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Slide Presentations: Wednesday, October 26, 2011 |

FREEDOM-M: Efficacy and Safety of Oral Treprostinil Diethanolamine as Monotherapy in Patients With Pulmonary Arterial Hypertension FREE TO VIEW

Lewis Rubin, MD; Keyur Parikh, MD; Tomas Pulido, MD; Carlos Jerjes-Sanchez, MD; Roblee Allen, MD; James White, MD; Adam Torbicki, MD; Kaifeng Xu, MD; David Yehle, BS; Kevin Laliberte, PharmD; Carl Arneson, MS; Zhi-Cheng Jing, MD
Chest. 2011;140(4_MeetingAbstracts):1044A. doi:10.1378/chest.1212098
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Abstract

PURPOSE: To determine the effects of chronically administered oral treprostinil diethanolamine (TRE), a prostacyclin analogue formulated as a sustained release tablet, on both exercise capacity and safety as monotherapy in patients with pulmonary arterial hypertension (PAH).

METHODS: Double-blind, randomized (2:1), placebo-controlled, parallel-group study comparing the twice daily (BID) administration of oral TRE to placebo (PBO) over 12 weeks in PAH patients not receiving approved PAH therapy. Study drug dose was titrated based on each patient’s clinical response and tolerability. Entry criteria included a confirmed diagnosis of PAH and a six-minute walk distance (6MWD) of 100-450 meters. The primary endpoint was change in 6MWD (compared to PBO) from baseline to Week 12 in the patients with access to 0.25 mg tablets at randomization. Secondary efficacy included changes in 6MWD at Weeks 4, 8, 11 (trough), WHO functional class, Borg Dyspnea Score, dyspnea-fatigue index, signs and symptoms of PAH, and clinical worsening.

RESULTS: 349 patients were enrolled at 52 centers, with 228 patients in the primary analysis population. Baseline characteristics of the primary population included mean age of 38 years (12-73) with 75% idiopathic PAH, and 66% WHO class III. Mean baseline 6MWD was 330 meters. Median 6MWD (peak) at Week 12 improved 23 m (Hodges-Lehmann; p=0.0125) compared to PBO (25 m for TRE and -5 m for PBO), while 6MWD at Weeks 4 and 8 improved 12 (p=0.05) and 17 meters (p=0.03). In addition, 36%, 34%, and 29% of active patients had a 40, 50, and 60 meter 6MWD improvement at Week 12, respectively. Mean dose was 1.6, 2.7, and 3.3 mg BID at Weeks 4, 8, and 12, respectively. The combined 6MWD and Borg Dyspnea Score rating was significantly improved (p=0.0497). Other secondary efficacy measures did not differ significantly between oral treprostinil and placebo (p>0.05). Analysis of all 349 enrolled patients resulted in similar findings. Safety data is currently being analyzed.

CONCLUSIONS: First-line monotherapy with oral TRE significantly improves exercise capacity in PAH.

CLINICAL IMPLICATIONS: Oral TRE is an investigational agent being evaluated for the treatment of PAH.

DISCLOSURE: Lewis Rubin: Consultant fee, speaker bureau, advisory committee, etc.: Lewis Rubin is a consultant for United Therapeutics

Keyur Parikh: Grant monies (from industry related sources): For participation in the FREEDOM-M study

Tomas Pulido: Grant monies (from industry related sources): For participation in the FREEDOM-M study

Carlos Jerjes-Sanchez: Grant monies (from industry related sources): For participation in the FREEDOM-M study

Roblee Allen: Grant monies (from industry related sources): For participation in the FREEDOM-M study

James White: Grant monies (from industry related sources): For participation in the FREEDOM-M study, Consultant fee, speaker bureau, advisory committee, etc.: For consultation with United Therapeutics

Adam Torbicki: Grant monies (from industry related sources): For participation in the FREEDOM-M study

Kaifeng Xu: Grant monies (from industry related sources): For participation in the FREEDOM-M study

David Yehle: Employee: Employee of United Therapeutics

Kevin Laliberte: Employee: Employee of United Therapeutics

Carl Arneson: Employee: Employee of United Therapeutics

Zhi-Cheng Jing: Grant monies (from industry related sources): For participation in the FREEDOM-M study

Oral treprostinil is an investigational drug under evaluation for the treatment of pulmonary arterial hypertension.

11:30 AM - 12:45 PM


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