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-523 in Healthy Volunteers
Overview
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Hutchmed
- Enrollment
- 26
- Locations
- 1
- Primary Endpoint
- PK parameter for HMPL-523: AUC0-inf
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-523 in Healthy Volunteers
Detailed Description
This study will be a single-center, open-label, 4-period, randomized,6-sequence study conducted with 24 healthy male or female subjects. The study will consist of a Screening Phase (Screening and Day -1), a Treatment Phase (Periods1, 2, 3,and 4), and an End of Study (EOS) Phase. Screening must occur within 28 days before the first study drug administration. There will be a washout of at least 7days between 4 administrations of HMPL-523.Subjects in Periods 1, 2, and 3 will be randomized into 1 of 6 treatment sequences, with all subjects then receiving the same treatment in Period 4.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Other
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •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.
- •Females must be postmenopausal (defined as absence of menses for at least 1year without alternative medical cause)or permanently sterile by total hysterectomy, bilateral oophorectomy, or bilateral salpingectomy.
- •Males, including those who have had a successful vasectomy, must use a condom during sexual intercourse with women of childbearing potential, starting from their first dose of study drug through 30 days after their last dose of study drug. Alternatively, abstinence is allowed if it is the normal and preferred lifestyle of the volunteer.
- •The volunteer must provide written informed consent prior to any study specific screening procedures.
- •The volunteer is willing and able to comply with all aspects of the protocol, as determined by the PI.
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). Note: Appendectomy and hernia repairs are allowed.
- •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 oradiastolic blood pressure \>90mmHg.
- •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.
- •The volunteer has a history of smoking or use of nicotine-containing substances within the previous 2 months, as determined by medical history or volunteer's verbal report and confirmed by cotinine test at check-in.
- •The volunteer has a history of drug or alcohol misuse within 6 months prior to screening or a positive urine drug test at screening or at check-in.
- •The volunteer has been diagnosed with acquired immune deficiency syndrome or has performed tests that are positive for human immunodeficiency virus (HIV), HepatitisBvirus (HBV), orHepatitis C virus (HCV).
- •The volunteer has participated in a clinical trial of other study drug before screening, and the time since the last use of other study drug is less than 5 times the half-life or 4 weeks, whichever is longer, or the volunteer is currently enrolled in another clinical trial.1
- •The volunteer has consumed grapefruit, starfruit, Seville oranges, or their products within 7 days prior to the first dose.
Arms & Interventions
Treatment A
Subjects in treatment A will fast overnight for at least 10 hours prior to HMPL-523 dosing.
Intervention: HMPL-523 (Drug)
Treatment B
Subjects in treatment B will receive a standardized high-fat meal approximately 30 minutes before HMPL-523 administration
Intervention: HMPL-523 (Drug)
Treatment C
Subjects in treatment C will receive a standardized low-fat meal approximately 30 minutes before HMPL-523 administration
Intervention: HMPL-523 (Drug)
Treatment D
Subjects in treatment D will receive rabeprazol 1 hour prior to receiving a standardized low-fat meal. On Day 26 subjects will also receive HMPL-523 approximately 30 minutes after the standardized low-fat breakfast
Intervention: HMPL-523 (Drug)
Treatment D
Subjects in treatment D will receive rabeprazol 1 hour prior to receiving a standardized low-fat meal. On Day 26 subjects will also receive HMPL-523 approximately 30 minutes after the standardized low-fat breakfast
Intervention: Rabeprazole (Drug)
Outcomes
Primary Outcomes
PK parameter for HMPL-523: AUC0-inf
Time Frame: Day 1 to Day 31
Area under the concentration time curve from time 0 extrapolated to infinity
PK parameter for HMPL-523: AUC0-t
Time Frame: Day 1 to Day 31
Area under the concentration time curve from time 0 to the last measurable concentration
PK parameter for HMPL-523: tmax
Time Frame: Day 1 to Day 31
Time to reach the maximum observed plasma concentration
PK parameter for HMPL-523: Cmax
Time Frame: Day 1 to Day 31
Maximum observed plasma concentration
Secondary Outcomes
- PK parameter for metabolite M1: AUC0-t(Day 1 to Day 31)
- PK parameter for metabolite M1: AUC0-inf(Day 1 to Day 31)
- Assessment of safety procedures findings(Day 1 to Day 31)
- PK parameter for metabolite M1: Cmax(Day 1 to Day 31)