ANDES-AGI-1067 as a Novel Antidiabetic Agent Evaluation Study (ANDES)

AGI-1067 as a Novel Antidiabetic Agent Evaluation Study

This double-blind, placebo-controlled, dose-finding study is designed to identify the lowest AGI-1067 dose that improves glycemic control as measured by HbA1c and fasting glucose in subjects with Type 2 diabetes mellitus. Glycemic control will be measured during a 6-month treatment period in subjects who are on 1 or no antidiabetic drugs

Study Overview

• Status: Unknown
• Conditions: Diabetes
• Intervention / Treatment: Drug: Placebo; Drug: AGI-1067; Drug: AGI-1067

• Study Type: Interventional
• Enrollment (Anticipated): 1012
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Bosnia and Herzegovina
  • Banja Luka, Bosnia and Herzegovina
    • Clinic for the Internal Medicine-Clinical Center Banja Luka
• Former Serbia and Montenegro
  • Belgrade, Former Serbia and Montenegro
    • Institute for Endocrinology, Diabetes and Metabolic-Clinical Center Serbia
  • Bijelo Polje, Former Serbia and Montenegro
    • Clinic for the Internal Medicine-Clinical Cente Bijelo Polje
  • Kotor, Former Serbia and Montenegro
    • Clinic for the Internal Medicine-Clinical Cente Kotor
  • Kragujevac, Former Serbia and Montenegro
    • Clinic for the Internal Medicine-Clinical Cente Kragujevac
  • Nis, Former Serbia and Montenegro
    • Clinic of endocrinologyClinical Center Nis
  • Podgorica, Former Serbia and Montenegro
    • Clinic for the Internal Medicine-Clinical Center Podgorica
• Georgia
  • Tbilisi, Georgia
    • Center of Endocrinology, Metabology & Nutriology
  • Tbilisi, Georgia
    • Diagnostic Services Ltd.
  • Tbilisi, Georgia
    • Georgian Diabetes Center
  • Tbilisi, Georgia
    • Healthy Life Center
  • Tbilisi, Georgia
    • Institute of Cardiology
  • Tbilisi, Georgia
    • Tbilisi Center of Endocrinology
  • Tbilisi, Georgia
    • Tbilisi State Medical University Clinic #1
• India
  • Ahmedabad, India
    • Second floor , Silver Brook Building,
  • Ahmedabad, India
    • Shantiniketan Hospital
  • Bangalore, India
    • Bhagwan Mahaveer Jain Hospital
  • Bangalore, India
    • Bangalore Diabetes
  • Bangalore, India
    • M.s. Ramaiah Memorial Hospital
  • Bangalore, India
    • St. Johns Medical College and Hospital,
  • Belgaum, India
    • Belgaum Diabetes Centre
  • Chennai, India
    • Dr. V Seshiah Diabetes Care and Research Institute
  • Chennai, India
    • Madras Research Center
  • Chennai, India
    • Sri Ramachandra Medical Centre
  • Cochin, India
    • Amrita Institute of Medical Sciences
  • Hyderabaad, India
    • Mediciti Hospital, 5-9-22
  • Hyderabaad, India
    • Medwin Hospitals
  • Hyderabaad, India
    • Sai's Endocrine and Growth Centre
  • Jaipur, India
    • Diabetes, Thyroid and Endocrine
  • Jaipur, India
    • Saytam Hospital and Research Centre
  • Ludhiana, India
    • Dayanand Medical College & Hospital
  • Mumbai, India
    • IRL-Synexus Clinical Research Centre
  • Mumbai, India
    • Medicine C Railway Hospital, Byculla
  • Mumbai, India
    • T.N.M. College & BYL Nair CH
  • Mumbai, India
    • TMMC&LTMGH, Sion Hospital
  • New Dehli, India
    • All India Institute of Medical Sciences
  • New Dehli, India
    • Apollo Health Education Research and Foundation(AHERF)
  • New Dehli, India
    • Fortis Flt. Lt. Rajan Dhall Hospital
  • New Dehli, India
    • Maulana Azad Medical College and Lok Nayak Hospital
  • New Dehli, India
    • Sir Ganga Ram Hospital
  • Pune, India
    • Jehangir Hospital
  • Pune, India
    • Orange Diabetes Speciality Clinic
  • Trivandrum, India
    • SUT Hospital
  • Visakhapatnam, India
    • Endocrine & Diabetes Centre
• Macedonia, The Former Yugoslav Republic of
  • Bitola, Macedonia, The Former Yugoslav Republic of
    • Clinical Hospital "Dr. Trifun Panovski"
  • Kumanovo, Macedonia, The Former Yugoslav Republic of
    • General Hospital, Kumanovo
  • Ohrid,, Macedonia, The Former Yugoslav Republic of
    • General Hospital, Ohrid,
  • Skopje, Macedonia, The Former Yugoslav Republic of
    • University Clinical Center Skopje
• South Africa
  • Bloemfontein, South Africa
    • Josha Research, Rubins Building
  • Bloemfontein, South Africa
    • Quinta Research
  • Cape Town, South Africa
    • 21 Concert Boulevard
  • Cape Town, South Africa
    • Brooklyn Medical Centre
  • Cape Town, South Africa
    • Paarl Research Centre, Medicross Paarl
  • Cape Town, South Africa
    • Tiervlei Trial Centre, Karl Bremer Hospital
  • Cape Town, South Africa
    • TREAD Research Tygerberg Hosp
  • Chatsworth, South Africa
    • 8 Flamco Terrace
  • Durban, South Africa
    • 203 Maxwell Centre
  • Durban, South Africa
    • 700 Medi Centre
  • Durban, South Africa
    • Mount Edgecombe Medical Centre, Suite 15
  • Durban, South Africa
    • Randles Rd Medical Centre
  • Johannesburg, South Africa
    • 1644 Starling Street
  • Johannesburg, South Africa
    • Centre for Diabetes & Endocrinology
  • Johannesburg, South Africa
    • DJW Navorsing
  • Johannesburg, South Africa
    • Melrose Arch
  • Johannesburg, South Africa
    • Seva Sadan, Room 6
  • Johannesburg, South Africa
    • Union Hospital, Room 209
  • Johannesburg, South Africa
    • Wits Donald Gordon Clinical Trial Site
  • Port elizabeth, South Africa
    • Mercantile Hospital
  • Pretoria, South Africa
    • Eastmed Medical Centre
  • Pretoria, South Africa
    • 122 Louis Pasteur Building
  • Pretoria, South Africa
    • 456 Leyd Steer
  • Pretoria, South Africa
    • GCT Trial Centre Jubilee, Jubilee Hospital
  • Richards Bay, South Africa
    • The Bay Hospital, Suite M5
  • Somerset West, South Africa
    • Helderberg Diabetes and Medical Centre
  • Umhlanga, South Africa
    • 14 Medgate Medical Centre
• Ukraine
  • Chernivtsy, Ukraine
    • Department of Endocrinology of Bukovina State Medical University
  • Kharkov, Ukraine
    • Institute of Problem of Endocrinological Pathology UAMS.
  • Kharkov, Ukraine
    • Kharkov Regional Clinical Hospital
  • Kiev, Ukraine
    • Bogomolets National Medical University
  • Kiev, Ukraine
    • Department of Endocrinology, Scientific Center of Radiation Medicine
  • Kiev, Ukraine
    • Komisarenko Institute of Endocrinology and Metabolism of UAMS
  • Kiev, Ukraine
    • Ukrainian Scientific and Practical Center of Endocrinology Surgery
  • Lviv, Ukraine
    • Lviv Regional Endocrinology Health Center
  • Odessa, Ukraine
    • Odessa State Medical University.
  • Poltava, Ukraine
    • M.V. Sklifosovskiy Regional Clinical Hospital.
  • Simferopol, Ukraine
    • Semashko Republic Clinical Hospital
  • Vinnitsa, Ukraine
    • Reginal Clinical Endocrinological Health Center
  • Zaporizhya, Ukraine
    • Basin Clinical Hospital
• United States
  • Georgia
    • Stockbridge, Georgia, United States, 30281
      • Clinical Research Atlanta
  • Texas
    • San Antonio, Texas, United States, 78237
      • Diabetes and Glandular Disease

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Provide informed written consent prior to entry.
2. Be male or female 18-75 years of age at the time of entry and have Type 2 diabetes for a minimum of 6 months prior to Screening 1 visit.
3. Have an HbA1c level measured at the Screening 1 and Screening 2 visits with a minimum level at ≥7.5% for both visits, as determined by the core lab analysis.
4. Be taking either 1 or no antidiabetic agents. If on an antidiabetic medication, it must be of the sulphonylurea, metformin, or glitazone class, and the dosage must have been stable for the last 3 months prior to the Screening 1 visit. Note that no combination medications (i.e., counted as more than 1 agent) will be permitted prior to Randomization and that the use of GLP mimetrics, DPPIV inhibitors, or colesevelam are not permitted (rescue medication will be allowed at 3 months).
5. Subjects who are using hormone replacement therapy must have been on stable doses of their hormone replacement therapy for at least 3 months prior to the Screening 1 visit.
6. Females must not be breast feeding or pregnant. If they are of child-bearing potential, they must be using a reliable method of birth control considered suitable by the Investigator. If on hormonal contraceptives for more than 6 months, subjects will be allowed to participate in the study provided that this therapy remains constant throughout the study and for a period of 2 months after the end of the study.

Exclusion Criteria:

1. Have Type 1 diabetes or history of ketoacidosis determined by medical history
2. Have an HbA1c of more than 10.5% or a fasting glucose of >240 mg/dL (13.3 mmol/L) at either the Screening 1 [Visit 1] or Screening 2 [Visit 2])
3. Have a history of severe diabetic neuropathy including autonomic neuropathy, gastroparesis, or lower limb ulceration or amputation.
4. Have a history of long-term therapy with insulin (>30 days) within the last year or >7 days within the last 3 months.
5. Require parenteral corticosteroids or recurrent continuous oral corticosteroid treatment (>2 weeks) within the last 3 months.
6. Use weight loss drugs (e.g., orlistat, sibutramine, phenylpropanolamine, phentermine, or similar prescription or over-the-counter medications) within 3 months of the Screening 1 visit or intentional weight loss of ≥4 kg in the previous 6 months.
7. Have had a new antidiabetic medication added, or the dose of an existing antidiabetic medication changed, in the last 3 months prior to the Screening 1 visit.
8. Have had a stroke, MI, coronary artery bypass graft (CABG), percutaneous transluminal coronary angioplasty (PTCA), or admission with unstable angina within the last 6 months prior to the Screening 1 visit.
9. Have congestive heart failure New York Heart Association Class III or IV (Appendix B).
10. Have taken any of the following drugs in 6 months prior to the Screening 1 visit: cholestyramine, colestid, cyclosporine, or isotretinoin.
11. Have acute infections requiring parenteral antibiotic treatment within the last 3 months.
12. Have uncontrolled hypertension (defined as systolic blood pressure >180 mmHg).
13. Have platelets <100,000 K/cu mm (x 103/μL) at the Screening 1 visit.
14. Have active liver disease or hepatic dysfunction (total bilirubin, aspartate aminotransferase [AST], alanine aminotransferase [ALT] >1.5 times upper limit of normal [ULN]) as determined by core lab analysis at either the Screening 1 visit or the Screening 2 visits.
15. Subjects with long QT syndrome as evidence by a QTc at the Screening 1 visit of >460 msec in males or >480 msec in females or subjects taking and requiring continued therapy with antiarrhythmic medications such as sotalol, quinidine, dofetilide, amiodarone or other drugs known to significantly prolong the QT interval (this will not include drugs associated with minor effect on the QT interval of less than 15 msec.)
16. Have known major chronic infection or major hematologic, renal, metabolic, gastrointestinal or endocrine dysfunction in the judgment of the Investigator (including diabetes mellitus too severe to allow the subject to safely participate in this study).
17. Have had a life-threatening illness or any history of cancer or malignancy within the past 5 years (except for basal cell carcinoma).
18. Have had surgery requiring inpatient admission within 30 days prior to the Screening 1 visit.
19. Considered unreliable as a study participant based on the Investigator's (or designee's) knowledge of the subject (e.g., history of alcohol or other drug abuse, inability or unwillingness to adhere to the protocol, or psychosis).
20. Have a history of intolerance or previous use of probucol within the last 5 years.
21. Have participated in a previous study with AGI-1067.
22. Have participated in any investigational drug study within 30 days prior to study entry, or expects to participate in any other investigational drug study during the course of ANDES.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1:A; Placebo	Drug: Placebo; Placebo tablet, once daily
Experimental: 2:B; AGI-1067 75 mg	Drug: AGI-1067; 75 mg AGI-1067 tablet, once daily; Other Names: AGI-1067 (succinobucol); Drug: AGI-1067; 150 mg AGI-1067 Tablet, once daily; Other Names: AGI-1067 (succinobucol)
Experimental: 3:C; AGI-1067 150 mg	Drug: AGI-1067; 75 mg AGI-1067 tablet, once daily; Other Names: AGI-1067 (succinobucol); Drug: AGI-1067; 150 mg AGI-1067 Tablet, once daily; Other Names: AGI-1067 (succinobucol)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in HbA1c to the 6-month time point is identical in the study groups (placebo and AGI-1067 treatment groups)	6 month

Secondary Outcome Measures

Outcome Measure	Time Frame
• Change of HbA1c from baseline throughout the study • Change of FPG from baseline throughout the study•	6 month

Collaborators and Investigators

• Sponsor: AtheroGenics
• Investigators: Study Chair: Walker Long, MD, AtheroGenics, Inc

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (Anticipated): June 1, 2008
• Study Completion (Anticipated): September 1, 2008

Study Registration Dates

• First Submitted: September 4, 2007
• First Submitted That Met QC Criteria: September 4, 2007
• First Posted (Estimate): September 6, 2007

Study Record Updates

• Last Update Posted (Estimate): February 6, 2008
• Last Update Submitted That Met QC Criteria: February 4, 2008
• Last Verified: February 1, 2008

More Information

Terms related to this study

• Keywords: Type 2 diabetes, glycemic control
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Protective Agents; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Antioxidants; Probucol
• Other Study ID Numbers: AGI-1067-052