A Single-dose Study of Octreotide Injection in Healthy Adult Subjects

Study Overview
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Brief Summary
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This is a single-centre, single-dose, dose-escalation, placebo and positive drug-controlled Phase I clinical study in healthy Chinese subjects to evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic profile of octreotide injection in healthy Chinese subjects.

Detailed Description
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This single centre study will be comprised of 6 cohorts. The single ascending dose part is comprises of 4 cohorts（5 mg, 10 mg, 20 mg, 30 mg). The other 2 cohorts are octreotide long-acting release ( Sandostatin LAR® ) 20 mg and Sandostatin® 0.1 mg.

Official Title
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A Single-dose Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Octreotide Injection in Healthy Adult Subjects

Conditions
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Acromegaly

Intervention / Treatment
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* Drug: SYHX2008 injection
* Drug: Octreotide Acetate Microspheres for Injection injection
* Drug: Sandostatin ® injection
* Drug: Placebo to SYHX2008 injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy, adult, male and female subjects, 22-45 years of age, inclusive, at screening; Body weight≥50 kg in male subjects or≥45 kg in female subjects, with BMI 19.0 - 28.0 kg/m^2 (inclusive); Good health without history of cardiovascular vascular, liver, kidney, respiratory system, digestive, nervous, blood, immune, cancer, endocrine disease or any system diseases that have completely recovery or no clinical significance by investigator's assessment; No clinically relevant findings in the physical examination, ECG, abdominal ultrasonography, vital signs, laboratory examination by investigator's assessment; Informed consent documents signed by subjects prior the study, and subjects could be able to read, comprehend the procedure or the adverse reaction about the trial; Subjects (including female and male subjects) have no pregnancy plan and sperm (egg) donation plan and voluntarily take effective contraceptive methods from signing the informed consent form until 3 months after administration of investigational product. Exclusion Criteria: The subject has a history of sensitivity (such as asthma, urticaria, eczema, etc), or has a known hypersensitivity to any of the test materials or related compounds, or has allergic constitution; The female subject of childbearing potential, is pregnant (as based on test results in the screening period) or is breast feeding; The subject with any one of HBsAg, hepatitis C antibody, anti-HIV antibody and antibody of treponema pallidum positive; The subject with chronic or acute gastrointestinal disease (such as dyspepsia, gastro-oesophageal reflux, gastric bleeding or peptic ulcer, etc), or has a history of gallbladder disease (such as gallstone, cholecystectomy, etc) and other diseases; The subject has a history of acupuncture syncope or blood phobia, or has difficulty with vein blood collection or venipuncture; The subject has difficulty with subcutaneous administration; The subject has a history of drug abuse or dependence, or has a positive result of drug abuse test in urine; The subject intake more than 14 units alcohol within 3 months before administration of investigational product (1 unit=360 mL of beer, or 45 mL spirits, or 150 mL grape wine), or can't control to drink alcohol; The subject smoke more than 5 cigarettes per day within 3 months before administration of investigational product, or smoke within 48h before administration of investigational product, or are unwilling to stop any tobacco products; The subject has a history of hospitalization or surgical operation within 3 months before screening; The subject has participated in other clinical trials within 3 months before administration of investigational product; The subject donated blood or lost blood >400 mL (except female physiological period) within 3 months before screening; The subject received prescription or non-prescription drugs within 28 days before administration of investigational product, including the drug effect on growth hormone and insulin-like growth factor (such as epinephrine, cholinergic drugs, etc); or received dietary supplements within 7 days before administration of investigational product (such as vitamin, protein powder, etc); The subject with consumption of food or beverage containing caffeine or xanthine within 72 hours before administration of investigational product (such as coffee, tea, cola, chocolate, etc), or grapefruit fruit, or products containing grapefruit ingredients; The subject has received any products containing alcohol within 48 hours before administration of investigational product or has a positive result of breath alcohol test; According to the investigator's judgment, there are other situations that are not suitable for participating in this clinical trial.

Ages Eligible for Study
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Minimum Age: 22 Years
Maximum Age: 45 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 5 mg cohort<br>Subjects will be randomly assigned 4:1 to single dose of either SYHX2008（octreotide long-acting injection) or placebo at dose of 5 mg (8 active : 2 placebo). | Drug: SYHX2008 injection<br>* Subcutaneous administration on Day 1.<br>Drug: Placebo to SYHX2008 injection<br>* Subcutaneous administration on Day 1.<br>|
| Experimental: 10 mg cohort<br>Subjects will be randomly assigned 4:1 to single dose of either SYHX2008 or placebo at dose of 10 mg (8 active : 2 placebo). | Drug: SYHX2008 injection<br>* Subcutaneous administration on Day 1.<br>Drug: Placebo to SYHX2008 injection<br>* Subcutaneous administration on Day 1.<br>|
| Experimental: 20 mg cohort<br>Subjects will be randomly assigned 4:1 to single dose of either SYHX2008 or placebo at dose of 20 mg (8 active : 2 placebo). | Drug: SYHX2008 injection<br>* Subcutaneous administration on Day 1.<br>Drug: Placebo to SYHX2008 injection<br>* Subcutaneous administration on Day 1.<br>|
| Experimental: 30 mg cohort<br>Subjects will be randomly assigned 4:1 to single dose of either SYHX2008 or placebo at dose of 30 mg (8 active : 2 placebo). | Drug: SYHX2008 injection<br>* Subcutaneous administration on Day 1.<br>|
| Experimental: Octreotide long-acting release ( Sandostatin LAR®) 20 mg cohort<br>Subjects will be treated with single dose of octreotide long-acting release ( Sandostatin LAR®) at dose of 20 mg. | Drug: Octreotide Acetate Microspheres for Injection injection<br>* Intramuscular administration on Day 1.<br>|
| Experimental: Sandostatin® 0.1mg cohort<br>Subjects will be treated with single dose of Sandostatin® at dose of 0.1mg. | Drug: Sandostatin ® injection<br>* Subcutaneous administration on Day 1.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of adverse events |  | Throughout the study period, with an average of 60 days. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration-time curve (AUC) | AUC from pre-dose to time 't' (AUC[0-t]) and pre-dose to infinite time (AUC[0-infinity]) of Octreotide | Pre-dose, 0.5 hour, 1 hour, 2 hour, 4 hour, 8 hour, 12 hour, 24 hour, 48 hour, 96 hour, 168 hour, 336 hour, 576 hour, 1008 hour, 1416 hour. | 
| Maximum plasma concentration (Cmax) | Maximum octreotide plasma concentration (Cmax) of Octreotide | Pre-dose, 0.5 hour, 1 hour, 2 hour, 4 hour, 8 hour, 12 hour, 24 hour, 48 hour, 96 hour, 168 hour, 336 hour, 576 hour, 1008 hour, 1416 hour. | 
| Time to maximum plasma concentration (Tmax) | Time to maximum octreotide plasma concentration (Tmax) of Octreotide | Pre-dose, 0.5 hour, 1 hour, 2 hour, 4 hour, 8 hour, 12 hour, 24 hour, 48 hour, 96 hour, 168 hour, 336 hour, 576 hour, 1008 hour, 1416 hour. | 
| Terminal elimination half-life (t1/2) | Plasma decay half-life is the time measured for the octreotide plasma concentration to decrease by one half. | Pre-dose, 0.5 hour, 1 hour, 2 hour, 4 hour, 8 hour, 12 hour, 24 hour, 48 hour, 96 hour, 168 hour, 336 hour, 576 hour, 1008 hour, 1416 hour. | 
| Apparent systemic clearance (CL/F) | CL/F is the volume of plasma cleared of octreotide per unit time. | Pre-dose, 0.5 hour, 1 hour, 2 hour, 4 hour, 8 hour, 12 hour, 24 hour, 48 hour, 96 hour, 168 hour, 336 hour, 576 hour, 1008 hour, 1416 hour. | 
| Apparent volume of distribution (Vz/F) | Vz/F is the apparent volume of distribution of octreotide during the terminal elimination phase . | Pre-dose, 0.5 hour, 1 hour, 2 hour, 4 hour, 8 hour, 12 hour, 24 hour, 48 hour, 96 hour, 168 hour, 336 hour, 576 hour, 1008 hour, 1416 hour. | 
| Insulin-like growth factor-1 (IGF-1) concentrations over time. | IGF-1 levels will be collected over time to compare the suppressive ability of octreotide. | Pre-dose, 1 hour, 4 hour, 12 hour, 24 hour, 48 hour, 96 hour, 168 hour, 336 hour, 576 hour, 1008 hour, 1416 hour. |