United Therapeutics Corporation (NASDAQ: UTHR) announced today the completion of its FREEDOM-C(2) Phase 3 trial of treprostinil diethanolamine (oral treprostinil), an investigational sustained release oral formulation of treprostinil, a stable synthetic form of prostacyclin, in patients with pulmonary arterial hypertension (PAH). Preliminary analysis demonstrates that the trial did not achieve statistical significance for the primary endpoint, six-minute walk distance (6MWD) at Week 16.
The FREEDOM-C(2) trial was a randomized, double-blind, placebo-controlled trial of patients with PAH, a chronic, life-threatening illness. The study population consisted of 310 patients who were optimized on an endothelin receptor antagonist, a phosphodiesterase-5 inhibitor, or both. In addition to one of these oral therapy regimens, patients were administered oral treprostinil or placebo twice daily with the dose titrated (increased to tolerability) over the 16-week trial. The majority (~73%) of patients were World Health Organization (WHO) Class III patients of varied etiologies, including idiopathic or familial PAH (~65%), collagen vascular disease associated PAH (~31%), and PAH associated with HIV or other associated conditions (~3%). Mean baseline walk distance was approximately 333 meters.
The primary efficacy endpoint of the trial was the median change in 6MWD at 16 weeks relative to baseline. With regard to the primary efficacy results, the placebo-corrected median change in 6MWD at Week 16 was 10 meterss pre-specified statistical analysis plan).
Overall, 132 (84%) oral treprostinil and 138 (90%) placebo patients completed Week 16 with an average dose of 3.0 plus or minus 1.9 mg twice daily in the oral treprostinil group. Discontinuations due to adverse events were 18 (11%) and 5 (3%) in the treprostinil and placebo groups, respectively. Adverse events associated with discontinuations were typically prostacyclin-related effects including headache, nausea and vomiting.
Preliminary analysis of other secondary efficacy measures, including time to clinical worsening, change in combined 6MWD and Borg Dyspnea Score rating (shortness of breath test) and Dyspnea-Fatigue index, WHO functional class, and PAH signs and symptoms, did not differ significantly between oral treprostinil and placebo (p>0.05).
Further review and analysis of the FREEDOM-C(2) preliminary results are ongoing. A summary of the preliminary analysis conducted thus far can be accessed via United Therapeutics' website at http://ir.unither.com/events.cfm beginning at 5:00 a.m. Eastern Time on August 24, 2011. Full data from FREEDOM-C(2) will be presented at an upcoming medical meeting and will also be available through the publication of peer-reviewed journal articles.
"While we did not achieve a statistically significant result for this trial, we believe the positive results from our previously-announced FREEDOM-M study support an NDA filing of oral treprostinil in treatment naive patients," said Roger Jeffs, Ph.D., United Therapeutics' President and Chief Operating Officer. "Given that treprostinil is already approved for use in PAH by subcutaneous, intravenous and inhaled routes of administration, we believe the data obtained from all FREEDOM trials support an NDA for oral treprostinil in this indication," added Dr. Jeffs. "We will now focus on completing the NDA for filing by the first half of 2012."
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