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

Phase 2

Completed

Conditions: Diabetes

Interventions: Drug: Oral Hepatic Directed Vesicles (HDV)-Insulin (U-5)
Drug: placebo
Drug: Oral Hepatic Directed Vesicles (HDV)-Insulin (U-15)

Registration Number: NCT00814294

Lead Sponsor: Diasome Pharmaceuticals

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 239

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2; Oral Hepatic Directed Vesicles (HDV)-Insulin (U-5)	Oral Hepatic Directed Vesicles (HDV)-Insulin (U-5)	Patients receive Oral HDV-Insulin (U-5).
1; Placebo	placebo	Patients receive a sugar pill.
3; Oral Hepatic Directed Vesicles (HDV)-Insulin (U-15)	Oral Hepatic Directed Vesicles (HDV)-Insulin (U-15)	Patients receive Oral HDV-Insulin (U-15).

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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
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