Tolerability, Safety, and Efficacy Study of INGAP Peptide to Treat Type 1 Diabetes Mellitus in Adults

This study has been terminated.
(Preserve clinical supplies)
Sponsor:
Information provided by (Responsible Party):
Exsulin Corporation
ClinicalTrials.gov Identifier:
NCT00995540
First received: October 13, 2009
Last updated: February 11, 2014
Last verified: February 2014
  Purpose

INGAP Peptide acetate is the active ingredient of INGAP Peptide Solution for Injection. It is being developed as an antidiabetic agent for the restoration of endogenous insulin secretion in patients with type 1 diabetes mellitus (T1DM) and in insulin-deficient patients with type 2 diabetes mellitus (T2DM). This clinical study is designed to generate additional data regarding the appropriate dose and dosing regimen and to evaluate safety and efficacy in patients with T1DM.


Condition Intervention Phase
Type 1 Diabetes Mellitus
Drug: INGAP Peptide
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Multiple-center, Randomized, Double-blind, Placebo-controlled, Parallel Study to Assess the Tolerability, Safety, and Efficacy of INGAP Peptide Given Subcutaneously as Injections t.i.d. for 12 Weeks in Adult Patients With Type 1 Diabetes Mellitus

Resource links provided by NLM:


Further study details as provided by Exsulin Corporation:

Primary Outcome Measures:
  • Injection tolerability [ Time Frame: 4-8-12-16 weeks ] [ Designated as safety issue: Yes ]
    Local injection site


Secondary Outcome Measures:
  • C-peptide [ Time Frame: 4-8-12-16 weeks ] [ Designated as safety issue: No ]
    Maximal C-peptide (Cmax) and C-peptide AUC during mixed meal test


Enrollment: 23
Study Start Date: November 2009
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Placebo subcutaneous injection tid for 12 weeks
Drug: Placebo
Placebo tid subcutaneous injection for 12 weeks
Active Comparator: 100 mg INGAP Peptide tid
100 mg INGAP Peptide tid subcutaneous injection for 12 weeks
Drug: INGAP Peptide
100 mg INGAP Peptide tid subcutaneous injection for 12 weeks
Other Name: Exsulin
Active Comparator: 200 mg INGAP Peptide tid
200 mg INGAP Peptide tid subcutaneous injection for 12 weeks
Drug: INGAP Peptide
200 mg INGAP Peptide tid subcutaneous injection for 12 weeks
Other Name: Exsulin

Detailed Description:

In contrast to currently approved therapies that are directed at controlling either the metabolic abnormalities or tissue complications of diabetes, INGAP Peptide therapy is intended to restore ß cell mass and islet cell function. INGAP Peptide has been identified as a substance that induces islet cell regeneration from progenitor cells resident in the pancreas in a manner that recapitulates islet development during normal embryogenesis.

INGAP Peptide therapy has been evaluated in phase 1 and 2 studies of both T1DM and T2DM patients (Dungan K, Diab Met Res Rev 2009; 25:558-565). Once daily injections of INGAP Peptide for 3 months caused a statistically significant increase in C peptide secretion in T1DM patients, and a trend towards increased C-peptide levels was seen in T2DM patients. Glycosylated hemoglobin (HbA1c) decreased by -0.6% (p<0.0125) in T2DM patients and by -0.4% (p<0.06) in T1DM patients.

Given the very short half-life or INGAP Peptide (i.e., <1 hour), the findings of these earlier phase 2 studies in patients with T1DM and T2DM are very encouraging in that despite suboptimal exposure to the drug, there was evidence of efficacy. Local injection site reactions observed in those studies may have been due to relatively large doses of formulations that were not optimized for tonicity and patient comfort.

This study has been designed such that the dose of INGAP Peptide will be divided across three daily administrations using a formulation that has been improved with respect to tonicity. The study will evaluate the safety, tolerability and C-peptide response associated with this dosing regimen in patients with T1DM.

  Eligibility

Ages Eligible for Study:   19 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients meeting all of the following criteria will be eligible for enrollment in the study:

  • Male and female patients between the ages of 19 and 60 years old, inclusive, with a history of T1DM for >2 years and ≤40 years;
  • Receiving multiple daily insulin injections or insulin pump therapy for >2 years;
  • Body mass index (BMI) ≤32 kg/m2;
  • HbA1c ≤7.7%;
  • Fasting C-peptide levels <0.6 ng/mL
  • Willing to sign the study informed consent document;
  • In good general health with no late severe complications or concomitant medical conditions that would influence the outcome of the trial, at the discretion of the Investigator and the Sponsor;
  • If treated with angiotensin-converting enzymes/angiotensin II receptor blockers (ACE/ARB), the doses should be unchanged for a month prior to enrollment; and
  • Females of child bearing potential must have a negative urine pregnancy test on Day 0 prior to dispensing drug and should additionally fulfill one of the following criteria:

    • Willing to use oral, implantable, transdermal, or injectable contraceptives for 21 days prior to the first dose and until 28 days after the last dose; or,
    • Willing to use another reliable means of contraception approved by the Investigator (intrauterine device, female condom, diaphragm with spermicide, cervical cap, use of condom by sexual partner, or a sterile sexual partner) from Screening until after the last blood sample (at Week 16).

Exclusion Criteria:

Patients meeting any of the following criteria will be excluded from study participation:

  • • Total daily insulin dosage exceeding 1.0 U/kg/day or a change in total daily insulin dose level of more than 50% (increase or decrease) within the past 3 months;
  • Treatment with any diabetes medication other than insulin;
  • A score of 4 or more restricted responses on the Clarke Hypoglycemia Awareness Survey;
  • Systolic or diastolic blood pressure >180 mmHg or >110 mmHg, respectively;
  • Clinical worsening of retinopathy or neuropathy in the previous 3 months;
  • Clinical worsening of nephropathy in the previous 3 months, or blood urea nitrogen (BUN) and serum creatinine exceeding 50 mg/dL and 2.0 mg/dL, respectively;
  • History or presence of acute or chronic pancreatitis, including a serum amylase level >1.5 times the upper limit of normal (ULN) or a serum lipase level >2 times ULN;
  • A history or presence of any illness, disease, or condition that could impact patient safety or evaluability of drug effect, in the Investigator's opinion;
  • An episode of severe hypoglycemia (change in mental status requiring assistance) during the previous 30 days;
  • An episode of acute glycemic decompensation with associated hyperosmolar non-ketotic state or diabetic ketoacidosis during the past 6 months;
  • A serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin level >2 times ULN;
  • Received any investigational product within 30 days of admission into this study or had any prior or existing exposure to INGAP Peptide or glucagon-like peptides (GLP 1, GLP 2, or analogs);
  • Concurrent or planned participation in any other clinical study during the conduct of this study;
  • Positive urine test for cocaine, opiates, amphetamines, or cannabinoids;
  • Inability to fill out and maintain a daily diary during the screening period prior to dosing; or,
  • Human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C seropositivity in blood sample taken during screening.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00995540

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Canada, Quebec
McGill University - Montreal General Hospital
Montreal, Quebec, Canada, H3G 1A4
Sponsors and Collaborators
Exsulin Corporation
Investigators
Principal Investigator: Yogish Kudva, M.D. Mayo Clinic
Principal Investigator: George Tsoukas, MD McGill University
  More Information

No publications provided

Responsible Party: Exsulin Corporation
ClinicalTrials.gov Identifier: NCT00995540     History of Changes
Other Study ID Numbers: E-201
Study First Received: October 13, 2009
Last Updated: February 11, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by Exsulin Corporation:
T1DM
Regeneration
Islet
Beta cell
INGAP Peptide

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Autoimmune Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Immune System Diseases
Metabolic Diseases

ClinicalTrials.gov processed this record on October 22, 2014