Safety, Tolerability, Pharmacokinetics,Pharmacodynamics Study of LAPS-Exendin in Subjects of Type 2 Diabetes Mellitus

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to investigate the safety and tolerability of repeated doses of HM11260C when given different regimens in subjects with type 2 diabetes mellitus (T2DM) on stable metformin monotherapy.

Official Title
-----------------
A Double-Masked, Randomized, Placebo-Controlled, Multiple Ascending Dose Phase 2 Study to Determine the Tolerability, Pharmacokinetics, and Pharmacodynamics of the GLP 1 Agonist HM11260C in Adult Subjects With Type 2 Diabetes Mellitus on Stable Metformin Monotherapy

Conditions
-----------------
Diabetes Mellitus

Intervention / Treatment
-----------------
* Drug: HM11260C
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Is male or female and 18 to 65 years of age, inclusive, at screening Has a history of T2DM and a stable dose of metformin Has HbA1c levels at screening between 7% and 10% Exclusion Criteria: Is pregnant or lactating Has type 1 diabetes Has a significant change in body weight in the 3 months before screening Has a fasting plasma glucose level greater than 240 mg/dL (13.3 mmol/L) at screening Has an estimated glomerular filtration rate rate <75 mL/min/1.73 m2 or has ≥75 mL/min/1.73 m2 <estimated glomerular filtration rate <90 mL/min/1.73 m2 with a urine albumin to urine creatinine ratio >30 mg/g. Has alanine aminotransferase or aspartate aminotransferase values >2.0 × upper limit of normal or total bilirubin >1.5 × upper limit of normal unless the subject has a known history of Gilbert's syndrome Has fasting serum triglycerides >400 mg/dL (>4.52 mmol/L) or >250 mg/dL (>2.85 mmol/L) if not on stable lipid-lowering therapy for at least 4 weeks prior to screening, or has calcitonin ≥50 ng/L. Subjects with a history of Fredrickson's Type I, IV or V hyperlipidemia will be excluded. Has any history of GI intolerance, chronic diarrhea, inflammatory bowel disease, partial bypass or gastric banding Has any acute illness within 5 days before first study drug administration Has elevated amylase, ongoing cholelithiasis, cholecystitis at screening, or history of pancreatitis Is a heavy tobacco user(more than 10 cigarettes a day) Is a heavy alcohol user Has a positive screen for drugs of abuse

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Placebo for 8 weekly subcutaneous injections for cohorts W1, W2 and W3. Placebo for 3 monthly subcutaneous injections for for cohorts M1, M2 and M3<br>|
| Active Comparator: HM11260C<br>HM11260C | Drug: HM11260C<br>* 1, 2, and 4 mg for 8 weekly subcutaneous injections for cohorts W1, W2 and W3. 8, 12 and 16 mg for 3 monthly subcutaneous injections for cohorts M1, M2 and M3<br>* Other names: LAPS-Exendin4;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with adverse events as a measure of safety and tolerability | Number of subjects with adverse events as a measure of safety and tolerability when given different regimens to subjects in T2DM with metformin monotherapy | Up to 106 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The pharmacokinetics in repeat-dose | Before dosing on the first dosing day (Day 1) After the first dose: 8, 24, 48, 72, 96, 120, and 144 hours after dosing Trough samples (ie, immediately before dosing) will be taken prior to dosing on Days 8, 22, 36, 57, 71, and 85 After the last dose (thirteenth dose) at 8, 24, 48, 72, 96, 120, and 144 hours after dosing and 7, 10, 14, 21, 28, and 35 days after dosing to define the elimination period of HM11260C | Day 1 up to Day 92 | 
| The pharmacodynamics in repeat-dose | HbA1c, glycosylated albumin, fructosamine, insulin, and fasting glucose: For all cohorts: screening; Day -1; before dosing on Days 29, 57, and 85; and at follow-up. | Up to 106 days |