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A Phase 1b, 12-Month, Randomized, Double-Blind, Placebo-Controlled Study of the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of Salsalate in Patients With Mild to Moderate Alzheimer’s Disease


Brief Summary:

The purpose of the study is to test the safety and tolerability of twice daily Salsalate in
patients with mild to moderate Alzheimer’s Disease. Half of the participants will receive
Salsalate and half will receive placebo during the 1-year duration of the study.


Inclusion Criteria:

1. Between 50 and 85 years of age (inclusive);

2. Meets National Institute on Aging-Alzheimer’s Association Workgroups criteria for
probable AD dementia (McKhann et al. 2011) (30);

3. MRI at Screening is consistent with AD (≤ 4 microhemorrhages, and no large strokes or
severe white matter disease);

4. MHIS at Screening is ≤ 4;

5. MMSE at Screening is between 14 and 30 (inclusive);

6. FDA-approved AD medications are allowed as long as the dose is stable for 2 months
prior to initial Screening visit. Other medications (except those listed under
exclusion criteria) are allowed as long as the dose is stable for 30 days prior to
initial Screening visit;

7. Has a reliable study partner who agrees to accompany the subject to visits, and spends
at least 5 hours per week with the subject;

8. Agrees to the lumbar puncture and CSF collection at Screening and after 11.5 months of
study drug administration. The lumbar puncture and CSF collection at the end of Month
6 is optional and is not required for eligibility;

9. Positive amyloid PET scan at Screening. Previous amyloid PET scan positivity or
previous AD biomarker (Aβ/tau level) positivity may be used instead of performing an
amyloid PET scan at Screening at the Investigator’s discretion;

10. Signed and dated written informed consent obtained from the subject and the subject’s
caregiver in accordance with local IRB regulations;

11. Males and all WCBP agree to abstain from sex or use an adequate method of
contraception for the duration of the study and for 30 days after the last dose of
study drug.

Exclusion Criteria:

1. Any medical condition other than AD that could account for cognitive deficits (e.g.,
active seizure disorder, stroke, vascular dementia);

2. History of negative AD biomarker studies (CSF Aβ/tau levels or amyloid PET), or a
negative amyloid PET scan during Screening;

3. History of significant cardiovascular, hematologic, renal, or hepatic disease (or
laboratory evidence thereof);

4. Systolic blood pressure exceeding 180 mmHg or diastolic blood pressure exceeding 100
mmHg at Screening or Baseline;

5. History of peptic ulcer disease or GI bleeding;

6. History of asthma, urticaria, or allergic-type reactions after taking NSAIDs or

7. History of aspirin triad (i.e., aspirin allergy, nasal polyps, and asthma);

8. History of autoimmune disorders deemed clinically significant by the Investigator;

9. History of major psychiatric illness or major depression that in the opinion of the
Investigator would pose a safety risk or interfere with the appropriate interpretation
of study data;

10. Neutrophil count <1,500/mm3, platelets <100,000/mm3, serum creatinine >1.5 x upper
limit of normal (ULN), total bilirubin >1.5 x ULN, alanine aminotransferase (ALT) >3 x
ULN, aspartate aminotransferase (AST) >3 x ULN, or INR >1.2 at Screening;

11. Evidence of any clinically significant findings on Screening or baseline evaluations
which, in the opinion of the Investigator would pose a safety risk or interfere with
appropriate interpretation of study data;

12. Current or recent history (within four weeks prior to Screening) of a clinically
significant bacterial, fungal, or mycobacterial infection;

13. Current clinically significant viral infection. Subjects with chicken pox, influenza,
or flu symptoms are not eligible;

14. Major surgery within four weeks prior to initial Screening visit;

15. Unable to tolerate MRI scan at Screening;

16. Any contraindication to or unable to tolerate lumbar puncture at Screening, including
use of anti-coagulant medications such as warfarin. Daily administration of 81 mg
aspirin will be allowed as long as the dose is stable for 30 days prior to initial
Screening visit;

17. Chronic use of other NSAIDs or salicylates for any reason, except for daily baby
aspirin (81 mg);

18. Chronic use of oral corticosteroids or other immunosuppressants;

19. Subjects who, in the opinion of the Investigator, are unable or unlikely to comply
with the dosing schedule or study evaluations;

20. Participation in another AD clinical trial within 3 months of initial Screening visit
or treatment with another investigational drug within 30 days of initial Screening

21. Known hypersensitivity to the inactive ingredients in the study drug (placebo or

22. Pregnant or lactating;

23. Positive pregnancy test at Screening or Baseline (Day 1);

24. Cancer within 5 years of initial Screening visit, except for non-metastatic skin
cancer or prostate cancer without signs of metastasis


  • University of California, San Diego, San Diego, California, United States, 92093
  • University of California, San Francisco, San Francisco, California, United States, 94158
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