A Phase 1, Open-label, 4-period, Randomized 6-sequence Study to Evaluate the Effect of Food and Rabeprazole, a Proton Pump Inhibitor, on the Pharmacokinetics of HMPL-453 in Healthy Volunteers
Overview
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Hutchmed
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- PK parameter for HMPL-453: AUC0-t
Overview
Brief Summary
A Phase 1, Open-label, 4-Period, Randomized 6-Sequence Study to Evaluate the Effect of Food and Rabeprazole, a Proton Pump Inhibitor, on the Pharmacokinetics of HMPL-453 in Healthy Volunteers
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Have fully understood the study and voluntarily signed the informed consent form;
- •The volunteer is male or female between the ages of 18 and 55 years old (inclusive) at the time of informed consent.
- •The volunteer has a body mass index (BMI)\>18 and ≤29.9 kg/m2at screening. Male need≥50 kg，famele need≥45 kg.
- •Female with fertility agree to adopt efficient contraceptive measures within 6 months after signing ICF until the end of the last HMPL-453 dosing, and agree not to donate eggs (or oocytes) for reproductive purposes during this period. Acceptable and efficient contraceptive methods include complete abstinence, bilateral tubal ligation, oral or injection contraceptives, intrauterine devices, or partner vas deferens ligation. All hormonal contraception measures must be combined with barrier measures such as the use of condoms by spouses. More information can be found in Attachment 12.3 \[Definition of Women with Fertility (WOCBP) and Acceptable and Unacceptable Contraceptive Methods\].
- •Male patients is willing to take contraception measures (during the study and for 3 months after the end of study treatment). Male patients should avoid donating or freezing sperm during this period.
- •The volunteer is willing and able to comply with all aspects of the protocol.
Exclusion Criteria
- •The volunteer has a known history of any gastrointestinal surgery or any condition possibly affecting drug absorption (eg, cholecystectomy, gastrectomy, achlorhydria, peptic ulcer disease, or history of stomach or intestinal surgery or resection).
- •The volunteer had a clinically significant illness within 8 weeks or a clinically significant infection within 4 weeks prior to the first dose.
- •The volunteer has evidence of a clinically significant deviation from normal in the physical examination, vital signs, or clinical laboratory determinations at screening or at Day -1 check-in (baseline).
- •The volunteer has systolic blood pressure \>140 mmHg diastolic blood pressure \>90mmHg.
- •Currently keratopathy confirmed by ophthalmological examination, including but not limited to bullae keratopathy, zonal corneal degenerations, corneal abrasion, corneal ulcer, and sclerokeratitis.
- •Current or prior history of retinal detachment.
- •The volunteer has a clinically significant ECG abnormality, including a marked baseline prolongation of QT/QTc interval (eg, repeated demonstration of a QTcF interval \>480msec), or hasa family history of prolonged QTc syndrome or sudden death.
- •Volunteers who smoke more than 10 cigarettes per day within the first 3 months of screening and are unable to completely quit smoking during the study period.
- •Volunteers who frequently drink alcohol within the first 6 months before screening, drink more than 14 units of alcohol per week。
- •The volunteer has a history of drug misuse within 6 months prior to screening (including those who have tested positive for morphine, methylenedioxymethamphetamine, methamphetamine, tetrahydrocannabinol acid, ketamine, cocaine, or a positive urine drug test at screening or at check-in).
Arms & Interventions
low-fat meal
Subjects in treatment C will administered HMPL-453 at low-fat meal condition.
Intervention: HMPL-453 (Drug)
fast overnight
Subjects in treatment A will administered HMPL-453 at fast overnight condition.
Intervention: HMPL-453 (Drug)
high-fat meal
Subjects in treatment B will administered HMPL-453 at high-fat meal condition.
Intervention: HMPL-453 (Drug)
rabeprazole
Subjects in treatment D will administered rabeprazole combined with HMPL-453 at low-fat meal condition hour prior to receiving a standardized low-fat meal.
Intervention: HMPL-453 (Drug)
rabeprazole
Subjects in treatment D will administered rabeprazole combined with HMPL-453 at low-fat meal condition hour prior to receiving a standardized low-fat meal.
Intervention: Rabeprazole (Drug)
Outcomes
Primary Outcomes
PK parameter for HMPL-453: AUC0-t
Time Frame: Day 1 to Day 33
Area under the concentration time curve from time 0 to the last measurable concentration
PK parameter for HMPL-453: AUC0-inf
Time Frame: Day 1 to Day 33
Area under the concentration time curve from time 0 extrapolated to infinity
PK parameter for HMPL-453: Cmax
Time Frame: Day 1 to Day 33
Maximum observed plasma concentration
Secondary Outcomes
- Assessment of safety procedures findings(Day 1 to Day 33)
- PK parameter for HMPL-453: tmax,t1/2(Day 1 to Day 33)