Analgesic onset and efficacy of a fast-acting formulation of acetaminophen in a postoperative dental impaction pain model

Figures & data

Figure 1. Patient disposition for Studies 1 and 2.

Figure 2. Kaplan-Meier plots of time to confirmed perceptible pain relief in Study 1 (a) and Study 2 (b).

Table 1. Summary of pain relief, pain intensity differences, use of rescue medication, and subject global evaluation during the 6 h treatment period.

Endpoint	Placebo	FA-Acetaminophen 1,000 mg	ES-Acetaminophen 1,000 mg	LG-Ibuprofen 400 mg
Number of Subjects
Study 1	60	59	60	61
Study 2	60	122	118	120
Median TCPR (min) (95% CI)
Study 1	NE	15.2 (13.6–17.6)^a	21.6 (16.6–26.5)^a^,^b	27.5 (24.3–31.7)^a^,^c
Study 2	NE	18.8 (15.8–22.5)^a	22.5 (16.9–26.4)^a	24.5 (21.3–27.0)^a
Median TMPR (min) (95% CI)
Study 1	NE	33.2 (27.1–49.5)^a	50.5 (38.4–66.8)^a	56.3 (46.1–64.9)^a^,^c
Study 2	NE	42.6 (38.5–53.2)^a	52.8 (45.9–68.6)^a	43.6 (38.8–56.5)^a
% Rescuing by 6 h
Study 1	83.3%	32.2%^a	46.7%^a	29.5%^a
Study 2^d	71.2%	25.4%	26.3%	10.0%
Median Time to Rescue (min)
Study 1	105.0	NE^a	NE^a	NE^a
Study 2	102.0	NE^a	NE^a	NE^a^,^c
SPID 0–6 LS Mean (SE)
Study 1	−1.01 (1.82)	20.53 (1.84)^a	16.05 (1.82)^a	23.40 (1.81)^a
Study 2	3.66 (1.83)	22.06 (1.28)^a	22.46 (1.30)^a	28.20 (1.30)^a^,^c
TOTPAR 0–6 LS Mean (SE)
Study 1	5.94 (2.20)	28.53 (2.21)^a	24.00 (2.20)^a	32.32 (2.18)^a
Study 2	11.01 (2.24)	30.96 (1.57)^a	31.14 (1.60)^a	38.86 (1.58)^a^,^c
Mean SGE LS Mean (SE)
Study 1	0.5 (0.13)	2.4 (0.13)^a	2.1 (0.13)^a	2.7 (0.13)^a
Study 2	0.8 (0.14)	2.3 (0.10)^a	2.4 (0.10)^a	2.8 (0.10)^a^,^c

^a p < .001 treatment vs placebo.

^b p < .05 FA-Acetaminophen vs ES-Acetaminophen.

^c p < .05 FA-Acetaminophen vs LG-Ibuprofen (superiority of treatment varies by endpoint).

^d No statistical comparisons performed for this variable in Study 2.

Abbreviations: CI, confidence interval; LS Mean, least squares mean; NE, not estimable, <50% subjects achieved endpoint; TCPR, time to confirmed perceptible pain relief; TMPR, time to meaningful pain relief; SPID, summary of pain intensity differences; TOTPAR, time weighted sum of pain relief scores; SE, standard error; SGE, subject global evaluation.

Figure 3. Kaplan-Meier plots of time to meaningful pain relief in Study 1 (A) and Study 2 (B).

Figure 4. Time course of pain intensity difference (PID) scores for each treatment in Study 1 (A) and Study 2 (B). Data presented as least squares mean (LSMean) ± standard error (SE).

Table 2. Plasma concentrations (μg/mL) following a single oral dose of study drug.

Mean plasma concentrations	FA-acetaminophen 1,000 mg Study 1 (N = 59) Study 2 (N = 40)	ES-Acetaminophen 1,000 mg Study 1 (N = 60) Study 2 (N = 40)	LG-Ibuprofen 400 mg Study 1 (N = 61) Study 2 (N = 40)
10 min
Study 1	2.57 ± 4.52	0.51 ± 2.08	0.12 ± 0.20^a
Study 2	2.48 ± 3.70	0.71 ± 2.57	0.54 ± 1.13
20 min
Study 1	12.22 ± 7.95^b	5.18 ± 7.03	9.49 ± 15.50
Study 2	8.51 ± 6.61	4.41 ± 5.67	12.55 ± 15.81
40 min
Study 1	15.10 ± 5.04	12.16 ± 6.82^c	32.52 ± 16.15^a
Study 2	12.29 ± 5.21	8.83 ± 5.86	35.40 ± 13.77
90 min
Study 1	12.41 ± 3.00^b	13.71 ± 3.47^c	33.24 ± 8.35
Study 2	11.42 ± 3.35	11.19 ± 3.96	34.49 ± 6.66
240 min
Study 1	6.00 ± 2.01	6.68 ± 2.25	12.96 ± 4.12
Study 2	6.08 ± 1.78	5.83 ± 2.19	11.73 ± 3.93
360 min
Study 1	3.47 ± 1.42	3.68 ± 1.56	6.36 ± 2.70
Study 2	3.57 ± 1.33	3.32 ± 1.49	5.65 ± 2.86

^a N = 60.

^b N = 58.

^c N = 59.