President Obama was dealt a significant setback Tuesday afternoon after Senate Democrats blocked a motion to begin debate on a fast-tracked Trans-Pacific Partnership (TPP) trade deal.

Forty-five senators voted against moving the secretive bill forward, while 52 voted in favor, with only one Democrat, Sen. Tom Carper of Delaware, supporting it. The motion needed 60 votes to cut off a filibuster and proceed with debates, reported The New York Times.

The Obama administration spent weeks intensely lobbying Democrats to support fast-track but has been been met with significant resistance, led by Senate Minority Leader Harry Reid, D-Nev., and Sen. Elizabeth Warren, D-Mass.

TPP opponents argue that the 12-country trade agreement is essentially a corporate handout that would override U.S. financial and environmental regulations, allow domestic policies to be contested  by corporations in an international court, favor businesses over workers and strengthen copyright laws.

Warren said the TPP "would let derivatives traders on Wall Street gamble with taxpayer money and get bailed out by the government when their risky bets threaten to blow up our financial system" and "give protections to international corporations that are not available to U.S. environmental and labor groups," according to The Hill.

Opponents also point to the agreement's classified nature as being suspicious. Members of Congress are only allowed to look at one section at a time in the Capitol's basement without the ability to take notes, while access is given to government-appointed trade advisory committees providing advice to the U.S. negotiators, such as AT&T, General Electric, Apple, Dow Chemical, Nike, Walmart and the American Petroleum Institute, according to The Intercept.

Democrats also said they couldn't move forward on Tuesday unless two additional committee-approved bills were added to the deal, but Senate Majority Leader Mitch McConnell, R-Ky., said it was unacceptable to attempt to "craft a bill before we even get on it," reported USA Today.

Republicans, on the other hand, in a rare display of support for the president's agenda, lined up to back the measure. Following the vote, a number of Republicans expressed frustration with their Democratic counterparts.

"What we've just saw here is pretty shocking," McConnell said on the Senate floor after the vote, reported CNN. "What we've just witnessed here is the Democratic Senate shut down the opportunity to debate the top economic priority of the Democratic President of the United States."

The White House chalked the blunder up to a procedural setback. "It is not unprecedented - to say the least - for the United States Senate to encounter procedural snafus," said press secretary Josh Earnest.

Tuesday's failure could mark the beginning of the end of the landmark trade negotiations, though Democratic Senator Chris Coons told reporters that he thinks it will be back.

"I don't think today's vote is a death knell for TPA, but it is a very strong warning shot to the majority leader ... that without worker protections, without enforcement provisions, they will likely not move forward," he said, reported Reuters.

Following the trade bill rebellion, Obama began privately working with Senate Democrats to "discuss a path forward for this legislation," an administration official said, according to CNN.

"The President reiterated his view, which he has shared in numerous similar conversations with members over the past several weeks, that passing TPA is an important step toward finalizing the Trans-Pacific Partnership - the most progressive trade agreement in our history, which levels the playing field for American workers and puts in place new, high-standards environmental, labor, and human rights protections," the administration official said, according to CNN.

TPP negotiators maintain that 11 other countries participating in the trade talks won't agree to finalize the partnership until the bill is passed.