6.1Clinical 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 practice. In a 12-week randomized, placebo-controlled, double-blind, fixed-dose study of SOMAVERT in subjects with acromegaly, 32 subjects received placebo and 80 subjects received SOMAVERT once daily [see Clinical Studies (14) ] .
A total of 108 subjects (30 placebo, 78 SOMAVERT) completed 12 weeks of study treatment. Overall, eight patients with acromegaly (5.3%) withdrew from pre-marketing clinical studies because of adverse events, including two patients with marked transaminase elevations, one patient with lipohypertrophy at the injection sites, and one patient with substantial weight gain. Most adverse events did not appear to be dose-dependent.
Table 3 shows the incidence of adverse events that were reported in at least two patients treated with SOMAVERT and at frequencies greater than placebo during the 12-week, placebo-controlled study. Table 3. Adverse Reactions in a 12-week Placebo-Controlled Study in Patients with Acromegaly Table includes only those events that were reported in at least 2 patients and at a higher incidence in patients treated with SOMAVERT than in patients treated with placebo.
Placebo n=32 SOMAVERT 10 mg/day n=26 15 mg/day n=26 20 mg/day N=28 Infection The 6 events coded as "infection" in the group treated with SOMAVERT 10 mg were reported as cold symptoms (3), upper respiratory infection (1), blister (1), and ear infection (1). The 2 events in the placebo group were reported as cold symptoms (1) and chest infection (1). 2 (6%) 6 (23%) 0 0 Pain 2 (6%) 2 (8%) 1 (4%) 4 (14%) Nausea 1 (3%) 0 2 (8%) 4 (14%) Diarrhea 1 (3%) 1 (4%) 0 4 (14%) Abnormal liver function tests 1 (3%) 3 (12%) 1 (4%) 1 (4%) Flu syndrome 0 1 (4%) 3 (12%) 2 (7%) Injection site reaction 0 2 (8%) 1 (4%) 3 (11%) Dizziness 2 (6%) 2 (8%) 1 (4%) 1 (4%) Accidental injury 1 (3%) 2 (8%) 1 (4%) 0 Back pain 1 (3%) 2 (8%) 0 1 (4%) Sinusitis 1 (3%) 2 (8%) 0 1 (4%) Chest pain 0 1 (4%) 2 (8%) 0 Peripheral edema 0 2 (8%) 0 1 (4%) Hypertension 0 0 2 (8%) 0 Paresthesia 2 (6%) 0 0 2 (7%)
6.2Postmarketing Experience Adverse Reactions from Postmarketing Spontaneous Reports
The following adverse reactions have been identified during post-approval use of SOMAVERT. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Systemic hypersensitivity reactions including anaphylactic reactions, laryngospasm, angioedema, generalized skin reactions (rash, erythema, pruritus, urticaria) have been reported in post-marketing use.
Some patients required hospitalization. Symptoms did not re-occur in all patients after re-challenge [see Warnings and Precautions (5.5) ] . Adverse Reactions from an Observational Study ACROSTUDY was an international observational registry that captured long term safety data in 2221 patients with acromegaly treated with SOMAVERT for a mean treatment duration of 8.5 years. Patients could also receive other therapy for acromegaly during the registry period.
Treatment dose and schedule were at the discretion of each treating healthcare provider. Although safety monitoring as per the recommended schedule was mandatory, not all assessments were performed at all time points for every patient. Because of this, comparison of rates of adverse events to those in the original clinical trial is not appropriate. Of the 1327 patients who had a normal AST and ALT at baseline, 20 (1.5%) patients had elevated tests >3-5 times ULN, and 22 (1.7%) patients had elevated tests >5 times ULN.
Lipohypertrophy was reported in 35 (1.6%) patients. Of the 1795 patients who had a MRI reported at baseline and at least once during follow up in the study, MRI results showed that 128 (7.1%) were reported to have an increase, 310 (17.3%) were reported to have a decrease, 81 (4.5%) had both increase and decrease, and 1276 (71.1%) had no change.
