This study is currently recruiting participants.
Number
001972-CH
Sponsoring Institute
National Institute of Child Health and Human Development (NICHD)
Recruitment Detail
Type: Participants currently recruited/enrolled Gender: Male & Female Min Age: 6 Years Max Age: 17 Years
Referral Letter Required
No
Population Exclusion(s)
Pregnant Women;Adults who are or may become unable to consent
Keywords
Pituitary Gland; Adrenocorticotropic Hormone (ACTH); Urinary Free Cortisol (UFC); mean Urinary Free Cortisol (mUFC)
Recruitment Keyword(s)
None
Condition(s)
Cushing's Disease
Investigational Drug(s)
Osilodrostat
Investigational Device(s)
Intervention(s)
Drug: osilodrostat
Supporting Site
National Institute of Child Health and Human Development
Cushing s disease causes high levels of a hormone called cortisol throughout the body. These levels can have many effects in children and adolescents, including weight gain, slowed growth, and changes in facial appearance. Osilodrostat is an FDA-approved drug for treating Cushing s disease in adults. Researchers want to find out if this drug can help treat Cushing s disease in younger people, too.
Objective:
To test osilodrostat in children and teens with Cushing s disease.
Eligibility:
People aged 6 to 17 years with Cushing s disease.
Design:
Participants will first be screened. The screening period will last up to 4 weeks. Participants may be asked to stop taking their current medications during the screening period. They will have a physical exam with blood tests. Saliva samples may be collected. They will have a test of their heart function. They will have imaging scans and X-rays. Participants will collect 24-hour urine samples; that is, they will collect all of their urine in a jug for 1 day at a time.
If they are eligible, osilodrostat will be started. Osilodrostat is a tablet taken by mouth once or twice a day. Participants may be asked to take more than 1 tablet at a time. Their dose may change during the study.
Participants will have up to 4 clinic visits in the first 12 weeks while they are taking the drug. Imaging scans, blood tests, urine collection, and other exams will be repeated throughout the study.
If the drug is helping them, participants may continue in the study for 9 more months. They will have 7 clinic visits during that time.
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INCLUSION CRITERIA: 1. Male and female children and adolescents from 6 to < 18 years of age with Cushing s disease of endogenous origin: Who have failed surgery (or) who are awaiting surgery (or) for whom surgery is not an immediate option. For patients who are awaiting surgery, the study treatment could be less than 12 weeks. 2. Patients must weigh > 30 kg. 3. The diagnosis of Cushing's disease must be confirmed by each of the following: 3a. The clinical criterion of decreasing growth percentiles with increasing weight (as evidenced by the presence of a contrast in height and BMI SD scores, defined as height SDS < 0 and BMI SDS > 0, and a strong clinical suspicion of Cushing s disease, such as photographic evidence of a change in facial appearance); 3b. Abnormal low-dose (0.5 mg Q6h x 48 hours) dexamethasone suppression test, defined as plasma cortisol levels > 1.8 mcg/dl, at time point 48 hours after the first dose of dexamethasone; 3c. Measurable morning ACTH levels, assessed before 10 am; 3d. Two 24-hour urinary free cortisol values > 1.3 x ULN; 3e. If the dexamethasone suppression test does not meet the above-mentioned criteria, the diagnosis of Cushing s disease may be confirmed by the following: Midnight serum cortisol levels > ULN, assessed while the patient is sleeping and after pre-cannulation (OR) two samples of late night salivary cortisol greater than ULN for the assay. 4. Able to swallow study drug tablets (not crushed or split). 5. Parents or legal guardians able to provide consent/assent. EXCLUSION CRITERIA: 1. Patients with macroadenoma complicated by compressive symptoms (requiring urgent surgical intervention) or at high risk for compressive symptoms due to mass effect of tumor (concern of corticotroph tumor progression). 2. Insufficient washout period from any other medication used to lower cortisol levels (5 half-lives of any drug). 3. Use of other investigational drugs at the time of enrollment, or within 30 days, or prior to completion of a wash-out duration that is at least 5 half-lives of the drug, at the time of enrollment, whichever is longer. Local regulations may require a longer wash-out period or specify other limitations for participation in an investigational trial, in which case they will be applicable as well. 4. History of hypersensitivity to drugs of the same or similar chemical classes as osilodrostat. 5. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases. 6. Patients with moderate to severe renal impairment (estimated GFR < 60 mL/min by the Creatinine-based Bedside Schwartz equation). 7. Patients with serum ALT and/or AST > 3 x ULN, or total bilirubin > 1.5 x ULN. 8. History of thrombosis. 9. Patients with risk factors for QTc prolongation or Torsade de Pointes, including: 9a. patients with a baseline QTcF > 450 ms 9b. personal or family history of long QT syndrome 9c. concomitant medications known to prolong the QT interval 9d. patients with hypokalemia, hypocalcaemia, or hypomagnesaemia, if not corrected before pre-dose Day 0. In case of uncorrected hypokalemia (<3.5 mEq/L), the screening period may be used to correct hypokalemia prior to starting study drug. Use of potassium supplements and/or mineralocorticoid antagonists is permitted during the study. 9e. Patients with a history of significant cardiovascular disease (based on the opinion of the investigator) such as: structural cardiovascular abnormalities, arrhythmia, etc. 10. Hypertensive patients with uncontrolled blood pressure defined as SBP > 150 and/or DBP > 100 or not optimally treated for hypertension as judged by the investigator. 11. Patients who have undergone any major surgery within 1 month. 12. Patients who have undergone trans-sphenoidal pituitary surgery within 6 weeks prior to screening are not eligible, unless they have clear evidence of persistent hypercortisolism or persistent biochemical changes consistent with Cushing s disease. 13. Use of or anticipated use of systemic glucocorticoid medications 1 month prior to screening. 14. Uncontrolled hypothyroidism as evidenced by Free T4 < 0.8 ng/dl. 15. Uncontrolled hyper thyroidism. 16. Diabetic patients with poorly controlled diabetes as evidenced by HbA1c > 8.5 percent or not optimally treated for diabetes mellitus as judged by the investigator. 17. Positive pregnancy test in females of childbearing potential. 18. Female patients of childbearing potential who do not agree to use highly effective birth control methods. 19. Pregnant or nursing (lactating) women. 20. Any medical condition that would, in the investigator s judgment, prevent the patient s participation in the clinical study due to safety concerns or compliance with clinical study procedures. Any severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study treatment administration or that may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for the study. 21. Use of concomitant prohibited medications.
1. Male and female children and adolescents from 6 to < 18 years of age with Cushing s disease of endogenous origin: Who have failed surgery (or) who are awaiting surgery (or) for whom surgery is not an immediate option. For patients who are awaiting surgery, the study treatment could be less than 12 weeks.
2. Patients must weigh > 30 kg.
3. The diagnosis of Cushing's disease must be confirmed by each of the following:
3a. The clinical criterion of decreasing growth percentiles with increasing weight (as evidenced by the presence of a contrast in height and BMI SD scores, defined as height SDS < 0 and BMI SDS > 0, and a strong clinical suspicion of Cushing s disease, such as photographic evidence of a change in facial appearance);
3b. Abnormal low-dose (0.5 mg Q6h x 48 hours) dexamethasone suppression test, defined as plasma cortisol levels > 1.8 mcg/dl, at time point 48 hours after the first dose of dexamethasone;
3c. Measurable morning ACTH levels, assessed before 10 am;
3d. Two 24-hour urinary free cortisol values > 1.3 x ULN;
3e. If the dexamethasone suppression test does not meet the above-mentioned criteria, the diagnosis of Cushing s disease may be confirmed by the following: Midnight serum cortisol levels > ULN, assessed while the patient is sleeping and after pre-cannulation (OR) two samples of late night salivary cortisol greater than ULN for the assay.
4. Able to swallow study drug tablets (not crushed or split).
5. Parents or legal guardians able to provide consent/assent.
EXCLUSION CRITERIA:
1. Patients with macroadenoma complicated by compressive symptoms (requiring urgent surgical intervention) or at high risk for compressive symptoms due to mass effect of tumor (concern of corticotroph tumor progression).
2. Insufficient washout period from any other medication used to lower cortisol levels (5 half-lives of any drug).
3. Use of other investigational drugs at the time of enrollment, or within 30 days, or prior to completion of a wash-out duration that is at least 5 half-lives of the drug, at the time of enrollment, whichever is longer. Local regulations may require a longer wash-out period or specify other limitations for participation in an investigational trial, in which case they will be applicable as well.
4. History of hypersensitivity to drugs of the same or similar chemical classes as osilodrostat.
5. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
6. Patients with moderate to severe renal impairment (estimated GFR < 60 mL/min by the Creatinine-based Bedside Schwartz equation).
7. Patients with serum ALT and/or AST > 3 x ULN, or total bilirubin > 1.5 x ULN.
8. History of thrombosis.
9. Patients with risk factors for QTc prolongation or Torsade de Pointes, including:
9a. patients with a baseline QTcF > 450 ms
9b. personal or family history of long QT syndrome
9c. concomitant medications known to prolong the QT interval
9d. patients with hypokalemia, hypocalcaemia, or hypomagnesaemia, if not corrected before pre-dose Day 0. In case of uncorrected hypokalemia (<3.5 mEq/L), the screening period may be used to correct hypokalemia prior to starting study drug. Use of potassium supplements and/or mineralocorticoid antagonists is permitted during the study.
9e. Patients with a history of significant cardiovascular disease (based on the opinion of the investigator) such as: structural cardiovascular abnormalities, arrhythmia, etc.
10. Hypertensive patients with uncontrolled blood pressure defined as SBP > 150 and/or DBP > 100 or not optimally treated for hypertension as judged by the investigator.
11. Patients who have undergone any major surgery within 1 month.
12. Patients who have undergone trans-sphenoidal pituitary surgery within 6 weeks prior to screening are not eligible, unless they have clear evidence of persistent hypercortisolism or persistent biochemical changes consistent with Cushing s disease.
13. Use of or anticipated use of systemic glucocorticoid medications 1 month prior to screening.
14. Uncontrolled hypothyroidism as evidenced by Free T4 < 0.8 ng/dl.
15. Uncontrolled hyper thyroidism.
16. Diabetic patients with poorly controlled diabetes as evidenced by HbA1c > 8.5 percent or not optimally treated for diabetes mellitus as judged by the investigator.
17. Positive pregnancy test in females of childbearing potential.
18. Female patients of childbearing potential who do not agree to use highly effective birth control methods.
19. Pregnant or nursing (lactating) women.
20. Any medical condition that would, in the investigator s judgment, prevent the patient s participation in the clinical study due to safety concerns or compliance with clinical study procedures. Any severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study treatment administration or that may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for the study.
21. Use of concomitant prohibited medications.
Principal Investigator
Referral Contact
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