A Study To Evaluate The Effect Of Rifampicin Or Ltraconazole On Pharmacokinetics Of Ensartinib In Healthy Volunteers

A Phase 1, Open-label, 2-period, Fixed Sequence, Cross-over Study To Investigate The Effect Of Multiple Doses Of Rifampicin Or Itraconazole On The Pharmacokinetics Of Single Dose Ensartinib In Healthy Volunteers.

The purpose of this study is to estimate the effect of rifampicin or itraconazole on the single dose PK of ensartinib.

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy
• Intervention / Treatment: Drug: Ensartinib; Drug: Rifampicin; Drug: Ensartinib; Drug: Itraconazole

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Bo Jiang, Ph.D; Phone Number: 0571-87783759; Email: jiangbo@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • The Second Affiliated Hospital of Zhejiang University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male body weight ≥ 50kg, female body weight ≥ 45kg, body mass index (BMI) within the range of 19 ~ 26kg /m2;
• Clinical laboratory evaluations within the reference range for the test laboratory, unless deemed not clinically significant by the Investigator;
• The subjects should took effective contraceptive measures voluntarily from informed consent until 3 months after Study Completion；
• Able to comprehend and willing to sign an informed consent form.

Exclusion Criteria:

• Those with a history of chronic systemic or serious diseases such as cardiovascular, liver, kidney, lung, gastrointestinal, nervous, musculoskeletal, hematopoietic or metabolic diseases, especially surgical conditions or conditions that may affect drug absorption, distribution, metabolism and excretion；
• Family history or presence of long QTc syndrome; History or presence of an abnormal ECG；
• Hepatitis B virus surface antigen (HBsAg), hepatitis C virus antibody (HCV-Ab), treponema pallidum antibody or human immunodeficiency virus antigen/antibody (HIV-Ag/Ab) is positive；
• Use of any medications (prescription drugs, over-the-counter drugs, Chinese herbal medicines, health products, moderate or strong CYP3A inhibitors or inducers, etc) within 14 days prior to the first administration；
• Those who have special dietary requirements (habitual consumption of grapefruit juice or excessive tea, coffee and/or caffeinated beverages) and are unable to withdraw during the trial；
• Drug abusers, smokers or alcoholics；
• Those with a history of fear of needles and hemophobia, difficulty in blood collection or inability to tolerate venipuncture blood collection;
• Donation of blood ≥ 400 mL or receipt of blood products within 3 months before enrollment;
• Receive any vaccine within 1 months before enrollment；
• Participation in any other investigational drug study within 3 months before enrollment；
• History of significant hypersensitivity to any drug compound or food；
• Other conditions that, in the opinion of the investigator, are not suitable for the subject to participate in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; All subjects in this cohort will receive the same dose of Ensartinib in both periods. Subjects will receive Ensartinib Alone in Period 1 followed by Ensartinib with Rifampicin in Period 2.	Drug: Ensartinib; 225 mg oral dose on day 1 in period 1 and on day 18 in period 2; Drug: Rifampicin; 600 mg QD from day 9 to day 22 in period 2; Drug: Ensartinib; 100 mg oral dose on day 1 in period 1 and on day 12 in period 2
Experimental: Cohort 2; All subjects in this cohort will receive the same dose of Ensartinib in both periods. Subjects will receive Ensartinib Alone in Period 1 followed by Ensartinib with Itraconazole in Period 2.	Drug: Ensartinib; 225 mg oral dose on day 1 in period 1 and on day 18 in period 2; Drug: Ensartinib; 100 mg oral dose on day 1 in period 1 and on day 12 in period 2; Drug: Itraconazole; 200 mg QD from day 9 to day 19 in period 2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma AUC0-t for Ensartinib Given Alone and With Rifampicin	AUC0-t is the plasma area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration (Clast).	Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose on Day 1 after Ensartinib 225 mg administration in Period 1, and at the same time points on Day 18 after Ensartinib 225 mg with rifampin administration in Period 2.
Plasma AUC0-t for Ensartinib Given Alone and With Itraconazole	AUC0-t is the plasma area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration (Clast).	Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post-dose on Day 1 after Ensartinib 100 mg administration in Period 1, and at the same time points on Day 12 after Ensartinib 100 mg with Itraconazole administration in Period 2.
Plasma AUC0-∞ for Ensartinib Given Alone and With Rifampicin	AUC0-∞ is the plasma area under the plasma concentration-time profile from time 0 extrapolated to infinite time.	Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose on Day 1 after Ensartinib 225 mg administration in Period 1, and at the same time points on Day 18 after Ensartinib 225 mg with rifampin administration in Period 2.
Plasma AUC0-∞ for Ensartinib Given Alone and With Itraconazole	AUC0-∞ is the plasma area under the plasma concentration-time profile from time 0 extrapolated to infinite time.	Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post-dose on Day 1 after Ensartinib 100 mg administration in Period 1, and at the same time points on Day 12 after Ensartinib 100 mg with Itraconazole administration in Period 2.
Plasma Cmax for Ensartinib Given Alone and With Rifampicin	Maximum plasma concentration	Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose on Day 1 after Ensartinib 225 mg administration in Period 1, and at the same time points on Day 18 after Ensartinib 225 mg with rifampin administration in Period 2.
Plasma Cmax for Ensartinib Given Alone and With Itraconazole	Maximum plasma concentration	Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post-dose on Day 1 after Ensartinib 100 mg administration in Period 1, and at the same time points on Day 12 after Ensartinib 100 mg with Itraconazole administration in Period 2.

Collaborators and Investigators

• Sponsor: Betta Pharmaceuticals Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2024
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: July 1, 2024
• First Submitted That Met QC Criteria: July 1, 2024
• First Posted (Actual): July 9, 2024

Study Record Updates

• Last Update Posted (Actual): July 9, 2024
• Last Update Submitted That Met QC Criteria: July 1, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Bacterial Agents; Protein Kinase Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Leprostatic Agents; Hormone Antagonists; Cytochrome P-450 Enzyme Inducers; Antifungal Agents; Steroid Synthesis Inhibitors; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; 14-alpha Demethylase Inhibitors; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Rifampin; Itraconazole; Ensartinib
• Other Study ID Numbers: BTP-42319

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No