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Clinical Trial
. 2017;58(2):401-411.
doi: 10.3233/JAD-160965.

A Randomized, Double-Blind, Placebo-Controlled, Phase II Study of Oral ELND005 (scyllo-Inositol) in Young Adults with Down Syndrome without Dementia

Michael S Rafii  1   2 , Brian G Skotko  3   4 , Mary Ellen McDonough  3 , Margaret Pulsifer  4   5 , Casey Evans  5 , Eric Doran  6 , Gabriela Muranevici  2 , Patrick Kesslak  7 , Susan Abushakra  8 , Ira T Lott  6 ; ELND005-DS Study Group
Affiliations
Clinical Trial

A Randomized, Double-Blind, Placebo-Controlled, Phase II Study of Oral ELND005 (scyllo-Inositol) in Young Adults with Down Syndrome without Dementia

Michael S Rafii et al. J Alzheimers Dis. 2017.

Abstract

Background: ELND005 (scyllo-Inositol; cyclohexane-1,2,3,4,5,6-hexol) has been evaluated as a potential disease-modifying treatment for Alzheimer's disease (AD). Individuals with Down syndrome (DS) have an increased risk for developing AD dementia.

Objective: To evaluate the safety and tolerability of ELND005 and to determine its pharmacokinetics (PK) and relationship between PK parameters, safety outcome measures, and exploratory efficacy outcome measures in young adults with DS without dementia.

Methods: This was a prospective, randomized, double-blind, placebo-controlled, parallel-group, three-arm, multicenter Phase II study of the safety and pharmacokinetics of ELND005 administered orally for 4 weeks (ClinicalTrials.gov NCT01791725). Participants who met study eligibility criteria were randomly assigned in a 2 : 1:1 ratio to receive ELND005 at either 250 mg twice daily (BID) or 250 mg once daily (QD) or matching placebo for 4 weeks.

Results: There were no apparent treatment group-related trends on cognitive or behavioral measures and there were no SAEs and no deaths in the study. Overall, mean changes from baseline in clinical laboratory parameters, vital sign measurements, electrocardiogram results, and other physical findings were unremarkable. ELND005 accumulation averaged approximately 2-fold with QD dosing, and 3- to 4-fold with BID dosing.

Conclusion: Overall, treatment of adults with DS with ELND005 at both doses was well tolerated, achieved measurable blood levels and demonstrated no safety findings. Further studies will be needed to test efficacy.

Keywords: Alzheimer’s disease; Down syndrome; Myo-inositol; amyloid; dementia.

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Figures

Figure 1
Figure 1. Participant Flow
Abbreviations: BID = twice daily, mITT = modified intent to treat, QD = once daily
Figure 2
Figure 2. Mean (SD) Plasma Concentration of ELND005 (μg/mL) versus Time
Plasma levels were calculated based on peripheral venous blood samples that were collected from indwelling catheters or by direct venipuncture into collection tubes. Baseline (Visit 2) and Day 28 (EOS) blood samples for ELND005 plasma levels were collected before dosing (time 0), and at 1.5 (±0.5), 3 (±0.5), and 4.5 (±0.5) hours after dosing. In addition, patients were encouraged to provide blood samples at 6 (±1) and 8 (±1) hours after dosing. At Day 14, one blood sample was collected (either before or after the first dose of study drug on Day 14).
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References

    1. de Graaf G, Buckley F, Skotko BG. Live births, natural losses, and elective terminations with Down syndrome in Massachusetts. Genet Med. 2016;18:459–66. - PubMed
    1. Gardiner K, Herault Y, Lott I, Antonarakis S, Reeves RH, Dierssen M. Down syndrome: from understanding the neurobiology to therapy. J Neurosci. 2010;30:14943–5. - PMC - PubMed
    1. Pinter JD, Brown WE, Eliez S, Schmitt JE, Capone GT, Reiss AL. Amygdala and hippocampal volumes in children with Down syndrome: a high-resolution MRI study. Neurology. 2001;56:972–4. - PubMed
    1. Edgin JO, Mason GM, Allman MJ, Capone GT, Deleon I, Maslen C, Reeves RH, Sherman SL, Nadel L. Development and validation of the Arizona Cognitive Test Battery for Down syndrome. J Neurodev Disord. 2010;2:149–164. - PMC - PubMed
    1. Lott IT, Dierssen M. Cognitive deficits and associated neurological complications in individuals with Down’s syndrome. Lancet Neurol. 2010;9:623–33. - PubMed

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