatment)

Study Arms (4)

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

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

Drug: Fosnetupitant 235 mg solution

Study Part A - cohort 3

EXPERIMENTAL

Fosnetupitant free base 235 mg administered as single 5 min intravenous infusion

Drug: Fosnetupitant 235 mg solution

Study Part A - cohort 4

EXPERIMENTAL

Fosnetupitant free base 235 mg administered as single 2 min intravenous infusion

Drug: Fosnetupitant 235 mg solution

Interventions

Fosnetupitant 235 mg solution DRUG

Fosnetupitant free base 235 mg (corresponding to 260 mg of the chloride hydrochloride salt) in 20 mL ready to use injectable solution for intravenous administration

Also known as: Helsinn Fosnetupitant solution

Study Part A - cohort 1; Study Part A - cohort 2; Study Part A - cohort 3; Study Part A - cohort 4

Akynzeo solution DRUG

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®

Study Part A - cohort 1

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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:
• 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:
• months of spontaneous amenorrhea or
• months of spontaneous amenorrhea with serum FSH levels \> 40 mIU/mL or
• 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

You may not qualify if:

• Physical examination findings: clinically significant abnormal physical findings which could interfere with the objectives of the study
• 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)

Sponsors & Collaborators

• Helsinn Healthcare SA: lead

Study Sites (1)

CROSS Research S.A.

Arzo, Canton Ticino, CH-6864, Switzerland

Location

MeSH Terms

Interventions

Solutions; netupitant, palosentron drug combination

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations

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.

Results Point of Contact

• Title: Tulla Spinelli
• Organization: Helsinn Healthcare SA

Tulla.Spinelli@helsinn.com

+41.91.985.21.21

Study Officials

• Milko Radicioni

  Cross Research S.A.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open label, single dose, two parts (part A and part B), safety and pharmacokinetic phase I study.

Study Record Dates

• First Submitted: February 11, 2025
• First Posted: February 21, 2025
• Study Start: June 17, 2023
• Primary Completion: October 18, 2023
• Study Completion: October 23, 2023
• Last Updated: May 4, 2025
• Results First Posted: May 4, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)