3-month Study of MSDC-0160 Effects on Brain Glucose Utilization, Cognition & Safety in Subjects With Alzheimer's Disease
Condition: Alzheimer's Disease
MeSH terms: Alzheimer Disease
Intervention: MSDC-0160; Placebo
Intervention description: MSDC-0160 150 mg capsules given once daily for 90 days; Placebo capsules given once daily for 90 days
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 29.0
Sex: All
Minimum age: 55 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: Alzheimer's disease; cognitive function; brain glucose utilization; FDG-PET

Summary:

      This study will evaluate the effect of 150 mg MSDC-0160 taken daily for 90 days compared to
      the effect of placebo on changes in brain glucose utilization using FDG-PET and cognition in
      older persons with mild Alzheimer's disease. Safety and tolerability of MSDC-0160 in this
      population will also be studied. These results will be used to design larger studies of
      MSDC-0160 in persons with mild Alzheimer's disease.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or females 55-85 years of age.

          2. Females should be either postmenopausal or surgically sterilized. Males with female
             partners of child-bearing potential must use contraception if engaging in sexual
             intercourse.

          3. Diagnosis of probable Alzheimer's disease based on NIA-AA criteria with MMSE scores of
             20 or greater.

          4. Willing and able to take part in up to six study visits over a 5-month period, with
             the support of a caregiver as needed.

          5. Willing and able to sign an informed consent document indicating understanding the
             purpose of and procedures required for the study and willingness to participate in the
             study, with the support of a caregiver as needed.

        Exclusion Criteria:

          1. Diagnosis of diabetes, including use of anti-diabetic medications, or fasting plasma
             glucose >125 mg/dl or Hemoglobin A1c>6.4%.

          2. Unable to participate in FDG-PET scanning, including:

               -  Inability to cooperate/claustrophobia (no sedation offered for this protocol).

               -  Inability to lie still on the scanner bed for 40 minutes.

               -  Total radiation dose exposure to the subject in any given year exceeds the limits
                  of annual and total dose commitment of 50 mSv (5 REMs). The two FDG-PET scans
                  will result in an approximate exposure of 10 mSv (1 REM).

          3. Diagnosis of significant neurological/psychiatric disease other than AD, including,
             but not limited to, any of the following: vascular dementia according to NINDS-AIREN
             criteria, space occupying cerebral lesion, Huntington's Disease, Parkinson's Disease,
             normal pressure hydrocephalus, and seizures.

          4. History of heart failure (including CHF).

          5. Previous cardiovascular event (myocardial infarct, by-pass surgery, or PTCA) within
             the past 6 months prior to screening.

          6. Inability to undergo a clinical (1.5T) MRI of the brain without contrast and lack of a
             usable (less the 12 months prior to screening) MRI on record. Contraindications to
             undergoing an MRI of the brain include, but are not limited to, pacemakers;
             implantable cardioverter defibrillators; cochlear implants; cerebral aneurysm clips;
             implanted infusion pumps; implanted nerve stimulators; metallic splinters in the eye;
             and, other magnetic, electronic or mechanical implants or clinical findings that in
             the judgment of the investigator would pose a potential hazard in combination with
             MRI.

          7. ALT and/or AST levels that are twice the upper limit of normal; bilirubin levels that
             exceed 2 mg/dL; serum creatinine >1.5 mg/dL in men or > 1.4 mg/dL in women.

          8. Current or history of severe or unstable disorder (medical or psychiatric) requiring
             treatment that may make the subject unlikely to complete the study.

          9. Malignancy (other than non-melanoma skin cancer) within the last 5 years.

         10. Known history of HIV, hepatitis B, or hepatitis C.

         11. Blood pressure greater than 160/100 mmHg. Subjects with elevated BP will be allowed at
             the discretion of the principal investigator. Individuals with hypertension must have
             been stabilized to the current treatment regimen for at least 6 weeks prior to
             screening and not need adjustments to their treatment regimen during the entire study
             period.

         12. Change in other medications to treat Alzheimer's disease within 3 months prior to
             screening. Change in medication to treat other conditions within 6 weeks prior to
             screening or during the study period.

         13. Known or suspected intolerance or hypersensitivity to the study drugs, closely related
             compounds, or any of their stated ingredients.

         14. History of alcohol or drug abuse within 6 months of screening.

         15. Have participated in an investigational study or received an investigational drug
             within 30 days or 5 half-lives (whichever is longer) prior to study drug
             administration.

         16. Single 12-lead ECG demonstrating a QTcB >450 msec or other clinically significant
             finding at screening. A single repeat ECG may be done at the investigator's
             discretion.

         17. Any surgical or medical condition which may significantly alter the absorption of any
             drug substance including, but not limited to, any of the following: history of major
             gastrointestinal tract surgery, currently active inflammatory bowel syndrome.

         18. Evidence of clinically relevant pathology that in the investigator's opinion could
             interfere with the study results or put the subject's safety at risk.