Mifepristone in Children With Refractory Cushing's Disease

NCT01925092 | Withdrawn Phase 3 DMC

• 2 other identifiers: 13-CH-017002811-12
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Cushing's Disease

Keywords

Cushing's disease; Mifepristone; Cushing's syndrome; Pharmacokinetic-pharmacodynamic; Child/pediatric population; Safety-efficacy

Outcome Measures

Primary Outcomes (1)

• Adverse events

  Patients who have received at least 1 dose of mifepristone will be included in the safety evaluations.

  collected during the12 week study and 4 week follow-up period; up to 16 weeks total.

Study Arms (1)

mifepristone

EXPERIMENTAL

Daily doses of mifepristone over 84 days.

Drug: mifepristone

Interventions

mifepristone DRUG

tablets

Also known as: Korlym

mifepristone

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Males and females 6-17 years at informed consent
• Active Cushing's disease as demonstrated by the following:
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Corcept Therapeutics: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

National Institute of Child Health and Human Development (NICHD)

Bethesda, Maryland, 20892-1103, United States

Location

Related Links

• An Open-Label Study of The Safety, Pharmacokinetics and Pharmacodynamics of Mifepristone in Children With Refractory Cushing's Disease

MeSH Terms

Conditions

Pituitary ACTH Hypersecretion; Cushing Syndrome

Interventions

Mifepristone

Condition Hierarchy (Ancestors)

Hyperpituitarism; Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases; Adrenocortical Hyperfunction; Adrenal Gland Diseases

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2013
• First Posted: August 19, 2013
• Study Start: August 1, 2013
• Primary Completion: December 1, 2016
• Last Updated: August 4, 2014

Record last verified: 2014-07

Locations

US (1)