Clofutriben And Placebo Phase 2 Trial Against INtractable Type 2 Diabetes (CAPTAIN-T2D)
CAPTAIN-T2D will take place in two parts. Part 1 (Screening) will evaluate patients with type 2 diabetes and elevated cortisol risk factors for trial eligibility and the presence of elevated cortisol. Participants deemed eligible from Part 1 will be randomized to either clofutriben or placebo in the double-blind (participant and investigator), dose-ranging, interventional Part 2 (Treatment).
• From Screening 1
‣ Age at least 18 years.
⁃ HbA1c ≥7.5% documented within 3 months prior to Screening 1. (The historical HbA1c value must have been obtained after at least 2 months on the current \[as of Screening 1\] regimen).
⁃ Treatment with stable and adequate doses of ≥2 injectable or oral ADMs. (An ADM will be deemed stable if the dose has been the same for at least 3 months prior to Screening 1 and without change between Screening 1 and Day 1) (An ADM dose will be deemed adequate if it is at or above the maximal labelled dose, or a sub-maximal, but not starting, dose if limited by tolerability (confer with MM if less than half-maximal dose).
⁃ Adequate total daily insulin is defined as at least 0.3 units/kg/day. Insulin dose will be deemed stable with adjustments of up to 20% total daily dose during the 3 months prior to Screening 1 or between Screening 1 and Day 1.
⁃ Use of insulin pumps or insulin brand changes (e.g., due to insurance change or shortage) are to be discussed with the MM.
⁃ At least one of the following
• ≥3 stable and adequate ADMs;
∙ diabetes complication (retinopathy, nephropathy, neuropathy, atherosclerotic heart disease);
∙ hypertension requiring ≥2 adequately dosed AHMs;
∙ adequately dosed basal or basal plus prandial insulin in addition to at least 1 other ADM; and
∙ adequately dosed incretin agonist (a single or combination agent counts as one ADM) in addition to at least 1 other ADM;
∙ evidence or history of osteoporosis or non-traumatic fracture (e.g., vertebral body compression);
∙ or established diagnosis of a neoplastic (non-malignant) source of hypercortisolism and have failed, are ineligible for, or declined surgery.
⁃ At DST • Post-DST cortisol level \>1.8 µg/dL and serum dexamethasone ≥140 ng/dL. Patients with an established diagnosis of neoplastic hypercortisolism do not require a DST.
⁃ At Screening 2
• HbA1c ≥7.5% at Screening 2. At Day 1
• No change in, or initiation of, medications for hypertension within 1 month prior to Day 1.