Tame! Newcastle after setback having big clear-out (5)
I believe the answer is:
enema
'big clear-out' is the definition.
'tame newcastle after setback having' is the wordplay.
'having' indicates the answer is hidden within the clue.
'after setback' says the letters should be written backwards.
'amene' is hidden within 'tame newcastle'.
'amene' written backwards gives 'ENEMA'.
(Other definitions for enema that I've seen before include "medicine to get you going" , "fundamental procedure?" , "Liquid injection given as a laxative" , "Procedure for vacating the bowels" , "Fluid injected rectally" .)