Safety analyses
urinary-related TEAEs, rhinorrhea, TEAEs, dizziness, abnormal systolic blood pressure, insomnia, pollakiuria, headache, abnormal diastolic blood pressure, polyuria, deaths, urinary TEAEs
ADVERSE EVENT
Overall, 12 participants (44.4%) had TEAEs, 10 (37.0%) of which had TEAEs considered related to study drug. Most TEAEs were mild or moderate, with one case of severe insomnia during the danavorexton 112 mg treatment period. No deaths, SAEs, or TEAEs leading to discontinuation occurred during the study. Four participants (16.0%) had urinary TEAEs during the danavorexton treatment period (pollakiuria in three participants, and micturition urgency, polyuria, and increased urinary output in one participant each), all of which were mild in severity. No urinary-related TEAEs occurred during the placebo treatment period. The most common TEAEs during the danavorexton treatment period were pollakiuria, dizziness, rhinorrhea, and headache (Summary of TEAEsTEAE, treatment-emergent adverse event.
No clinically significant changes in serum chemistry, hematology (hematocrit, hemoglobin, platelets, red/white blood cell counts), urinalysis, heart rate measurements, or ECG (mean heart rate or QTcF interval values) were reported in comparison with baseline. On 12-lead ECG, one participant had a marked increase in PR interval of ≥ 200 ms following placebo administration, and six had a reduction in QRS duration to ≤ 80 msc (three while receiving placebo and three while receiving danavorexton).Overall, mean BP was elevated with danavorexton compared with placebo during infusion (SBP: LS mean increase of 3.99 mmHg vs placebo; DBP: LS mean increase of 3.58 mmHg vs placebo), with no clinically relevant differences between treatment groups 24 h post-infusion start. Markedly abnormal blood pressure values were observed in both treatment periods; all those occurring while on danavorexton were low. Four participants had markedly abnormal diastolic blood pressure (DBP; <50 or ≥ 100 mmHg or > 20 mmHg change from pre-dose) values at one or more time points: one (4.0%) had an abnormal DBP value (<50 mmHg) while receiving danavorexton, and four (14.8%) had a change from the pre-dose value of > 20 mmHg while receiving placebo. Eight participants had markedly abnormal systolic blood pressure (SBP; <90 or ≥ 160 mmHg or > 20 mmHg change) values at one or more time points: SBP < 90 mmHg was observed in three participants (12.0%) while on danavorexton, and in four participants (14.8%) while on placebo; and SBP change from pre-dose > 20 mmHg was observed in three (11.1%) participants receiving placebo. Two of the participants had SBP < 90 mmHg following both placebo and danavorexton treatment periods.