Carlisle manager Greg Abbott found a sympathetic ear from counterpart Russell Slade after Leyton Orient administered a heavy 5-1 defeat on the Cumbrians on their home turf at Brunton Park.
Carlisle were just a goal down when they lost skipper Lee Miller to a red card on the half-hour mark and they never really recovered from that upset.
O's, who led 2-1 at half-time, went on to win convincingly and have now scored a total of 13 goals against Abbott's men in their last three meetings.
Slade said: "I feel for Greg, who is a good friend of mine, because with all the preparation you do you can't legislate for that first half and Miller getting sent off.
"We were at the top of our game, but I'm sure Carlisle will be fine. Things conspired against them and I'm just happy to get that first win under our belts. We have taken the first step, but there's still a lot of work to be done and I thought we showed our adaptability."
O's scored twice with headers in the first half - Kevin Lisbie glancing in Clarke's long throw before Scott Cuthbert thumped home from Lloyd James' corner.
There was a glimmer of hope for Carlisle when David Amoo rolled home a penalty after Mathieu Baudry had handled a Josh Gillies shot.
However, O's took charge again when David Mooney got on the end of a Moses Obubajo cross to head past goalkeeper Mark Gillespie, and then substitute Dean Cox added a late brace to make it five.
Cumbrians boss Abbott admitted his side were "too frail and weak" to combat a street wise Orient outfit.
However, he said: "I'm still optimistic for the season, but we have to play with a full complement of players. Whatever I say will make me angry and frustrated. I didn't see a red card from where I was. We lost our leader, captain and talisman and it's difficult once he's gone."