Safety and tolerability of an intravenously administered alpha1-proteinase inhibitor at an increased infusion rate: a novel, randomized, placebo-masked, infusion rate-controlled, crossover study in healthy adults

Figures & data

Figure 1 Placebo-masked, infusion rate controlled investigational product administration.

Table 1 Treatment assignment and study design

Study group	Infusion rate
	Day 1		Day 15
1 (n= 15)	AIPI 0.04 mL/kg/min + Placebo^a 0.2 mL/kg/min		AIPI 0.2 mL/kg/min + Placebo^a 0.04 mL/kg/min
2 (n=15)	AIPI 0.2 mL/kg/min + Placebo^a 0.04 mL/kg/min		AIPI 0.04 mL/kg/min + Placebo^a 0.2 mL/kg/min

Note:

a Simultaneous infusion of a placebo solution was used to mask the infusion rate of the AIPI solution.

Abbreviations: AIPI, alphal-proteinase inhibitor; min, minute.

Table 2 Number (%) of all adverse events reported, regardless of causality

AE	AIPI infusion rate		Overall
	0.04 mL/kg/min	0.2 mL/kg/min
Total AEs	22 (100)	14 (100)	36 (100)
Headache	7 (31.8)	5 (35.7)	12 (33.3)
Dizziness	2 (9.1)	1 (7.1)	3 (8.3)
Back pain	1 (4.5)	2 (14.3)	3 (8.3)
Pain in extremity	2 (9.1)	0	2 (5.6)
Epistaxis	1 (4.5)	1 (7.1)	2 (5.6)
Abdominal pain	1 (4.5)	0	1 (2.8)
Chest discomfort	1 (4.5)	0	1 (2.8)
Fatigue	1 (4.5)	0	1 (2.8)
Vessel puncture site pain	1 (4.5)	0	1 (2.8)
Asymptomatic bacteriuria	1 (4.5)	0	1 (2.8)
Upper respiratory tract infection	0	1 (7.1)	1 (2.8)
Urethritis	0	1 (7.1)	1 (2.8)
Arthropod bite	1 (4.5)	0	1 (2.8)
Sunburn	1 (4.5)	0	1 (2.8)
Blood CK increased	1 (4.5)	0	1 (2.8)
Hemoglobin decreased	0	1 (7.1)	1 (2.8)
somnolence	0	1 (7.1)	1 (2.8)
Hematuria	0	1 (7.1)	1 (2.8)
Erythematous rash	1 (4.5)	0	1 (2.8)

Abbreviations: AIPI, alphal-proteinase inhibitor; AE, adverse event; CK, creatine kinase; min, minute.

Table 3 Summary of infusions associated with adverse events

Time^a	Number (%) of infusions
	Group 1		Group 2		Overall
	AIPI 0.04 mL/kg/min Ni =15	AIPI 0.2 mL/kg/min Ni =15	AIPI 0.04 mL/kg/min Ni =15	AIPI 0.2 mL/kg/min Ni =15	AIPI 0.04 mL/kg/min Ni =30	AIPI 0.2 mL/kg/min Ni =30
Within 1 hour	2 (13.3%)	0	1 (6.7%)	1 (6.7%)	3 (10.0%)	1 (3.3%)
Within 24 hours	4 (26.7%)	0	1 (6.7%)	3 (20.0%)	5 (16.7%)	3 (10.0%)
Within 72 hours	5 (33.3%)	0	2 (13.3%)	5 (33.3%)	7 (23.3%)	5 (16.7%)

Notes:

a Adverse events began during or within 1, 24, and 72 hours of completion of an infusion, regardless of causality. The numbers of infusions in each time category are inclusive.

Abbreviations: AIPI, alphal-proteinase inhibitor; min, minute; Ni, number of infusions.