Safety, tolerability and efficacy of the glutaminyl cyclase inhibitor PQ912 in Alzheimer’s disease: results of a randomized, double-blind, placebo-controlled phase 2a study

Table 3 Safety and tolerability endpoints

	Placebo (N = 60), n (%)	PQ912 (N = 60), n (%)	P
Safety
Composite safety	0 (0.0)	6 (10.0)	0.027
Discontinuation of subject due to SAE	0 (0.0)	6 (10.0)	0.027
Discontinuation of subject due to AE with severity ≥ 3 according to CTCAE	0 (0.0)	6 (10.0)	0.027
Discontinuation of subject due to extreme safety laboratory parameters	0 (0.0)	0 (0.0)	–
Number of subjects with SAEs	5 (8.3)^d	8 (13.3)	0.558
Number of subjects with AEs with severity ≥ 3 according to CTCAE	3 (5.0)^e	8 (13.3)	0.204
Tolerability
Composite tolerability	6 (10.0)	27 (45.0)	<.001
Dose adjustment during treatment period^a	5 (8.3)	5 (8.3)	1.000
Nonadherence to randomized treatment^b	2 (3.3)	26 (43.3)	<.001
Discontinued due to related AE^c	0 (0.0)	19 (31.7)	<.001
Discontinued due to nonrelated AE	0 (0.0)	1 (1.7)	1.000
Withdrawal of consent by subject	0 (0.0)	1 (1.7)	1.000
Continued	2 (3.3)	5 (8.3)	0.439

CTCAE common terminology criteria for adverse events, N number of subjects in population, n number of subjects, (S)AE (serious) adverse event
^aDose adjustment defined as reduction of dose from 800 mg bid to 400 mg bid, as allowed within the study protocol
^bNonadherence defined as: using < 75% of prescribed dose in 4 consecutive weeks including at least 1 week with less than 50%; or 3 or more consecutive days in total or 7 days of interrupted use during the full 12 weeks. Subjects could qualify for more than one criterion, but were listed once; reason ranked for relevance for tolerance
^cIncludes possibly related, probably related and related according to investigator
^dTreatment emergent in three subjects
^eTreatment emergent in one subject

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