Long-term safety of duloxetine during open-label compassionate use treatment of patients who completed previous duloxetine clinical trials.
ABSTRACT To provide duloxetine for the treatment of major depressive disorder (MDD), generalized anxiety disorder (GAD), fibromyalgia (FM) and diabetic peripheral neuropathic pain (DPNP) to patients who had previously completed a duloxetine clinical study and for whom, in the opinion of the investigator, no effective alternative therapy was available.
Adult outpatients who had previously completed a duloxetine study for the treatment of MDD, GAD, DPNP, or FM received duloxetine 30 mg to 120 mg daily up until its local commercial availability. Safety analyses included treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), AEs reported as reason for discontinuation, and vital signs. No efficacy measures were collected.
Of 667 patients enrolled, 282 (42.3%) were still participating at the time the drug was made commercially available in their countries. Most patients had previously participated in a duloxetine MDD study (76.2%); were female (68.1%) and Caucasian (94.9%). The median duration of exposure was 328 days (range 3-1718 days). The most common reasons for discontinuation were patient decision (25.3%), adverse event (8.4%), and lack of efficacy (8.4%). Of the 86 SAEs experienced by 46 patients, most (including one death) were judged by the investigator to be unrelated to duloxetine treatment. The most common TEAEs were in the System Organ Class of gastrointestinal (28.3%), nervous system (28.0%), and psychiatric (25.8%) and were predominantly mild to moderate in severity. Increases of systolic blood pressure (1.9 mm Hg) and pulse rate (2.2 bpm) at endpoint were reported.
The safety data from this long-term compassionate use study of duloxetine were consistent with previous experience and revealed no new safety signals. Limitations: The limitations include: lack of a control arm, no efficacy data were collected to assess the long-term efficacy, the results may not necessarily generalize to other ethnic groups as most patients were Caucasians, and lack of consistency in regard to duration of exposure at study entry as patients came from different trials with different study designs. CLINICAL TRIAL REGISTRY ID: www.clinicaltrials.gov--NCT00071708.