Chemotherapy-induced nausea and vomiting Cancer
Conditions
Interventions
The study is divided into two parts (A and B). Part A is composed of 3 consecutive cohorts of 8 subjects each (fosnetupitant/palonosetron 235 mg/0.25 mg injectable solution, IV NEPA FDCliq, given over
Sponsors
Helsinn (Switzerland)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed written informed consent before inclusion in the study 2. Aged 18 and 55 years 3. Body Mass Index (BMI) between 18.5 and 30 kg/m2 4. Vital signs, measured after 5 min at rest in the sitting position: 4.1. Systolic blood pressure between 100 and 139 mmHg 4.2. Diastolic blood pressure between 50 and 89 mmHg 4.3. Pulse rate between 50 and 90 bpm 5. Able to comprehend the full nature and purpose of the study, including possible risks and side effects, and able to co-operate with the Investigator and to comply with the requirements of the entire study 6. Women of child-bearing potential must have a negative pregnancy test result at screening and admission (Day -1) and be using at least one of the following reliable methods of contraception: 6.1. Hormonal oral, implantable, transdermal, or injectable contraceptives for at least 2 months before the screening visit 6.2. A non-hormonal intrauterine device [IUD] or female condom with spermicide or contraceptive sponge with spermicide or diaphragm with spermicide or cervical cap with spermicide for =2 months before the screening visit 6.3. A male sexual partner who agrees to use a male condom with spermicide 6.4. A sterile sexual partner 7. Women of non-child-bearing potential or in post-menopausal status for =1 year
Exclusion criteria
Exclusion criteria: 1. Electrocardiogram (ECG) 12-lead (supine position) with clinically significant abnormalities at screening 2. Clinically significant abnormal physical findings that could interfere with the objectives of the study 3. Clinically significant abnormal laboratory values at screening indicative of physical illness, or suggesting the subject’s exclusion is in their best interest 4. Ascertained or presumptive hypersensitivity to the active principles and/or formulations' ingredients, or history of anaphylaxis to drugs or allergic reactions in general, which the Investigator considers may affect the outcome of the study 5. Significant history, in the opinion of the Investigator, of renal, hepatic, gastrointestinal, cardiovascular (in particular history of superficial thrombophlebitis or deep vein thrombosis), respiratory, skin, hematological, endocrine, or neurological diseases that may interfere with the aim of the study 6. Taking medications, including over the counter (OTC) medications and herbal remedies, other than hormonal contraceptives for women in the 2 weeks before the first visit of the study 7. Use of an inducer or inhibitor of CYP3A4 enzymes (drugs, food, herbal remedies) in the 28 days (part A) or in the 7 days (part B) before the planned first study drug administration, and during the whole study period 8. Participation in the evaluation of any investigational product in the 3 months (calculated as the time between the first calendar day of the month that follows the last visit of the previous study and the first visit of the present study) before the first visit of this study 9. Blood donations or significant blood loss in the 3 months before the first visit of this study 10. History of drug, alcohol (>1 drink/day for women and >2 drinks/day for men, defined according to the USDA Dietary Guidelines 2015-2020), caffeine (>5 cups coffee/tea/day), or tobacco abuse (=10 cigarettes/day) 11. Positive result at the urine drug screening test at screening or Day -1 12. Positive alcohol breath test at Day -1 13. Vegetarian or abnormal diets (3500 kcal/day), or substantial changes in eating habits in the 4 weeks before screening 14. Pregnancy, breastfeeding, or positive or missing pregnancy test at screening or Day -1 15. Enrolment in a previous study of netupitant or fosnetupitant (alone or in combination with palonosetron)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part A: 1. The shortest safe and tolerable duration of IV bolus injection of the liquid formulation assessed using the following: 1.1. Heart rate, electrical axes, and RR, PR, QRS, QT, QTcB, and QTcF intervals measured using electrocardiogram (ECG) at pre-dose, 30 min, and 6 h post-dose 1.2. Systolic blood pressure, diastolic blood pressure, and pulse rate measured using sphygmomanometer at pre-dose, 30 min, and 6 h post-dose 1.3. Adverse events measured from participant history up to 6 days post-dose Part B: 1. Bioequivalence of the liquid formulation (at the injection duration defined in Part A) and the lyophilized formulation, estimated in terms of the extent of exposure to netupitant and palonosetron (area under the plasma drug concentration–time curve, AUC0-t), using a fully validated liquid chromatography with tandem mass spectrometry (LC-MSMS) at pre-dose, 30 and 45 min post-dose, and at 1, 1.5, 2, 3, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168 and 192 h post-dose | — |
Secondary
| Measure | Time frame |
|---|---|
| Part A: 1. Characterization of the pharmacokinetic (PK) profile in plasma of fosnetupitant, netupitant, and palonosetron using serum samples after injection of the liquid formulation measured immediately post-dose, between either 2-5 or 10-15 min (on the basis of the treatment period), 20, 30, and 45 min, 1, 1.5, 2, 3, 4, 8, 12 and 24 h post-dose Part B: 1. Pharmacokinetic (PK) profile and kinetic parameters of netupitant and palonostren measured using fully validated liquid chromatography with tandem mass spectrometry (LC-MS-MS) at pre-dose, 30 and 45 min post-dose, and at 1, 1.5, 2, 3, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168 and 192 h post-dose 2. Safety and tolerability of the liquid formulation and the lyophilized formulation during the overall trial assessed using the following: 1.1. Heart rate, electrical axes, and RR, PR, QRS, QT, QTcB, and QTcF intervals measured using electrocardiogram (ECG) at pre-dose, immediately post-dose, 30 min, 6, and 24 h post-dose 1.2. Systolic blood pressure, diastolic blood pressure, and pulse rate measured using sphygmomanometer at pre-dose, immediately post-dose, 30 min, 6, and 24 h post-dose 1.3. Adverse events measured from participant history up to 9 days post-dose | — |
Countries
Switzerland
Contacts
Public ContactTulla Spinelli
Outcome results
None listed