A Food Effect Study of SHR1459 on Healthy Chinese Adult Subjects

A Randomized, Open, Single-center, Two-cycle, Double-sequence Crossover Study to Investigate the Effects of a High-fat Diet on the Pharmacokinetics of Healthy Chinese Adult Subjects After Oral Administration of SHR1459 Tablets

The primary objective of the study is to evaluate the effect of high-fat diet on pharmacokinetics of healthy Chinese adult subjects after oral administration of SHR1459 tablets.

The secondary objective of the study is to evaluate the safety of single dose of SHR1459 orally in healthy subjects.

Study Overview

• Status: Completed
• Conditions: Healthy Adult Subjects
• Intervention / Treatment: Drug: SHR1459 fasted in P1, high-fat diet in P2; Drug: SHR1459 high-fat diet in P1, fasted in P2

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical College

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy male or female subjects aged 18 or above (including 18 years old) at the date of signing the informed consent;
2. Male body weight ≥ 50kg, female body weight ≥ 45kg, body mass index (BMI) within the range of 19 ~ 28kg /m2 (including 19 and 28) (BMI= weight (kg)/height 2 (m2));
3. During screening period physical examination, vital signs, blood routine, urine routine, blood biochemistry, coagulation, abdominal ultrasound, chest X-ray and other examination results must be within the normal range consistent with age and gender, or in accordance with the protocol, or judged to be "no clinical significance (NCS)" if beyond the normal range;
4. The 12-lead ECG should be normal, with male QTcF < 430ms and female QTcF < 450ms; QTc interval is corrected by Fridericia formula (QTcF = QT/(RR^0.33), RR is the standardized heart rate value, calculated by dividing heart rate by 60);
5. Negative pregnancy test for women of child-bearing age;
6. Agree to abstain from sex or use effective non-drug contraceptives from screening to at least 3 months after the last study drug administration (female subjects are also required to abstain or use effective non-drug contraceptives two weeks prior to study entry);
7. The subject can communicate well with the researcher, understand and comply with the requirements of the study, understand and sign the informed consent.

Exclusion Criteria:

1. Allergic constitution or known allergy to the research drug/similar drugs;
2. Frequent use of sedatives, sleeping pills or other addictive drugs; History of drug abuse within 12 months prior to first administration or drug abuse screening positive;
3. Alcoholic or often drinkers within 6 months prior to screening, the average drinking amount is more than 14 units a week (1 unit= 360 ml beer or 45 ml alcohol content of 40% spirits or 150 ml wine), a heavy smoker or quitting time less than 3 months, alcohol breath test positive and nicotine test positive, and can't quit smoking and alcohol during the study;
4. Use any prescription drug or herbal tonic within one month before the first dose; Use any over-the-counter (OTC) or food supplement (including vitamins, calcium tablets, etc.) within 2 weeks before the first dose; Use of birth control pills within two weeks prior to first administration;
5. Those who have participated in other clinical trials and taken the research drugs within 3 months before the first drug administration;
6. Blood donation within 3 months before the first drug administration (including component blood donation) or blood loss greater than 400 mL, blood donation within 1 month before screening (including component blood donation) or blood loss greater than 200 mL, or receiving blood transfusion；
7. A history of autonomic dysfunction and/or a history of present illness (e.g., recurrent episodes of syncope, palpitations, etc.) within 3 years prior to first administration;
8. Previous medical history of cardiovascular, liver, kidney, lung, digestive tract, nervous system diseases, etc., which may significantly affect the absorption, distribution, metabolism and excretion of drugs, or may pose a hazard to the subjects participating in the study. The following medical history or conditions should be considered: inflammatory gastroenteritis, gastroesophageal reflux, gastrointestinal or rectal bleeding; History of pancreatic injury or pancreatitis; Greater surgical history such as gastrectomy, gastroenterostomy, or enterectomy; History of acute and chronic renal insufficiency, history of renal transplantation;
9. A history of severe vomiting and diarrhea in the previous week;
10. Female subjects during pregnancy and lactation, and female subjects of child-bearing age who cannot use contraception as required;
11. Hepatitis B surface antigen positive, hepatitis C2 antibody positive, syphilis antibody positive, HIV antibody positive;
12. Those who have special dietary requirements and cannot comply with the diet provided and the corresponding regulations;
13. Subjects refused to stop using any beverage or food containing methyl xanthine, such as coffee, tea, cola, chocolate, etc. from 48 hours before the first administration until the end of the study;
14. Subjects refused to stop using any drink or food containing grapefruit 7 days before the first dose until the end of the study;
15. Difficulty in venous blood collection or inability to tolerate venipuncture;
16. Other factors (including but not limited to inability to understand the requirements of the study, poor compliance, physical weakness, etc.) that are not suitable for participating in the study, as judged by the researcher.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A	Drug: SHR1459 fasted in P1, high-fat diet in P2; SHR1459 administration in fasted condition in period 1, SHR1459 administration after high-fat diet in period 2
Experimental: B	Drug: SHR1459 high-fat diet in P1, fasted in P2; SHR1459 administration after high-fat diet in period 1, SHR1459 administration in fasted condition in period 2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics parameter: Cmax of SHR1459	Peak Plasma Concentration (Cmax) of SHR1459	through study completion, an average of 23 days
Pharmacokinetics parameter: AUC of SHR1459	Area under the plasma concentration versus time curve (AUC) of SHR1459	through study completion, an average of 23 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics parameter: Tmax of SHR1459	Time of maximum observed concentration (Tmax) of SHR1459	through study completion, an average of 23 days
Pharmacokinetics parameter: T1/2 of SHR1459	Half time (T1/2) of SHR1459	through study completion, an average of 23 days
Pharmacokinetics parameter: CL/F of SHR1459	Total body clearance for extravascular administration (CL/F) of SHR1459	through study completion, an average of 23 days
Pharmacokinetics parameter: Vz/F of SHR1459	Volume of distribution (Vz/F) of SHR1459	through study completion, an average of 23 days
Number of patients with Adverse Events (AEs)	To assess the adverse events according to CTCAE5.0	through study completion, an average of 23 days
Vital sign (Blood pressure [BP])	To assess the vital signs as a criteria of safety and tolerability variables.	through study completion, an average of 23 days
Vital sign (pulse)	To assess the vital signs as a criteria of safety and tolerability variables.	through study completion, an average of 23 days
Vital sign (temperature)	To assess the vital signs as a criteria of safety and tolerability variables.	through study completion, an average of 23 days
Resting and digital electrocardiograms (ECGs)	To assess the cardiovascular system functioning as a criteria of safety and tolerability variables.	through study completion, an average of 23 days
Physical examination	To assess the physical conditions as a criteria of safety and tolerability variables.	through study completion, an average of 23 days
Laboratory assessments	To assess the hematology, clinical chemistry and urinalysis as a criteria of safety and tolerability variables.	through study completion, an average of 23 days

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.
• Investigators: Principal Investigator: Juan Li, M.D., Ph.D., The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2020
• Primary Completion (Actual): June 3, 2020
• Study Completion (Actual): June 29, 2020

Study Registration Dates

• First Submitted: February 25, 2020
• First Submitted That Met QC Criteria: February 27, 2020
• First Posted (Actual): March 2, 2020

Study Record Updates

• Last Update Posted (Actual): July 27, 2020
• Last Update Submitted That Met QC Criteria: July 23, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Other Study ID Numbers: SHR1459-I-103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No