A Study to Evaluate the Safety, Tolerability and Pharmacokinetics/Pharmacodynamics of Oral Doses of H008
Condition: Erosive Esophagitis
MeSH terms: Esophagitis
Study type: Interventional
Phase: Phase 1

Summary: 
      This will be a Phase I, randomized, double-blind, positive- and placebo-controlled study to
      evaluate the safety, tolerability, and PK/PD of multiple oral doses of H008 in healthy adult
      subjects.

      Two dose levels of H008 at 20 mg and 40 mg will be studied in two sequential cohorts. Each
      cohort will be enrolled with 12 subjects (8 on H008, 2 on placebo and 2 on positive control
      drug). Subjects are only allowed to participate in one of the two cohorts. Both the
      investigational product and placebo will be given in a double blinded manner, while the
      positive control drug will be given in an open-label manner.Dose escalation to the next
      cohort will be permitted only when safety data until follow-up and PK data until 48 hours
      post-last dose, from all subjects in previous cohorts are reviewed, and the investigational
      product is deemed well tolerated.

      The study will consist of a screening period, a baseline period, a 7-day repeated-dose period
      and a safety follow-up period.
    

Detailed description: 
      Screening Period

      After signing the informed consent, all subjects will undergo a screening assessment within 4
      weeks prior to the start of study treatment (Days -28 to -3).

      Baseline Period

      Eligible subjects at screening will come to the clinic 2 days prior to the first dosing and
      begin their 11-day confinement period (Day -2 to Day 9). On Day -2, subjects will undergo
      baseline examinations. On Day -1, subjects will be monitored for their intragastric pH using
      a pH probe inserted into the stomach. The intragastric pH will be measured continuously for
      48 h (Day -1 to Day 2), and data within the first 24 h will be used as baseline for PD
      evaluation. Subject's eligibility will be confirmed prior to first dosing (morning of Day 1).

      Repeated-dose Period On each day during the treatment period, subjects will receive the
      investigational product (H008, 20 mg or 40 mg), matching placebos or positive control drug
      (Lansoprazole, 30 mg) according to the randomization schedule after a minimum 10-hour
      overnight fasting. No water is allowed within 1 hour before the drug administration. Subjects
      will be instructed to take the drugs with approximately 240 mL (8 oz) room temperature water,
      and swallow the tablets or capsules whole without chewing. On Days 1 to 7, no food or water
      is allowed within at least 2 hours post-dose, except the water ingested during dosing.
      Subjects should avoid lying down for 2 hours post-dose, except when ECG or vital sign
      measurements are performed. Standard lunch and dinner will be provided at approximately 4 and
      10 hours post-dose on Days 1 and 7. On Days 2 to 6, standard breakfast, lunch and dinner will
      be provided at approximately 2, 5 and, 10 hours post-dose.

      Serial PK blood samples will be collected for all subjects from pre-dose (Day 1) to 48 h
      after the last dose (Day 9). Detailed PK sampling plan is presented in Table 1.3-1. Another
      24-h intragastric pH measurement will be performed from pre-dose on Day 7 until 24 h after
      the Day 7 dosing. All subjects will be closely monitored for safety during their stay in the
      clinic. Subjects will be discharged 48 hours after their last dosing (Day 9) if no clinically
      significant adverse events occur.

      Follow-up Period

      A follow-up safety assessment will be performed on Day 16 ± 1 at clinic. Unscheduled
      follow-ups should be performed for any clinically significant AE until it returns to normal
      or baseline or steady state.
    

Intervention name(s): H008; H008 placebo; Lansoprazole
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Drug administration after a minimum 10-hour overnight fasting. Subjects will be instructed to take the drugs with approximately 240 ml (8 oz) room temperature water.; Drug administration after a minimum 10-hour overnight fasting. Subjects will be instructed to take the drugs with approximately 240 ml (8 oz) room temperature water; Drug administration after a minimum 10-hour overnight fasting. Subjects will be instructed to take the drugs with approximately 240 ml (8 oz) room temperature water
Intervention MeSH terms: Lansoprazole; Dexlansoprazole
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention model description: Two dose levels of H008 at 20 mg and 40 mg will be studied in two sequential cohorts. Each cohort will be enrolled with 12 subjects (8 on H008, 2 on placebo and 2 on positive control drug). Subjects are only allowed to participate in one of the two cohorts. Dose escalation to the next cohort will be permitted only when safety data until follow-up and PK data until 48 hours post-last dose, from all subjects in previous cohorts are reviewed, and the investigational product is deemed well tolerated.
Masking: Double (Participant, Investigator)
Primary purpose: Treatment