Clinical trial NCT02077452: Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HMS5552 in Patients With Type 2 Diabetes
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 2 Diabetes Mellitus
Keywords: Glucokinase activator
Phase I
Type 2 diabetes mellitus
Lead sponsor: Hua Medicine Limited
Sponsor class: INDUSTRY
First posted: 2014-03-04
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety and tolerability of HMS5552 will be assessed by adverse event monitoring, physical examinations, 12 lead ECGs, vital sign, and safety laboratory measurements.
timeFrame: up to 15 days after study drug administration
Secondary outcomes:
measure: 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.
timeFrame: up to day 8 post-dose
measure: 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.
timeFrame: up to 4 hour post-dose and up to 24 hour post-dose
measure: Insulin, C-peptide, glucagon and glucagon-like peptide 1 up to 6hr post-dose following single dose and steady state (fasting and postprandial)
timeFrame: up to 6 hour post-dose
Other outcomes:
Locations:
Study officials:
affiliation: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
name: Dalong ZHU, MD
role: PRINCIPAL_INVESTIGATOR
References: