Study of AC-201 in Patients With Type 2 Diabetes Mellitus

This is a 24-week randomized placebo-controlled study to investigate the effect of an oral IL-1beta inhibitor AC-201 in patients with type 2 diabetes mellitus already treated on different background diabetes therapies.

• Drug: AC-201
  Capsule, 25mg BID
• Drug: AC-201
  Capsule, 75mg BID
• Drug: Placebo
  Capsule, BID
• Drug: AC-201
  Capsule, 50mg BID

• Experimental: AC-201, 25mg BID
  Intervention: Drug: AC-201
• Experimental: AC-201, 50mg BID
  Intervention: Drug: AC-201
• Experimental: AC-201, 75mg BID
  Intervention: Drug: AC-201
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

Inclusion Criteria:

• Understanding of the study procedures and agreement to participate in the study by giving written informed consent;
• Males and females age 20 to 75 years, inclusive;
• HbA1c ≥7.5% and ≤10%;
• BMI ≤45 kg/m2;
• FPG ≤270 mg/dL;
• Diagnosis of type 2 diabetes mellitus for ≥6 months;
• On a stable regimen of oral anti-diabetic medications for ≥3 months: monotherapy with metformin, SFU, non-SFU insulin secretagogues, DPP-4 inhibitors, TZD, alpha-glucosidase inhibitors, or a combination of up to 3 of these medications;
• Willingness to maintain stable diet and exercise throughout the study;
• Willingness to maintain current doses/regimens of vitamins and dietary supplements throughout the study; and
• Female patients of childbearing potential and female partners of male patients must be willing to use adequate contraception (double barrier methods, hormonal contraceptives, or intrauterine device) during the study. All females of childbearing potential must have a negative urine pregnancy test at screening.

Exclusion Criteria:

• History of type 1 diabetes and/or history of ketoacidosis;
• History of diabetic neuropathy resulting in significant functional impairment and/or requiring active medical or surgical management, including chronic pain syndromes, gastroparesis, skin ulceration, or amputation;
• History of long-term therapy with insulin (>30 days) within 1 year of screening;
• Pregnancy or lactation;

• Current treatment with any of the following medications within 2 months of screening:

  • Anti inflammatory drugs, including chronic daily use of systemic corticosteroids (aspirin ≤325 mg per day is allowed);
  • IL-1 modulators: anakinra and rilonacept; or
  • Immunosuppressive drugs: TNF inhibitors (etanercept and pegsunercept) and IL-6 monoclonal antibody (elsilimomab);
• History of severe hypoglycemic episodes within 6 months of screening (see Section 6.3);
• Hypersensitivity to AC-201 or anthraquinone derivatives;
• Surgery within 30 days prior to screening;
• Serum creatinine >1.5 mg/dL for males or >1.4 mg/dL for females;
• Presence of cancer or history of cancer within the past 5 years other than basal or squamous cell carcinoma of the skin and carcinoma in situ of the cervix;
• Advanced stage heart failure: New York Heart Association Class III or IV cardiac status or hospitalization for congestive heart failure;
• History of unstable angina, myocardial infarction, uncontrolled arrhythmias, cerebrovascular accident, transient ischemic attack, or any revascularization, including percutaneous transluminal coronary angioplasty, within 6 months of screening;
• Uncontrolled hypertension (defined as systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg on ≥3 assessments at screening);
• Known to be infected with human immunodeficiency virus (HIV);
• History of acquired immune deficiency syndrome;
• History of TB, active TB (pulmonary, extra-pulmonary, or military), or a positive test for TB confirmed by a PA chest x-ray within 6 months prior to screening;
• History of acute infection with Epstein-Barr Virus (EBV), cytomegalovirus (CMV), or hepatitis C virus (HCV) within 4 weeks prior to screening;
• History of chronic active (not latent) hepatitis B virus, HCV, or CMV infection;
• History of drug or alcohol abuse;
• Aspartate aminotransferase >3 × the upper limit of normal (ULN) or alanine aminotransferase >3 × ULN at screening;
• Total bilirubin >1.5 × ULN at screening;
• Triglycerides >500 mg/dL at screening;
• Poor mental function or any other reason to expect patient difficulty in complying with the study requirements;
• Acute infections that may affect blood glucose control within 4 weeks prior to screening;
• Known bilateral renal artery stenosis, patient with a solitary kidney, or a post renal transplant;
• History of autoimmune disease or collagen vascular disease;
• History of hyperthyroidism or hypocorticism;
• Participation in any AC-201 studies within 1 year prior to screening;
• Participation in an investigational drug study within 30 days prior to screening; or
• Any other serious diseases which, in the opinion of the investigator, might pose a risk to the patient or make participation not in the patient's best interest.