A Study of AB-106 in Chinese Healthy Adult Men Evaluated the Effects of Itraconazole and Rifampicin on AB-106 PK

A Phase I, Single-center, Open-label, Fixed-sequence Study of AB-106 in Chinese Healthy Adult Men Evaluated the Effects of Itraconazole and Rifampicin on AB-106 Pharmacokinetics

AB-106-C110 is China-only study, for investigating the drug interaction between AB-106 and CYP3A4 inhibitor (Itraconazole)/CYP3A4 inducer (Rifampin)（n=56）

Study Overview

• Status: Completed
• Conditions: Solid Tumor
• Intervention / Treatment: Drug: AB-106, Itraconazole; Drug: AB-106, Rifampicin

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Xuanwu Hospital of Capital Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. The subject is willing to give written informed consent.
2. The subject is capable to communicate well with investigator and comply with comply with protocol throughout the study.
3. Aged between 18 to 55 at giving written informed consent.
4. Chinese male healthy subjects (No clinical abnormality by medical history query, physical examination, vital signs, 12 lead ECG and clinical laboratory test)
5. Body weight greater than 50.0 kg, and body mass index between 19 and 26 kg/m2, inclusive.
6. For fertile males, agree to use effective contraception methods during the study intervention period and for at least 90 days after the last dose of investigational drug, and agree not to donate sperm during this period.

Exclusion Criteria:

1. Any presence or history of clinically significant hematology, nephrology, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, mental, neurological, or allergic diseases (including drug allergy, but not including untreated, asymptomatic seasonal allergies when administered).
2. Any clinically significant laboratory abnormality (hematology, biochemistry [fasting], coagulation, thyroid function, urinalysis.)
3. systolic blood pressure (SBP) < 90 mmHg or ≥140 mmHg, diastolic blood pressure (DBP) < 50 mmHg or ≥ 90 mmHg, and clinically significant abnormality based on the judgment of investigators
4. Any presence or history of eye disease in whom the risk is increased by the participation to the study or treatment with investigational drug in the opinion of the investigator, such as glaucoma, retinal detachment, vitreous turbidity, and moths.
5. The 12-lead ECG showed QTcF > 450 milliseconds (msec) or QRS interval > 120 msec. If QTcF exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated 2 more times, and the average of 3 QTcF or QRS values should be used to determine subject's eligibility.
6. Fever within 5 days before the administration.
7. Active hepatitis B virus (HBV) surface antigen, hepatitis C virus antibody (HCV Ab), human immunodeficiency virus (HIV) or treponema pallidum (TP) antibody
8. Within 28 days prior to the first dose of study treatment, use of food or drugs that are known potent CYP3A4 inhibitors including (but not limited to) atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, aceto-eandomycin, voriconazole, grapefruit, grapefruit juice, grapefruit, citrus fruits or grapes Pomelo mixed species; or potent CYP3A4 inducers including (but not limited to) carbamazepine, phenobarbital, phenytoin, rifabutin, and rifampin and St. John's wort; or CYP3A4 substrates with narrow therapeutic window including (but not limited to)dihydroergotamine, ergotamine, pimozide, astemizole, cisapride, and terfenadine.
9. Chinese herbal medicine or tonic must be withdrawn at least 28 days prior to the first dose of study treatment; Any clinical study drug is prohibited within 3 months or 5 half-lives prior to the first dose of investigational drug; Any prescription/over-the-counter drug/dietary supplement is prohibited within 14 days or 5 half-lives prior to the first dose of investigational drug; as an exception, acetaminophen/paracetamol can be used at a dose of 1 g/day.
10. Vaccinated with live or attenuated vaccine within 28 days prior to the first dose of study treatment
11. Subject is unwilling to withdraw foods containing caffeine or purines (such as coffee, tea, cola, chocolate) from 48h before first dose to finishing the last PK sample collection.
12. Alcohol intake is greater than 14 units/week (1 unit of alcohol is equivalent to 360 mL of beer, or 150 mL of wine, or 45 mL of baijiu), or subject is unwilling to withdraw alcohol from 48h before first dose to finishing the last PK sample collection.
13. Smoking more than 5 cigarette per day, or subject is unwilling to withdraw nicotine from 48h before first dose to finishing the last PK sample collection.
14. Any drug abuse, or taking any soft drug (such as marijuana) or hard drugs (heroin, cocaine, etc.) from 1 year before and during the study period.
15. Any significant surgical history within 6 months prior to the first dose of study treatment.
16. Blood donation or blood loss ≥ 400 mL within 3 months or ≥ 200 mL within 1 month prior to the first dose of study treatment.
17. Presence of gastrointestinal, liver, kidney disease or other diseases or sequelae that are known to interfere with drug absorption, distribution, metabolism, or excretion. With a history of sensitivity to heparin or heparin-induced thrombocytopenia
18. Unwilling or incapable to follow the lifestyle standard described in the protocol.
19. Staff members of any institution affiliated with the clinical site and their immediate family members. Immediate family members refer to persons with blood or legal relationship, including spouses, children, parents, and siblings.
20. Ineligible to participate in the study based on the judgement of investigators

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Itraconazole cohort	Drug: AB-106, Itraconazole; single dose AB-106 at Day1, Itraconazole QD at Day14~Day28, single dose AB-106 at Day17
Experimental: Rifampicin cohort	Drug: AB-106, Rifampicin; single dose AB-106 at Day1, Itraconazole QD at Day14~Day32, single dose AB-106 at Day21

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AB-106 PK Exposure Parameters	Peak Plasma Concentration (Cmax)	29 days
AB-106 PK Exposure Parameters	Area under the plasma concentration versus time curve (AUC)	29 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AB-106 PK Parameters	Time to drug peak plasma concentration (Tmax)	29 days
AB-106 PK Parameters	Percentage of area under the curve from time of the last quantifiable concentration to infinity to area under the curve to infinity (AUC_extr%)	29 days
AB-106 PK Parameters	Lambda_z, first-order rate constant associated with the terminal portion of the curve (λz)	29 days
AB-106 PK Parameters	Terminal phase elimination half life (t1/2)	29 days
AB-106 PK Parameters	Apparent total clearance (CL/F)	29 days
AB-106 PK Parameters	Apparent volume of distribution (Vz/F)	29 days
Safety Assessment	Adverse events (AEs)	47 days

Collaborators and Investigators

• Sponsor: Nuvation Bio Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 19, 2021
• Primary Completion (Actual): December 3, 2021
• Study Completion (Actual): December 3, 2021

Study Registration Dates

• First Submitted: July 9, 2021
• First Submitted That Met QC Criteria: April 27, 2022
• First Posted (Actual): May 3, 2022

Study Record Updates

• Last Update Posted (Estimated): November 21, 2024
• Last Update Submitted That Met QC Criteria: November 19, 2024
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anti-Bacterial Agents; Anti-Infective Agents; Antifungal Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Enzyme Inhibitors; Nucleic Acid Synthesis Inhibitors; Steroid Synthesis Inhibitors; Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Antibiotics, Antitubercular; Antitubercular Agents; Cytochrome P-450 CYP3A Inhibitors; Leprostatic Agents; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Cytochrome P-450 CYP3A Inducers; 14-alpha Demethylase Inhibitors; Rifampin; Itraconazole
• Other Study ID Numbers: AB-106-C110

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No