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CAPTAIN-T2D: testing clofutriben for hard-to-control Type 2 diabetes with cortisol excess

Clofutriben And Placebo Phase 2 Trial Against INtractable Type 2 Diabetes (CAPTAIN-T2D)

Phase 2 Interventional Sparrow Pharmaceuticals · NCT07296484

This will test whether clofutriben can improve blood sugar control in adults with type 2 diabetes who have signs of cortisol excess.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment1500 (estimated)
Ages18 Years and up
SexAll
SponsorSparrow Pharmaceuticals Industry-sponsored
Locations52 sites (Chandler, Arizona and 51 other locations)
Trial IDNCT07296484 on ClinicalTrials.gov

What this trial studies

CAPTAIN-T2D is a two-part, multicenter, randomized, double-blind, placebo-controlled, dose-ranging Phase 2 trial of the HSD-1 inhibitor clofutriben in adults with type 2 diabetes and evidence of cortisol excess. Part 1 (about 5–9 weeks) screens participants, including a dexamethasone suppression test, to confirm elevated cortisol risk and eligibility. In Part 2, eligible participants are randomized to placebo or one of four clofutriben doses for 24 weeks, with a follow-up call 4 weeks after the last dose. The primary goals are to define the dose–response relationship for glycemic control and to identify dose(s) suitable for Phase 3 evaluation.

Who should consider this trial

Good fit: Adults (≥18 years) with type 2 diabetes, HbA1c ≥7.5% despite a stable regimen of at least two antidiabetic medications or adequate insulin dosing, and evidence of cortisol excess who can attend in-person visits and undergo dexamethasone testing are ideal candidates.

Not a fit: Patients without evidence of cortisol excess, with well-controlled diabetes (HbA1c <7.5%), unstable or inadequate diabetes regimens, or who have contraindications to HSD-1 inhibitors are unlikely to benefit.

Why it matters

Potential benefit: If successful, clofutriben could lower HbA1c and improve blood sugar control in people with T2D linked to cortisol excess, potentially reducing diabetes-related complications.

How similar studies have performed: HSD-1 inhibitors have been studied before for metabolic conditions with mixed results, so targeting cortisol in T2D is promising but not yet proven in large Phase 3 trials.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* 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.

Exclusion Criteria:

* New-onset diabetes (onset \<1 year in the past).
* Unwillingness to maintain with current glucose-lowering regimen during the trial.
* Unwillingness to adjust, add, replace, or discontinue current or other glucose-lowering medications during the trial as directed by the investigator.
* Unwillingness to comply with CGM or other trial procedures.
* Investigator considers the patient will otherwise be unwilling or unable to complete the trial.
* Night-shift worker or otherwise habitually awake from 23:00 to 07:00 h.
* Evidence for significant hypoglycemia while on their current diabetic treatment regimen(This includes episodes of symptomatic Level 3 hypoglycemia requiring external assistance for recovery, or CGM-documented prolonged \[\>15 min\] or repeated episodes of either Level 2 hypoglycemia leading to \>1%, or Level 1 hypoglycemia leading to \>4%, in "time below range" within 3 months prior to Screening 1 or between Screening 1 and Day 1).
* Any of the following in medical history:

  * Type 1 diabetes mellitus (T1D), latent autoimmune diabetes in adults (LADA), or familial forms of maturity-onset diabetes of the young (MODY);
  * A hemoglobinopathy or other condition which may interfere with measurement of HbA1c (e.g., sickle cell disease HbSS or other variants HbEE thalassemia, hemolytic anemia, recent blood transfusion);
  * Hypersensitivity or severe reaction to dexamethasone;
  * Pheochromocytoma, or suspicion thereof;
  * Anorexia, or other eating disorder;
  * Glucocorticoid resistance;
  * Multiple sclerosis;
  * Significant hepatic impairment (e.g., Child-Pugh Class B or C);
  * Idiopathic thrombocytopenic purpura;
  * Untreated or inadequately controlled moderate-to-severe sleep apnea (apnea-hypopnea index ≥15). (Patients whose condition has been well controlled with Continuous Positive Airway Pressure (CPAP) use for at least 3 months prior to Screening 1 are not excluded. Patients with a STOP-BANG score 5-8 should be referred for a sleep study outside the trial and may rescreen if found not to have moderate-to-severe sleep apnea);
  * Current alcohol consumption \>14 units/week or \>4 units in a single day for males, or \>7 units/week or \>3 units in a single day for females. (Patients with a CAGE score 2-4 should be evaluated further outside the trial and may be rescreened if found not to have an alcohol \[or other substance\] use disorder);
  * Untreated or inadequately controlled major depressive disorder, generalized anxiety disorder, bipolar disorder, post-traumatic stress disorder, or schizophrenia.(Patients whose condition has been well controlled with stable medical therapy, or has been asymptomatic, for at least 3 months prior to Screening 1 are not excluded); or
  * Any other medical condition (including malignancy) that is likely to interfere with trial assessments or the patient's ability to complete the trial.
  * Any of the following in medication history:
  * Any of the excluded medications listed in Section 6.9;
  * Any investigational drug within 4 weeks or within less than five times the drug's half-life, whichever is longer, prior to Screening 1 or between Screening 1 and Day 1;
  * Woman of childbearing potential (WOCBP) not willing to adhere to highly effective contraception or strict abstinence for the duration of the trial and for 90 days post completion/discontinuation; and
  * Pregnancy (including a positive urine test) or current breast feeding.

From Screening 2

• Prior probability of undiagnosed endogenous Cushing syndrome based on either of:

* wo morning serum cortisol values after dexamethasone suppression \>5.0 mcg/dL together with plasma dexamethasone \>140 ng/mL; or
* a morning serum cortisol value after dexamethasone suppression \>1.8 mcg/dL, together with plasma dexamethasone \>140 ng/mL and any one of the following that is not attributable to an etiology other than endogenous Cushing's syndrome:
* supraclavicular/dorsocervical fat accumulation;
* irounding of the face (especially compared with prior photos);
* skin changes (violaceous striae, skin thinning, or excessive bruising);
* proximal muscle weakness on exam; or
* history of deep vein thrombosis/pulmonary embolism.
* Plans for, or medically unable to forego, treatment for endogenous Cushing syndrome or ACS within the next 8 months. (For clarity, patients with EnCS or ACS, not having such treatment plans, and medically able to forego treatment for 8 months may enroll if otherwise eligible).
* Severe, poorly controlled hypertension (mean systolic BP \>160 mmHg or mean diastolic BP \>100 mmHg) at Screening 2 or between Screening 2 and Day 1, including by at-home monitoring. (Such patients will be eligible to rescreen for Part 2 when they restore BP \<160/100 mmHg for 1 month on a new stable medication regimen).
* Positive urine screen for recreational drugs (except tetrahydrocannabinol (THC)).
* Glomerular filtration rate (GFR) (determined using Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\]) \<45 mL/min/1.73 m².
* Poorly controlled hyperthyroidism/hypothyroidism (confirmed by TSH or Free thyroxine \[fT4\]).
* Liver enzymes \>3 × upper limit of normal (ULN) (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or bilirubin \>1.5 × ULN.(excepting benign conditions such as Gilbert's)
* Known hypersensitivity to clofutriben or to any of the product

Where this trial is running

Chandler, Arizona and 51 other locations

+2 more sites — see ClinicalTrials.gov for the full list.

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Type 2 DiabetesCortisol ExcesshypercortisolismCortisol excesselevated cortisol
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.