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This is a three-part, single-center, open-label phase I clinical study to characterize the DDIs potential of SKLB1028 with Itraconazole, Gemfibrozil or Rifampicin in healthy subjects. This study also aims to evaluate the safety and tolerability of SKLB1028 in the presence of Itraconazole, Gemfibrozil or Rifampicin.
SKLB1028 is the potential substrate of CYP3A4, CYP2C8 and P-gp. This study conducted in three parts to characterize the DDIs potential of SKLB1028 with the perpetrator drugs ( Itraconazole, Gemfibrozil, Rifampicin) in Healthy Subjects. Each part of this study consists of a screening period (Day -14 to Day -2), a baseline period (Day -1), a treatment period, and a follow-up visit period.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| The DDI of SKLB1028 and Itraconazole | Experimental | Eligible subjects received a single dose of SKLB1028 100 mg on Day 1, then took Itraconazole 200 mg twice-daily on Day 8 and 200 mg once-daily on Day 9 through Day 18, and took a single dose of SKLB1028 100 mg on Day 11. |
|
| The DDI of SKLB1028 and Gemfibrozil | Experimental | Eligible subjects received a single dose of SKLB1028 100 mg on Day 1, then took Gemfibrozil 600 mg twice-daily on Day 8 through Day 19, and took a single dose of SKLB1028 100 mg on Day 12. |
|
| The DDI of SKLB1028 and Rifampicin | Experimental | Eligible subjects received a single dose of SKLB1028 150 mg on Day 1, then took Rifampicin 600 mg once-daily on Day 8 through Day22, and took a single dose of SKLB1028 150 mg on Day 15. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SKLB1028 | Drug | SKLB1028, capsule, oral |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum concentration (Cmax) of SKLB1028 | Up to 22 days | |
| Area under the concentration-time curve (AUC) from 0 to the last measurable concentration (AUC0-t) of SKLB1028 | Up to 22 days | |
| AUC extrapolated to infinity (AUCinf) of SKLB1028 | Up to 22 days |
| Measure | Description | Time Frame |
|---|---|---|
| Time to Cmax (Tmax) of SKLB1028 | Up to 22 days | |
| Terminal elimination half-life (t1/2) of SKLB1028 | Up to 22 days | |
| Apparent Clearance (CLz/F) of SKLB1028 |
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Inclusion Criteria:
-
Healthy subjects:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beijing Friendship Hospital, Capital Medical University | Beijing | China |
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| Itraconazole | Drug | Itraconazole, capsule, oral |
|
| Gemfibrozil | Drug | Gemfibrozil, capsule, oral |
|
| Rifampicin | Drug | Rifampicin, capsule, oral |
|
| Up to 22 days |
| Apparent volume of distribution (Vz/F) of SKLB1028 | Up to 22 days |
| Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 | Up to approximately 30 days |
| Clinically significant changes from baseline in routine blood test were recorded as AEs at each visit time point. | Routine blood test included cell count (white blood cells, platelets, basophils, eosinophils, neutrophils, lymphocytes and monocytes) in 10^9/L. | Up to approximately 30 days |
| Clinically significant changes from baseline in routine blood test were recorded as AEs at each visit time point. | Routine blood test included red blood cell count in 10^12/L. | Up to approximately 30 days |
| Clinically significant changes from baseline in routine blood test were recorded as AEs at each visit time point. | Routine blood test included hemoglobin in g/L. | Up to approximately 30 days |
| Clinically significant changes from baseline in blood biochemistry test were recorded as AEs at each visit time point. | Blood biochemistry test included total bilirubin and serum creatinine in μmol/L. | Up to approximately 30 days |
| Clinically significant changes from baseline in blood biochemistry test were recorded as AEs at each visit time point. | Blood biochemistry test included alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and creatine kinase in U/L. | Up to approximately 30 days |
| Clinically significant changes from baseline in blood biochemistry test were recorded as AEs at each visit time point. | Blood biochemistry test included total protein and albumin in g/L. | Up to approximately 30 days |
| Clinically significant changes from baseline in blood biochemistry test were recorded as AEs at each visit time point. | Blood biochemistry test included total cholesterol, triglyceride and blood glucose in mmol/L. | Up to approximately 30 days |
| Clinically significant changes from baseline in routine urine test were recorded as AEs at each visit time point. | Routine urine test included protein, urobilinogen, glucose and ketones (positive or negative). | Up to approximately 30 days |
| Clinically significant changes from baseline in routine urine test were recorded as AEs at each visit time point. | Routine urine test included pH value and specific gravity. | Up to approximately 30 days |
| Clinically significant changes from baseline in coagulation function test were recorded as AEs at each visit time point. | Coagulation function test included prothrombin time and activated partial thromboplastin time in seconds. | Up to approximately 30 days |
| Clinically significant changes from baseline in coagulation function test were recorded as AEs at each visit time point. | Coagulation function test included antithrombin III as percentage. | Up to approximately 30 days |
| Clinically significant changes from baseline in coagulation function test were recorded as AEs at each visit time point. | Coagulation function test included fibrinogen in g/L. | Up to approximately 30 days |
| Clinically significant changes from baseline in 12-lead electrocardiogram (ECG) examination were recorded as AEs at each visit time point. | ECG monitoring included heart rate in bpm. | Up to approximately 30 days |
| Clinically significant changes from baseline in 12-lead electrocardiogram (ECG) examination were recorded as AEs at each visit time point. | ECG monitoring included P-R, QRS, QT and QTcF in ms. | Up to approximately 30 days |
| Clinically significant changes from baseline in vital signs examination were recorded as AEs at each visit time point. | Vital signs monitoring included body temperature in degrees Celsius. | Up to approximately 30 days |
| Clinically significant changes from baseline in vital signs examination were recorded as AEs at each visit time point. | Vital signs monitoring included respiratory rate and pulse in times per minute. | Up to approximately 30 days |
| Clinically significant changes from baseline in vital signs examination were recorded as AEs at each visit time point. | Vital signs monitoring included systolic blood pressure and diastolic blood pressure in mmHg. | Up to approximately 30 days |
| Clinically significant changes from baseline in physical examination were recorded as AEs at each visit time point. | Physical examination included general conditions, skin, mucous membranes, head, neck, chest, abdomen, spine, limbs, nervous system, and lymphatic system. | Up to approximately 30 days |
| ID | Term |
|---|---|
| C576190 | SKLB1028 |
| D017964 | Itraconazole |
| D015248 | Gemfibrozil |
| D012293 | Rifampin |
| ID | Term |
|---|---|
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D010879 | Piperazines |
| D058607 | Fibric Acids |
| D058610 | Isobutyrates |
| D002087 | Butyrates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
| D010421 | Pentanoic Acids |
| D014631 | Valerates |
| D010647 | Phenyl Ethers |
| D004987 | Ethers |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D005232 | Fatty Acids, Volatile |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| D012294 | Rifamycins |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D047029 | Lactams, Macrocyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
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