Mifepristone as Adjunctive Therapy in Alzheimer's Disease

Alzheimer's Disease Clinical Trial

Official title:

A Double-blind, Placebo-controlled Trial of the Safety and Efficacy of C-1073 (Mifepristone) as Adjunctive Therapy in Alzheimer's Disease

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00105105
• Other study ID #: IA0069
• Status: Terminated
• Phase: Phase 2
• First received: March 4, 2005
• Last updated: December 10, 2009
• Start date: April 2003
• Est. completion date: November 2005

Study information

• Verified date: September 2005
• Source: National Institute on Aging (NIA)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 160
• Est. completion date: November 2005
• Est. primary completion date: November 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Drug:
• Mifepristone

Locations

Country	Name	City	State
United States	Baumel-Eisner Neuromed Inst	Boca Raton	Florida
United States	ATP Clinical Trials	Fountain Valley	California
United States	Baumel-Eisner Neuromed Inst	Ft. Lauderdale	Florida
United States	Clinical Physiology Associates	Ft. Myers	Florida
United States	Memory Enhancement Center	Long Branch	New Jersey
United States	Pivotal Research Center	Mesa	Arizona
United States	Baumel-Eisner Neuromed Inst	Miami Beach	Florida
United States	Eastside Medical Research	New York	New York
United States	Pahl Pharmaceutical Research, LLC	Oklahoma City	Oklahoma
United States	UCI Irvine Medical Center	Orange	California
United States	Pivotal Research Center	Peoria	Arizona
United States	Clinical Trials Research Services	Pittsburgh	Pennsylvania
United States	International Clinical Research Associates	Richmond	Virginia
United States	California Neuroscience Research Medical Group, Inc.	Sherman Oaks	California
United States	Johnnie B. Byrd, Sr. Alzheimer's Center & Research Inst	Tampa	Florida
United States	Stedman Clinical Trials	Tampa	Florida
United States	Neuro Center of Ohio	Toledo	Ohio
United States	AVI Clinical Research	Torrance	California
United States	Clinical Pharmaceutical Trials, Inc.	Tulsa	Oklahoma
United States	International Clinical Research Associates	Virginia Beach	Virginia
United States	Grayline Clinical Drug Trials	Wichita Falls	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Corcept Therapeutics	Institute for the Study of Aging (ISOA)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Belanoff JK, Jurik J, Schatzberg LD, DeBattista C, Schatzberg AF. Slowing the progression of cognitive decline in Alzheimer's disease using mifepristone. J Mol Neurosci. 2002 Aug-Oct;19(1-2):201-6. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	effects on cognition
Secondary	effects on behavior and activities of daily living

External Links

•   Corcept Therapeutics