Study of the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Characteristics of PA1010 in HBV Patients

• Status: Recruiting
• Trial end date: 2022-03-01
• Target enrollment: 0
• Participant gender: All

Summary

The primary objective of this study is to evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic characteristics of multiple ascending dose (MAD) of PA1010 tablets in Chinese adults with Chronic Hepatitis B.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Zhejiang Palo Alto Pharmaceuticals, Inc.

Criteria

Inclusion Criteria:

1. Must sign the informed consent form to indicate willingness to participate in the study;

2. Male or female, aged from 18 to 65 years (including upper and lower limits);

3. Without treatments with nucleoside or nucleoside analogues within 6 months prior to the first dose, or treatments with nucleoside or nucleoside analogues or interferon but discontinued for more than 6 months;

4. HBV DNA > 2 × 105 IU/mL for HBeAg-positive patients; HBV DNA > 2 × 104 IU/mL for HBeAg-negative patients; 5.1.2 × upper limit of normal (ULN) ≤ alanine aminotransferase (ALT) ≤ 10 × ULN; Serum total bilirubin ≤ 2 × ULN; Creatinine clearance (CLCr) > 70 mL/min (using the Cockcroft-Gault method);

6.Urine protein negative or 1 + (if 1 +, 24-h urine protein quantification is required, and if it is within the normal range, it can be enrolled); 7.No history of major diseases, and the physical examination, vital signs, 12-lead electrocardiogram (ECG) and laboratory test results are normal during the screening period, or outside of normal reference range, but not clinically significant judged by the investigator; 8.Subjects are prohibited from donating blood or using drugs during the study until 30 days after the last dose; 9.Donation of sperm and eggs is prohibited during the study (from signing the informed consent form to the last follow-up visit) and for 6 months after the last dose, and there is no possibility of conception (or conception of a sexual partner), childbearing or breastfeeding, i.e., at least one of the following:

1. Women who have been menopausal for > 12 months or who have undergone sterilization (Such as hysterectomy, bilateral tubal ligation, or bilateral oophorectomy), i.e., postmenopausal women;

2. Non-menopausal women, pregnancy test is negative at screening and baseline, who is willing to use more than 1 effective contraceptive method from screening to 6 months after the last dose, including intrauterine device, tubal ligation, double barrier method (condom/vaginal diaphragm + spermicide), and vasectomy of male partner, etc., but excluding oral contraceptives;

3. Men are willing to use more than 1 effective contraceptive method, including vasectomy, double barrier method, female partner use of contraceptives, intrauterine device or tubal ligation, etc., from the time of taking the drug to 6 months after the last dose;

4. Avoid sexual activity during the study until 6 months after the last dose; 10.Ability to communicate with clinical staff and comply with the requirements of this study.

Exclusion Criteria:

1. Any medical condition with increased risk judged by the investigator (especially a history of esophageal or gastrointestinal ulcers), may interfere with drug absorption, distribution, metabolism, excretion, possible impair protocol compliance;

2. Patients with other liver diseases other than hepatitis B, including but not limited to chronic alcoholic hepatitis, drug-induced liver injury, autoimmune liver disease, known Gilbert syndrome, and other hereditary liver diseases;

3. Any medical history or current signs of hepatic insufficiency (i.e. ascites, hepatic encephalopathy or variceal bleeding);

4. Subjects who have received solid organ or bone marrow transplantation;

5. History of serious kidney disease (judged by the investigator) or current signs;

6. Severe bone disease (e.g., osteomalacia, chronic osteomyelitis, osteogenesis imperfecta, chondropathy) or multiple fractures;

7. Malignant neoplasm of the liver or other diagnosed untreated malignancy before the first dose of study drug;

8. Participate in other drug clinical trials within 90 days prior to the first dose of study drug;

9. Use of other nucleoside or nucleoside analogues or interferon therapy within 6 months prior to the first dose of study drug;

10. Prescription or over-the-counter medications drugs which will affect the assessment of this study with less than 14 days or 5 half-lives judged by the investigator;

11. Donation of blood or massive blood loss (> 400 mL) within 3 months;

12. Major surgery or major trauma within 6 months;

13. Consumption of beverages or foods containing grapefruit, pomegranate, papaya, grapes, carambola within 14 days, or do not agree to refrain from taking those beverages or foods every day during the study;

14. Any caffeine- and xanthine-rich food or drink (coffee, tea, cola, chocolate, seafood, animal liver, etc.) within 48 hours, or do not agree to refrain from taking those food or drink every day during the study;

15. Abnormal ECG and clinically significant judged by the investigator; Or QTcF > 450 ms at screening or baseline phase;

16. History of cardiac disease, including family history of sudden cardiac death or sudden death due to QT prolongation syndrome;

17. Difficulty in venous blood collection, or a known history of needle/ blood sickness;

18. Clinical or laboratory evidence of hepatitis C virus (HCV), hepatitis D virus (HDV), treponema pallidum (TP), or human immunodeficiency virus (HIV);

19. Known history of allergy to the study drug and its excipients;

20. Any history of drug abuse or drug test in urine is positive (+) at screening phase;

21. History of regular alcohol consumption within 6 months prior to screening, more than 7 cups/week for women and more than 14 cups/week for men (1 cup = 5 ounces of wine or 12 ounces of beer or 1.5 ounces of spirits) or alcohol test is out of normal range at screening phase;

22. Subjects who do not agree to stop smoking during the study or have a positive dipstick (urine nicotine test) at screening phase.