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This study will treat patients with advanced NSCLC who have progressed following prior therapy in order to assess the effect of DZD9008 on exposure of midazolam, digoxin and rosuvastatin, through multiple PK parameters, when administrated as a single dose alone and in combination with DZD9008. Also, it will assess the safety and tolerability of DZD9008 in the presence and absence of co-administration of cocktail probes.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| DZD9008 + Probe Drugs | Experimental | Single dose of 2 mg midazolam (oral solution), 0.25 mg digoxin (tablet) and 10mg rosuvastatin (tablet) and in combination with 300 mg DZD9008 (tablet) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| DZD9008 and Probe drugs (midazolam, digoxin, rosuvastatin) | Drug | Patients will receive single oral doses of probe drugs alone and after at least 27 days of treatment with DZD9008, 300 mg, once daily, until a treatment discontinuation criterion is met. Each patient will receive a single oral dose of DZD9008 on Day 7, and DZD9008 once daily for 27 days from Day 9 to Day 35. Patients will also receive a single oral dose of 2 mg midazolam on Day 1 and Day 32, and oral dose of 10 mg rosuvastatin and 0.25 mg digoxin cocktail on Day 2, Day 7 and Day 33. |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax of midazolam, 1-OH Midazolam, digoxin and rosuvastatin alone and in combination with DZD9008 | Days 1-35 | |
| AUC0-t of midazolam, 1-OH Midazolam, digoxin and rosuvastatin alone and in combination with DZD9008 | Days 1-35 | |
| Ratio of AUC of midazolam, 1-OH midazolam, digoxin and rosuvastatin between substrate alone and with DZD9008 | Days 1-35 | |
| Ratio of Cmax of midazolam, 1-OH midazolam, digoxin and rosuvastatin between substrate alone and with DZD9008 | Days 1-35 | |
| AUC0-inf of midazolam, 1-OH Midazolam, digoxin and rosuvastatin alone and in combination with DZD9008, if applicable | Days 1-35 |
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Inclusion Criteria:
Exclusion Criteria:
Other protocol-defined inclusion/exclusion criteria may apply.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Shandong Cancer Hospital (Shandong Provincial Institute of Cancer Prevention and Treatment) | Jinan | Shandong | 250117 | China |
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|
|
| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| D008874 | Midazolam |
| D004077 | Digoxin |
| D000068718 | Rosuvastatin Calcium |
| ID | Term |
|---|---|
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D004071 | Digitalis Glycosides |
| D002298 | Cardenolides |
| D002301 | Cardiac Glycosides |
| D002297 | Cardanolides |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D005464 | Fluorobenzenes |
| D006845 | Hydrocarbons, Fluorinated |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
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