Forest Laboratories Inc. must conduct a cardiovascular safety trial for Tudorza Pressair, which FDA approved July 23 for long-term maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease, including bronchitis and emphysema.

The lone post-marketing requirement for Tudorza Pressair (aclidinium bromide) will be a randomized controlled trial to evaluate the risk of major adverse cardiac events, FDA said. Details on the trial are not yet available.

Forest indicated during a February advisory committee that CV safety already was part of its post-market study considerations. The company discussed plans for a randomized trial with about 4,000 patients for three years to compare aclidinium to placebo plus standard of care with a look at the drug’s effect on cardiovascular safety and severe exacerbations.

Agency reviewers had voiced uncertainty about the drug’s cardiovascular safety going into the session because of 10 deaths among patients receiving the 400 mcg indicated dose during clinical trials Also see "FDA Questions CV Events, Small Database Heading Into Aclidinium Bromide Advisory Committee" - Pink Sheet, 21 February, 2012..

Members of the Pulmonary-Allergy Drugs Advisory Committee agreed with those concerns, recommending approval of aclidinium on a 12-2 vote, but noting the need for a post-marketing study of cardiovascular issues ([A#14120223005]).

Forest expects Tudorza to be available to wholesalers in the fourth quarter of 2012. The drug is a long-acting antimuscarinic agent delivered as a dry powder through an inhaler from Almirall SA. The twice-daily drug causes bronchodilation by inhibiting acetylcholine’s effect on muscarinic receptors in the airway’s smooth muscle.

Tudorza is not indicated as rescue therapy. It should be used with caution in those with narrow-angle glaucoma, urinary retention, or severe hypersensitivity to milk proteins.

In three clinical trials, Forest reports Tudorza had statistically significant improvements in bronchodilation as measured by change from baseline in morning pre-dose trough forced expiratory volume in one second (FEV₁) at 12 weeks compared to placebo. The mean peak improvements in lung function (FEV₁) assessed after the first dose of aclidinium were similar to those observed at week 12 in each study.

Tudorza originally had an April user fee date, but that was extended for three months to allow FDA more time for its review.

Forest Tudorza Pressair Approval For COPD Includes Post-marketing CV Safety Study

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