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

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus
• Intervention / Treatment: Drug: Placebo; Drug: HM11260C

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Ohio, Ohio, United States

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:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; 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
ACTIVE_COMPARATOR: HM11260C	Drug: HM11260C; 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; 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

Collaborators and Investigators

• Sponsor: Hanmi Pharmaceutical Company Limited

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (ACTUAL): June 1, 2013

Study Registration Dates

• First Submitted: October 4, 2011
• First Submitted That Met QC Criteria: October 13, 2011
• First Posted (ESTIMATE): October 14, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): August 9, 2016
• Last Update Submitted That Met QC Criteria: August 8, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Obesity Agents; Incretins; Exenatide
• Other Study ID Numbers: HM-EXC-202