Safety evaluation
dry skin, epistaxis, stomatitis, abnormal dreams, TEAEs, pain, dizziness, nasal congestion, headache, paraesthesia, dysgeusia, TEAE, SAD
STOMATITIS, MEDICAL DEVICE SITE IRRITATION, EVENT, HYPERBILIRUBINAEMIA, DRY EYE, OCULAR HYPERAEMIA, PARAESTHESIA, EPISTAXIS, EVENTS, INJECTION SITE BRUISING, HYPERTRIGLYCERIDAEMIA
An overview of treatment‐emergent AEs (TEAEs) is provided for SAD in Table Across the SAD substudy, 56 TEAEs were reported by 31/56 (55.4%) participants. No dose relationship for any TEAE was evident. The most common TEAEs reported in the KCL‐286 treated participants included abnormal dreams (3 participants), skin exfoliation (3 participants), medical device site irritation (3 participants), headache (2 participants), dry eye (2 participants), dry skin (2 participants) and injection site bruising (2 participants). The most common TEAEs in placebo participants were abnormal dreams and headache (each in 2 participants). All other TEAEs were reported by no more than 1 participant. The events of medical device site irritation and injection site bruising resulted from study procedures (electrocardiogram electrodes and cannulation for blood draws). There was 1 clinically significant laboratory event of mild and reversible transaminase increase reported as a TEAE in a participant treated with a single 12‐mg dose.One participant in the 100‐mg cohort reported a mild unrelated TEAE of visual field defect on Day 2 that resolved within an hour. In the FI substudy, 8 TEAEs were reported by 6/7 (85.7%) participants during the fasted period and 2 TEAEs were reported by 2/7 (28.6%) participants during the fed period. In the fasted period, TEAEs reported were headache (2 participants), dizziness, dysgeusia, epistaxis, nasal congestion, pain in extremity and skin exfoliation (each in 1 participant). In the fed period, TEAEs reported were dizziness and dry skin (each in 1 participant).Across the MAD part of the study, 27 TEAEs were reported by 20/40 (50.0%) participants. The most common TEAEs reported in the KCL‐286 treated participants included dry skin (4 participants) and stomatitis (2 participants). The events of dry skin were reported in the 72‐ and 100‐mg multiple dosing groups and started within 6 days of dosing and resolved after 6–8 days. The events of stomatitis were reported in the 72‐mg multiple dosing group and started within 2 days of dosing and resolved after 11–12 days following nonpharmacological treatment. The most common TEAEs in placebo participants was dry skin (2 participants) that started on Day 2 and Day 10 and latest for 10–11 days. All other TEAEs were reported by no more than 1 participant. In the placebo group, there were 2 mild TEAEs reported for clinically significant laboratory events; these were mild hyperbilirubinaemia, which started on Day 3 and was still ongoing at follow‐up and was considered unrelated to IMP, and mild hypertriglyceridaemia, which started on Day 3 and resolved after 8 days and was considered possibly related to IMP.TEAEs reported in participants excluded from the safety analyses were reported in 3/5 participants in the MAD substudy. Two TEAEs of dry skin were reported in 1 participant in the 6‐mg MAD group; 1 event started on Day 2 and the second event on Day 3; both were considered mild and possibly related to treatment and resolved after 9 and 12 days, respectively. One TEAE of ocular hyperaemia was reported in 1 participant in the 6 mg MAD group; the event started on Day 3 and lasted for 7 days. The TEAE of ocular hyperaemia was considered mild and possibly related to treatment. One TEAE of paraesthesia was reported in the same participant; the event started on Day 1 and lasted for 20 min. The TEAE of paraesthesia was considered mild and unrelated to treatment.