HMPL-523 Food Effect and Proton Pump Inhibitor Study

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Relapsed or Refractory Lymphoma

Intervention / Treatment
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* Drug: HMPL-523
* Drug: Rabeprazole


Participation Criteria
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Eligibility Criteria
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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. The volunteer has consumed herbal preparations/medications, including, but not limited to, St. John's Wort, kava, ephedra (ma huang), Ginkgo biloba, dehydroepiandrosterone, yohimbe, saw palmetto, and ginseng, within 7 days prior to the first dose (21days for St.John's Wort). The volunteer has experienced a weight loss or gain of >10% within 4 weeks prior to the first dose as noted by medical history and weight at screening and check-in. The volunteer has received blood or blood products within 4 weeks, donated blood or blood products within 8 weeks prior to the first dose or donated double red cell within 16weeks prior to first dose. The volunteer has used any over-the-counter (OTC) medications or prescription drugs (medications that can lower gastric acid in particular) within 2 weeks prior to the first dose. The volunteer is allergic to any of the study drugs (or its excipients) to be given in this study. A female participant is pregnant, lactating, or breastfeeding. A male volunteer who plans to donate sperm or father a child within 30 days after receiving the study drug. The volunteer has any condition that would make him or her, in the opinion of the PIor Sponsor, unsuitable for the study, or who, in the opinion of the PI, is not likely to complete the study for any reason.Note: One repeat of laboratory assessments, including vital signs and ECG,may be performed at screening and at -check-in(Day-1) at the discretion of the PI.

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

Sexes Eligible for Study
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All

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: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Open-label, 4-Period, Randomized 6-Sequence Study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A<br>Subjects in treatment A will fast overnight for at least 10 hours prior to HMPL-523 dosing. | Drug: HMPL-523<br>* 700 mg HMPL-523 will be administered by mouth once daily on Day 1, Day 8, Day 15, and Day 26<br>|
| Experimental: Treatment B<br>Subjects in treatment B will receive a standardized high-fat meal approximately 30 minutes before HMPL-523 administration | Drug: HMPL-523<br>* 700 mg HMPL-523 will be administered by mouth once daily on Day 1, Day 8, Day 15, and Day 26<br>|
| Experimental: Treatment C<br>Subjects in treatment C will receive a standardized low-fat meal approximately 30 minutes before HMPL-523 administration | Drug: HMPL-523<br>* 700 mg HMPL-523 will be administered by mouth once daily on Day 1, Day 8, Day 15, and Day 26<br>|
| Experimental: Treatment D<br>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 | Drug: HMPL-523<br>* 700 mg HMPL-523 will be administered by mouth once daily on Day 1, Day 8, Day 15, and Day 26<br>Drug: Rabeprazole<br>* 40 mg of rabeprazole will be administered by mouth once daily in the morning from Day 20 to Day 26<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK parameter for HMPL-523: AUC0-t | Area under the concentration time curve from time 0 to the last measurable concentration | Day 1 to Day 31 | 
| PK parameter for HMPL-523: AUC0-inf | Area under the concentration time curve from time 0 extrapolated to infinity | Day 1 to Day 31 | 
| PK parameter for HMPL-523: Cmax | Maximum observed plasma concentration | Day 1 to Day 31 | 
| PK parameter for HMPL-523: tmax | Time to reach the maximum observed plasma concentration | Day 1 to Day 31 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of safety procedures findings | Any untoward medical occurrence associated with the study drug | Day 1 to Day 31 | 
| PK parameter for metabolite M1: AUC0-t | Area under the concentration time curve from time 0 to the last measurable concentration | Day 1 to Day 31 | 
| PK parameter for metabolite M1: AUC0-inf | Area under the concentration time curve from time 0 extrapolated to infinity | Day 1 to Day 31 | 
| PK parameter for metabolite M1: Cmax | Maximum observed plasma concentration | Day 1 to Day 31 |