Evaluation of a Novel Insulin Sensitizer in People With Type 1 Diabetes

Evaluation of a Novel Insulin Sensitizer on Glycemic Control, Insulin Usage, and Cardiovascular Biomarkers in People With Type 1 Diabetes Who Use Closed-loop Automated Insulin Delivery

The purpose of this study is to see if the study drug CIR-0602K will improve glucose time-in-range and/or lower total daily insulin dose in people with type 1 diabetes who are using closed-loop automated insulin delivery. Researchers will compare CIR-0602K to a placebo (a look-alike substance that contains no drug) to see if it achieves the investigational endpoints. If the study results show that the drug works to increase time-in-range and lower insulin doses, this will lead to further studies which may then make the drug available to the public.

Participants in the study will:

• Come to the Clinical Research Unit (CRU) at UVA Medical Center for 3 visits: Screening, Baseline (Admission 1) and End-of-Study (Admission 2).
• Complete various tests of cardiovascular health at each visit.
• Take either an experimental drug (CIR-0602K) or placebo for 12 weeks.
• Wear a study CGM with their personal insulin pump for 12 weeks.
• Be given a ketone meter and strips and be asked to take a fingerstick ketone reading every morning for 12 weeks.
• The study team will contact the participants regularly during the study to check their health and how they are tolerating the study drug/placebo.
• Return the study CGM, ketone meter, and remaining supplies, etc. at the end of the study.
• Notify the study team of any illness, injury, hypoglycemic or hyperglycemic events during the study

Inclusion Criteria:

1. Provision of signed and dated informed consent form

2. Stated willingness to comply with all study procedures and availability for the duration of the study

3. History of type 1 diabetes for at least one year

4. Age 18-45 years

5. HbA1c <10%

   • BMI 18-35 kg/m2. Within this criterion, participants must have either BMI ≥25 or total daily insulin dose of ≥0.5 units/kg/day.
   • Currently utilizing closed-loop AID therapy that is compatible with Dexcom G7 CGM.
   • On stable regimen of non-diabetic medications for the last 6 months.
   • All screening labs within normal limits or not clinically significant.
   • Ability to take oral medication and be willing to adhere to the study drug/placebo for 12 weeks.
   • For females and males of reproductive potential: agreement to use adequate contraception during study participation and for an additional 2 weeks after the end of CIR-0602K administration.
   • For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner during study intervention.
   • Agreement to adhere to Lifestyle Considerations throughout study duration.

Exclusion Criteria:

• Current Pregnancy or currently breastfeeding.
• History of smoking tobacco products within the last two years.
• History of alcohol abuse or illicit drug abuse within 6 months of screening.
• Known history of human immunodeficiency virus (HIV).
• History of other significant disease (e.g., cardiac, cerebrovascular, gastrointestinal, liver, renal, or endocrine) that could, in the investigator's view, alter study outcomes
• Any surgical or medical condition which may significantly alter the absorption of the study drug including but not limited to the following: history of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, bowel resection, gastric bypass, gastric stapling, or gastric banding, currently active inflammatory bowel syndrome.
• Current use of any antihyperglycemic medication beyond insulin (i.e., GLP-1 receptor agonists, SGLT2 inhibitors, etc.).
• Unstable doses (i.e., dose change within the last 4 months) of vasoactive medications (e.g., calcium-channel blockers, statins, angiotensin-converting enzyme inhibitors, diuretics, nitrates, alpha-blockers, beta-blockers, etc.).
• Daily use of anti-inflammatory medications (e.g., ibuprofen, aspirin, prednisone, dexamethasone, etc.).
• Diagnosis of peripheral neuropathy (assessed by screening monofilament exam).
• Macroalbuminuria (i.e., urine albumin: creatinine >300 mg per g).
• Retinopathy beyond mild, nonproliferative retinopathy.
• History of Level 3 hypoglycemia within the last 12 months.
• History of diabetic ketoacidosis (DKA) within the last 12 months.
• Screening electrocardiogram (ECG) findings indicative of arrhythmia, sinus node disease, or ischemic heart disease.
• Screening oxygen saturation <90%
• History of hypersensitivity or prior adverse reaction to the study drug, closely-related compounds, or any of the stated ingredients.
• Use of concomitant medications with a known significant metabolism by CYP2C8 or CYP2C (including paclitaxel, phenytoin, warfarin, celecoxib, tolbutamide, or repaglinide) for the duration of the study.
• Participation in an investigational study (other than a non-treatment registry study) or received an investigational drug withing 30 days or 5 half-lives (whichever is longer) prior to randomization.