Type 2 Diabetes Mellitus
Conditions
Keywords
AC-201, Interleukin 1 inhibitor
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.
Interventions
DRUGAC-201, 25mg
Capsule, 25mg BID
DRUGAC-201, 50mg
Capsule, 50mg BID
DRUGAC-201, 75mg
Capsule, 75mg BID
DRUGPlacebo
Placebo BID
Sponsors
TWi Biotechnology, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1c From Baseline | 24 weeks | For efficacy analyses, the primary analysis was at Week 24 Endpoint, defined as the last valid post-baseline measurement taken at or before Week 24. Efficacy results for treatment groups were considered statistically significant if change from baseline relative to placebo had p\<0.05. |
Countries
Taiwan, United States
Participant flow
Recruitment details
The participants were recruited in 21 study centers, which were located in 2 countries (USA and Taiwan)
Participants by arm
| Arm | Count |
|---|---|
| AC-201, 25mg BID AC-201: Capsule, 25mg BID | 65 |
| AC-201, 50mg BID AC-201: Capsule, 50mg BID | 64 |
| AC-201, 75mg BID AC-201: Capsule, 75mg BID | 65 |
| Placebo Placebo: Capsule, BID | 65 |
| Total | 259 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 3 | 11 | 3 |
| Overall Study | Insufficient therapeutic effects | 0 | 0 | 2 | 0 |
| Overall Study | Lack of Efficacy | 0 | 1 | 0 | 1 |
| Overall Study | Lost to Follow-up | 2 | 1 | 1 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 1 | 1 |
| Overall Study | Protocol Violation | 1 | 1 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 6 | 3 | 1 | 6 |
Baseline characteristics
| Characteristic | AC-201, 25mg BID | AC-201, 50mg BID | AC-201, 75mg BID | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 56 years STANDARD_DEVIATION 9 | 55 years STANDARD_DEVIATION 9 | 57 years STANDARD_DEVIATION 9 | 55 years STANDARD_DEVIATION 8 | 56 years STANDARD_DEVIATION 9 |
| HbA1c | 8.4 % STANDARD_DEVIATION 0.6 | 8.3 % STANDARD_DEVIATION 0.7 | 8.5 % STANDARD_DEVIATION 0.7 | 8.4 % STANDARD_DEVIATION 0.7 | 8.4 % STANDARD_DEVIATION 0.7 |
| Region of Enrollment Taiwan | 27 participants | 27 participants | 27 participants | 28 participants | 109 participants |
| Region of Enrollment United States | 38 participants | 37 participants | 38 participants | 37 participants | 150 participants |
| Sex: Female, Male Female | 38 Participants | 33 Participants | 27 Participants | 33 Participants | 131 Participants |
| Sex: Female, Male Male | 27 Participants | 31 Participants | 38 Participants | 32 Participants | 128 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 19 / 65 | 25 / 64 | 38 / 65 | 15 / 65 |
| serious Total, serious adverse events | 3 / 65 | 2 / 64 | 2 / 65 | 1 / 65 |
Outcome results
Primary
Change in HbA1c From Baseline
For efficacy analyses, the primary analysis was at Week 24 Endpoint, defined as the last valid post-baseline measurement taken at or before Week 24. Efficacy results for treatment groups were considered statistically significant if change from baseline relative to placebo had p\<0.05.
Time frame: 24 weeks
Population: The Full Analysis Set included all randomized patients who received at least 1 dose of study drug and had a baseline and at least 1 post-baseline HbA1c assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AC-201, 25mg BID | Change in HbA1c From Baseline | 0.03 percentage points | Standard Error 0.123 |
| AC-201, 50mg BID | Change in HbA1c From Baseline | -0.07 percentage points | Standard Error 0.126 |
| AC-201, 75mg BID | Change in HbA1c From Baseline | -0.13 percentage points | Standard Error 0.125 |
| Placebo | Change in HbA1c From Baseline | 0.22 percentage points | Standard Error 0.123 |
Comparison: Change from baseline in HbA1c was analyzed using an analysis of covariance model with change in HbA1c as the dependent variable, treatment as a fixed effect, and baseline HbA1c as a covariate.p-value: 0.04495% CI: [-0.7, -0.01]ANCOVA
Comparison: Change from baseline in HbA1c was analyzed using an analysis of covariance model with change in HbA1c as the dependent variable, treatment as a fixed effect, and baseline HbA1c as a covariate.p-value: 0.097995% CI: [-0.64, 0.05]ANCOVA
Comparison: Change from baseline in HbA1c was analyzed using an analysis of covariance model with change in HbA1c as the dependent variable, treatment as a fixed effect, and baseline HbA1c as a covariate.p-value: 0.264395% CI: [-0.54, 0.15]ANCOVA