A Single Dose Study of SHR0410 in Healthy Male Participants

Phase 1

Completed

• Conditions: Acute Pain
• Interventions: Drug: 10μg/kg SHR0410; Drug: 0.5μg/kg SHR0410; Drug: 1μg/kg SHR0410; Drug: 2μg/kg SHR0410; Drug: 20μg/kg SHR0410; Drug: 5μg/kg SHR0410

• Registration Number: NCT03493191
• Lead Sponsor: Atridia Pty Ltd.

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2018-03-26
• Study First Submitted QC: 2018-04-03
• Study First Posted: 2018-04-10
• Study Start: 2018-04-15
• Status Verified: 2018-05
• Primary Completion: 2018-06-29
• Study Completion: 2018-07-14
• Last Update Submitted: 2019-02-25
• Last Update Posted: 2019-02-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 48

Inclusion Criteria

1. Male between the ages of 18 and 45 years, inclusive.
2. Body mass index (BMI) of 18.0 to 30.0 kg/m2 and a total body weight of 50 kg to 125kg, inclusive.
3. Considered generally healthy upon completion of medical history, physical examination, vital signs, SpO2, laboratory parameters, and ECG, as judged by the Investigator.

Exclusion Criteria

1. Known sensitivity to any of the components of the investigational product formulation, or any other opioids.
2. 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).
3. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
10 μg/kg SHR0410	10μg/kg SHR0410	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)
0.5 μg/kg SHR0410	0.5μg/kg SHR0410	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)
1 μg/kg SHR0410	1μg/kg SHR0410	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)
2 μg/kg SHR0410	2μg/kg SHR0410	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)
20 μg/kg SHR0410	20μg/kg SHR0410	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)
5 μg/kg SHR0410	5μg/kg SHR0410	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)

Primary Outcome Measures

Name	Time	Method
Incidence of Adverse events in terms of changes in Physical examinations	Up to Day 8	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
Incidence of Adverse events in terms of changes in Vital signs	Up to Day 8	Oral temperature, respiratory rate, blood pressure, and pulse rate
Incidence of Adverse events in terms of changes in Hematology	Up to Day 8	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
Incidence of Adverse events in terms of changes in Urinalysis	Up to Day 8	Urobilinogen Dipstick urinalysis, including: pH, Specific gravity, Protein, Blood, Leukocytes, Glucose, Ketones, Bilirubin, Nitrites
Incidence of Adverse events in terms of changes in Biochemistry (fasting)	Up to Day 8	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
Incidence of Adverse events in terms of changes in 12-lead ECGs	Up to Day 8	The 12-lead ECGs must be recorded after the subjects have rested in the supine position for 5 minutes to ensure a stable baseline.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Linear Clinical Research Limited; 🇦🇺 Nedlands, Australia