A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of Oral HRS5091 in Healthy Subjects and Chronic Hepatitis B Patients

NCT04480294 | Unknown Phase 1

• 1 other identifier: HRS5091-101
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

Brief Summary

The study is a randomized, Double-Blind, Placebo-Controlled study to evaluate the safety, tolerability and pharmacokinetics, pharmacodynamics and food effect of HRS5091. The study will be conducted in three parts sequentially: Part 1a will consist of 58 healthy subjects, 5 groups. The purpose of this part is to explore the safety, tolerability and pharmacokinetics of single doses of HRS5091 tablet in healthy subjects. Part 1b will consist of 18 healthy subjects and it is one of groups in Part 1a.The purpose of this part is to explore food effect of HRS5091 in healthy subjects. Part 1c will consist of 10 healthy subjects, 1 groups. The purpose of this part is to explore the safety, tolerability and pharmacokinetics of multiple doses of HRS5091 tablet in healthy subjects. Part 2 will consist of 30 CHB patients.The purpose of this part is to explore the safety, tolerability and pharmacokinetics, pharmacodynamics of multiple doses of HRS5091 tablet in naïve and treatment-discontinued chronic hepatitis B (CHB) patients.

Conditions

Chronic Hepatitis B

Outcome Measures

Primary Outcomes (8)

• The incidence and severity of treatment-related

  adverse events as assessed by CTCAE v5.0

  29 DAYS for Group 1.2.4.5; 58 DAYS for Group 3; 42 DAYS for Group 6；56 DAYS for Group 7-9；

• Maximum Plasma Concentration [Cmax]

  Pharmacokinetic parameters of HRS5091, main metabolite and identified major metabolites in plasma

  0-672 hours after each dose for Group 1-9

• Area under the concentration time curve [AUC]

  Pharmacokinetic parameters of HRS5091, main metabolite and identified major metabolites in plasma

  0-672 hours after each dose for Group 1-9

• Time to maximum plasma concentration [Tmax]

  Pharmacokinetic parameters of HRS5091, main metabolite and identified major metabolites in plasma

  0-672 hours after each dose for Group 1-9

• Apparent clearance [CL/F]

  Pharmacokinetic parameters of HRS5091, main metabolite and identified major metabolites in plasma

  0-672 hours after each dose for Group 1-9

• Half-time [t1/2]

  Pharmacokinetic parameters of HRS5091, main metabolite and identified major metabolites in plasma

  0-672 hours after each dose for Group 1-9

• Apparent volume of distribution [Vz/F(Vd)]

  Pharmacokinetic parameters of HRS5091, main metabolite and identified major metabolites in plasma

  0-672 hours after each dose for Group 1-9

• Mean retention time [MRT]

  Pharmacokinetic parameters of HRS5091, main metabolite and identified major metabolites in plasma

  0-672 hours after each dose for Group 1-9

Study Arms (10)

Part 1a Treatment group 1

EXPERIMENTAL

Intervention: Drug1: HRS5091, dose 1; Drug2: Placebo Healthy subjects

Drug: HRS5091

Part 1a Treatment group 2

EXPERIMENTAL

Intervention: Drug1: HRS5091, dose 2; Drug2: Placebo Healthy subjects

Drug: HRS5091

Part 1a Treatment group 3

EXPERIMENTAL

Intervention: Drug1: HRS5091, dose 3; Drug2: Placebo Healthy subjects

Drug: HRS5091

Part 1a Treatment group 4

EXPERIMENTAL

Intervention: Drug1: HRS5091, dose 4; Drug2: Placebo Healthy subjects

Drug: HRS5091

Part 1a Treatment group 5

EXPERIMENTAL

Intervention: Drug1: HRS5091, dose 5; Drug2: Placebo Healthy subjects

Drug: HRS5091

Part 1b Treatment group 3

EXPERIMENTAL

Intervention: Drug1: HRS5091, dose 3; Drug2: Placebo Healthy subjects Food effect

Drug: HRS5091

Part 1c Treatment group 6

EXPERIMENTAL

Intervention: Drug1: HRS5091, dose 3; Drug2: Placebo Healthy subjects

Drug: HRS5091

Part 2 Treatment group 7

EXPERIMENTAL

Intervention: Drug1: HRS5091, dose 3; Drug2: Placebo CHB subjects

Drug: HRS5091

Part 2 Treatment group 8

EXPERIMENTAL

Intervention: Drug1: HRS5091, dose 4; Drug2: Placebo CHB subjects

Drug: HRS5091

Part 2 Treatment group 9

EXPERIMENTAL

Intervention: Drug1: HRS5091, dose 5; Drug2: Placebo CHB subjects

Drug: HRS5091

Interventions

HRS5091 DRUG

Single dose in group 1-5 Multiple doses in group 6-9

Also known as: Placebo

Part 1a Treatment group 1; Part 1a Treatment group 2; Part 1a Treatment group 3; Part 1a Treatment group 4; Part 1a Treatment group 5; Part 1b Treatment group 3; Part 1c Treatment group 6; Part 2 Treatment group 7; Part 2 Treatment group 8; Part 2 Treatment group 9

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy subjects
• Signed informed consent.
• Aged 18\~55.
• Body weight ≥ 50 kg for male; ≥ 45 kg for female, body mass index (BMI) between 18 to 28 kg/m².
• Vital signs, physical examination, laboratory results are within normal range or considered not clinically significant.
• Female subjects (including partner) of childbearing potential must be using a medically acceptable form of birth control.
• CHB subjects
• Signed informed consent.
• Aged 18\~65.
• CHB subjects should meet one of the following two criteria:
• IgM(immunoglobulin M) HBcAb negative and HBsAg positive.
• Two recorded HBsAg positive, and the time interval between the two tests was at least 6 months, one of which was the result of this screening
• CHB subjects should also meet the following criteria:
• No treatment with nucleosides analogues or discontinued treatment with nucleosides analogues least 6 months at screening
• Have not received interferon therapy or discontinued treatment with interferon analogues least 3 months at screening

You may not qualify if:

• Healthy subjects
• Currently suffering from cardiovascular, liver, kidney, digestive, nervous, blood, thyroid or mental diseases.
• Have a digestive system disease or a medical history of severe digestive system disease at present or in the past month.
• Have severe infection, severe trauma or major surgical operations within 3 months. Plan to receive surgery during the trial and within two weeks after the end of the trial.
• ECG test have clinical significant abnormality or the QT interval (QTc) \> 470 ms(male)/QTc)\> 480 ms(male) or\<300ms(female).
• Have a medical history of immune-mediated diseases.
• Screening for infectious diseases is positive,Including HBsAg, Anti-HCV(hepatitis C virus), TPPA(Treponema pallidum particle agglutination assay), Anti-HIV.Treponema pallidum antibody screen positive, at the investigator's discretion in conjunction with RPR(rapid plasma reagin assay) results.
• Suspected allergy to any ingredient in the study drug.
• Have any drug that inhibits or induces liver metabolism within 1 month.
• Take any prescription drugs, over-the-counter drugs and Chinese herbal medicines within 14 days before taking the study drug, or plan to take other drugs during the test period.
• Participated in clinical trials of any drug or medical device within 3 months before screening.
• Had donated blood/blood transfusion≥ 200 mL within 1 months prior to screening or donated blood or blood transfusion≥ 450 mL within 3 months prior to screening.
• The average daily smoking ≥ 5 cigarettes within three months; the average daily alcohol intake in a month exceeds 15 g (15 g alcohol is equivalent to 450 mL beer or 150 mL wine or 50 mL low-alcohol);
• Keep smoking, drinking alcohol or consuming caffeinated foods or beverages (more than 8 cups, 1 cup = 250 mL) 2 days before taking the study drug and during the study; and those who have special dietary requirements and cannot follow the unified diet;
• Pregnant or lactating women;

Sponsors & Collaborators

• Jiangsu HengRui Medicine Co., Ltd.: lead

Study Sites (1)

Shanghai Changhai Hospital

Shanghai, Shanghai Municipality, 200433, China

Location

MeSH Terms

Conditions

Hepatitis B, Chronic

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2020
• First Posted: July 21, 2020
• Study Start: July 28, 2020
• Primary Completion: November 23, 2021
• Study Completion: November 23, 2021
• Last Updated: October 22, 2021

Record last verified: 2021-10

Locations

CN (1)