A Single Dose Study of SHR0410 in Healthy Male Participants

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

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.

Study Overview

• Status: Completed
• Conditions: Acute Pain
• Intervention / Treatment: 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

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 Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Nedlands, Australia
    • Linear Clinical Research Limited

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 0.5 μg/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)	Drug: 0.5μg/kg SHR0410; a single dose of 0.5μg/kg SHR0410
Experimental: 1 μg/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)	Drug: 1μg/kg SHR0410; a single dose of 2μg/kg SHR0410
Experimental: 2 μg/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)	Drug: 2μg/kg SHR0410; a single dose of 2μg/kg SHR0410
Experimental: 5 μg/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)	Drug: 5μg/kg SHR0410; a single dose of 5μg/kg SHR0410
Experimental: 10 μg/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)	Drug: 10μg/kg SHR0410; a single dose of 10μg/kg SHR0410
Experimental: 20 μg/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)	Drug: 20μg/kg SHR0410; a single dose of 20μg/kg SHR0410

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Atridia Pty Ltd.
• Collaborators: Linear Clinical Research

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2018
• Primary Completion (Actual): June 29, 2018
• Study Completion (Actual): July 14, 2018

Study Registration Dates

• First Submitted: March 26, 2018
• First Submitted That Met QC Criteria: April 3, 2018
• First Posted (Actual): April 10, 2018

Study Record Updates

• Last Update Posted (Actual): February 26, 2019
• Last Update Submitted That Met QC Criteria: February 25, 2019
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Acute Pain
• Other Study ID Numbers: SHR0410-101-AU

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No