Trial Against INtractable Type 2 Diabetes (CAPTAIN-T2D)
Purpose
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).
Conditions
- Type 2 Diabetes
- Cortisol Excess
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
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
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Other
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Dose 1 |
clofutriben .2 mg oral tablet daily |
|
|
Experimental Dose 2 |
clofutriben 2mg oral tablet daily |
|
|
Experimental Dose 3 |
clofutriben 6mg oral tablet daily |
|
|
Experimental Dose 4 |
clofutriben 12 mg oral tablet daily |
|
|
Placebo Comparator placebo |
placebo control oral tablet daily |
|
Recruiting Locations
Medstar Health Research Institute
Olney 4364537, Maryland 4361885 20832
Olney 4364537, Maryland 4361885 20832
More Details
- Status
- Recruiting
- Sponsor
- Sparrow Pharmaceuticals
Study Contact
Detailed Description
CAPTAIN-T2D is a two-part, multicenter, randomized, double-blind, parallel group, placebo- controlled trial of the 11-hydroxysteroid dehydrogenase type 1 (HSD-1) inhibitor clofutriben. The primary objectives of this trial are to characterize the relationship of clofutriben dose to improved glycemic control, and to identify one or more doses suitable for Phase 3 evaluation, in patients with T2D and elevated cortisol. The trial consists of two parts. Part 1 (Screening) will last between approximately 5 to 9 weeks for most participants. The screening period duration allows for (sequentially) initial eligibility screen, dexamethasone suppression test, and further eligibility assessments. During Part 2 (Treatment), participants will be randomized to placebo or one of four clofutriben doses. Part 2 will last 24 weeks with a follow-up phone call 4 weeks after the last dose of trial medication.