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
Arizona Clinical Trials - Pecos
Chandler, Arizona 85225
Chandler, Arizona 85225
Arizona Clinical Trials - Broadway
Tucson, Arizona 85711
Tucson, Arizona 85711
Ark Clinical Research - Fountain Valley
Fountain Valley, California 92708
Fountain Valley, California 92708
Velocity Clinical Research, Huntington Park
Huntington Park, California 90255
Huntington Park, California 90255
Velocity Clinical Research - Gardena
La Mesa, California 91942
La Mesa, California 91942
Ark Clinical Research - Long Beach
Long Beach, California 90815
Long Beach, California 90815
Los Angeles Institute for Metabolic Research
Los Angeles, California 90015
Los Angeles, California 90015
Velocity Clinical Research, Los Angeles
Los Angeles, California 90057
Los Angeles, California 90057
Amicis Research Center- Nordhoff
Northridge, California 98433
Northridge, California 98433
Velocity Clinical Research, New Smyrna Beach
Edgewater, Florida 32132
Edgewater, Florida 32132
The Center for Diabetes and Endocrine Care
Fort Lauderdale, Florida 33312
Fort Lauderdale, Florida 33312
Admed Research LLC
Miami, Florida 33173
Miami, Florida 33173
Progressive Medical Research
Port Orange, Florida 32127
Port Orange, Florida 32127
Emory University School of Medicine
Atlanta, Georgia 30303
Atlanta, Georgia 30303
IACT Health-Brookstone Centre Pkwy
Columbus, Georgia 31904
Columbus, Georgia 31904
Chicago Clinical Research Institute
Chicago, Illinois 60607
Chicago, Illinois 60607
Velocity Clinical Research, Sioux City
Sioux City, Iowa 51106
Sioux City, Iowa 51106
Iowa Diabetes and Endocrinology Research Center
West Des Moines, Iowa 50226
West Des Moines, Iowa 50226
St. Elizabeth Healthcare
Edgewood, Kentucky 41017
Edgewood, Kentucky 41017
Velocity Clinical Research, Lafayette
Lafayette, Louisiana 70508
Lafayette, Louisiana 70508
NOLA Care Clinical Research
Metairie, Louisiana 70006
Metairie, Louisiana 70006
Tulane University School of Medicine
New Orleans, Louisiana 70112
New Orleans, Louisiana 70112
Velocity Clinical Research, Rockville
Rockville, Maryland 20854
Rockville, Maryland 20854
Elixia SISU BHR - Springfield
Springfield, Massachusetts 011030
Springfield, Massachusetts 011030
Oakland Medical Research Center
Troy, Michigan 48085
Troy, Michigan 48085
Velocity Clinical Research, Lincoln
Lincoln, Nebraska 68510
Lincoln, Nebraska 68510
Velocity Clinical Research, Omaha
Omaha, Nebraska 68134
Omaha, Nebraska 68134
Palm Research Center, Inc.
Las Vegas, Nevada 89148
Las Vegas, Nevada 89148
Endocrine Associates of Long Island, P.C.
Smithtown, New York 11787
Smithtown, New York 11787
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina 27514
Chapel Hill, North Carolina 27514
Physicians East
Greenville, North Carolina 27834
Greenville, North Carolina 27834
Lucas Research Inc
Morehead City, North Carolina 28557
Morehead City, North Carolina 28557
Velocity Clinical Research, Cincinnati, Mt. Auburn
Cincinnati, Ohio 45219
Cincinnati, Ohio 45219
Velocity Clinical Research - Cincinnati, Blue Ash
Cincinnati, Ohio 45242
Cincinnati, Ohio 45242
Endocrinology Associates, Inc
Columbus, Ohio 43201
Columbus, Ohio 43201
Remington Davis, Inc
Columbus, Ohio 43215
Columbus, Ohio 43215
Suburban Research Associates
West Chester, Pennsylvania 19380
West Chester, Pennsylvania 19380
Velocity Clinical Research, Anderson
Anderson, South Carolina 29621
Anderson, South Carolina 29621
Velocity Clinical Research, Austin
Austin, Texas 78759
Austin, Texas 78759
Velocity Clinical Research - Dallas
Dallas, Texas 75230
Dallas, Texas 75230
Juno Research, LLC
Houston, Texas 77040
Houston, Texas 77040
Radiance Clinical Research
Lampasas, Texas 76550
Lampasas, Texas 76550
Texas Diabetes & Endocrinology, P.A. - Round Rock
Round Rock, Texas 78681
Round Rock, Texas 78681
Diabetes & Glandular Disease Clinic, P.A.
San Antonio, Texas 78229
San Antonio, Texas 78229
Elevate Clinical Research
Seabrook, Texas 77586
Seabrook, Texas 77586
Texas Valley Clinical Research, LLC
Weslaco, Texas 78596
Weslaco, Texas 78596
Velocity Clinical Research, Salt Lake City
West Jordan, Utah 84088
West Jordan, Utah 84088
Velocity Clinical Research, Suffolk
Suffolk, Virginia 23435
Suffolk, Virginia 23435
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.