Mifepristone in Children With Refractory Cushing's Disease
Primary Purpose
Cushing's Disease
Status
Withdrawn
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
mifepristone
Sponsored by
About this trial
This is an interventional treatment trial for Cushing's Disease focused on measuring Cushing's disease, Mifepristone, Cushing's syndrome, Pharmacokinetic-pharmacodynamic, Child/pediatric population, Safety-efficacy
Eligibility Criteria
Inclusion Criteria:
- Males and females 6-17 years at informed consent
- Active Cushing's disease as demonstrated by the following:
- 24 hour Urinary Free Cortisol greater than the upper limit of normal for age on two urine collections during screening and
- midnight serum cortisol >4.4 mcg/dL (mean of two determinations on a single day at 2330 and 2400 during screening)
- Previous trans-sphenoidal surgery (TSS) for ACTH secreting pituitary tumor at least 3 months prior to screening
- Increased body weight defined by BMI Z-score of 1.5 or above
- Able to provide consent/assent
- Able to swallow study drug tablets (not crushed or split)
- Willing to use non-hormonal method of contraception in patients of reproductive potential
- Primary health care provider in home location
Exclusion Criteria:
- Hypercortisolism not due to Cushing's disease.
- Type 1 diabetes mellitus
- HbA1c ≥9.5% at Screening
- Body weight <25 kg
- Use of certain medications that are CYP3A substrates with narrow therapeutic ranges, such as simvastatin, lovastatin, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus during the 4 weeks prior to starting study drug. Use of these medications is also prohibited until 2 weeks after end of dosing.
- Use of certain medications that are strong CYP3A inhibitors such as itraconazole, nefazodone, ritonavir, nelfinavir, indinavir, atazanavir, amprenavir, fosamprenavir, boceprevir, clarithromycin, conivaptan, lopinavir, mibefradil, posaconazole, saquinavir, telaprevir, telithromycin, and voriconazole during the 2 weeks prior to starting study drug. Use of these medications is also prohibited until 2 weeks after end of dosing. Grapefruit and grapefruit juice, as well as grapefruit-related fruits and their juice (e.g. Seville oranges, pomelos), are prohibited during this time frame.
- Use of certain medications that are strong inducers of CYP3A such as rifampin, rifabutin, rifapentine, phenobarbital, phenytoin, carbamazepine, St. John's wort during the 2 weeks prior to starting study drug. Use of these medications is also prohibited until 2 weeks after end of dosing.
- Use of medications used to treat hypercortisolism from the duration indicated below prior to Day 1. Use of the medications is also prohibited until after the end of study 4 week follow up visit.
- steroidogenesis inhibitors such as ketoconazole, metyrapone: 4 weeks
- cabergoline, bromocriptine, somatostatin analogs such as octreotide, lanreotide, pasireotide long acting formulations: 8 weeks (immediate release formulations: 2 weeks)
- mitotane: 8 weeks
- Use of systemic glucocorticoid medications beginning 1 month prior to screening or anticipated use of these medications except for the treatment of adrenal insufficiency. Use of glucocorticoid medications is prohibited during the study until after the end of study 4 week study visit.
- Inflammatory, rheumatological, proliferative or other disorder(s) that would be anticipated to worsen with glucocorticoid blockade (e.g. inflammatory bowel disease, rheumatoid arthritis, psoriasis, etc.).
- Uncontrolled hypo- or hyperthyroidism.
- Uncorrected hypokalemia (<3.5 mEq/L). The screening period may be used to correct hypokalemia prior to starting study drug. Use of potassium and/or mineralocorticoid antagonists is permitted during the study.
- QTc ≥450 msec on Screening electrocardiogram
- Unexplained vaginal bleeding in females and/or any history of endometrial pathology.
- Positive pregnancy test in females.
Sites / Locations
- National Institute of Child Health and Human Development (NICHD)
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
mifepristone
Arm Description
Daily doses of mifepristone over 84 days.
Outcomes
Primary Outcome Measures
Adverse events
Patients who have received at least 1 dose of mifepristone will be included in the safety evaluations.
Secondary Outcome Measures
Full Information
NCT ID
NCT01925092
First Posted
August 8, 2013
Last Updated
July 31, 2014
Sponsor
Corcept Therapeutics
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
1. Study Identification
Unique Protocol Identification Number
NCT01925092
Brief Title
Mifepristone in Children With Refractory Cushing's Disease
Official Title
An Open-label Study of the Safety, Pharmacokinetics and Pharmacodynamics of Mifepristone in Children With Refractory Cushing's Disease
Study Type
Interventional
2. Study Status
Record Verification Date
July 2014
Overall Recruitment Status
Withdrawn
Why Stopped
Lack of enrollment
Study Start Date
August 2013 (undefined)
Primary Completion Date
December 2016 (Anticipated)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Corcept Therapeutics
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Study objectives are to obtain safety, pharmacokinetic, and pharmacodynamic data on the effect of mifepristone on glucose metabolism, body weight and the growth-hormone-IGF in children with refractory Cushing's disease.
Detailed Description
The study is being done to examine the effects of a medication called mifepristone in children with Cushing's disease. Since a child's body may absorb and use mifepristone in a different way than adults, it is important to have information about the amount of mifepristone to give children and what will happen to it. Mifepristone has been FDA approved for use only in adults with Cushing's syndrome, and it is important to learn if mifepristone improves the symptoms and signs of Cushing's disease in children. The study is limited to children with Cushing's syndrome due to a pituitary tumor (Cushing's disease) and will not enroll children with Cushing's syndrome due to other causes. The study will investigate how children's bodies absorb and process mifepristone, how it works in children and what effect it has on the use of sugar in the body, on the child's weight and on growth hormone. An important part of the study is to evaluate the side effects of mifepristone in children.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cushing's Disease
Keywords
Cushing's disease, Mifepristone, Cushing's syndrome, Pharmacokinetic-pharmacodynamic, Child/pediatric population, Safety-efficacy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
mifepristone
Arm Type
Experimental
Arm Description
Daily doses of mifepristone over 84 days.
Intervention Type
Drug
Intervention Name(s)
mifepristone
Other Intervention Name(s)
Korlym
Intervention Description
tablets
Primary Outcome Measure Information:
Title
Adverse events
Description
Patients who have received at least 1 dose of mifepristone will be included in the safety evaluations.
Time Frame
collected during the12 week study and 4 week follow-up period; up to 16 weeks total.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Males and females 6-17 years at informed consent
Active Cushing's disease as demonstrated by the following:
24 hour Urinary Free Cortisol greater than the upper limit of normal for age on two urine collections during screening and
midnight serum cortisol >4.4 mcg/dL (mean of two determinations on a single day at 2330 and 2400 during screening)
Previous trans-sphenoidal surgery (TSS) for ACTH secreting pituitary tumor at least 3 months prior to screening
Increased body weight defined by BMI Z-score of 1.5 or above
Able to provide consent/assent
Able to swallow study drug tablets (not crushed or split)
Willing to use non-hormonal method of contraception in patients of reproductive potential
Primary health care provider in home location
Exclusion Criteria:
Hypercortisolism not due to Cushing's disease.
Type 1 diabetes mellitus
HbA1c ≥9.5% at Screening
Body weight <25 kg
Use of certain medications that are CYP3A substrates with narrow therapeutic ranges, such as simvastatin, lovastatin, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus during the 4 weeks prior to starting study drug. Use of these medications is also prohibited until 2 weeks after end of dosing.
Use of certain medications that are strong CYP3A inhibitors such as itraconazole, nefazodone, ritonavir, nelfinavir, indinavir, atazanavir, amprenavir, fosamprenavir, boceprevir, clarithromycin, conivaptan, lopinavir, mibefradil, posaconazole, saquinavir, telaprevir, telithromycin, and voriconazole during the 2 weeks prior to starting study drug. Use of these medications is also prohibited until 2 weeks after end of dosing. Grapefruit and grapefruit juice, as well as grapefruit-related fruits and their juice (e.g. Seville oranges, pomelos), are prohibited during this time frame.
Use of certain medications that are strong inducers of CYP3A such as rifampin, rifabutin, rifapentine, phenobarbital, phenytoin, carbamazepine, St. John's wort during the 2 weeks prior to starting study drug. Use of these medications is also prohibited until 2 weeks after end of dosing.
Use of medications used to treat hypercortisolism from the duration indicated below prior to Day 1. Use of the medications is also prohibited until after the end of study 4 week follow up visit.
steroidogenesis inhibitors such as ketoconazole, metyrapone: 4 weeks
cabergoline, bromocriptine, somatostatin analogs such as octreotide, lanreotide, pasireotide long acting formulations: 8 weeks (immediate release formulations: 2 weeks)
mitotane: 8 weeks
Use of systemic glucocorticoid medications beginning 1 month prior to screening or anticipated use of these medications except for the treatment of adrenal insufficiency. Use of glucocorticoid medications is prohibited during the study until after the end of study 4 week study visit.
Inflammatory, rheumatological, proliferative or other disorder(s) that would be anticipated to worsen with glucocorticoid blockade (e.g. inflammatory bowel disease, rheumatoid arthritis, psoriasis, etc.).
Uncontrolled hypo- or hyperthyroidism.
Uncorrected hypokalemia (<3.5 mEq/L). The screening period may be used to correct hypokalemia prior to starting study drug. Use of potassium and/or mineralocorticoid antagonists is permitted during the study.
QTc ≥450 msec on Screening electrocardiogram
Unexplained vaginal bleeding in females and/or any history of endometrial pathology.
Positive pregnancy test in females.
Facility Information:
Facility Name
National Institute of Child Health and Human Development (NICHD)
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892-1103
Country
United States
12. IPD Sharing Statement
Links:
URL
http://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2013-CH-0170.html
Description
An Open-Label Study of The Safety, Pharmacokinetics and Pharmacodynamics of Mifepristone in Children With Refractory Cushing's Disease
Learn more about this trial
Mifepristone in Children With Refractory Cushing's Disease
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