A Study Evaluating the Effect of Aumolertinib on the Pharmacokinetics of Midazolam in Patients With NSCLC

NCT ID: NCT06926413

Last Updated: 2025-04-13

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-02-20
• Study Completion Date: 2025-10-31

Brief Summary

This is an open-label, fixed-sequence Phase I clinical study that evaluates the effect of multiple doses of aumolertinib on the pharmacokinetics of midazolam (CYP 3A4 probe substrate) in sensitive EGFR (Epidermal Growth Factor Receptor) mutation-harboring patients with locally advanced or metastatic non-small cell lung cancer (NSCLC).

Detailed Description

This is an open-label, fixed-sequence Phase I clinical study that evaluates the effect of multiple doses of aumolertinib on the pharmacokinetics of midazolam (CYP 3A4 probe substrate) in sensitive EGFR (Epidermal Growth Factor Receptor) mutation-harboring patients with locally advanced or metastatic non-small cell lung cancer (NSCLC).

The study includes D1 (Day 1)-D2 (Day 2) of run-in period, C1D1 (Cycle 1 Day 1)-C1D21 (Cycle 1 Day 21) and C2D1 (Cycle 2 Day 1)-C2D2 (Cycle 2 Day 2). The enrolled subjects will receive a single oral dose of midazolam 2 mg (2 mg/mL, 1 mL) on D1 of the run-in period and on C2D1; and receive oral dose of aumolertinib 110 mg (55 mg/tablet, 2 tablets) once daily from C1D1 to C2D2.

Conditions

Non Small Cell Lung Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

HS-10296

Group Type: EXPERIMENTAL

Aumolertinib；midazolam

Intervention Type: DRUG

Midazolam :

The enrolled subjects will receive a single oral dose of Midazolam 2 mg (2 mg/mL, 1 mL) on D1 of the run-in period and on C2D1.

Aumolertinib :

Starting from C1D1, the enrolled subjects will receive oral dose of aumolertinib 110 mg (55 mg/tablet, 2 tablets) once daily until the criteria for terminating treatment are met.

Interventions

Aumolertinib；midazolam

Midazolam :

The enrolled subjects will receive a single oral dose of Midazolam 2 mg (2 mg/mL, 1 mL) on D1 of the run-in period and on C2D1.

Aumolertinib :

Starting from C1D1, the enrolled subjects will receive oral dose of aumolertinib 110 mg (55 mg/tablet, 2 tablets) once daily until the criteria for terminating treatment are met.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 1. Participant should sign an informed consent form before the trial. 2. Male or female age≥18 years, at the time of signing the informed consent. 3. Histologically or cytological confirmation diagnosis of locally advanced or metastatic (IIIB/IIIC/IV) NSCLC; 4. Participant must fulfill one of below:

1. Participants who have not received any prior anti-tumor systemic therapy, and the tumor must harbor at least one of the EGFR mutations (ex19del or L858R, single mutation or combined with other EGFR mutations are both acceptable).

2. Participant who received first-generation EGFR-TKI in the locally advanced or metastatic setting and have documented radiological progression prior to enrolling in the study, and the tumor must harbor EGFR T790M mutation.

5. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0-1 and no deterioration in the previous two weeks with a minimum life expectancy of 12 weeks.

6. Male or female should take appropriate contraceptive measures from screening to 3 months after stopping the study treatment and female should not breastfeed.

Exclusion Criteria

• 1. Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at the time of starting study intervention with the exception of alopecia and Grade 2 neurotoxicity related to prior platinum-therapy.

2. Spinal cord compression or brain metastases unless asymptomatic, stable, and not requiring steroids for at least four weeks prior to start of study intervention.

3. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding within two weeks prior to the first dose of study intervention, active infection (e.g., active HBV infection, HCV infection), or HIV infection, which in the Investigator's opinion makes it undesirable for the participant to participate in the study or which would jeopardise compliance with the protocol.

4. Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.

5. Refractory nausea, vomiting, or chronic GI disorders; Participants unable to swallow oral medication or participants with GI disorders or significant GI resection likely to interfere with the absorption of study intervention.

6. Participant has any disease or condition that, in the judgment of the physician, may increase the risk to the safety or interfering with study assessments.

7. Participant with a known hypersensitivity to study intervention (Aumolertinib and Midazolam), structural analog, or any of the excipients of the products.

8. Past medical history of ventilation difficulties or severe sleep apnea syndrome.

9. Patient with acute angle-closure glaucoma or untreated open-angle glaucoma. 10. Patient which in the Investigator's opinion makes it undesirable for the participant to participate in the study or which would jeopardise compliance with the protocol.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jiangsu Hansoh Pharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Ethics Committee of the First Addiliated Hospital, College of Medicine, Zhejiang University

Hangzhou, Zhejiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

Qingwei Zhao

Role: CONTACT

yixuelunli123@163.com

86-571-87236685

Ke Niu

Role: CONTACT

niuk1@hspharm.com

Facility Contacts

Qingwei Zhao

Role: primary

yixuelunli123@163.com

86-571-87236685

Other Identifiers

HS-10296-109

Identifier Type: -

Identifier Source: org_study_id