Mifepristone as Adjunctive Therapy in Alzheimer's Disease
Mifepristone as Adjunctive Therapy in Alzheimer's Disease
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).
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.
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)