A Single Dose Study of SHR0410 in Healthy Male Participants

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled, single ascending-dose study to investigate the effect of a single intravenous (IV) dose of SHR0410 at 6 dose levels (0.5 μg/kg, 1 μg/kg, 2 μg/kg, 5 μg/kg, 10 μg/kg and 20 μg/kg) in healthy participants.

Detailed Description
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Forty eight eligible participants will be enrolled into the 6 dose cohorts. For each cohort, a sentinel group of 2 subjects (1 receiving SHR0410 and 1 receiving placebo) will be dosed first (1:1 ratio). If no drug related adverse events occur in the sentinel participants, the remaining 6 subjects in a cohort will be dosed on the next day or later in a 5:1 ratio (5 subjects receiving SHR0410 and 1 subject receiving placebo). SHR0410 will be diluted in saline and administered as a 15 min constant dose IV infusion at a rate of 20 ml/hr on Day 1.

Official Title
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A Phase I, Randomized, Double-blind, Placebo-Controlled, Single Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Intravenous SHR0410 in Healthy Male Participants

Conditions
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Acute Pain

Intervention / Treatment
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* Drug: 0.5μg/kg SHR0410
* Drug: 1μg/kg SHR0410
* Drug: 2μg/kg SHR0410
* Drug: 5μg/kg SHR0410
* Drug: 10μg/kg SHR0410
* Drug: 20μg/kg SHR0410


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male between the ages of 18 and 45 years, inclusive. Body mass index (BMI) of 18.0 to 30.0 kg/m2 and a total body weight of 50 kg to 125kg, inclusive. Considered generally healthy upon completion of medical history, physical examination, vital signs, SpO2, laboratory parameters, and ECG, as judged by the Investigator. Exclusion Criteria: Known sensitivity to any of the components of the investigational product formulation, or any other opioids. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing). Any other medical or psychological condition, which in the opinion of the Investigator, might create undue risk to the participant or interfere with the participant's ability to comply with the protocol requirements, or to complete the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 0.5 μg/kg SHR0410<br>8 subjects will be randomized in a 3:1 ratio to receive a single dose of either 0.5μg/kg SHR0410 (n=6) or placebo (n=2) | Drug: 0.5μg/kg SHR0410<br>* a single dose of 0.5μg/kg SHR0410<br>|
| Experimental: 1 μg/kg SHR0410<br>8 subjects will be randomized in a 3:1 ratio to receive a single dose of either 1μg/kg SHR0410 (n=6) or placebo (n=2) | Drug: 1μg/kg SHR0410<br>* a single dose of 2μg/kg SHR0410<br>|
| Experimental: 2 μg/kg SHR0410<br>8 subjects will be randomized in a 3:1 ratio to receive a single dose of either 2μg/kg SHR0410 (n=6) or placebo (n=2) | Drug: 2μg/kg SHR0410<br>* a single dose of 2μg/kg SHR0410<br>|
| Experimental: 5 μg/kg SHR0410<br>8 subjects will be randomized in a 3:1 ratio to receive a single dose of either 5μg/kg SHR0410 (n=6) or placebo (n=2) | Drug: 5μg/kg SHR0410<br>* a single dose of 5μg/kg SHR0410<br>|
| Experimental: 10 μg/kg SHR0410<br>8 subjects will be randomized in a 3:1 ratio to receive a single dose of either 10μg/kg SHR0410 (n=6) or placebo (n=2) | Drug: 10μg/kg SHR0410<br>* a single dose of 10μg/kg SHR0410<br>|
| Experimental: 20 μg/kg SHR0410<br>8 subjects will be randomized in a 3:1 ratio to receive a single dose of either 10μg/kg SHR0410 (n=6) or placebo (n=2) | Drug: 20μg/kg SHR0410<br>* a single dose of 20μg/kg SHR0410<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse events in terms of changes in Hematology | Hemoglobin Hematocrit Erythrocytes count Mean cell volume, Mean cell hemoglobin concentration, Leukocytes count, Neutrophils count, Lymphocytes count, Monocytes count, Eosinophils count, Basophils count, Platelets count | Up to Day 8 | 
| Incidence of Adverse events in terms of changes in Urinalysis | Urobilinogen Dipstick urinalysis, including: pH, Specific gravity, Protein, Blood, Leukocytes, Glucose, Ketones, Bilirubin, Nitrites | Up to Day 8 | 
| Incidence of Adverse events in terms of changes in Biochemistry (fasting) | Including Serum creatinine, Urea, Alanine aminotransferase, Aspartate aminotransferase, Gamma glutamyl transferase, Total bilirubin, Total protein, Albumin, Alkaline phosphatase, Serum uric acid, Glucose, Triglycerides, Total cholesterol, High-density lipoprotein cholesterol, Low-density lipoprotein cholesterol | Up to Day 8 | 
| Incidence of Adverse events in terms of changes in Physical examinations | Review of body weight and height; general appearance; head; eyes; ears/nose/throat; neck; lymph nodes; neurological and musculoskeletal systems; heart; lungs; abdomen; skin; and extremities | Up to Day 8 | 
| Incidence of Adverse events in terms of changes in Vital signs | Oral temperature, respiratory rate, blood pressure, and pulse rate | Up to Day 8 | 
| Incidence of Adverse events in terms of changes in 12-lead ECGs | The 12-lead ECGs must be recorded after the subjects have rested in the supine position for 5 minutes to ensure a stable baseline. | Up to Day 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration versus time curve (AUC) | Plasma SHR0410 Area Under the Concentration-time Curve (AUC) | Up to 24 hours post dose | 
| Time to the peak plasma concentration (Tmax) | Time to Maximum Plasma SHR0410 Concentration | Up to 24 hours post dose | 
| Peak Plasma Concentration (Cmax) | Peak Plasma SHR0410 Concentration | Up to 24 hours post dose | 
| Half-time (T1/2) | Half-time of SHR0410 | Up to 24 hours post dose | 
| Urine output rate | Changes in urine output rate from baseline | Up to 48 hours post dose | 
| Serum prolactin release rate | Changes in serum prolactin release rate from baseline | Up to 48 hours post dose |