Boehringer Ingelheim announced that it has initiated a 12-week clinical trial investigating the safety, tolerability, and pharmacokinetics of pirfenidone (marketed as Esbriet by Genentech) as an add-on to treatment with OFEV (nintedanib). The study will compare the combination therapy to treatment with OFEV alone in idiopathic pulmonary fibrosis (IPF) patients.

Enrollment for the study began in November 2015, and Boehringer Ingelheim plans to enroll 100 people from 25 study centers in the United States, Canada, Italy, Germany, France, and the Netherlands.

Both drugs are relative newcomers to the U.S. market, having been approved by the U.S. Food and Drug Administration (FDA) in October 2014. OFEV was approved in the EU in January 2015, while pirfenidone has been in use in the EU since 2011.

OFEV and pirfenidone represent the first FDA-approved drug treatments for IPF, and are also the first drugs able to reduce lung scarring, slowing disease progression and reducing mortality in IPF patients.

While most of the safety and tolerability data for a new drug is acquired during a Phase 1 clinical trial, the collection of data continues throughout Phase 2-3 trials and following the drug’s introduction to the market after approval.

However, when drugs are given in combination, new safety and tolerability issues might arise, since the substances may interact, affecting their pharmacokinetics (absorption, distribution, metabolism, and excretion).

The most frequent side effects associated with OFEV use are gastrointestinal problems, such as diarrhea, nausea, abdominal pain, and vomiting. Pirfenidone also frequently gives rise to similar side effects. Since combined therapies might increase the risk of adverse events, the study will focus on the percentage of people with gastrointestinal problems, or other effects, throughout its 12 weeks.

As a secondary endpoint, the study will investigate levels of OFEV and pirfenidone in the blood to assess if the drugs interact when taken simultaneously. The study will not, however, look into the efficacy of the combination.

“This trial is being initiated to provide the scientific and healthcare communities with important information about the safety of OFEV® when combined with another FDA-approved treatment for IPF,” said Danny McBryan, MD, vice president, Clinical Development and Medical Affairs, Respiratory, Boehringer Ingelheim Pharmaceuticals. “Boehringer Ingelheim has a long-standing and continued commitment to addressing the significant unmet needs of people affected by serious respiratory diseases like IPF.”

Lisa H. Lancaster, associate professor at the Division of Allergy, Pulmonary, and Critical Care Medicine at Vanderbilt University Medical Center, added: “Last year’s FDA approval of the first two treatment options for IPF, followed shortly by their conditional recommendation in International Treatment Guidelines, represented major accomplishments in treating this devastating disease. At the same time, healthcare providers have limited evidence of the safety of combining these two treatments, and the results from this new trial will provide important information to improve the understanding of how these drugs may be able to be used together.”

More information about this trial is available here.