Study of AC-201 in Patients With Type 2 Diabetes Mellitus
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: AC-201, 25mg; AC-201, 50mg; AC-201, 75mg; Placebo
Intervention description: Capsule, 25mg BID; Capsule, 50mg BID; Capsule, 75mg BID; Placebo BID
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 259.0
Sex: All
Minimum age: 20 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: AC-201; Interleukin 1 inhibitor

Summary:

      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.
    

Eligibility criteria:

        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

          -  Willingness to maintain stable diet and exercise throughout the study

          -  Willingness to maintain current doses/regimens of vitamins and dietary supplements
             throughout the study

          -  Female patients of childbearing potential and female partners of male patients must be
             willing to use adequate contraception 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

          -  Immunosuppressive drugs: TNF inhibitors and IL-6 monoclonal antibody

          -  History of severe hypoglycemic episodes within 6 months of screening

          -  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

          -  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.