An exploratory Phase 2 study of Prometic‘s investigative oral therapy PBI-4050 in patients with idiopathic pulmonary fibrosis (IPF) showed “encouraging” results and no safety concerns, a study reports.
The trial’s data was described in the article “Phase 2 clinical trial of PBI-4050 in patients with idiopathic pulmonary fibrosis,” published in the European Respiratory Journal.
Encouraging results seen in animal models support this first study of the compound in IPF patients.
The Phase 2 trial (NCT02538536) was an open-label, 12-week study to collect first-hand evidence of PBI-4050’s safety, efficacy, and availability in the body (pharmacokinetics) for people with IPF.
It enrolled 41 patients, ages 46 to 83, with mild or moderate IPF, at several sites in Canada. They were divided into three groups: Nine patients were assigned to receive PBI-4050 alone (200 mg capsules, four times daily), or in combination with Ofev (16 patients) or with Esbriet (16 patients) for those 12 weeks.
Current guidelines recommend Ofev or Esbriet (pirfenidone) for the treatment of IPF based on their efficacy in clinical trials, which showed they could slow lung function loss by approximately 50% as compared to placebo.
PBI-4050’s pharmacokinetic profiles — which reflect the compound’s absorption, bioavailability, distribution, metabolism and elimination in the body — were evaluated by measuring the PBI-4050 concentration in the blood (plasma) over time.
Similar profiles were seen for patients given PBI-4050 alone or in combination with Ofev, but a reduced absorption rate and a faster metabolization (shorter half-life) were seen when it was paired with Esbriet. This suggested a drug-drug interaction between both compounds.
PBI-4050 was well-tolerated alone or in combination with both Ofev and Esbriet, and side effects were mild or moderate. Most patients (83%) had at least one adverse event, the most common being diarrhea, nausea, and headache. The only serious adverse event recorded, a pneumonia, was considered by researchers to be related to IPF and not the treatment.
One patient in the Esbriet group withdrew early from the study, owing to a disease exacerbation or flare.
There were no changes in laboratory test results, vital signs, physical examination, or electrocardiogram (ECG) findings.
Although an exploratory study, efficacy was measured over the 12 weeks. Patients in the group taking PBI-4050 alone or combined with Ofev at the trial’s end showed no decline in lung function, as measured by forced vital capacity (FVC) (% predicted), an indication of airflow obstruction, the study reported.
In contrast, patients on PBI-4050 plus Esbriet had a mean FVC reduction of 2.69% at the end of those 12 weeks.
The apparent lower efficacy of this combination is supported by the lower absorption and shorter half-life seen earlier.
No significant changes in lung function, assessed by carbon monoxide diffusing capacity (DLCO), were shown from the study’s start (baseline) to its end in any of the treatment groups.
“In summary, there were no safety concerns with PBI-4050 alone or in combination with nintedanib or pirfenidone after 12 weeks of treatment in patients with predominantly mild or moderate IPF,” the researchers concluded.
“FVC results were encouraging for PBI-4050 alone and in combination with nintedanib, despite limitations in sample size and study design,” as is common in an exploratory, rather than pivotal, clinical trial.