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Assessing 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 (WU-KONG19)

Primary Purpose

Non-small Cell Lung Cancer

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
DZD9008 and Probe drugs (midazolam, digoxin, rosuvastatin)
Sponsored by
Dizal Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-small Cell Lung Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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 Exclusion Criteria: 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-19. 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.

Sites / Locations

  • Shandong Cancer Hospital (Shandong Provincial Institute of Cancer Prevention and Treatment)Recruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

DZD9008 + Probe Drugs

Arm Description

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)

Outcomes

Primary Outcome Measures

Cmax of midazolam, 1-OH Midazolam, digoxin and rosuvastatin alone and in combination with DZD9008
AUC0-t of midazolam, 1-OH Midazolam, digoxin and rosuvastatin alone and in combination with DZD9008
Ratio of AUC of midazolam, 1-OH midazolam, digoxin and rosuvastatin between substrate alone and with DZD9008
Ratio of Cmax of midazolam, 1-OH midazolam, digoxin and rosuvastatin between substrate alone and with DZD9008
AUC0-inf of midazolam, 1-OH Midazolam, digoxin and rosuvastatin alone and in combination with DZD9008, if applicable

Secondary Outcome Measures

Full Information

First Posted
June 22, 2023
Last Updated
September 6, 2023
Sponsor
Dizal Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT05926180
Brief Title
Assessing 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 (WU-KONG19)
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 31, 2023 (Actual)
Primary Completion Date
August 19, 2024 (Anticipated)
Study Completion Date
August 19, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Dizal Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-small Cell Lung Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
31 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
DZD9008 + Probe Drugs
Arm Type
Experimental
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
DZD9008 and Probe drugs (midazolam, digoxin, rosuvastatin)
Other Intervention Name(s)
Inapplicable
Intervention Description
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.
Primary Outcome Measure Information:
Title
Cmax of midazolam, 1-OH Midazolam, digoxin and rosuvastatin alone and in combination with DZD9008
Time Frame
Days 1-35
Title
AUC0-t of midazolam, 1-OH Midazolam, digoxin and rosuvastatin alone and in combination with DZD9008
Time Frame
Days 1-35
Title
Ratio of AUC of midazolam, 1-OH midazolam, digoxin and rosuvastatin between substrate alone and with DZD9008
Time Frame
Days 1-35
Title
Ratio of Cmax of midazolam, 1-OH midazolam, digoxin and rosuvastatin between substrate alone and with DZD9008
Time Frame
Days 1-35
Title
AUC0-inf of midazolam, 1-OH Midazolam, digoxin and rosuvastatin alone and in combination with DZD9008, if applicable
Time Frame
Days 1-35

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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-19. 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yanrong Cai, MD
Phone
+86 021-61095805
Email
cyrus.cai@dizalpharma.com
Facility Information:
Facility Name
Shandong Cancer Hospital (Shandong Provincial Institute of Cancer Prevention and Treatment)
City
Jinan
State/Province
Shandong
ZIP/Postal Code
250117
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xing
Phone
+86 0531-67626819
Email
xinglg@medmail.com.cn

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Assessing 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 (WU-KONG19)

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