Does it happen with all books or just the one? I'd try deleting all books, then load a different book onto the reader and see if it still happens.
While I love Calibre for some things, I'd open up the book in Sigil and do a check there. And just as another thing to check, make sure it's divided up into smaller html pages and it's not one huge html file for the entire book (yes, I've actually purchased books like that). Most readers will choke on one huge file. Once they're divided up properly, response on the reader is back to what it should be.
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