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Two-in-One Drug Succeeds in Lung Disease Trial

Glycopyrronium/formoterol fumarate studied in COPD patients

Positive results have been reported from the phase III PINNACLE program, which included two pivotal 24-week studies (PINNACLE 1 and PINNACLE 2) that investigated the potential of PT003 (AstraZeneca) to improve lung function in patients with chronic obstructive pulmonary disease (COPD).

PT003 is a twice-daily fixed-dose combination of glycopyrronium, a long-acting muscarinic antagonist (LAMA), and formoterol fumarate, a long-acting beta-2 agonist (LABA). PT003 is the first LAMA/LABA combination to be delivered in a pressurized metered-dose inhaler (pMDI) using porous particle co-suspension technology developed by Pearl Therapeutics, which was acquired by AstraZeneca in 2013.

The development program also included an assessment of the individual components of PT003 –– glycopyrronium pMDI (PT001) and formoterol fumarate pMDI (PT005).

The PT003 program consists of PINNACLE 1, PINNACLE 2, and an extension study, PINNACLE 3. Overall, the phase III program enrolled more than 3,700 patients with COPD.

PINNACLE 1 and PINNACLE 2 were randomized, double-blind, placebo-controlled studies. In both trials, the efficacy and safety of PT003 administered twice daily via pMDI were compared with that of its monotherapy components (PT001 and PT005) and placebo. PT001 and PT005 were also compared with placebo. In PINNACLE 1, open-label tiotropium was included as an active control. Both studies were conducted for 24 weeks.

PINNACLE 3 was a randomized, double-blind, parallel-group, chronic-dosing, active-controlled, 28-week safety extension study of the PINNACLE 1 and PINNACLE 2 trials. It was designed to evaluate the long-term safety, tolerability, and efficacy of PT003 administered twice daily via pMDI compared with that of PT001 and PT005 in patients with moderate to very severe COPD over a total observation period of 52 weeks. Open-label tiotropium served as the active control.

In both the PINNACLE 1 and PINNACLE 2 studies, the primary objective was to assess beneficial effects on lung function, as measured by trough forced expiratory volume in 1 second (FEV1). PT003 demonstrated statistically significant improvements in trough FEV1 compared with PT001, PT005 and placebo. Both PT001 and PT005 also demonstrated statistically significant improvements in trough FEV1 compared with placebo.

In the PINNACLE 1 and PINNACLE 2 trials, the most common adverse events across all treatment arms, including placebo, were nasopharyngitis, upper respiratory tract infection, and dyspnea. The incidence of adverse events was generally similar across all treatment groups. Safety information from the PINNACLE 3 trial is not yet available.

AstraZeneca plans to file global regulatory applications for PT003 beginning in 2015.

COPD is a progressive disease associated mainly with tobacco smoking, air pollution, or occupational exposure, which can obstruct airflow in the lungs, resulting in debilitating bouts of breathlessness. The disease affects an estimated 300 million people worldwide and is predicted to be the third leading cause of death by 2020. Although COPD is widely regarded as a disease of the elderly, 50% of patients are estimated to be between 50 and 65 years of age, meaning that half of the COPD population is likely to be affected at a stage in their life when they are at the peak of their earning potential.

Source: AstraZeneca; March 18, 2015.

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