Acute Pain
Conditions
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.
Interventions
DRUG0.5μg/kg SHR0410
a single dose of 0.5μg/kg SHR0410
DRUG1μg/kg SHR0410
a single dose of 2μg/kg SHR0410
DRUG2μg/kg SHR0410
a single dose of 2μg/kg SHR0410
DRUG5μg/kg SHR0410
a single dose of 5μg/kg SHR0410
DRUG10μg/kg SHR0410
a single dose of 10μg/kg SHR0410
DRUG20μg/kg SHR0410
a single dose of 20μg/kg SHR0410
Sponsors
Linear Clinical Research
Atridia Pty Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| Urine output rate | Up to 48 hours post dose | Changes in urine output rate from baseline |
| Serum prolactin release rate | Up to 48 hours post dose | Changes in serum prolactin release rate from baseline |
Countries
Australia
Outcome results
None listed