Extended Release Osmotic Tablet

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

In a 12-week placebo-controlled monotherapy study (Study 1; WHO Group 1; functional class IIIII), the most commonly reported adverse reactions that occurred in patients receiving Orenitram included: headache, diarrhea, nausea,, and flushing. Table 1 lists the most common adverse reactions that occurred at a rate on Orenitram at least 5% higher than on placebo.

Orenitram patients in Table 1 for Study 1 (N = 151) had access to 0.25 mg tablets at randomization. Approximately 91% of such patients experienced an adverse reaction, but only 4% discontinued therapy for an adverse reaction (compared to 3% receiving placebo). The overall discontinuation rate for any reason was 17% for active and 14% for placebo.

Table 1: Adverse Reactions with Rates at Least 5% Higher on Orenitram Monotherapy than on Placebo

Orenitram was studied in a long-term, open-label extension study in which 824 patients were dosed for a mean duration of approximately 2 years. About 70% of patients continued treatment with Orenitram for at least a year. The mean dose was 4.2 mg BID at one year.

The adverse reactions were similar to those observed in the placebo-controlled trials. The safety of Orenitram was also evaluated in an open-label study transitioning patients from Remodulin. The safety profile during this study was similar to that observed in the three pivotal studies.