Renexxion is gearing up for two Phase II trials investigating naronapride in patients with cystic fibrosis (CF) and gastrointestinal (GI) dysmotility, says CEO Dr Peter Milner. After the opening of the FDA’s investigational new drug (IND) application earlier this month, Renexxion expects to initiate the studies in Q2 or Q3 this year.

Milner explains that one of the biggest complaints of people with CF is their GI tract. Indeed, CF affects pancreatic activity in about 90% of patients. “We are attempting with the Cystic Fibrosis Foundation to really impress upon the FDA and show how important this is to the individual patients,” Milner says.

Naronapride is a small molecule agonist of the 5HT4 receptor and an antagonist of the dopamine D2 receptor. According to the company’s website, stimulation of the 5HT4 receptor releases acetylcholine, which increases GI motility, while the inhibition of D2 receptors “removes the brakes on the motility of the gut.” The drug is ingested as a pill and acts topically in the gut.

Phase II trials in upper and lower GI

Renexxion is planning to conduct two Phase II trials investigating naronapride as a treatment for upper and lower GI tract symptoms. Each trial will recruit 45 cystic fibrosis patients with either reflux and gastroparesis or constipation, with a one-month run-in period.

After the run-in period, patients will be randomised to placebo, low-dose (20mg), and mid-dose (60mg) arms. After one month of treatment, participants will be blindly evaluated. If the symptoms were relieved, patients will stay on the same dose for another month.

In the event of inadequate relief, each treatment arm will move up a dose. The low dose of 20mg will receive 40mg, and the mid dose of 60mg will receive 80mg. Milner notes that this trial design has been approved by the FDA and the Cystic Fibrosis Foundation.

As for endpoints, the trials will use patient-reported outcomes to evaluate the treatment effect. Renexxion is currently in discussions with the FDA and Cystic Fibrosis Foundation to determine which of the symptomatic endpoints are validated in CF. In addition, the lower GI study will measure the spontaneous and complete spontaneous bowel motion, and the Bristol Stool Form Scale, a seven-point scale used for stool form and type measurement.

Renexxion is planning to open five US-based sites for each study with 10 patients per site.