Study of Two Doses of Oral HDV-Insulin and Placebo With Background Metformin Treatment in Patients With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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The primary objective of this trial is to compare the reduction in mean glycated hemoglobin levels (HbA1c) between 2 doses of oral HDV-I and placebo in type 2 diabetic patients on background metformin therapy at the end of 18 weeks of treatment. The secondary objectives are: To evaluate the effects of oral HDV-I versus placebo on the 7-point glucose test, fasting plasma glucose (FPG), insulin, homeostasis model assessment of insulin resistance (HOMA-IR), homeostasis model assessment of β-cell function (HOMA-β), frequency of hypoglycemic events, body weight, and lipid levels; and To evaluate the safety and tolerability of oral HDV-I.

Detailed Description
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This is a multicenter, randomized, double-blind, placebo-controlled study with a washout/stabilization period of up to 12 weeks in duration and an 18-week double-blind treatment period. There will be a total of 8 visits.

Official Title
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An 18-Week Randomized, Double-Blind, Multicenter, Comparator Study of Two Doses of Oral HDV-Insulin and Placebo With Background Metformin Treatment in Patients With Type 2 Diabetes Mellitus

Conditions
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Diabetes

Intervention / Treatment
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* Drug: placebo
* Drug: Oral Hepatic Directed Vesicles (HDV)-Insulin (U-15)
* Drug: Oral Hepatic Directed Vesicles (HDV)-Insulin (U-5)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 to 70 years, inclusive; Diagnosis of type 2 diabetes mellitus; Fasting plasma glucose <=250 mg/dL; BMI <=45 kg/m2; HbA1c levels as follows at Screening: On a stable dose of metformin monotherapy with an HbA1c >=7.5% and <=9.5%; On metformin and 1 other OAD (excluding TZD, exenatide, or insulin) with an HbA1c >=6.8% and <=9.0%; Naïve to antidiabetic therapy or have not been on a stable dose of metformin monotherapy for <12 weeks with an HbA1c >=8.0% and <=10.5%; Understanding of the study procedures and agreement to participate in the study, giving written informed consent; Women may be enrolled if all of the following criteria (in addition to the above criteria) are met: They are not pregnant (women of childbearing potential must have a negative serum pregnancy test at Visit 1); They are not breast-feeding; They do not plan to become pregnant during the study; and They have had a hysterectomy or tubal ligation 6 months prior to the study, have been post-menopausal for 1 year, or will practice a method of birth control throughout the study. Exclusion Criteria: History of type 1 diabetes and/or history of ketoacidosis; History of chronic (>2 months) use of insulin therapy or recent initiation of insulin use intended for chronic administration; Use of TZD (pioglitazone or rosiglitazone) or exenatide within 3 months prior to Screening; Use of prescription or over the counter weight loss agents within 1 month prior to Screening; Use of any lipid-altering, antihypertensive, and other chronic use medication not stable for 1 month prior to Screening; Use of any medication that may alter blood glucose analyses; Any serious disorder including cardiac, pulmonary, hepatic, uncontrolled endocrine/metabolic, hematologic/oncologic (within the last 5 years), neurologic, and psychiatric diseases that would interfere with the conduct of the study or interpretation of the data; Require regular use of medication that interferes with the oral absorption and/or metabolism of insulin or metformin; History of pancreatitis; History of acquired immune deficiency syndrome or human immunodeficiency virus; History of drug or alcohol abuse within the past 2 years; Hospitalization for any cause within 14 days prior to the study; History of an allergic or toxic response to oral HDV-I; Uncontrolled hypertension: systolic blood pressure >160 mmHg and diastolic blood pressure >95 mmHg; Triglycerides >400 mg/dL; Aspartate aminotransferase or alanine aminotransferase >2.5 times the upper limit of normal (ULN); Creatine phosphokinase >3 times the ULN; Patients on a weight loss program with ongoing weight loss, or starting an intensive exercise program within 4 weeks of starting the study; Use of any investigational drug within 30 days preceding the first dose of study medication; or Employment by the research center.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1; Placebo<br>Patients receive a sugar pill. | Drug: placebo<br>* placebo capsule,0 units, quater in die (QID) for 18 weeks<br>|
| Experimental: 2; Oral Hepatic Directed Vesicles (HDV)-Insulin (U-5)<br>Patients receive Oral HDV-Insulin (U-5). | Drug: Oral Hepatic Directed Vesicles (HDV)-Insulin (U-5)<br>* Oral HDV-I; Caps; 5 U; quater in die (QID) for 18 weeks.<br>|
| Experimental: 3; Oral Hepatic Directed Vesicles (HDV)-Insulin (U-15)<br>Patients receive Oral HDV-Insulin (U-15). | Drug: Oral Hepatic Directed Vesicles (HDV)-Insulin (U-15)<br>* Oral HDV-I Caps; 15 U; quater in die (QID) for 18 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary objective of this trial is to compare the reduction in mean glycated hemoglobin levels (HbA1c) between 2 doses of oral HDV-I and placebo in type 2 diabetic patients on background metformin therapy at the end of 18 weeks of treatment. |  | 18 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the effects of oral HDV-I versus placebo on the 7-point glucose test |  | 18 weeks | 
| To evaluate the effects of oral HDV-I versus placebo on fasting plasma glucose (FPG) and insulin |  | 18 weeks | 
| To evaluate the effects of oral HDV-I versus placebo on the homeostasis model assessment of insulin resistance (HOMA-IR)and homeostasis model assessment of β-cell function (HOMA-β) |  | 18 Weeks | 
| To evaluate the effects of oral HDV-I versus placebo on frequency of hypoglycemic events, body weight, and lipid levels |  | 18 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2