A Multiple-dose Study in Chinese Subjects to Evaluate Safety,Tolerability,PK and PD of ZM-H1505R
Condition: Healthy Volunteers; Hepatitis B, Chronic
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis
Study type: Interventional
Phase: Phase 1

Summary: 
      This phase Ib study included two parts in which Part I was to evaluate the safety and bridge
      for PK among healthy Chinese subjects and Part II were about study among Chinese chronic
      hepatitis B virus-infected patients. Study of Part II was carried out following the safety
      assessment and racial difference evaluation in Part I.
    

Detailed description: 
      This is a randomized, double-blind, placebo-controlled, multiple-dose phase Ib study.

      It aimed in this study to evaluate the safety and tolerability and to characterize the
      pharmacokinetics of ZM-H1505R among Chinese healthy subjects following single and multiple
      doses administration, and to assess whether there are ethnic differences in PK characteristic
      among Chinese and American healthy subjects. Study was also conducted to evaluate the safety
      and tolerability, to characterize the pharmacokinetics and to assess the preliminary
      pharmacodynamics of ZM-H1505R following multiple ascending dose administration among chronic
      hepatitis B virus-infected patients; the PK/PD model was established among adults to provide
      a basis for the oral doses determination in subsequent clinical studies of ZM-H1505R.

      Part I: Study among healthy subjects for safety evaluation and PK bridging Based on the PK
      results among American healthy subjects in Phase Ia study, 75 mg (cohort 1) was selected for
      PK bridging. Twelve healthy subjects were enrolled, of which 8 subjects received ZM-H1505R
      and 4 subjects received placebo.

      Part II: Study among chronic hepatitis B virus-infected patients Subjects in four cohorts
      (scheduled as cohort 2, 50 mg; cohort 3, 100 mg; cohort 4, 200 mg; cohort 5, 300 mg) were
      enrolled in sequence from 50 mg dose group (cohort 2). Dose ascending was continued when
      safety evaluation on Day 8 showed that the lower dose could be tolerated. Based on the
      results of PK and tolerability and PD, dose ascending to 300 mg dose group (cohort 5) from
      200 mg dose group (cohort 4) was discontinued determined by sponsor and investigators. Ten
      chronic hepatitis B virus-infected patients were enrolled in each cohort to receive ZM-H1505R
      (n=8) or placebo (n=2).
    

Intervention name(s): ZM-H1505R; ZM-H1505R Placebo
Intervention type(s): Drug; Other
Intervention description(s): Part 1 dosage form:75mg dosage:Tablet frequency: Quaque die duration: Day1; Day 4~ Day 14
Cohort 1 of Part 2 dosage form:50mg dosage:Tablet frequency: Quaque die duration: Day 1~ Day 28
Cohort 2 of Part 2 dosage form:100mg dosage:Tablet frequency: Quaque die duration: Day 1~ Day 28
Cohort 3 of Part 2 dosage form:200mg dosage:Tablet frequency: Quaque die duration: Day 1~ Day 28; Part 1 dosage form:75mg dosage:Tablet frequency: Quaque die duration: Day1; Day 4~ Day 14
Cohort 1 of Part 2 dosage form:50mg dosage:Tablet frequency: Quaque die duration: Day 1~ Day 28
Cohort 2 of Part 2 dosage form:100mg dosage:Tablet frequency: Quaque die duration: Day 1~ Day 28
Cohort 3 of Part 2 dosage form:200mg dosage:Tablet frequency: Quaque die duration: Day 1~ Day 28
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Hepatitis B, Chronic; randomized; double-blind; placebo-controlled; phase Ib