Abstract
EP526 - ECE_3731 - CAPTAIN-T2D: A Bayesian Response-Adaptive Randomization (RAR) Dose Range-Finding (DRF) Trial of Clofutriben (CLO) as add-on treatment in patients with Type 2 Diabetes (T2D) and Elevated Cortisol (EC)
European journal of endocrinology, Vol.195(Supplement_1), lvag0961005
08/01/2026
DOI: 10.1093/ejendo/lvag096.1005
Abstract
Introduction Many patients with T2D who exhaust typical treatment options also have EC, which impedes achieving glycemic control. CLO, a selective 11β-hydroxysteroid dehydrogenase type 1 inhibitor that reduces intracellular cortisol, was associated with improved HbA1c and fasting glucose in a prior diabetes clinical trial. This Phase 2 trial in patients with T2D and EC will evaluate the dose-response relationship of CLO and identify the dose(s) suitable for Phase 3 evaluation. Methods CAPTAIN-T2D is a double-blind, placebo-controlled, RAR DRF trial. Adults with T2D, HbA1c ≥7.5%, treated with ≥2 anti-diabetic medications (ADMs), and with ≥1 EC risk factor (eg, ≥3 ADMs, diabetic complication, hypertension requiring ≥2 antihypertensive medications) will undergo an overnight dexamethasone suppression test (DST). Those with post-DST cortisol >1.8 and ≤5.0 mcg/dL will be screened further for eligibility, including by pre-enrolment in-clinic and at-home monitoring for risk of hypoglycemia or hypotension. Neoplastic etiologies of EC will be screened for using medical history, exam, repeated DST cortisol >5.0 mcg/dL, and adrenal imaging to guide therapy decisions; participants with repeated DST cortisol >5.0 mcg/dL may be eligible with further evaluation. Up to 210 participants will receive oral CLO (no titration) or placebo QD for 24 weeks. The first 60 will be randomized equally to placebo and 4 CLO doses. Thereafter, a RAR algorithm will adjust dose allocations at pre-planned enrolment intervals based on the posterior probability that each dose has ≥90% maximum effect (ED90) on HbA1c at Week 24 or is the minimal effective dose. The algorithm will stop enrolment if a dose has >80% probability of being the ED90. Safety will be reviewed regularly by an independent safety committee. Outcomes The prevalence of EC in the screened population and safety will be reported. The primary analysis will be a Bayesian hierarchical Emax model for dose-response relationship on change in HbA1c at Weeks 4, 12, and 24. A supportive analysis will be a mixed model for repeated measures (MMRM) of HbA1c change from baseline. Changes in other glycemic, lipid, anthropometric, and BP measures will be estimated using MMRM. Conclusions CAPTAIN-T2D aims to define the dose-response relationship and therapeutic potential of CLO in patients with T2D and EC. By reducing excess intracellular cortisol that exacerbates T2D without impairing the HPA axis, adrenal cortisol synthesis, or its interaction with the glucocorticoid receptor, CLO might provide a targeted therapeutic option for patients with difficult-to-control T2D and EC that avoids complex monitoring or dose modifications.
Details
- Title: Subtitle
- EP526 - ECE_3731 - CAPTAIN-T2D: A Bayesian Response-Adaptive Randomization (RAR) Dose Range-Finding (DRF) Trial of Clofutriben (CLO) as add-on treatment in patients with Type 2 Diabetes (T2D) and Elevated Cortisol (EC)
- Creators
- Frank CzerwiecLindsay BerryNathan JamesJennifer SmithKarisse Roman-TorresGuohua AnTodd BernerSarah HooperDora FerrariVivian FonsecaJohn BuseDavid A Katz
- Resource Type
- Abstract
- Publication Details
- European journal of endocrinology, Vol.195(Supplement_1), lvag0961005
- DOI
- 10.1093/ejendo/lvag096.1005
- ISSN
- 0804-4643
- eISSN
- 1479-683X
- Publisher
- Oxford University Press
- Language
- English
- Date published
- 08/01/2026
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9985218634002771
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