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

The safety of Moxidectin Tablets was evaluated in two randomized, double-blind, active-controlled studies in patients with confirmed onchocerciasis  (Trial 1 and Trial 2)

No patients withdrew from either trial due to adverse reactions. Adverse Reactions reported in Trial 1 in > 10% of patients are summarized in Table 2. Most were related to physical, vital signs and laboratory changes associated with Mazzotti reaction

*Lymphocytopenia is defined as absolute lymphocyte count less than 1 x 10

**Neutropenia is defined as absolute neutrophil count less than 1 x 10

The most common adverse reactions in patients (N = 38) treated with 8 mg moxidectin in Trial 2 were similar to the adverse reactions noted in Trial 1 described in Table 2above.

The following adverse reactions occurred in less than 10% of subjects receiving Moxidectin Tablets in Trial 1:

*Includes “visual impairment”, “blurred vision” and “low vision acuity”

**Includes “foreign body sensation”, “ocular discomfort” and “abnormal sensation in the eye”

More patients in the moxidectin arm experienced elevation in bilirubin above the upper limit of normal and elevation in transaminases > 5x upper limit of normal. Twenty-seven (2.8%) patients in the moxidectin arm and 3 (0.6%) patients in the ivermectin arm had hyperbilirubinemia. Most of the patients had single measurements of hyperbilirubinemia without concurrent elevation in transaminases.

Nine (1%) patients in the moxidectin arm and 2 (0.4%) patients in the ivermectin arm had elevation in ALT of more than 5x upper limit of normal; ten (1%) patients in the moxidectin arm and 3 (0.6%) patients in the ivermectin arm had elevation in AST to more than 5x upper limit of normal.

Laboratory abnormalities occurring in at least 1% of patients in Trial 1 are described in Table 4.

The safety of Moxidectin Tablets in pediatric patients is based on data from 2 studies, Trial 1 and Trial 3 (NCT01035619).

Trial 1 included 53 pediatric patients aged 12 to less than 18 years with confirmed onchocerciasis who received a single dose of Moxidectin Tablets 8 mg. Pediatric patients with confirmed infection experienced efficacy-related adverse reactions (Mazzotti reactions) such as abdominal pain, tachycardia, pyrexia, rash, peripheral swelling, and lymph node pain at a prevalence and severity similar to infected adults. Overall, the safety profile relative to age was similar across pediatric and adult patients studied in Trial 1.

Trial 3 was a single-arm, open-label, age-stratified, multi-cohort, safety and pharmacokinetic trial that evaluated 36 pediatric patients aged 4 to less than 18 years with unknown O. volvulus infection status from an onchocerciasis-endemic area in Ghana. Patients were stratified by age to receive a single dose of Moxidectin Tablets as follows: aged 12 to less than 18 years received 8 mg (N = 9), 8 to less than 12 years received 8 mg (N = 9) or 6 mg (N = 9), and 4 to less than 8 years received 4 mg (N = 9). Median weight was 34.8 kg (range: 30.8 to 55.5 kg) in patients 12 to less than 18 years of age, 25.1 kg (range: 19.4 to 36.8 kg) in patients 8 to less than 12 years, and 15.6 kg (range: 13.6 to 20.6 kg) in patients 4 to less than 8 years. A majority of patients were female (58%) and 100% were black. Mazzotti reactions were not seen in this population with unknown O. volvulus infection. The most common adverse reactions in these pediatric patients were abdominal pain and diarrhea, in 3/36 (8%) patients each. No new safety signals were noted in this pediatric patient population that were not already noted in Trial 1.