A Study on the Effect of AB-106 on the Pharmacokinetics of Digoxin

Study Overview
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Brief Summary
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AB-106-C111 is China-only study, for investigating the drug interaction between AB-106 and P-gp substrate (Digoxin). （n=16）

Official Title
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A Phase I, Single-center, Open-label, Fixed-sequence Study in Chinese Healthy Male Adults to Evaluate the Effect of AB-106 on the Pharmacokinetics of Digoxin

Conditions
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Solid Tumor

Intervention / Treatment
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* Drug: AB-106, digoxin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chinese male healthy subjects (No clinical abnormality by medical history query, physical examination, vital signs, 12 lead ECG and clinical laboratory test) Aged between 18 to 55 at giving written informed consent. Body weight greater than 50.0 kg, and body mass index between 19 and 26 kg/m2, inclusive. The subject is willing to give written informed consent. The subject is capable to communicate well with investigator and comply with comply with protocol throughout the study. 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: Any presence or history of clinically significant hematology, nephrology, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, mental, neurological, or allergic diseases (including drug allergy). Any clinically significant laboratory abnormality (hematology, biochemistry [fasting], urinalysis.) 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 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. The 12-lead ECG showed QTcF > 450 milliseconds (msec) or QRS interval > 120 msec. Fever within 5 days before the administration. Active hepatitis B virus (HBV) surface antigen, hepatitis C virus antibody (HCV Ab), human immunodeficiency virus (HIV) or treponema pallidum (TP) antibody 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. Within 28 days prior to the first dose of study treatment, use of food or drugs that are known p-gp substrates including (but not limited to) amiodarone, carvedilol, clarithromycin, dronedarone, itraconazole, lapatinib, lopinavir and ritonavir, propafenone, quinidine, ranolazine, Tonavir, Saquinavir and Ritonavir, Trapevir, Telanavir and Ritonavir, Verapamil. 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. Vaccinated with live or attenuated vaccine within 28 days prior to the first dose of study treatment 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. 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. 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. Any significant surgical history within 6 months prior to the first dose of study treatment. Blood donation or blood loss ≥ 400 mL within 3 months or ≥ 200 mL within 1 month prior to the first dose of study treatment. 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 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. Unwilling or incapable to follow the lifestyle standard described in the protocol. 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. Ineligible to participate in the study based on the judgement of investigators.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: digoxin cohort<br> | Drug: AB-106, digoxin<br>* Period 1, single dose of 0.25mg digoxin; Period 2, Coadministrate AB-106 600mg and 0.25mg digoxin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The PK exposure parameters of digoxin | Area under the plasma concentration versus time curve (AUC) | 17 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The PK parameters of digoxin | Peak Plasma Concentration (Cmax) | 17 days | 
| The PK parameters of digoxin | Time to drug peak plasma concentration (Tmax) | 17 days | 
| The PK parameters of digoxin | Percentage of area under the curve from time of the last quantifiable concentration to infinity to area under the curve to infinity (AUC_extr%) | 17 days | 
| The PK parameters of digoxin | Lambda_z, first-order rate constant associated with the terminal portion of the curve (λz) | 17 days | 
| The PK parameters of digoxin | Terminal phase elimination half life (t1/2) | 17 days | 
| The PK parameters of digoxin | Apparent total clearance (CL/F), Vz/F | 17 days | 
| The PK parameters of digoxin | Apparent volume of distribution (Vz/F) | 17 days | 
| Safety assessment | Adverse events (AEs) | 35 days |