A Clinical Trial to Evaluate the Safety and Tolerability of Dexlansoprazole Injection in Healthy Chinese Adults（Part 2）

Study Overview
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Brief Summary
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This is a single center, open-label, multiple-dose phase 1 clinical trial. This study will determine the pharmacokinetics (PK), pharmacodynamics (PD), safety and side-effect profile of an investigational dexlansoprazole injection after multiple intravenous administration in healthy Chinese adults.

Detailed Description
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This is a single center, open-label, multiple-dose clinical trial. 5 dosing groups were designed, including 15mg q12h,30mg q12h,15mg qd,30mg qd in dexlansoprazole treatment arm for 5 days, and 30 mg q12h in an active comparator, lansoprazole, treatment arm for 5 days. The study will enroll approximately 70 participants with 14 cases in each group. Participants will make 3 visits to the clinic including 8-day of confinement to the clinic.

Official Title
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A Phase 1 Clinical Trial to Evaluate Pharmacokinetics (PK), Pharmacodynamics (PD), and Safety in Healthy Chinese Adults After Multiple Intravenous Administration of Dexlansoprazole

Conditions
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Effect of Drugs, Safety Issues

Intervention / Treatment
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* Drug: Dexlansoprazole Injection
* Drug: Lansoprazole Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 Years; Male (weight ≥50kg) or female (weight ≥45kg); Body mass index (BMI) between 19 28 kg/m2; In good health as determined by a physician/investigator based on medical history, vital signs, electrocardiogram (ECG), laboratory tests and physical examination findings at screening; Subject who totally understand the aim and progress of this clinical trial, make decision by his/her free will, and signed a consent form to follow the progress; Female participant of childbearing potential must have a negative serum pregnancy test at screening, and agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study and for 6 months following the last dose of study drug; Male participant agrees to use adequate contraception and have no plan to donate sperm from signing of informed consent form throughout the duration of the study and for 6 months after the last dose of study drug; In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements. Exclusion Criteria: Positive breath test result for H pylori at Screening; Cannot tolerate placement of the pH probe; Has poor peripheral venous access; Allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator; Subject who has past or present history of any serious diseases, including (but not limited to) digestive, cardiovascular, respiratory, urinary, musculoskeletal, endocrine, psychiatric or neurological, hematologic, immunological or metabolic disorders; Human immunodeficiency virus(HIV), hepatitis B virus(HBV), or syphilis positive; Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse (defined as alcohol consumption exceeding 14 units per week) within 6 months preceding this study or is unwilling to agree to abstain from alcohol and drugs throughout the study; Heavy smokers (>5 cigarettes per day) within 6 months preceding this study or is unwilling to agree to abstain from smoking throughout the study; Participation in another study with an investigational drug within the last 3 months preceding this study; Blood donation within the last 2 months (>= 400 ml), or have a plan to donate blood within 1 month after this study; Intake of any other drug which might influence the results of the trial during two weeks previous to the start of the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dexlansoprazole Injection<br>15mg q12h,30mg q12h,15mg qd,30mg qd in dexlansoprazole treatment arm for 5 days | Drug: Dexlansoprazole Injection<br>* 15mg q12h,30mg q12h,15mg qd,30mg qd for 5 days<br>|
| Active Comparator: Lansoprazole Injection<br>30 mg q12h in lansoprazole treatment arm for 5 days. | Drug: Lansoprazole Injection<br>* 30 mg q12h for 5 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage time with the intragastric potential of hydrogen (pH)>4 | Duration of intragastric pH>4 within 24 hours postdose | 24 hours post-dose on Day 5 | 
| Percentage time with the intragastric pH>6 | Duration of intragastric pH>6 within 24 hours postdose | 24 hours post-dose on Day 5 | 
| The time of the intragastric pH reaching 4 | The time of intragastric pH reaching 4 after the last dose | 12 hours post-dose on Day 5 | 
| The time of the intragastric pH reaching 6 | The time of intragastric pH reaching 6 after the last dose | 12 hours post-dose on Day 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean intragastric pH | Mean intragastric pH | 24 hours post-dose on Day 5 | 
| Mean intragastric pH per hour | Mean intragastric pH per hour | 24 hours post-dose on Day 5 | 
| Percentage time with the intragastric pH>4 during the first 4 hours | Duration of intragastric pH>4 within first 4 hours postdose | 4 hours post-dose on Day 5 | 
| Percentage time with the intragastric pH>6 during the first 4 hours | Duration of intragastric pH>6 within first 4 hours postdose | 4 hours post-dose on Day 5 | 
| Percentage of the participants with duration time of intragastric pH>4 over 12h | Numbers of participants with duration time of intragastric pH>4 over 12h | 12 hours post-dose on Day 5 | 
| Percentage of the participants with duration time of intragastric pH>6 over 12h | Numbers of participants with duration time of intragastric pH>6 over 12h | 12 hours post-dose on Day 5 | 
| Cmax on day 1 | Maximum observed plasma concentration for dexlansoprazole | 12 hours post-dose on Day 5 | 
| Cmax on day 5 | Maximum observed plasma concentration for dexlansoprazole | 12 hours post-dose on Day 5 | 
| Area under the plasma concentration-time curve (AUC) on day 1 | AUC from time 0 to the time of the last quantifiable concentration on day 1 | 12 hours post-dose on Day 5 | 
| AUC(0-12h) on day 5 | AUC from time 0 to the time of the last quantifiable concentration on day 5 | 12 hours post-dose on Day 5 | 
| AUC(0-inf) on day 1 | AUC from time 0 to extrapolated to infinity on day 1 | 12 hours post-dose on Day 5 | 
| AUC(0-inf) on day 5 | AUC from time 0 to extrapolated to infinity on day 5 | 12 hours post-dose on Day 5 |