Mifepristone as Adjunctive Therapy in Alzheimer's Disease

Corcept Therapeutics

Status and phase

Terminated

Phase 2

Conditions

Alzheimer's Disease

Treatments

Drug: Mifepristone

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00105105

IA0069

Details and patient eligibility

About

The purpose of this study is to evaluate the effects of C-1073 (Mifepristone) on cognition in patients with Alzheimer's disease (AD) who are also taking an acetylcholinesterase inhibitor (Aricept, Exelon or Reminyl).

Full description

This will be a double blind, placebo controlled study of C-1073 to evaluate the effects on cognition in patients with mild to moderate Alzheimer's disease who are already receiving an acetylcholinesterase inhibitor and have been on a stable dose for at least 12 weeks. Patients will be randomized (1:1) to either daily dosing with 300 mg C-1073 or a placebo for 16 weeks. Patients will continue the stable daily dose of acetylcholinesterase inhibitor throughout the study.

Visits will be weekly at the beginning of the study, then every two weeks, and every 4 weeks after week 12. Assessments during these visits may include cognition and behavior, depression, safety, as well as physical exams, clinical laboratory tests, EKG and adverse event reporting.

Sex

All

Volunteers

No Healthy Volunteers

Inclusion criteria

Diagnosis of Alzheimer's disease
Women must have had a partial or complete hysterectomy
Mini Mental Status Evaluation score of 18-27
HAM-D score less than or equal to 18
Able to provide written informed consent
On a stable dose of an acetylcholinesterase inhibitor for at least 12 weeks prior to screening visit
Ambulatory, or ambulatory with walker or cane
Sufficient hearing and vision to enable the patient to comply with the study procedures
Caregiver available to participate in the assessment of the patient and monitor dosing

Exclusion criteria

Women with an intact uterus
A clinically significant medical condition, including lab abnormality, which in the opinion of the investigator would place the patient at undue risk, or would impair the patient's ability to participate in the study. These include but are not limited to: history of cerebral vascular accident (CVA), adrenal insufficiency, porphyrias, autoimmune disorders, type I diabetes, chronic obstructive pulmonary disease (COPD), hematologic or oncologic disorders in the previous 2 years, vitamin B12 or folate deficiency
A clinically significant active gastrointestinal, renal, hepatic, endocrine, or cardiovascular system disease that is not well controlled by diet, pharmacological treatment, or other therapeutic intervention
History of psychotic episodes or bipolar disorder, or additional diagnosis of delusions, delerium, or depression
Evidence of other psychiatric or neurologic disorders (e.g., stroke, schizophrenia, or Parkinson disease)
Hachinski ischemia score of 5 or more
Known hypersensitivity to cholinesterase inhibitors
Use of systemic or pulmonary inhaled corticosteroids within the 30 days prior to randomization, or require use of these medications during the study
Use of memantine (Namenda) within the 30 days prior to randomization, or require use of this medication during the study
Currently taking medications known to significantly induce or inhibit the metabolism of CYP 3A4, or have taken these medications 7 days prior to randomization (see list below under prohibited medications)
Use of anticholinergic compounds within the 30 days prior to randomization, or require use of this medication during the study
History of electroconvulsive therapy (ECT); patients may not undergo ECT during the course of the trial
Positive urine drug screen for any non-prescribed drug of abuse (including but not limited to amphetamines, cannabinoids, barbiturates, cocaine, opiates, benzodiazepines)
History of illicit drugs usage or a history of drug or alcohol dependence
Known to have another form of dementia that may also explain the patient's deficits including reversible dementias, Binswanger's, Parkinson's dementia complex, Korsakoff's, mental retardation or vascular dementia. Patients who meet clinical criteria for AD but who have deep white matter lesions on MRI or CT scan will be accepted.
Currently taking prescription anticoagulants such as warfarin (Coumadin)
Planned surgical procedures during the study period, including the 4 week off drug period between weeks 16 and 20
Participation in a clinical investigation of any drug, or other biological or investigational therapy within 30 days prior to dosing
Previous participation in a trial using mifepristone, or known sensitivity or allergy to C-1073 (mifepristone) or its constituents
Body Mass Index (BMI) over 35

Prohibited Medications:

Medications known to significantly induce or inhibit the metabolism of CYP 3A4, specifically:

carbamazepine (Carbatrol® Tegretol®)
modafinil (Provigil®)
nefazodone (Serzone®)
droperidol
erythromycin
fluconazole (Diflucan®)
itraconazole (Sporanox®)
ketoconazole (Nizoral®)
simvastatin (Zocor®)
lovastatin (Mevacor®)
vinblastine
vincristine
paclitaxel (Taxol®)
tamoxifen (Nolvadex®)
cyclosporine (Neoral®, Sandimmune®)
tacrolimus (Gengraf®)
sirolimus (Rapamune®)
midazolam (Versed®)
nicardipine (Cardene®)
nifedipine (Adalat®, Procardia®)
felodipine (Lexxel®, Plendil®)
thioridizine
pimozide (Orap®)
quinidine
Patient may also not take St. John's Wort during the study or within 7 days prior to study entry
the use of grapefruit juice will be excluded during the course of the study.
use of anticholinergic compounds over the past 30 days prior to randomization
warfarin (Coumadin)
all systemic and inhaled pulmonary corticosteroids
memantine (Namenda)