Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HMS5552 in Patients With Type 2 Diabetes

Phase 1

Completed

• Conditions: Type 2 Diabetes Mellitus
• Interventions: Drug: HMS5552; Drug: Placebo

• Registration Number: NCT02077452
• Lead Sponsor: Hua Medicine Limited

Brief Summary

The objectives of this study is to determine the safety, tolerability, pharmacokinetics and pharmacodynamics of HMS5552 following multiple ascending doses in patients with type 2 diabetes mellitus.

Detailed Description

This will be a randomized, double-blind and placebo-controlled study with multiple oral doses of HMS5552 given to patients with type 2 diabetes mellitus who never accepted anti-diabetic drug for treatment before.

The primary objective is to characterize the safety and tolerability of HMS5552 following multiple ascending doses in patients with type 2 diabetes mellitus after BID dosing for 8 days.

The secondary objectives include:

1. To determine the single dose and steady state pharmacokinetics of HMS5552 in patients with type 2 diabetes

2. To evaluate the single dose and steady state pharmacodynamics of HMS5552 in patients with type 2 diabetes

3. To further explore food-effect on HMS5552 pharmacokinetics and pharmacodynamics

A maximum total of 80 patients (10 in each dose group and assuming a maximum of 5\~8 dose levels). There will be 8 active and 2 placebo patients in each dose group. The safety, tolerability, pharmacokinetics and pharmacodynamics data after each dose cohort will be reviewed in blinded fashion before escalation to the next dose cohort.

Study Timeline

• Study Start: 2014-03
• Study First Submitted: 2014-03-02
• Study First Submitted QC: 2014-03-03
• Study First Posted: 2014-03-04
• Primary Completion: 2014-09
• Study Completion: 2014-10
• Status Verified: 2017-11
• Last Update Submitted: 2017-11-17
• Last Update Posted: 2017-11-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 53

Inclusion Criteria

• Male and female subjects with type 2 diabetes
• Age: 18 to 65 years
• BMI: 20 to 29 kg/m2
• Mentally, physically and legally eligible to give informed consent.
• Willingness to adhere to the protocol requirement.

Exclusion Criteria

• Subjects with type 1 diabetes
• Episodes of hypoglycemia
• Unstable cardiovascular diseases
• Hepatic diseases
• Kidney disease
• Mental or central nervous system diseases
• Clinical abnormal findings in ECG, labs and physical exams

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
HMS5552 dose 3	HMS5552	HMS5552 25\~400mg. Oral administration, twice per day.
HMS5552 dose 4	HMS5552	HMS5552 25\~400mg. Oral administration, once per day.
HMS5552 dose 4	Placebo	HMS5552 25\~400mg. Oral administration, once per day.
HMS5552 dose 5	HMS5552	HMS5552 25\~400mg. Oral administration, twice per day.
HMS5552 dose 5	Placebo	HMS5552 25\~400mg. Oral administration, twice per day.
HMS5552 dose 1	HMS5552	HMS5552 25\~400mg. Oral administration, twice per day.
HMS5552 dose 1	Placebo	HMS5552 25\~400mg. Oral administration, twice per day.
HMS5552 dose 2	HMS5552	HMS5552 25\~400mg. Oral administration, twice per day.
HMS5552 dose 2	Placebo	HMS5552 25\~400mg. Oral administration, twice per day.
HMS5552 dose 3	Placebo	HMS5552 25\~400mg. Oral administration, twice per day.

Primary Outcome Measures

Name	Time	Method
Safety and tolerability of HMS5552 will be assessed by adverse event monitoring, physical examinations, 12 lead ECGs, vital sign, and safety laboratory measurements.	up to 15 days after study drug administration

Secondary Outcome Measures

Name	Time	Method
The single dose and steady state pharmacokinetics (with food and fasting) of HMS5552 will be described by estimating parameters of AUCinf, AUC0-t, Cmax, Tmax, Ae, T1/2, CL/f, CLr/f, accumulation index and fluctuation index.	up to day 8 post-dose	1. Single dose (Day 1) plasma and urine pharmacokinetic parameters (postprandial); 2. Single dose (Day 3) plasma and urine pharmacokinetic parameters (fasting); 3. Steady state (Day 7) plasma and urine pharmacokinetic parameters (postprandial); 4. Steady state (Day 8) plasma and urine pharmacokinetic parameters (fasting)
Insulin, C-peptide, glucagon and glucagon-like peptide 1 up to 6hr post-dose following single dose and steady state (fasting and postprandial)	up to 6 hour post-dose
The single dose and steady state (fasting and postprandial) pharmacodynamic variables will include maximum absolute and percent change in plasma glucose level, AUC0-4, AUC0-16, AUC16-24, AUC0-24 hr of plasma glucose.	up to 4 hour post-dose and up to 24 hour post-dose