A 6 Month, Open-Label, Pilot Futility Clinical Trial of Oral Salsalate for Progressive Supranuclear Palsy

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Brief Title

A 6 Month, Open-Label, Pilot Futility Clinical Trial of Oral Salsalate for Progressive Supranuclear Palsy

Official Title

A 6 Month, Open-Label, Pilot Futility Clinical Trial of Oral Salsalate for Progressive Supranuclear Palsy

Brief Summary

      This is a multi-center, open label, pilot futility clinical trial of the safety,
      tolerability, pharmacodynamics and preliminary efficacy of oral salsalate in up to 10
      patients with PSP.
    

Detailed Description

      This is a multi-center, open label, pilot futility clinical trial of the safety,
      tolerability, pharmacodynamics and preliminary efficacy of oral salsalate in up to 10
      patients with PSP. All participants will be administered 2,250 mg daily [1,500 mg every day
      before noon (every AM) and 750 mg every night at bedtime (every HS)] for 6 months.

      If ≥3 patients experience drug limiting toxicity (DLT), as defined below, the study will be
      terminated.

      A DLT is defined as: 1) any Grade 3 or higher adverse event (AE) per National Cancer
      Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) for which there is
      reasonable possibility that salsalate caused the event, 2) any Grade 2 AE in the CTCAE system
      organ class of nervous system disorders that is considered clinically significant and for
      which there is reasonable possibility that salsalate caused the event, or 3) any Grade 2 or
      higher treatment-related adverse events during administration that do not resolve promptly
      with supportive treatment.

      An interim futility analysis will be performed after five subjects have completed 6 months of
      study drug treatment. If the criteria listed in the Statistical Methods section of this
      synopsis are met, an additional 5 subjects will be enrolled in the trial. If not, the trial
      will be terminated.
    

Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

Number of patients experiencing drug limiting toxicity (DLT),

Secondary Outcome

 Changes in motor function

Condition

Progressive Supranuclear Palsy

Intervention

Salsalate

Study Arms / Comparison Groups

 Salsalate
Description:  All participants will be administered 2,250 mg daily [1,500 mg every day before noon (every AM) and 750 mg every night at bedtime (every HS)] for 6 months.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

10

Start Date

April 2015

Completion Date

December 2019

Primary Completion Date

December 2019

Eligibility Criteria

        Inclusion Criteria:

          1. Meets National Institute of Neurological Disorders and Stroke - Society for
             Progressive Supranuclear Palsy (NINDS-SPSP) probable or possible PSP criteria,(Litvan
             1996a) as modified from the AL-108-231 trial.(Boxer 2014)

          2. Aged 50-85

          3. Agrees to 3 magnetic resonance imaging (MRI) or subject to investigator's discretion

          4. MRI at screening is consistent with PSP (≤4 microhemorrhages and no large strokes or
             severe white matter disease)

          5. Mini-Mental State Examination (MMSE) score 14-30

          6. Stable medications for 2 months prior to screening, including FDA approved Alzheimer's
             disease (AD) medications and Parkinson's disease medications

          7. Availability of a study partner who knows the patient well and is willing to accompany
             the patient to all trial visits and to participate in questionnaires

          8. Agrees to 2 lumbar punctures for cerebrospinal fluid (CSF) examination

          9. Signed and dated written informed consent obtained from the subject and subject's
             caregiver in accordance with local IRB regulations

         10. 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.

               -  Adequate contraceptive methods include those with a low failure rate, i.e., less
                  than 1% per year, when used consistently and correctly, such as complete
                  abstinence from sexual intercourse with a potentially fertile partner, and some
                  double barrier methods condom with spermicide) in conjunction with use by the
                  partner of an intrauterine device (IUD), diaphragm with spermicide, oral
                  contraceptives, birth control patch or vaginal ring, oral, or injectable or
                  implanted contraceptives.

               -  For this study, a woman who has been surgically sterilized or who has been in a
                  state of amenorrhea for more than two years will be deemed not to be of
                  childbearing potential;

        Exclusion Criteria:

          1. Meets National Institute on Aging-Alzheimer's Association Workgroups criteria for
             probable AD (McKhann et al. 2011);

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

          3. A prominent and sustained response to levodopa therapy;

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

          5. History of hypertension (repeated elevations in blood pressure exceeding 180 mm Hg
             systolic or 100 mm Hg diastolic; medical intervention indicated);

          6. History of severe gastrointestinal bleed, or gastric or peptic ulcers;

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

          8. History of major psychiatric illness or untreated depression;

          9. 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 evaluations;

         10. 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;

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

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

         13. Major surgery within four weeks prior to Screening;

         14. 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 Screening;

         15. Treatment with another investigational drug or participation in another interventional
             clinical trial within 3 months of Screening;

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

         17. Concurrent treatment with thiazides or loop diuretics;

         18. Concurrent use of oral corticosteroids or angiotensin-converting enzyme (ACE)
             inhibitors;

         19. Treatment with any human blood product, including intravenous immunoglobulin, during
             the 6 months prior to Screening or during the trial;

         20. Known hypersensitivity to the inactive ingredients in the study drug;

         21. Pregnant or lactating;

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

         23. Cancer within 5 years of Screening, except for non-metastatic skin cancer or
             nonmetastatic prostate cancer not expected to cause significant morbidity or mortality
             within one year of Baseline.
      

Gender

All

Ages

50 Years - 85 Years

Accepts Healthy Volunteers

No

Contacts

Adam Boxer, MD, PhD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT02422485

Organization ID

Salsalate PSP


Responsible Party

Sponsor-Investigator

Study Sponsor

Adam Boxer


Study Sponsor

Adam Boxer, MD, PhD, Principal Investigator, University of California, San Francisco


Verification Date

March 2021