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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Withdrawn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
Corcept Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

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

6 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

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

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)
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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

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Mifepristone in Children With Refractory Cushing's Disease

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