Safety.
paraesthesia, toxicities, paresthesia, TEAEs, back pain, xerosis, constipation, arthralgia, pruritus, conjunctivitis, pollakiuria, headache, ecchymosis, alopecia, photophobia, lacrimation increase, SAD
PARAESTHESIA, ADVERSE EVENTS, PARESTHESIA, EVENT, XEROSIS, CONJUNCTIVITIS, ECCHYMOSIS, EVENTS, ALOPECIA
In the SAD study, the most commonly reported TEAEs in the combined OPC-167832 groups were headache (3/36 [8.3%]), constipation (2/36 [5.6%]), and back pain (2/36 [5.6%]) (Table S5). All TEAEs were mild and none led to study discontinuation; no dose-limiting toxicities were reported in any of the 6 cohorts, indicating the maximum tolerated single dose for OPC-167832 was not reached by 480 mg. TEAEs assessed by the investigator as potentially related to OPC-167832 treatment included 2 cases of mild constipation (1 case each in the 60-mg and 480-mg cohorts) and 1 case of mild paresthesia in the 240-mg cohort. In addition, 1 subject had mild lacrimation increase, photophobia, eye irritation, and headache that was potentially related to OPC-167832 treatment, as well as mild conjunctivitis that was considered unrelated to study drug. No serious TEAEs were reported. Alterations in physical examination findings, vital signs, and clinical laboratory results were minimal in all dosing cohorts. Abnormal electrocardiogram results were rare and not considered to be clinically significant.In the food effects study, the most common TEAEs in the combined treatment sequences were alanine transaminase (ALT) increase (2/12 [16.7%] participants) and pruritus (2/12 [16.7%] participants) (Table S6). ALT elevation and pruritus events occurred in separate participants. All TEAEs were considered mild, except for 1 case of moderate transient blood creatine phosphokinase increase. TEAEs assessed by the investigator as potentially related to OPC-167832 treatment included mild arthralgia and ecchymosis after a standard meal in one subject; mild headache, pruritus, and xerosis after fasting in one subject; mild eye irritation after fasting in one subject; mild paraesthesia and pollakiuria after fasting and mild alopecia after a standard meal in one subject; and two events of mild ALT increase in one subject, one event occurring after a standard meal and the other after a high-fat meal, which were not thought to be clinically significant. No serious TEAEs were reported. Alterations in physical examination findings and vital signs were minimal in both treatment sequences. No consistent, clinically significant ECG changes were observed following OPC-167832 administration.In the MAD/EBA study, the most common TEAEs in the combined OPC-167832 groups were headache (12/59 [20.3%]) and pruritus (11/59 [18.6%] participants) (Incidence of all treatment-emergent adverse events in the MAD/EBA studyRHEZ, Rifafour e-275.