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

A Randomized, Double-blinded, Placebo-Controlled Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple Ascending Doses of HMS5552 in Adult Patients With Type 2 Diabetes Mellitus

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Placebo; Drug: HMS5552

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 Type: Interventional
• Enrollment (Actual): 53
• 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:

• 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 Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HMS5552 dose 1; HMS5552 25~400mg. Oral administration, twice per day.	Drug: Placebo; Drug: HMS5552
Experimental: HMS5552 dose 2; HMS5552 25~400mg. Oral administration, twice per day.	Drug: Placebo; Drug: HMS5552
Experimental: HMS5552 dose 3; HMS5552 25~400mg. Oral administration, twice per day.	Drug: Placebo; Drug: HMS5552
Experimental: HMS5552 dose 4; HMS5552 25~400mg. Oral administration, once per day.	Drug: Placebo; Drug: HMS5552
Experimental: HMS5552 dose 5; HMS5552 25~400mg. Oral administration, twice per day.	Drug: Placebo; Drug: HMS5552

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Measure Description	Time Frame
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.	Single dose (Day 1) plasma and urine pharmacokinetic parameters (postprandial); Single dose (Day 3) plasma and urine pharmacokinetic parameters (fasting); Steady state (Day 7) plasma and urine pharmacokinetic parameters (postprandial); Steady state (Day 8) plasma and urine pharmacokinetic parameters (fasting)	up to day 8 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
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

Collaborators and Investigators

• Sponsor: Hua Medicine Limited
• Investigators: Principal Investigator: Dalong ZHU, MD, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: March 2, 2014
• First Submitted That Met QC Criteria: March 3, 2014
• First Posted (Estimate): March 4, 2014

Study Record Updates

• Last Update Posted (Actual): November 20, 2017
• Last Update Submitted That Met QC Criteria: November 17, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: Phase I; Type 2 diabetes mellitus; Glucokinase activator
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: HMM0102