Clinical trial NCT00525577: ANDES-AGI-1067 as a Novel Antidiabetic Agent Evaluation Study
Official title: AGI-1067 as a Novel Antidiabetic Agent Evaluation Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Diabetes
Keywords: Type 2 diabetes, glycemic control
Lead sponsor: AtheroGenics
Sponsor class: INDUSTRY
First posted: 2007-09-06
Enrollment: 1012
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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.

Primary outcomes:
measure: Change from baseline in HbA1c to the 6-month time point is identical in the study groups (placebo and AGI-1067 treatment groups)
timeFrame: 6 month
Secondary outcomes:
measure: • Change of HbA1c from baseline throughout the study • Change of FPG from baseline throughout the study•
timeFrame: 6 month
Other outcomes:
Locations:
city: Stockbridge
country: United States
facility: Clinical Research Atlanta
state: Georgia
city: San Antonio
country: United States
facility: Diabetes and Glandular Disease
state: Texas
city: Banja Luka
country: Bosnia and Herzegovina
facility: Clinic for the Internal Medicine-Clinical Center Banja Luka
city: Belgrade
country: Former Serbia and Montenegro
facility: Institute for Endocrinology, Diabetes and Metabolic-Clinical Center Serbia
city: Bijelo Polje
country: Former Serbia and Montenegro
facility: Clinic for the Internal Medicine-Clinical Cente Bijelo Polje
city: Kotor
country: Former Serbia and Montenegro
facility: Clinic for the Internal Medicine-Clinical Cente Kotor
city: Kragujevac
country: Former Serbia and Montenegro
facility: Clinic for the Internal Medicine-Clinical Cente Kragujevac
city: Nis
country: Former Serbia and Montenegro
facility: Clinic of endocrinologyClinical Center Nis
city: Podgorica
country: Former Serbia and Montenegro
facility: Clinic for the Internal Medicine-Clinical Center Podgorica
city: Tbilisi
country: Georgia
facility: Center of Endocrinology, Metabology & Nutriology
city: Tbilisi
country: Georgia
facility: Diagnostic Services Ltd.
city: Tbilisi
country: Georgia
facility: Georgian Diabetes Center
city: Tbilisi
country: Georgia
facility: Healthy Life Center
city: Tbilisi
country: Georgia
facility: Institute of Cardiology
city: Tbilisi
country: Georgia
facility: Tbilisi Center of Endocrinology
city: Tbilisi
country: Georgia
facility: Tbilisi State Medical University Clinic #1
city: Ahmedabad
country: India
facility: Second floor , Silver Brook Building,
city: Ahmedabad
country: India
facility: Shantiniketan Hospital
city: Bangalore
country: India
facility: Bangalore Diabetes
city: Bangalore
country: India
facility: Bhagwan Mahaveer Jain Hospital
city: Bangalore
country: India
facility: M.s. Ramaiah Memorial Hospital
city: Bangalore
country: India
facility: St. Johns Medical College and Hospital,
city: Belgaum
country: India
facility: Belgaum Diabetes Centre
city: Chennai
country: India
facility: Dr. V Seshiah Diabetes Care and Research Institute
city: Chennai
country: India
facility: Madras Research Center
city: Chennai
country: India
facility: Sri Ramachandra Medical Centre
city: Cochin
country: India
facility: Amrita Institute of Medical Sciences
city: Hyderabaad
country: India
facility: Mediciti Hospital, 5-9-22
city: Hyderabaad
country: India
facility: Medwin Hospitals
city: Hyderabaad
country: India
facility: Sai's Endocrine and Growth Centre
city: Jaipur
country: India
facility: Diabetes, Thyroid and Endocrine
city: Jaipur
country: India
facility: Saytam Hospital and Research Centre
city: Ludhiana
country: India
facility: Dayanand Medical College & Hospital
city: Mumbai
country: India
facility: IRL-Synexus Clinical Research Centre
city: Mumbai
country: India
facility: Medicine C Railway Hospital, Byculla
city: Mumbai
country: India
facility: T.N.M. College & BYL Nair CH
city: Mumbai
country: India
facility: TMMC&LTMGH, Sion Hospital
city: New Dehli
country: India
facility: All India Institute of Medical Sciences
city: New Dehli
country: India
facility: Apollo Health Education Research and Foundation(AHERF)
city: New Dehli
country: India
facility: Fortis Flt. Lt. Rajan Dhall Hospital
city: New Dehli
country: India
facility: Maulana Azad Medical College and Lok Nayak Hospital
city: New Dehli
country: India
facility: Sir Ganga Ram Hospital
city: Pune
country: India
facility: Jehangir Hospital
city: Pune
country: India
facility: Orange Diabetes Speciality Clinic
city: Trivandrum
country: India
facility: SUT Hospital
city: Visakhapatnam
country: India
facility: Endocrine & Diabetes Centre
city: Bitola
country: Macedonia, The Former Yugoslav Republic of
facility: Clinical Hospital "Dr. Trifun Panovski"
city: Kumanovo
country: Macedonia, The Former Yugoslav Republic of
facility: General Hospital, Kumanovo
city: Ohrid,
country: Macedonia, The Former Yugoslav Republic of
facility: General Hospital, Ohrid,
city: Skopje
country: Macedonia, The Former Yugoslav Republic of
facility: University Clinical Center Skopje
city: Bloemfontein
country: South Africa
facility: Josha Research, Rubins Building
city: Bloemfontein
country: South Africa
facility: Quinta Research
city: Cape Town
country: South Africa
facility: 21 Concert Boulevard
city: Cape Town
country: South Africa
facility: Brooklyn Medical Centre
city: Cape Town
country: South Africa
facility: Paarl Research Centre, Medicross Paarl
city: Cape Town
country: South Africa
facility: Tiervlei Trial Centre, Karl Bremer Hospital
city: Cape Town
country: South Africa
facility: TREAD Research Tygerberg Hosp
city: Chatsworth
country: South Africa
facility: 8 Flamco Terrace
city: Durban
country: South Africa
facility: 203 Maxwell Centre
city: Durban
country: South Africa
facility: 700 Medi Centre
city: Durban
country: South Africa
facility: Mount Edgecombe Medical Centre, Suite 15
city: Durban
country: South Africa
facility: Randles Rd Medical Centre
city: Johannesburg
country: South Africa
facility: 1644 Starling Street
city: Johannesburg
country: South Africa
facility: Centre for Diabetes & Endocrinology
city: Johannesburg
country: South Africa
facility: DJW Navorsing
city: Johannesburg
country: South Africa
facility: Melrose Arch
city: Johannesburg
country: South Africa
facility: Seva Sadan, Room 6
city: Johannesburg
country: South Africa
facility: Union Hospital, Room 209
city: Johannesburg
country: South Africa
facility: Wits Donald Gordon Clinical Trial Site
city: Port elizabeth
country: South Africa
facility: Mercantile Hospital
city: Pretoria
country: South Africa
facility: 122 Louis Pasteur Building
city: Pretoria
country: South Africa
facility: 456 Leyd Steer
city: Pretoria
country: South Africa
facility: Eastmed Medical Centre
city: Pretoria
country: South Africa
facility: GCT Trial Centre Jubilee, Jubilee Hospital
city: Richards Bay
country: South Africa
facility: The Bay Hospital, Suite M5
city: Somerset West
country: South Africa
facility: Helderberg Diabetes and Medical Centre
city: Umhlanga
country: South Africa
facility: 14 Medgate Medical Centre
city: Chernivtsy
country: Ukraine
facility: Department of Endocrinology of Bukovina State Medical University
city: Kharkov
country: Ukraine
facility: Institute of Problem of Endocrinological Pathology UAMS.
city: Kharkov
country: Ukraine
facility: Kharkov Regional Clinical Hospital
city: Kiev
country: Ukraine
facility: Bogomolets National Medical University
city: Kiev
country: Ukraine
facility: Department of Endocrinology, Scientific Center of Radiation Medicine
city: Kiev
country: Ukraine
facility: Komisarenko Institute of Endocrinology and Metabolism of UAMS
city: Kiev
country: Ukraine
facility: Ukrainian Scientific and Practical Center of Endocrinology Surgery
city: Lviv
country: Ukraine
facility: Lviv Regional Endocrinology Health Center
city: Odessa
country: Ukraine
facility: Odessa State Medical University.
city: Poltava
country: Ukraine
facility: M.V. Sklifosovskiy Regional Clinical Hospital.
city: Simferopol
country: Ukraine
facility: Semashko Republic Clinical Hospital
city: Vinnitsa
country: Ukraine
facility: Reginal Clinical Endocrinological Health Center
city: Zaporizhya
country: Ukraine
facility: Basin Clinical Hospital
Study officials:
affiliation: AtheroGenics, Inc
name: Walker Long, MD
role: STUDY_CHAIR
References: