A Phase 1, Randomized, Placebo-controlled, Multiple Dose Escalation Study to Investigate Safety, Pharmacokinetics, and Pharmacodynamics of SHR0534 in Chinese Type 2 Diabetic Patients

This is a randomized, placebo-controlled, multiple dose escalation study to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of SHR0534. The study will be conducted with dose of 5 mg, 10mg and 25 mg. Chinese Type 2 Diabetic patients will be randomized in each cohort to receive the study drug or placebo.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetic Patients
• Intervention / Treatment: Drug: Placebo; Drug: SHR0534

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Type 2 diabetes diagnosed for more than 3 months;
• HbA1c between ≥7.0 and ≤10.5% for naive patients, or ≥6.5 and ≤9.5% for patients treated with single oral drug, with FPG ≤13.9 mmol/L at randomization;
• Body Mass Index (BMI) between 18 and 40 kg/m^2 (inclusive) with a total body weight of at least 50 kg;
• Agree to stop any other drugs for diabetes during washout and study period;
• Serum C peptide concentration ≥0.8ng/mL at randomization.

Exclusion Criteria:

• Participated any drug clinical trials within 3 months or ≥3 times during the last year, or had blood donation/loss≥400mL or as Blood recipient within 3 months before randomization;
• History use of Insulin within 6 months;
• Drug or alcohol abuse within 6 months;
• Use any other hypoglycemic drugs or weight reducing drugs within 3 months, or use any grug or dietary supplements within 1 weeks prior to screening ;
• Underwent surgical procedures within 1 month prior to screening, or planned major surgical procedures during the study period;
• Subject who cannot refrain from smoking, eating and/or drinking containing xanthine/caffeine, or strenuous exercise, or others that affect drug absorption, distribution, metabolism and excretion within 2 days before the study drug administration;
• With active hepatitis;
• Uncontrolled endocrine system diseases (such as hyperthyroidism, hypothyroidism, Cushing syndrome, multiple endocrine neoplasia);
• Uncontrolled hypertension with systolic blood pressure (SBP) > 160mmHg and / or diastolic pressure (DBP) > 100 mmHg after drug treatment;
• History of recurrent severe hypoglycemia;
• With severe chronic gastrointestinal disease (e.g., an active ulcer within 6 months) or treatment that may affect drug absorption (e.g., gastrointestinal surgery);
• With any cancer (other than skin basal cell carcinoma) that has been treated or untreated within the last 5 years;
• History of decompensated heart failure (NYHA grade III and IV), unstable angina, stroke or transient ischemic attack, persistent myocardial infarction, and the clinical significance of arrhythmia (such as frequent contractions), or had coronary artery bypass grafting or percutaneous coronary intervention within 6 months;
• History of acute metabolic complications, or proliferative retinopathy or maculopathy which required acute treatment within 6 months;
• Severe trauma or severe infection that may affect glycemic control within 1 months before screening;
• AST, ALT or TBIL>1.5×UNL, or Cre>1.5 mg/dL(male)/1.4 mg/dL(female), or ACR>300mg/g at screening;
• Positive of hepatitis B surface antigen, hepatitis C antibody, HIV antibody or syphilis antibody;
• With clinical significance abnormal of ECGs, such as II or III degree atrioventricular block (except right bundle branch block), long QT syndrome or QTc>500 MS;
• Subject was not suitable for the study as determined by the Investigator.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Twelve Type 2 Diabetic Patients were randomized in 5:1 ratio to receive multiple (30 days) oral dose of 5 mg SHR0534 or matching placebo.	Drug: Placebo; Drug: SHR0534
Experimental: Cohort 2; Twelve Type 2 Diabetic Patients were randomized in 5:1 ratio to receive multiple (30 days) oral dose of 10 mg SHR0534 or matching placebo.	Drug: Placebo; Drug: SHR0534
Experimental: Cohort 3; Twelve Type 2 Diabetic Patients were randomized in 5:1 ratio to receive multiple (30 days) oral dose of 25 mg SHR0534 or matching placebo.	Drug: Placebo; Drug: SHR0534

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of treatment emergent adverse events	From baseline up to 8 days after last treatment (Day 38)
Area under the plasma concentration curve after the first and last multiple oral dose (AUC)	From time 0 to 24 hours for the first dose, and from time 0 to 192 hours after the last dose
Peak plasma concentration (Cmax) after the first and last multiple oral dose	From time 0 to 24 hours for the first dose, and from time 0 to 192 hours after the last dose
Terminal elimination halflife (t½) for SHR0534 after the last multiple oral dose	From time 0 to 192 hours after the last dose
Changes in the concentrations of blood glucose and insulin after multiple oral dose	From baseline up to 24 hours after last treatment (Day 31)]

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: December 28, 2016
• First Submitted That Met QC Criteria: December 28, 2016
• First Posted (Estimate): December 30, 2016

Study Record Updates

• Last Update Posted (Estimate): December 30, 2016
• Last Update Submitted That Met QC Criteria: December 28, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Other Study ID Numbers: SHR0534-Ib

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO