A Clinical Trial to Evaluate the Effect of Itraconazole and Rifampicin on ABSK021

NCT06089733 | Completed Phase 1

• 1 other identifier: ABSK021-103
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a single center, open lable and fixed sequence test conducted in healthy subjects to evaluate the pharmacokinetic effects of Itraconazole and Rifampicin on a single dose of ABSK021 Oral administration. It is planned to enroll 32 healthy subjects and assign them to two parallel test groups, Part A (ABSK021 combined with Itraconazole) and Part B (ABSK021 combined with Rifampicin).

Conditions

Healthy Subjects

Outcome Measures

Primary Outcomes (4)

• Part A_(1)Pharmacokinetic Outcome Measures of ABSK021 after single oral administration of ABSK021 capsules and combination of itraconazole oral solution using Peak Plasma Concentration (Cmax)

  Collect plasma samples of ABSK021 and its metabolites (if data allows), as well as itraconazole and its metabolite hydroxyitraconazole, from all subjects before and after administration for PK evaluation. Plasma samples of ABSK021 and its metabolites (if data allows) are collected at C1 and C2, while plasma samples of itraconazole and its metabolite hydroxyitraconazole are collected at C2.

  Conduct testing within 1 month after all volunteers collect PK samples at all time points required by the protocol

• Part A_(2)Pharmacokinetic Outcome Measures of ABSK021 after single oral administration of ABSK021 capsules and combination of itraconazole oral solution using Area under the plasma concentration versus time curve (AUC)

  Collect plasma samples of ABSK021 and its metabolites (if data allows), as well as itraconazole and its metabolite hydroxyitraconazole, from all subjects before and after administration for PK evaluation. Plasma samples of ABSK021 and its metabolites (if data allows) are collected at C1 and C2, while plasma samples of itraconazole and its metabolite hydroxyitraconazole are collected at C2.

  Conduct testing within 1 month after all volunteers collect PK samples at all time points required by the protocol

• Part B_(1)Pharmacokinetic Outcome Measures of ABSK021 after single oral administration and in combination with Rifampicin using Peak Plasma Concentration (Cmax).

  Collect plasma samples of ABSK021 and its metabolites (if data allows) and rifampicin from all subjects before and after administration for PK evaluation. Plasma samples of ABSK021 and its metabolites (if data allows) are sampled at C1 and C2, while rifampicin plasma samples are sampled at C2.

  Conduct testing within 1 month after all volunteers collect PK samples at all time points required by the protocol

• Part B_(2)Pharmacokinetic Outcome Measures of ABSK021 after single oral administration and in combination with Rifampicin using Area under the plasma concentration versus time curve (AUC).

  Collect plasma samples of ABSK021 and its metabolites (if data allows) and rifampicin from all subjects before and after administration for PK evaluation. Plasma samples of ABSK021 and its metabolites (if data allows) are sampled at C1 and C2, while rifampicin plasma samples are sampled at C2.

  Conduct testing within 1 month after all volunteers collect PK samples at all time points required by the protocol

Study Arms (1)

ABSK201 and Itraconazole/Rifampicin

EXPERIMENTAL

Part A: Subjects will receive a single 10mg Oral administration of ABSK021 at C1D1, followed by a washout period of at least 14 days. The second cycle (C2): after the end of the first cycle, the subjects will receive 200 mg of C2D1-C2D24 Itraconazole oral liquid and a single 10 mg of ABSK021 Oral administration at C2D4. Part B: Subjects will receive a single dose of 50 mg of ABSK021 Oral administration once at C1D1, followed by a washout period of at least 14 days. Subjects will receive 600 mg of Rifampicin capsules once a day at C2D1-C2D15 and a single dose of ABSK021 Oral administration at C2D7, with the dose of 50 mg.

Drug: Part A ABSK201 and Itraconazole; Drug: Part A ABSK201 and Rifampicin

Interventions

Part A ABSK201 and Itraconazole DRUG

Subjects will receive a single 10mg Oral administration of ABSK021 at C1D1, followed by a washout period of at least 14 days. The second cycle (C2): after the end of the first cycle, the subjects will receive 200 mg of C2D1-C2D24 Itraconazole oral liquid and a single 10 mg of ABSK021 Oral administration at C2D4.

ABSK201 and Itraconazole/Rifampicin

Part A ABSK201 and Rifampicin DRUG

Subjects will receive a single dose of 50 mg of ABSK021 Oral administration once at C1D1, followed by a washout period of at least 14 days. Subjects will receive 600 mg of Rifampicin capsules once a day at C2D1-C2D15 and a single dose of ABSK021 Oral administration at C2D7, with the dose of 50 mg.

ABSK201 and Itraconazole/Rifampicin

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy subjects aged between 18 and 45 years old (including 18 and 45 years old) during screening, with no less than 6 single gender subjects in each group;
• Male weight ≥ 50 kg, female weight ≥ 45 kg, body mass index (BMI) between 19 and 28 (including 19 and 28), BMI=weight (kg)/height (m) \^2;
• Medical history, physical examination, clinical laboratory examination, and other relevant examinations before screening that have been determined by the researcher to be normal or abnormal without clinical significance;
• Male or female subjects with Fertility must agree to use an effective contraceptive method (see 5.4 for details) during the study period and within 6 months after the last dose of test drug administration, and male subjects will not donate sperm during this period; Female subjects must be non pregnant and non breast-feeding female subjects. Pregnancy is defined as women who are pregnant until the termination of pregnancy. It is determined by the laboratory hCG test within 7 days before the start of the study;
• Voluntarily participate in this clinical trial, understand the research procedure, and sign an informed consent form before screening; Good compliance and willingness to follow research procedures.

You may not qualify if:

• If there is a history of cardiovascular, respiratory, blood, liver, kidney, gastrointestinal, endocrine or Nervous system disease diseases, the absorption, metabolism or elimination of drugs are significantly affected, and the investigator judges that the use of experimental drugs may pose risks, interfere with the interpretation of data or affect the ability of subjects to participate in the study;
• Known or persistent mental disorders that may interfere with the participant's participation in the study, as determined by the researcher;
• Known to have a history of allergy to food, experimental drug ABSK021, Rifampicin, Itraconazole or other drugs;
• Those who have participated in drug clinical trials as subjects within the past 3 months;
• I have previously participated in this study or any other studies related to ABSK021 as a subject and have taken ABSK021.
• Those who have applied CYP3A4 strong inhibitor or inducer within 14 days before the first administration (including Grapefruit juice, Grapefruit hybrids, pomegranate, carambola, grapefruit, seville orange, juice or other processed products);
• There are factors that significantly affect the absorption, distribution, metabolism and excretion of drugs, such as inability to take test drugs orally, obvious nausea, vomiting and Malabsorption;
• Those who are unwilling to comply with the dietary requirements/restrictions during the study period, the specific dietary requirements are: (i) only consume the meals provided by the research center during hospitalization, (ii) avoid consuming CYP3A4 strong inhibitors or inducers during the study period;
• Within the first 3 months of screening, those who consume more than 14 units of alcohol per week (1 unit of alcohol is approximately 360mL of beer or 45mL of 40% alcohol or 150mL of wine), or who are positive for alcohol screening, or are unwilling to comply with the alcohol restrictions specified in section 5.3.3;
• Smoking at least 5 cigarettes per day (or corresponding amounts of tobacco or nicotine products) within the first 3 months of screening; Or those who are unwilling to comply with the smoking restrictions specified in Section 5.3.3;
• The researcher judged that there were people who had excessive intake of methyl Xanthine/caffeine in the past 6 months (excessive intake is defined as more than 6 units of caffeine per day, and 1 unit of caffeine is equivalent to 177 milliliters of coffee, 355 milliliters of tea, 355 milliliters of cola, or 85 grams of chocolate), or were unwilling to comply with the restrictions on the use of methyl Xanthine/caffeine in 5.3.3 during the study period;
• People with positive serum hepatitis B B surface antigen (HBsAg), hepatitis B B e antigen (HBeAg), hepatitis B B e antibody (HBeAb), hepatitis B core antibody (HBcAb), hepatitis C virus (HCV) antibody, HIV (HIV) antibody screening;
• Those with a history of bacterial, fungal, parasitic, viral (excluding nasopharyngitis, COVID-19), mycobacterial infection, or clinically significant abnormal chest X-ray results within 45 days before the first administration (determined by the investigator);

Sponsors & Collaborators

• Abbisko Therapeutics Co, Ltd: lead

Study Sites (1)

Huashan Hospital Fudan University

Shanghai, Shanghai Municipality, 201203, China

Location

MeSH Terms

Interventions

Itraconazole; Rifampin

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Jing Zhang, Professor

  Huashan Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: On Day 1, subjects will receive a single oral dose of approximately 50 mg ABSK021 containing approximately 100 μCi of \[14C\] ABSK021 in the fasted state.

Study Record Dates

• First Submitted: June 13, 2023
• First Posted: October 18, 2023
• Study Start: April 11, 2023
• Primary Completion: August 30, 2023
• Study Completion: September 1, 2023
• Last Updated: August 12, 2024

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)