Concert Pharmaceuticals, Inc., which is developing new small molecule drugs through its DCE (deuterated chemical entity) Platform, recently announced positive results from a Phase 1 clinical trial of its cystic fibrosis (CF) treatment, CTP-656 (deuterium-modified ivacaftor). The data, which included a positive safety and tolerability profile, support the continuing development of CTP-656 as a potential treatment for CF patients with certain mutations.
Concert aims to present the results at the 39th European Cystic Fibrosis Conference, set for June 8–11 in Basel, Switzerland.
CTP-656, developed as a monotherapy or for use with other CFTR (cystic fibrosis transmembrane conductance regulator) modulators, was developed through the DCE Platform by modification of ivacaftor (Kalydeco). Initially, the company will be developing CTP-656 as a monotherapy for minimal mutations of the CFTR gene and CF gating.
The Phase 1 trial, titled “A Two-Part Phase 1 Healthy Volunteer Study: A Crossover Comparison of CTP-656 Solid Dose Formulation vs. Kalydeco® and a Double-Blind, Placebo-Controlled, Ascending Multiple Dose Evaluation of CTP-656,” was divided into two parts to assess safety, tolerability, and pharmacokinetics of CTP-656 as a tablet formulation.
In the first part, the researchers compared a single, 150 mg dose of CTP-656 versus 150 mg of Kalydeco. In the second part, three ascending doses of CTP-656, ranging from 75 mg up to 300 mg per day for seven days, were studied in comparison to placebo. Highlights from the study’s second part include a dose-proportional increase in exposure with repeated dosing for the 75 mg and 150 mg doses, metabolite profile, at steady state, similar to the profile previously demonstrated in the single-ascending dose phase, and positive safety results comparable to Kalydeco’s safety profile, with no serious adverse events.
These results are aligned with equally positive data from the first part of the trial, and with previously reported results from a clinical trial testing a single escalating dose of CTP-656 as an aqueous solution.
“We believe that we have identified a safe and well-tolerated dose range for CTP-656 that will provide effective clinical CFTR potentiation. Importantly, we believe we have the necessary data to select the doses for our Phase 2 trial that bracket parent drug exposure associated with the commercial dose of Kalydeco,” said James Cassella, PhD, chief development officer of Concert Pharmaceuticals, in a press release.
The company also recently completed a Phase 1 clinical trial (NCT02680249) evaluating the effects of food on the pharmacokinetics and bioavailability of CTP-656. The drug was tested with patients dosed while fasting, or being given a medium- or low-fat meal, and in healthy volunteers, with positive results. “We are pleased to see that full bioavailability of CTP-656 was retained even with a low-fat meal,” Dr. Cassella said.