Single Ascending Dose and Multiple Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of SHR-1816 in Healthy Subjects

Diabetes Clinical Trial

Official title:

A Phase 1, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose and Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of SHR-1816 in Healthy Subjects

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05330208
• Other study ID #: SHR-1816-101
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: April 30, 2022
• Est. completion date: April 30, 2023

Study information

• Verified date: March 2022
• Source: Beijing Suncadia Pharmaceuticals Co., Ltd
• Contact: Liang Peng
• Phone: +86 15211153194
• Email: liang.peng.lp1[@]hengrui.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a randomized, double-blind, placebo-controlled study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of SHR-1816 after single and multiple injection with different dose regimens in healthy subjects.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 96
• Est. completion date: April 30, 2023
• Est. primary completion date: April 30, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

1. Males and infertility females aged between 18 years and 55 years at screening.

2. Male subjects weight =50kg, female subjects weight =45kg. Body mass index (BMI) in the range of 19-26kg /m2.

3. HbA1c<6.2% at screening.

4. FPG>3.9mmol/L (70mg/dL) and <6.1mmol/L (110mg/dL) at screening

5. Agree to take effective contraceptive methods.

6. Able and willing to provide a written informed consent.

Exclusion Criteria:

1. The following clinical laboratory tests or examination abnormalities exist during the screening period:

1) Any clinically significant lab tests abnormal with one-time retest. 2) ALT and AST were higher than the upper limit of normal value. 3) Subject who has fatty liver disease diagnosed by ultrasound examination. 4) Subject who has abnormal thyroid function. 5) The 12-lead electrocardiogram (ECG) is abnormal and clinically significant, or shows QTcF>450 ms in male and 470 ms in female.

6) Positive infectious diseases screening tests: HBsAg, HCV-Ab, TP-Ig G, HIV-Ab 2. Having any of the following diseases or history:

1. Subject with a history of hypertension or with abnormal vital signs and clinical significance.

2. Subject with a history of life-threatening diseases within the previous 5 years prior to screening.

3. Subject with severe systemic infectious diseases within 1 month prior to screening.

4. Subject with medical history or family history of medullary thyroid cancer, multiple endocrine adenomatosis type 2, and previous history of pancreatitis.

5. Subject with major medical history of heart, liver, kidney, endocrine, digestive, blood, respiratory and genitourinary system or existing diseases of the above systems.

3. Use of any other medicine or other non-drug operations:

1. Prescription drugs, non-prescription drugs, food supplements, vitamins and Chinese herbal medicines within 2 weeks before administration.

2. Subject who received bariatric surgery or procedures, or use of weight-reducing drugs within 3 months prior to administration, or body weight change of more than ±10% within 3 months prior to administration.

3. Drugs that may affect glucose metabolism were used within 1 month before administration.

4. Subject who undergone other gastrointestinal surgery that could lead to malabsorption, or long-term use of drugs that had a direct impact on gastrointestinal motility prior to screening.

4. Any of the following conditions exists:

1. History of allergy to the study drug or any component of it.

2. Treatment with an investigational drug or device within 3 months (or 5 half-lives, whichever is longer) prior to screening.

3. History of regular alcohol consumption in the past week exceeding an average 15g per day and positive alcohol test.

4. More than 5 cigarettes per day or cigarettes in 48 hours before treatment and positive nicotine test.

5. Long time or in 48 hours before treatment drinking for tea, cola, coffee or any other soft drinking within 48 hours.

6. Strenuous exercise in 48 hours before treatment.

7. Subject with known or suspected history of drug abuse or positive urine drug screening test during screening.

8. Unwillingness to comply with lifestyle requirements during the trial.

9. Donate blood within 1 month before screening, or screening trauma or major surgical operation patients who donated blood =400 mL or lost blood =400 mL within 3 months before the screening.

10. Mentally incapacitated or language impaired subject cannot fully understand or participate in the test process.

11. The investigator assessed the subject's poor compliance or inability to draw blood due to arm vein conditions, or history of needle and blood sickness.

5. Other conditions or laboratory abnormality that may affect trial evaluations associated with study participation reviewed by the investigators.

Related Conditions & MeSH terms

• Diabetes

Intervention

Drug:
• SHR-1816
SHR-1816
• Placebo
Placebo

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Beijing Suncadia Pharmaceuticals Co., Ltd

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of adverse Events		Day-2 to Day29/Day50
Primary	Incidence of hypoglycemic events		Day1 to Day8/Day29
Primary	Incidence of reaction of the injection sites		Day1 to Day8/Day29
Secondary	Pharmacokinetic (PK) profile of SHR-1816 - AUC0-t	AUC0-t, area under the concentration-time curve from time 0 to the time of last quantifiable concentration;	pre-dose, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 336 hours post-dose
Secondary	Pharmacokinetic (PK) profile of SHR-1816 - AUC0-inf	AUC0-inf, area under the concentration-time curve from time 0 to infinity;	pre-dose, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 336 hours post-dose
Secondary	Pharmacokinetic (PK) profile of SHR-1816 - Cmax	Cmax, observed maximum concentration;	pre-dose, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 336 hours post-dose
Secondary	Pharmacokinetic (PK) profile of SHR-1816 - Tmax	Tmax, time of occurrence of Cmax;	pre-dose, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 336 hours post-dose
Secondary	Pharmacokinetic (PK) profile of SHR-1816 - Vz/F	Vz/F, apparent volume of distribution;	pre-dose, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 336 hours post-dose
Secondary	Pharmacokinetic (PK) profile of SHR-1816 - CL/F	CL/F, apparent clearance;	pre-dose, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 336 hours post-dose
Secondary	Pharmacokinetic (PK) profile of SHR-1816 - t1/2	t1/2, terminal half-life;	pre-dose, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 336 hours post-dose
Secondary	Pharmacokinetic (PK) profile of SHR-1816 - MRTinf	MRTinf, mean residence time from time 0 to infinity.	pre-dose, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 336 hours post-dose
Secondary	Pharmacodynamic (PD) profile of doses of SHR-1816 - fasting blood glucose		Day-1 to Day15/Day29
Secondary	Pharmacodynamic (PD) profile of doses of SHR-1816 - insulin		Day-1 to Day15/Day29
Secondary	Pharmacodynamic (PD) profile of doses of SHR-1816 - C-peptide		Day-1 to Day15/Day29
Secondary	Pharmacodynamic (PD) profile of doses of SHR-1816 - glucagon		Day-1 to Day15/Day29
Secondary	Pharmacodynamic (PD) profile of doses of SHR-1816 - total GLP-1		Day-1 to Day15/Day29
Secondary	Pharmacodynamic (PD) profile of doses of SHR-1816 - active GLP-1		Day-1 to Day15/Day29
Secondary	Pharmacodynamic (PD) profile of doses of SHR-1816 - fructosamine		Day-1 to Day15/Day29
Secondary	PD profile of multiple doses of SHR-1816 - HbA1c		Day-1, Day29
Secondary	PD profile of multiple doses of SHR-1816 - 7-points glucose profile		Day-1 to Day15/Day29
Secondary	PD profile of multiple doses of SHR-1816 - weight		Day-1 to Day15/Day29
Secondary	Immunogenicity	Incidence of SHR-1816 antibody formation.	Day1 to Day29/Day50