A Phase 1, Open-label, Non-Randomized Study to Assess the Effect of DZD9008 on the Pharmacokinetics of the Cocktail Probes Representative for CYP3A4, P-gp, BCRP and OATP1B1 in Patients with EGFR or HER2 Mutant Advanced Non-small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Cmax of midazolam, 1-OH Midazolam, digoxin and rosuvastatin alone and in combination with DZD9008
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged at least 18 years old, be able to provide a signed and dated, written informed consent.
- •Patients must have documented histologically or cytologically confirmed locally advanced or metastatic NSCLC with EGFR or HER2 mutations and have progressed from, been refractory to or are intolerant to prior standard therapy without preferred alternative therapy.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1 at ICF signature with no deterioration over the previous 2 weeks.
- •Predicted life expectancy ≥ 12 weeks
排除标准
- •Patients with a known hypersensitivity to DZD9008, rosuvastatin, digoxin, midazolam, or any of the excipients of the products.
- •Concomitant medication or any clinical condition contraindicated for use with rosuvastatin, digoxin, midazolam.
- •Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study treatment.
- •Patients currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be potent inhibitors or inducers of CYP3A4, BCRP, OATP1B1 and P-gp.
- •Patients who have BCRP (ABCG2) polymorphism c.421C>A (p.Q141K, rs2231142).
- •Patients with previous allogenic bone marrow transplant or non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection.
- •Patients with liver metastases, spinal cord compression or leptomeningeal metastasis.
- •Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses.
- •Participants with active infection including but not limited to hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) (refer to CSP) and active infection of COVID-
- •Inadequate bone marrow reserve or organ function.
- •Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease.
- •Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of study treatment.
- •Women who are pregnant or breast feeding.
- •Known history of bleeding diathesis, i.e., hemophilia, Von Willebrand disease.
- •History of stroke or intracranial haemorrhage within 6 months
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
DZD9008 + Probe Drugs
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)
干预措施: DZD9008 and Probe drugs (midazolam, digoxin, rosuvastatin) (Drug)
结局指标
主要结局
Cmax of midazolam, 1-OH Midazolam, digoxin and rosuvastatin alone and in combination with DZD9008
时间窗: Days 1-35
AUC0-inf of midazolam, 1-OH Midazolam, digoxin and rosuvastatin alone and in combination with DZD9008, if applicable
时间窗: Days 1-35
AUC0-t of midazolam, 1-OH Midazolam, digoxin and rosuvastatin alone and in combination with DZD9008
时间窗: Days 1-35
Ratio of Cmax of midazolam, 1-OH midazolam, digoxin and rosuvastatin between substrate alone and with DZD9008
时间窗: Days 1-35
Ratio of AUC of midazolam, 1-OH midazolam, digoxin and rosuvastatin between substrate alone and with DZD9008
时间窗: Days 1-35
次要结局
未报告次要终点