It happened just after 2 a.m. on Interstate 40 West near South Miami Boulevard.
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The driver of a 2012 Honda Accord was traveling westbound on I-40 when he collided with a tractor-trailer that was parked outside of the lane of travel. He was taken to a hospital where he later died from his injuries.
DPD said the victim was not wearing a seatbelt.
The driver of the tractor-trailer was inside the big rig at the time, but he was not injured.
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Police said they believed speed was a factor in the crash, but it remains under investigation.
The identity of the victim has not yet been released.
Anyone with any information is asked to call Investigator J.D. Colquitt at (919) 560-4935 ext. 29450.