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Reasons for study exclusion by sex in lanabecestat studies AMARANTH and DAYBREAK‐ALZ
Author(s) -
Zimmer Jennifer A.,
Andersen Scott W.,
Wessels Alette M.,
Shering Craig,
Sims John R.
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.038663
Subject(s) - medicine , dementia , amaranth , randomization , inclusion and exclusion criteria , disease , randomized controlled trial , pathology , biology , alternative medicine , agronomy
Background Sex‐based differences in pathophysiology and clinical presentation of Alzheimer’s Disease (AD) have been reported. These differences could impact trial eligibility. This analysis of screening data assesses the most common reasons for exclusion within sex. Method Phase 2/3 AMARANTH (NCT02245737) enrolled early AD (MCI due to AD, mild AD dementia) with MMSE 20‐30 and RBANS DMI ≤85. Phase 3 DAYBREAK‐ALZ (NCT02783573) enrolled mild AD with MMSE 20‐26. For MCI, NIA‐AA criteria were met, with CDR of 0.5 and memory box score ≥0.5. For mild AD, NIA‐AA criteria were met, with CDR of 0.5 or 1 and memory box score ≥0.5. Both studies enrolled participants 55‐85 years‐of‐age with proof of amyloid (PET scan or cerebrospinal fluid). Excluded participants meeting prespecified criteria were permitted ≤2 rescreens. Reasons for exclusion and patients randomized are presented by sex. The top three reasons for exclusion are compared by female and male subsets. In AMARANTH, participants could fail >1 criterion. For DAYBREAK‐ALZ, MMSE exclusion is further divided into MMSE score subsets (<20 or >26, when available). Statistical comparisons are made using Pearson’s Chi‐Square and not adjusted for multiplicity. Result For both studies, proportions of females represented in reasons for exclusion and randomization are similar (AMARANTH: 52% vs. 53%; DAYBREAK‐ALZ: 57% vs. 59%). In AMARANTH, MMSE score not within range was more commonly reported and lack of presence of amyloid was less commonly reported in the female subset than the male subset (17.8% vs 13.5% (p<0.001) and 22.4% vs 24.5% (p<0.05) of reasons, respectively). In DAYBREAK‐ALZ, proportions of reasons for exclusion in sex subsets were similar. However, MMSE score <20 was more common and MMSE score >26 less common as a reason for exclusion in the female subset compared to the male subset (females vs. males: score <20: 24.6% vs 18.3%, score >26: 12.8% vs 19.7%; p<0.001 for each). Conclusion These results suggest females presenting for screening may have more advanced disease. Possible reasons include late referral of females due to advanced verbal memory skills delaying recognition of disease, social circumstances, faster disease progression of females identified from clinical trial site databases, or differences in educational attainment.