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HMPL-453 Food Effect and PPI Study in Healthy Volunteer Study

Primary Purpose

Intrahepatic Cholangiocarcinoma

Status
Completed
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
HMPL-453
Rabeprazole
Sponsored by
Hutchmed
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Intrahepatic Cholangiocarcinoma

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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). The volunteer has been diagnosed with acquired immune deficiency syndrome or has performed tests that are positive for human immunodeficiency virus (HIV), Hepatitis B virus (HBV), or Hepatitis C virus (HCV). The volunteer has a clinically significant X-ray, 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. The volunteer has used CYP3A strong inducer or strong inhibitor, 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 has consumed alcohol, grapefruit, lime, and caffeine within 72 hours prior to the first dose. Taking drugs or dietary supplements (such as calcium, phosphorus, vitamin D, parathyroid hormone, etc.) that may cause blood phosphorus and/or blood calcium to rise within 2 weeks prior to the start of the study treatment. 18.Needle sickness, blood sickness or difficulty in collecting venous blood. 19.The volunteer is allergic to any of the study drugs (or its excipients) to be given in this study. 20.A female participant is pregnant, lactating, or breastfeeding. 21.Any other medical condition judged by the investigator would make the patients unsuitable to participate in this study.

Sites / Locations

  • Shanghai Xuhui Central Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

fast overnight

high-fat meal

low-fat meal

rabeprazole

Arm Description

Subjects in treatment A will administered HMPL-453 at fast overnight condition.

Subjects in treatment B will administered HMPL-453 at high-fat meal condition.

Subjects in treatment C will administered HMPL-453 at low-fat meal condition.

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.

Outcomes

Primary Outcome Measures

PK parameter for HMPL-453: AUC0-t
Area under the concentration time curve from time 0 to the last measurable concentration
PK parameter for HMPL-453: AUC0-inf
Area under the concentration time curve from time 0 extrapolated to infinity
PK parameter for HMPL-453: Cmax
Maximum observed plasma concentration

Secondary Outcome Measures

Assessment of safety procedures findings
Any untoward medical occurrence associated with the study drug
PK parameter for HMPL-453: tmax,t1/2
Time to reach the maximum observed plasma concentration, elimination half-life

Full Information

First Posted
May 22, 2023
Last Updated
August 31, 2023
Sponsor
Hutchmed
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1. Study Identification

Unique Protocol Identification Number
NCT05930119
Brief Title
HMPL-453 Food Effect and PPI Study in Healthy Volunteer Study
Official Title
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 Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
March 17, 2023 (Actual)
Primary Completion Date
August 28, 2023 (Actual)
Study Completion Date
August 28, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hutchmed

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Intrahepatic Cholangiocarcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Model Description
Open-label, 4-Period, Randomized 6-Sequence Study
Masking
None (Open Label)
Allocation
Randomized
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
fast overnight
Arm Type
Experimental
Arm Description
Subjects in treatment A will administered HMPL-453 at fast overnight condition.
Arm Title
high-fat meal
Arm Type
Experimental
Arm Description
Subjects in treatment B will administered HMPL-453 at high-fat meal condition.
Arm Title
low-fat meal
Arm Type
Experimental
Arm Description
Subjects in treatment C will administered HMPL-453 at low-fat meal condition.
Arm Title
rabeprazole
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
HMPL-453
Intervention Description
300 mg HMPL-453
Intervention Type
Drug
Intervention Name(s)
Rabeprazole
Intervention Description
20 mg of rabeprazole will be administered by mouth once daily.
Primary Outcome Measure Information:
Title
PK parameter for HMPL-453: AUC0-t
Description
Area under the concentration time curve from time 0 to the last measurable concentration
Time Frame
Day 1 to Day 33
Title
PK parameter for HMPL-453: AUC0-inf
Description
Area under the concentration time curve from time 0 extrapolated to infinity
Time Frame
Day 1 to Day 33
Title
PK parameter for HMPL-453: Cmax
Description
Maximum observed plasma concentration
Time Frame
Day 1 to Day 33
Secondary Outcome Measure Information:
Title
Assessment of safety procedures findings
Description
Any untoward medical occurrence associated with the study drug
Time Frame
Day 1 to Day 33
Title
PK parameter for HMPL-453: tmax,t1/2
Description
Time to reach the maximum observed plasma concentration, elimination half-life
Time Frame
Day 1 to Day 33

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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). The volunteer has been diagnosed with acquired immune deficiency syndrome or has performed tests that are positive for human immunodeficiency virus (HIV), Hepatitis B virus (HBV), or Hepatitis C virus (HCV). The volunteer has a clinically significant X-ray, 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. The volunteer has used CYP3A strong inducer or strong inhibitor, 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 has consumed alcohol, grapefruit, lime, and caffeine within 72 hours prior to the first dose. Taking drugs or dietary supplements (such as calcium, phosphorus, vitamin D, parathyroid hormone, etc.) that may cause blood phosphorus and/or blood calcium to rise within 2 weeks prior to the start of the study treatment. 18.Needle sickness, blood sickness or difficulty in collecting venous blood. 19.The volunteer is allergic to any of the study drugs (or its excipients) to be given in this study. 20.A female participant is pregnant, lactating, or breastfeeding. 21.Any other medical condition judged by the investigator would make the patients unsuitable to participate in this study.
Facility Information:
Facility Name
Shanghai Xuhui Central Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200031
Country
China

12. IPD Sharing Statement

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HMPL-453 Food Effect and PPI Study in Healthy Volunteer Study

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