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

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

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.

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.

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.