Table 2. Summary of Treatment-Emergent Serious Adverse Events, Adverse Events (On- and Off-Treatment), and Laboratory Findings (Safety Analysis Set)a.
| On/off-treatment, No./total No. (%) | |||
|---|---|---|---|
| Placebo (n = 185) | Atabecestat | ||
| 5 mg (n = 189) | 25 mg (n = 183) | ||
| Serious TEAEs and TEAEs (on treatment) | |||
| Participant, No. (%) | |||
| With ≥1 serious TEAEs | 8 (4.3) | 13 (6.9) | 19 (10.4) |
| With ≥1 TEAEs | 123 (66.5) | 140 (74.1) | 132 (72.1) |
| TEAEs (in >5% of participants and > placebo on-treatment/off-treatment) | |||
| Diarrhea | 7 (3.8)/0 | 12 (6.3)/4(2.2) | 28 (15.3)/2(1.2) |
| Urinary tract infection | 3 (1.6)/4(2.2) | 5 (2.6)/4(2.2) | 11 (6.0)/5(2.9) |
| Cough | 1 (0.5)/1(0.6) | 12 (6.3)/1(0.5) | 4 (2.2)/2(1.2) |
| Abnormal dreams | 1 (0.5)/0 | 4 (2.1)/0 | 11 (6.0)/0 |
| Other TEAEs of interest | |||
| Neuropsychiatric AEs, on-treatment, No. (%) | 5 (2.7) | 16 (8.5) | 30 (16.4) |
| Anxiety-related | 1 (0.5)/0 | 2 (1.1)/1(0.5) | 5 (2.7)/1(0.6) |
| Depression-related | 2 (1.1)/0 | 2 (1.1)/2(1.1) | 6 (3.3)/1(0.6) |
| Sleep dream-relatedb | 2 (1.1)/0 | 13 (6.9)/0 | 18 (9.8)/1(0.6) |
| Cognition-relatedc | 0/0 | 0/1(0.5) | 6 (3.3)/0 |
| Rash-related AEs | 7 (3.8)/1(0.6) | 8 (4.2)/2(1.1) | 13 (7.1)/1(0.6) |
| Treatment emergent high or low laboratory parameters (>5% and >placebo)d | |||
| Greater than ULN | |||
| Alanine aminotransferase | 25/168 (14.9) | 42/174 (24.1) | 58/172 (33.7) |
| Aspartate aminotransferase | 15/169 (8.9) | 40/176 (22.7) | 45/173 (26.0) |
| Bilirubin | 5/164 (3.0) | 4/172 (2.3) | 9/168 (5.4) |
| γ-Glutamyl transferase | 7/163 (4.3) | 8/169 (4.7) | 15/161 (9.3) |
| Less than LLN | |||
| Phosphate | 3/170 (1.8) | 6/176 (3.4) | 12/171 (7.0) |
| Serum glucose | 12/108 (11.1) | 21/117 (17.9) | 19/100 (19.0) |
| Serum urate, greater than ULN | 6/167 (3.6) | 9/178 (5.1) | 10/167 (6.0) |
| Lymphocytes | 5/166 (3.0) | 6/173 (3.5) | 11/168 (6.5) |
Abbreviations: AE, adverse events; LLN, lower limit of normal; ULN, upper limit of normal; TEAEs, treatment-emergent adverse events.
a
AEs and serious AEs were coded using the Medical Dictionary for Regulatory Activities (Med-DRA Version 19.1). Categories are groupings of clinically similar MedDRA preferred terms. On-treatment TEAEs defined as onset while receiving study treatment or within 7 days after the last dose; off-treatment AEs had onset more than 7 days after the last dose.
b
Insomnia was only sleep/dream-related adverse event reported off treatment.
c
Amnesia was only cognition-related adverse event reported off treatment.
d
No. is based on number of participants who were cognitively normal at baseline.