Concert Pharmaceuticals unveils positive data from multiple dose phase 1 trial of CTP-656

CTP-656 is a novel deuterium-modified version of ivacaftor. Ivacaftor is commercially available under the name Kalydeco®. The clinical trial results continue to support the development of CTP-656 as a once-daily potentiator for the treatment of cystic fibrosis patients with certain gating mutations.

In addition, CTP-656 demonstrated enhanced exposure to the parent drug and less exposure to metabolites after repeat dosing, confirming its differentiated metabolite profile relative to Kalydeco.

Results of the Phase 1 trial also showed that CTP-656 was well-tolerated and its safety profile was comparable to that of Kalydeco. The Company expects to present the Phase 1 multiple ascending dose results at the 39th European Cystic Fibrosis Conference being held June 8-11, 2016 in Basel, Switzerland.

"We are pleased with the profile of CTP-656 emerging from the Phase 1 program," said James Cassella, Ph.D., Chief Development Officer of Concert Pharmaceuticals.

"We believe its potential to be dosed once-daily as well as its improved metabolite profile may provide important patient benefits, including ease of adherence and potentially improved efficacy."

This Phase 1 trial was conducted in two parts and enrolled 38 healthy volunteers to assess safety, tolerability and pharmacokinetics of CTP-656 in a tablet formulation. The first part assessed a single dose pharmacokinetic comparison of 150 mg of CTP-656 versus 150 mg of Kalydeco. The second part assessed three doses of CTP-656, 75 mg, 150 mg and 225 mg, dosed daily for seven days compared to placebo. Clinical highlights from Part 2 include:

Pharmacokinetics. Across all doses, the average plasma half-life of CTP-656 was approximately 18 hours at steady state. CTP-656 showed a dose-proportional increase in exposure with repeated dosing for the 75 mg and 150 mg doses. The 225 mg dose group showed higher than dose-proportional exposure.
Metabolite Profile. The metabolite exposure profile of CTP-656 after seven days of dosing in the tablet formulation showed the greatest exposure in plasma was to parent drug. These findings confirmed that at steady state the metabolite profile was similar to the profile previously demonstrated in the single ascending dose Phase 1 trial.
Safety. There were no serious adverse events and the safety profile of CTP-656 has been comparable to that of Kalydeco.

Dr. Cassella added, "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."

The Company previously reported positive results from Part 1 of this Phase 1 clinical trial in which a single-dose tablet formulation of CTP-656 was compared to the commercial tablet formulation of Kalydeco.

The results from this trial confirmed CTP-656’s superior pharmacokinetic profile to Kalydeco as was previously reported from Concert’s single ascending dose trial, in which CTP-656 was dosed as an aqueous suspension. In that trial, CTP-656 demonstrated favorable pharmacokinetic properties including a longer half-life, reduced rate of clearance, substantially increased exposure and greater plasma levels at 24 hours.

Concert recently completed a Phase 1 trial to evaluate the bioavailability and pharmacokinetics of CTP-656 when dosed fasted, or with a low fat or medium fat-containing meal, in healthy volunteers. Results from this study showed that CTP-656’s exposure was consistent when dosed with either a low or moderate fat-containing meal and was also consistent with exposure previously observed when dosed with a high fat meal.

"We are pleased to see that full bioavailability of CTP-656 was retained even with a low fat meal," stated Dr. Cassella.