Principal Investigator: Norman Foster
Keywords: Alzheimer's disease , Dementia , Memory Department: Alzheimer's Center
IRB Number: 00096437
Specialty: Neurology, Neurology
Sub Specialties: Dementia, Cognitive Disorders
Recruitment Status: Not yet recruiting

Contact Information

Jenny Felter

Brief Summary

Primary Objective

To evaluate the efficacy of a 5-HT6 antagonist, SUVN-502 at daily doses of 50 mg or 100 mg compared to placebo, as adjunct treatment in subjects with moderate Alzheimer’s disease (Mini-Mental State Examination [MMSE] score of 12 to 20) currently treated with the acetylcholinesterase inhibitor, donepezil HCl, and the NMDA antagonist, memantine HCl. Efficacy will be assessed by the ADAS-Cog after 26 weeks of treatment.

Secondary Objective(s)

Secondary objectives of the study are:

  • To further evaluate the efficacy of these treatments using the following scales:
    • Clinical Dementia Rating Scale – Sum of Boxes (CDR-SB)
    • MMSE
    • Alzheimer’s Disease Co-operative Study Activity of Daily Living (ADCS-ADL)
    • Neuropsychiatric Inventory (NPI) 12 item
    • Cornell Scale for Depression and Dementia (C-SDD)
  • To evaluate the safety and therapeutic tolerability of these treatments using AEs, laboratory evaluations, blood pressure, ECGs, physical and neurological examination, and the Columbia Suicide Severity Rating Scale (C-SSRS)
  • To evaluate the pharmacokinetics of SUVN-502 administered in combination with donepezil HCl and memantine HCl
  • To explore the relationship between the efficacy of SUVN-502 and apolipoprotein E (APO-E) genotype, as well as analyze subjects more likely to have Alzheimer’s disease

Inclusion Criteria

Inclusion Criteria

Subjects must meet all of the following inclusion criteria to be enrolled into the study:

  1. Male or female subjects, aged between 50 and 85 years inclusive at screening.
  2. Has a diagnosis of probable Alzheimer’s disease based on the NINCDS-ADRDA criteria at least 1 year prior to the screening visit.
  3. Has a score between 12 and 20 inclusive on the MMSE at the screening and baseline visits.
  4. Has a MRI or CT scan performed within 12 months prior to screening with findings consistent with the diagnosis of dementia due to Alzheimer’s disease without any other clinically significant comorbid pathologies.
  5. Has a MHIS score of 4 or less.
  6. Must be receiving treatment with stable doses of donepezil HCl (10 mg qd), either as 10 mg donepezil HCl only or part of the combination therapy, Namzaric™ (28 mg memantine HCl extended-release / 10 mg donepezil HCl) qd for at least 3 months prior to screening visit. Subjects are likely to be maintained on this 10 mg daily dose of donepezil HCl or Namzaric™ for the entire duration of the study.
  7. Must be receiving treatment with stable doses of memantine HCl (10 mg bid) or Namenda XR® (28 mg memantine HCl extended-release qd) or as part of the combination therapy, Namzaric™ (28 mg memantine HCl extended-release / 10 mg donepezil HCl) qd for at least 3 months prior to the screening visit. Subjects are likely to be maintained on their current dose of memantine HCl or Namenda XR® or Namzaric™ for the duration of the study.
  8. Availability of a person (caregiver) who in the investigator's judgment has frequent and sufficient contact with the subject, such that this person is qualified, willing and able to provide accurate information regarding the subject's cognitive and functional abilities and will accompany the subject to study visits. The caregiver should have face to face contact with the subject for a minimum of approximately 12 hours per week spread over 3 to 5 days during the week (for example: 3 hours per day for 4 days a week, or 4 hours per day for 3 days a week).
  9. Must be living in the community or an assisted living facility. No subjects currently residing in a nursing home or anticipated to move into a nursing home during the study will be allowed entry into the study.
  10. Must be ambulatory or ambulatory aided (use of cane or walker).
  11. Must have vision and hearing (corrected) sufficient to comply with the testing procedures.
  12. Both subject and caregiver must be able to read and understand English or Spanish and have appropriate literacy skills to ensure compliance with the testing and study visit procedures.
  13. Is not pregnant or planning to become pregnant during the study. Women of childbearing potential must have a negative pregnancy test at screening and must be using oral or injectable contraception (non-childbearing potential is defined as post-menopausal for at least 1 year or surgical sterilization or hysterectomy at least 3 months before study start).

   14. Subject (or subject’s legally acceptable representative) and caregiver must sign an Informed Consent to              participate in the  study.

Exclusion Criteria

Exclusion Criteria

Subjects who meet any of the following exclusion criteria will not be allowed to be randomized into the study:

  1. Has a diagnosis of dementia due to other causes, including vascular disease, Parkinson’s disease, Lewy Body disease, AIDS, Creutzfeldt-Jakob disease, fronto-temporal dementia, Huntington’s disease, major head trauma, primary or secondary cerebral neoplasia, or other non-Alzheimer disorders. Subjects with major strokes (large cortical/subcortical or in brain areas related to cognition), based on medical history, physical exam or MRI, are excluded.
  2. Has a diagnosis of schizophrenia, bipolar disorder or current major depressive disorder (MDD) or subjects whose C-SDD scores are suggestive of probable depression (typically scores ≥12). Subjects with history of MDD who are currently treated and controlled on medication for at least 6 months may be enrolled. Subjects taking low doses of antipsychotics for the treatment of sleep disturbances or for agitation or aggression, for which the dose has been stable for at least 1 month and not anticipated to change during the course of the study, can be enrolled.
  3. Is taking cholinesterase inhibitors other than donepezil HCl, including rivastigmine and galantamine. Subjects currently taking 5 mg of donepezil HCl, or taking 23 mg daily doses of donepezil HCl or subjects taking 10 mg daily dose of donepezil HCl for whom the physician contemplates increasing the dose to 23 mg during the conduct of the study, will not be enrolled.
  4. Is taking doses of memantine HCl other than 10 mg bid or Namenda XR® (28 mg memantine HCl extended-release qd) or Namzaric™ (28 mg memantine HCl extended-release / 10 mg donepezil HCl) qd.
  5. Has uncontrolled cardiac disease or hypertension. This includes subjects with history of myocardial infarction within 6 months of screening visit; congestive heart failure; history of unstable angina within 6 months of screening visit; and clinically significant ECG at screening visit and subjects whose hypertension has not been controlled on medication for at least 3 months prior to screening.
  6. Has a history or current evidence of long QT syndrome, Fridericia’s formula corrected QT (QTcF) interval ≥ 470 ms (for male subjects) or ≥ 480 ms (for female subjects), or torsades de pointes, as determined by an ECG read by a central ECG vendor.
  7. Has bradycardia (<50 bpm) or tachycardia (>100 bpm) on the ECG at screening.
  8. Has uncontrolled Type-1 or Type-2 diabetes (glycated hemoglobin [HbA1c] above 6.5%). A Subject with HbA1c levels up to 7.5% can be enrolled if the investigator believes the subject’s diabetes is under control.
  9. Has cancer or a malignant tumor, or has been treated for an active malignancy within the past 5 years. Subjects with stable untreated prostate cancer, localized squamous cell cancer or basal cell cancer will be allowed.
  10. Has untreated thyroid disorder. Subjects who are considered euthyroid on medication with normal free thyroxine (T4) will be allowed.
  11. Has a history of seizure disorder.
  12. Has clinically significant renal or hepatic impairment.
  13. Has any clinically significant abnormal laboratory values. Subjects with liver function tests (aspartate aminotransferase [AST] or alanine aminotransferase [ALT]) greater than twice the upper limit of normal will be excluded.
  14. Is treated or likely to require treatment during the study, with any medications prohibited by the study protocol.
  15. Has abnormal vitamin B-12 levels that are lower than normal limits and remains low on repeat testing. Subjects taking vitamin B-12 supplements who are within normal limits or above at screening or within normal limits or above at repeat testing will be allowed.
  16. Has participated in a previous clinical study within 26 weeks of the screening visit, or has been previously treated with the investigational product, SUVN-502.
  17. Subject (or caregiver) is deemed otherwise ineligible for participation in this study in the investigator’s judgment.
  18. Is at imminent risk of self-harm, based on clinical interview and responses on the C-SSRS, or of harm to others in the opinion of the Investigators. Subjects must be excluded if they report suicidal ideation with intent, with or without a plan or method (e.g. positive response to Items 4 or 5 in assessment of suicidal ideation on the C-SSRS) in the past 2 months, or suicidal behavior in the past 6 months.