A Study of Inhaled Fentanyl Aerosol in Chinese Patients With Malignant Tumors

This study is a single-dose, open-label, 2-cycle crossover design, comparing the pharmacokinetic parameters and safety of Inhaled Fentanyl Aerosol and intravenous fentanyl injection.

Consenting patients who met inclusion and exclusion criteria were allowed to enter the study. The subjects will be randomly assigned (1:1) to receive an intravenous bolus (5 seconds) of 25μg fentanyl injection in the first cycle, and after a 2-week washout period, to receive a single dose of 25μg inhaled fentanyl aerosol through the Staccato delivery system in the second cycle; or to receive the same treatment in the opposite order.

Eligibility Criteria:
Inclusion Criteria:

1. Volunteer to participate, understand and sign the informed consent form before conducting the evaluation project;
2. Male or female subjects, aged between 18 and 55, including 18 and 55 years old;
3. Patients with malignant tumors diagnosed by histology or cytology;
4. Body Mass Index (BMI) is \>21 kg/m2, but \<30 kg/m2;
5. Have sufficient hematopoietic function and organ function within the last 14 days at random.

   1. The absolute neutrophil count is ≥1.5×109/L (has not received colony stimulating factor treatment within 14 days before the examination);
   2. Platelet count ≥80×109/L (without transfusion of platelets or other platelet-increasing drugs within 14 days before the examination);
   3. Hemoglobin ≥90g/L (without transfusion or treatment with other hemoglobin-increasing drugs within 7 days before the examination);
   4. Creatinine clearance rate (Ccr)≥30 ml/min, Cr≤2 times the upper limit of normal value;
   5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) should be ≤2.5×ULN, and for subjects with liver metastasis, it should be ≤5×ULN; total bilirubin should be ≤2 times the upper limit of normal value;
   6. Coagulation function INR≤1.5 ULN;
   7. In a non-oxygen-absorbing state, the oxygen saturation (from a pulse oximeter) is SaO2\>95%; pulmonary function shows FEV1/FVC\>70% and FEV1 as a percentage of the predicted value is\>80%;
6. All patients must agree to take effective contraceptive measures during the study and within one month after stopping treatment. Female patients of childbearing age must have a negative blood pregnancy test before administration;
7. The ECOG performance status score is 0\~1 points;

Exclusion Criteria:

1. Known or suspected allergy to opioids;
2. Have used opioids within 14 days before the first administration, including but not limited to: codeine, dihydrocodeine, hydromorphone, oxycodone, methadone, morphine, fentanyl, and pethidine (Demerol);
3. Within 14 days prior to the first dose or during the study, plan to receive radiotherapy and/or systemic chemotherapy (except for patients who are receiving maintenance treatment with immune checkpoint inhibitors or targeted drugs that are not CYP3A4 inhibitors/inducers and whose condition is stable);

Within 14 days prior to the first administration, the patient has received any treatment with monoamine oxidase (MAO) inhibitors (such as phenelzine, isocarboxazid, clozapine, toloxatone, moclobemide, selegiline, rasagiline, etc.); or has used CYP3A4 inhibitors (such as indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole, nefazodone, ketoconazole, telithromycin, aprepitant, eritromycin, fluconazole, grapefruit, verapamil, diltiazem, cimetidine, etc.).

(such as cimetidine) or CYP3A4 inducers (such as phenobarbital, carbamazepine, efavirenz, glucocorticoids, modafinil, nevirapine, oxcarbazepine, phenytoin, pioglitazone, rifabutin, rifampicin, etc.); 5. Participated in other clinical research or received surgical treatment within 30 days before the screening period, or had a surgical plan during the study; 6. Subjects who smoked more than 10 cigarettes per day in the 3 months prior to the screening period; 7. Subjects who have a history of drug or alcohol dependence or abuse within the past 2 years before the screening period; 8. The subjects often consume foods rich in xanthine (such as drinking more than 5 cups of coffee per day or foods containing an equivalent amount of xanthine); 9. Subjects who have hypotension (systolic blood pressure \<90 mmHg, or diastolic blood pressure \<60 mmHg) or uncontrollable hypertension (indicating that after standard treatment, the systolic blood pressure ≥160 mmHg, and/or diastolic blood pressure ≥100 mmHg); 10. After antiviral treatment, if the hepatitis B surface antigen \[HBsAg\] is positive and the HBV DNA is \>500 IU/mL or \>2500 copies/mL; if the hepatitis C surface antibody is positive and the HCV-RNA is positive; if the human immunodeficiency virus antibody is positive; or if the syphilis antibody is positive; 11. Subjects who test positive for alcohol or urine in any study visit; 12. Subjects whose expected survival time is less than 1 year; 13. Screen subjects whose ECG abnormalities are clinically significant during the screening period; 14. Subjects who have a history of lung diseases (asthma, bronchitis, bronchospasm, emphysema, interstitial lung disease, pulmonary fibrosis, etc., excluding lung malignancies); 15. Subjects who have a history of unstable angina, syncope, coronary artery disease, myocardial infarction, congestive heart failure (CHF), stroke, transient ischemic attack (TIA), or major neurological diseases; 16. Epilepsy associated with meningeal metastasis or CNS metastasis or malignant tumors that require clinical intervention; 17. Women of childbearing age or breastfeeding women who have a positive blood or urine pregnancy test; 18. The researchers consider any other situation that may affect the subjects' ability to provide informed consent or follow the trial protocol, or any situation in which the subjects' participation in the trial may affect the trial results or their own safety.