Clinical trial NCT01276106: Study of AC-201 in Patients With Type 2 Diabetes Mellitus
Official title: A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Phase II Study of AC-201 in Patients With Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 2 Diabetes Mellitus
Keywords: AC-201
Interleukin 1 inhibitor
Lead sponsor: TWi Biotechnology, Inc.
Sponsor class: INDUSTRY
First posted: 2011-01-13
Enrollment: 259
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Change in HbA1c From Baseline
timeFrame: 24 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Chino
country: United States
facility: Catalina Research Institute, LLC
state: California
city: Los Angeles
country: United States
facility: National Research Institute
state: California
city: Coral Gables
country: United States
facility: Clinical Research of South Florida
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Impotence Treatment Center
state: Florida
city: Chicago
country: United States
facility: Chicago Clinical Research Institute, Inc.
state: Illinois
city: Gurnee
country: United States
facility: Clinical Investigation Specialists, Inc.
state: Illinois
city: Indianapolis
country: United States
facility: Midwest Institute for Clinical Research, Inc.
state: Indiana
city: Louisville
country: United States
facility: L-MARC Research Center
state: Kentucky
city: New Orleans
country: United States
facility: New Orleans Center for Clinical Research
state: Louisiana
city: Cincinnati
country: United States
facility: Sterling Research Group, Ltd
state: Ohio
city: Kettering
country: United States
facility: PriMed Clinical Research
state: Ohio
city: Richmond
country: United States
facility: National Clinical Research-Richmond, Inc.
state: Virginia
city: Renton
country: United States
facility: Rainier Clinical Research Center, Inc.
state: Washington
city: Changhua
country: Taiwan
facility: Changhua Christian Hospital
city: Taichung
country: Taiwan
facility: Cheng Ching General Hospital
city: Taichung
country: Taiwan
facility: Chung Shan Medical University Hospital
city: Taichung
country: Taiwan
facility: Kuang Tien General Hospital
city: Taipei
country: Taiwan
facility: Cardinal Tien Hospital
city: Taipei
country: Taiwan
facility: Taipei Medical University Hospital
city: Taipei
country: Taiwan
facility: Taipei Medical University-Shuang Ho Hospital
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital
Study officials:
References: