Safety and Tolerance Study of Recombinant Human Albumin Injection in Healthy Subjects.

Study Overview
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Brief Summary
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A phase I, single-center, randomized, double-blind, placebo-controlled single dose escalation study, and a positive-controlled multiple dose extension study to evaluate the safety, tolerance, pharmacokinetics and immunogenicity of recombinant human albumin injection in healthy subjects

Detailed Description
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This study was to evaluate the safety, tolerability, pharmacokinetics and immunogenicity of recombinant human albumin injection in healthy volunteers. The safety, tolerance, pharmacokinetics and immunogenicity of recombinant human albumin injection were evaluated in a single center, randomized, double-blind, placebo-controlled single dose incremental trial in healthy volunteers. The study was divided into two stages: the first stage was a single dose and dose increasing stage (including 5 dose groups with increasing dose, and each group was set with placebo control); the second stage was multiple administration stage (with positive control). The safety, tolerance, pharmacokinetics, immunogenicity and other early clinical data of recombinant human albumin were collected and analyzed in the two stages. The initial dose was 1.25g. The highest dose group was set at 30g. The dose groups of 1.25, 5, 10, 20 and 30 g / time were preset in the single dose stage (dose increasing stage). The dosage was 10 g / Day in multiple administration stage.

Official Title
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Safety and Tolerance Study of Recombinant Human Albumin Injection in Healthy Subjects.

Conditions
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Ascites

Intervention / Treatment
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* Drug: recombinant human albumin injection
* Drug: Placebo
* Drug: human albumin injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1）Informed consent form signed; 2) To be able to complete the study; 3) Subjects (including partners) are willing to take contraceptive measures; 4) 18-55 years of age; 5) Male subjects are no less than 50 kg.Female subjects are no less than 45 kg. Body mass index is 18-28kg / m2; 6) Normal cardiac function, defined as left ventricular ejection fraction (LVEF) ≥ 50%; 7) Physical examination and vital signs are normal. Exclusion Criteria: Cigarettes Smoking subjects. Allergic constitution (multiple drugs and food allergies); History of drug use and/or alcohol abuse; Blood donation or massive blood loss (> 450 mL) within three months before screening; Taking any drugs, prescription, over-the-counter, vitamin products or herbal medicine within 14 days before screening; Diet or exercise have changed recently; Using study drugs within three months; Risk of bleeding, such as hemorrhoids, acute gastritis or stomach and duodenal ulcers; ECG abnormalities (QTc > 470ms for males, > 480ms for females); Female subjects are in lactation. Pregnancy test is positive; Other Clinical laboratory tests abnormalities; Viral screening test is positive, including HBV, HCV, HIV, and Treponema pallidum; Developing Acute disease; Eating chocolate, any caffeine-containing or jaundice-rich food or drink 24 hours prior to the use of the study drug; Taking any alcoholic products. Alcohol test is positive.. Drug test is positive. History of drug abuse or drug use in the past five years; Inability for intravenous injection or blood collection; Using biological products (including live vaccines) within the last 3 months. Planing to use vaccines during the study period. Having received corticosteroid or human plasma product system treatment within 1 month. Renal function is abnormal, glomerular filtration rate <80 mL/min (according to the simplified MDRD formula); History of glaucoma, eye disease. History of cancer or other serious systemic diseases, especially heart, liver, kidney, digestive tract, nervous system, metabolic abnormalities, immune abnormalities or mental disorders; History of immunodeficiency or hypofunction; Received major surgery within 2 years. Other subjects by investigator opinion..

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control: placebo<br>Subjects received 0.9% sodium chloride injection. | Drug: Placebo<br>* Single dose intravenous infusion of 0.9% sodium chloride injection<br>* Other names: Intravenous infusion of 0.9% sodium chloride injection;|
| Active Comparator: Control: Human Serum Albumin(HSA)<br>Subjects received Human Serum Albumin, 10 g for each day, three days for a cycle, and totally three cycles. | Drug: human albumin injection<br>* multiple doses of intravenous infusion<br>* Other names: Intravenous infusion of human albumin injection;|
| Experimental: Experimental:recombinant human albumin<br>Subjects received recombinant Human Serum Albumin, 1.25g, 5g, 10g, 20g, 30 g for the single dose study. For the multiple dose study, subjects received recombinant Human Serum Albumin, 10 g for each day, three days for a cycle, and totally three cycles. | Drug: recombinant human albumin injection<br>* single dose or multiple doses of intravenous infusion<br>* Other names: Intravenous infusion of recombinant human albumin injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerance | AE | Day 1-Day 57 for single doses study. Day 1-Day 106 for multiple doses study. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK parameters | Maximum Plasma Concentration（Cmax） | Day 1-Day 57 for single doses study. Day 1-Day 106 for multiple doses study. | 
| PK parameters | time to Maximum Plasma Concentration（Tmax） | Day 1-Day 57 for single doses study. Day 1-Day 106 for multiple doses study. | 
| PK parameters | half life (t1/2） | Day 1-Day 57 for single doses study. Day 1-Day 106 for multiple doses study. | 
| Pharmacodynamic parameters | Red blood cell specific volume | Day 1-Day 57 for single doses study. Day 1-Day 106 for multiple doses study. | 
| Pharmacodynamic parameters | Plasma colloid osmotic pressure | Day 1-Day 57 for single doses study. Day 1-Day 106 for multiple doses study. | 
| Immunogenicity | Percentage of patients with positive reaction | Day 1-Day 57 for single doses study. Day 1-Day 106 for multiple doses study. |