None listed
Conditions
Brief summary
HM30181 methanesulfonate monohydrate is a novel orally administered P-glycoprotein (P-gp) inhibitor that was discovered and originally developed by Hanmi Pharmaceutical Co., Ltd., Seoul, South Korea. The compound is in clinical development and is orally administered in combination with chemotherapeutic agents (paclitaxel, irinotecan) to enhance the oral bioavailability of these agents. Digoxin is a substrate of P-gp and influences intestinal absorption, renal tubular secretion and biliary-intestinal secretion. Therefore, drugs that inhibit P-gp have the potential to alter digoxin pharmacokinetics. HM30181A has low systemic bioavailability and is present in plasma at concentrations that are far below those calculated to inhibit systemic or renal P-gp. Thus, it is anticipated that any effect of HM30101A on the bioavailability of digoxin will be due to its effect on the gastrointestinal (GI) P-glycoprotein, and not upon renal clearance.
Interventions
Digoxin is a substrate of P-gp and influences intestinal absorption, renal tubular secretion and biliary-intestinal secretion. Therefore, drugs that inhibit P-gp have the potential to alter digoxin pharmacokinetics. The primary objective of this study is to determine the effect of multiple once-daily doses of HM30181A on the single-dose PK of digoxin.
Eligible participants will receive a single oral tablet dose of digoxin 0.25mg and will provide blood samples for analysis for 6 days post-dosing
Digoxin is a substrate of P-gp and influences intestinal absorption, renal tubular secretion and biliary-intestinal secretion. Therefore, drugs that inhibit P-gp have the potential to alter digoxin pharmacokinetics. The primary objective of this study is to determine the effect of multiple once-daily doses of HM30181A on the single-dose PK of digoxin. Eligible participants will receive a single oral tablet dose of digoxin 0.25mg and will provide blood samples for analysis for 6 days post-dosing (Treatment Period 1). After at least a 10 day washout, Treatment Period 2 will start. Participants will receive daily oral tablet doses of 15mg HM30181A for 3 days. One hour after the third dose (i.e. Day 3) they will receive another single oral tablet dose of digoxin 0.25mg. Blood samples will be collected for days 1-8, and at Day 17. Safety will be monitored regularly with laboratory tests, recording of AEs, ECGs and vital signs. Participants will be resident at the Zenith Clinical Site for dosing (all doses will be under the direct supervision of study site staff) and days when multiple blood samples are required.
Sponsors
Athenex Inc
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Males and females aged at least 18 years and up to 55 years on day of consent; Creatinine clearance >=80 mL/min; non-smoker; in good health; Body mass index (BMI) greater than or equal to 18.0 and <30.0 kg/m2 at Screening; willing to adhere to the alcohol and caffeine restrictions. Females must be postmenopausal or surgically sterile or must be using effective contraception for at least 4 weeks prior to dosing and agree to continue use of contraception for 30 days after their last dose.
Exclusion criteria
A history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases; an elevated prothrombin time (PT) or aPTT or platelet count below the lower limit of normal at Screening or Baseline; History of gastrointestinal bleeding, intracerebral bleeding or frequent nose-bleeds or active bleeding; prolonged QTc interval (QTc >450 ms), or PR interval >180ms or QRS interval >110ms on ECG at Screening; Heart rate <45bpm; Wolff-Parkinson-White syndrome; serum potassium or calcium concentration below the lower limit of normal; history of drug or alcohol abuse or dependence; taking any prescription drug or herbal medicine or supplement within 2 weeks or 5 half-lives prior to dosing, whichever is longer, or vitamin supplement within 1 week prior to dosing; clinically significant drug allergy.
Outcome results
None listed