The Comparative Pharmacokinetics of Physical Manipulation by Crushing of Xtampza^® ER Compared with OxyContin^®

Figures & data

Table 1. Baseline demographics and characteristics.

Characteristic	Xtampza^® ER		OxyContin^®		Oxycodone IR
	Intact (n = 38)	Crushed (n = 40)	Intact (n = 39)	Crushed (n = 39)	Crushed (n = 38)
Mean (SD) age, years	30.6 (5.82)	30.6 (5.81)	30.0 (6.07)	30.0 (6.07)	30.3 (6.22)
Sex, n (%):
– Male	28 (73.7)	29 (72.5)	29 (74.4)	29 (74.4)	28 (73.7)
– Female	10 (26.3)	11 (27.5)	10 (25.6)	10 (25.6)	10 (26.3)
Race, n (%):
– Black or African–American	19 (50.0)	20 (50.0)	18 (46.2)	18 (46.2)	17 (44.7)
– White	19 (50.0)	20 (50.0)	21 (53.8)	21 (53.8)	21 (55.3)
Ethnicity, n (%)
– Hispanic or latino	19 (50.0)	20 (50.0)	21 (53.8)	21 (53.8)	21 (55.3)
– Not hispanic or latino	19 (50.0)	20 (50.0)	18 (46.2)	18 (46.2)	17 (44.7)
Mean (SD) weight (kg)	77.72 (13.67)	77.72 (13.44)	77.80 (13.36)	77.80 (13.36)	77.95 (12.98)
Mean (SD) height (cm)	170.7 (7.29)	170.6 (7.21)	170.6 (7.25)	170.6 (7.25)	170.6 (7.20)
Mean (SD) BMI (kg/m^2)	26.56 (3.57)	26.61 (3.49)	26.62 (3.48)	26.62 (3.48)	26.71 (3.45)
Range	19.1–32.1	19.1–32.1	19.1–32.1	19.1–32.1	19.1–31.6

ER: Extended-release; IR: Immediate release; SD: Standard deviation.

Figure 1. Mean plasma oxycodone concentration over time following administration of Xtampza^® ER (intact and crushed; top panel), OxyContin^® (intact and crushed; bottom panel) and crushed oxycodone IR.

Error bars indicate the positive standard deviation (negative standard deviation not shown).

ER: Extended release; IR: Immediate release.

Table 2. Pharmacokinetic parameters.

Treatment	N	Mean (SD) Cmax (ng/ml)	Mean (SD) AUCinf, (h • ng/ml)	Median (range) Tmax, h
Intact Xtampza^® ER	38	56.9 (13.4)	534 (142)*	3.50 (1.00–5.50)
Crushed Xtampza ER	39	61.2 (13.1)	549 (143)	3.50 (2.50–5.50)
Intact OxyContin^®	38	63.7 (14.8)	574 (150)	4.51 (1.75–8.00)
Crushed OxyContin	39	79.9 (17.9)	540 (142)	1.75 (0.50–4.50)
Crushed oxycodone IR	37	78.1 (22.0)	497 (143)	1.50 (0.50–4.53)

*n = 37, one subject did not have a sufficient number of data points in the terminal phase of the pharmacokinetic profile to calculate AUC_inf by extrapolation.

AUC_inf: Area under the plasma concentration–time curve extrapolated to infinity; C_max: Maximum observed plasma concentration; ER: Extended release; IR: Immediate release; SD: Standard deviation; T_max: Time-to-reach maximum plasma concentration.

Table 3. Bioequivalence analysis.

Treatment	Parameter	LS mean ratio (%)	90% CI		Bioequivalent^†
			Lower bound	Upper bound
Xtampza^® ER
Crushed versus intact Xtampza ER	Cmax	106.99	99.23	115.35	Yes
	AUC0–t	104.79	98.11	111.93
	AUCinf	103.12	96.62	110.05
		103.12
Crushed Xtampza ER versus crushed oxycodone IR	Cmax	80.13	74.24	86.49	No, Cmax lower
	AUC0–t	113.54	106.20	121.40
	AUCinf	112.90	105.76	120.51
OxyContin^®
Crushed versus intact OxyContin	Cmax	125.98	116.85	135.83	No, Cmax higher
	AUC0–t	93.42	87.46	99.78
	AUCinf	93.48	87.67	99.68
Crushed OxyContin versus crushed oxycodone IR	Cmax	104.65	97.02	112.88	Yes
	AUC0–t	110.82	103.71	118.42
	AUCinf	110.60	103.69	117.98

† Comparisons were considered bioequivalent (bold type) if the 90% CI fell within 85 and 125%.

AUC_0–t: Area under the plasma concentration–time curve from 0 to final time with a concentration ≥ LLOQ; AUC_inf: Area under the plasma concentration–time curve extrapolated to infinity; C_max: Maximum observed plasma concentration; ER: Extended release; IR: Immediate release; LLOQ: Lower limit of quantitation; LS: Least square; SD: Standard deviation.

Figure 2. Cumulative partial area under the plasma concentration–time curve from 0 to 1.75 h for Xtampza^® ER (intact and crushed; top panel), OxyContin^® (intact and crushed; bottom panel) and crushed oxycodone IR.

Error bars indicate the positive standard deviation (negative standard deviation not shown).ER: Extended release; IR: Immediate release.

Figure 3. Mean abuse quotient of Xtampza^® ER (intact and crushed; top panel), OxyContin^® (intact and crushed; bottom panel) and crushed oxycodone IR.

Error bars indicate the positive standard deviation (negative standard deviation not shown).

AQ: Abuse quotient; ER: Extended release; IR: Immediate release.

Table 4. Adverse events reported in at least two subjects.

Preferred term	Subjects, n (%)
	Xtampza^® ER		OxyContin^®		Oxycodone IR
	Intact (n = 38)	Crushed (n = 40)	Intact (n = 39)	Crushed (n = 39)	Crushed (n = 38)
Subjects with at least one AE	4 (10.5)	6 (15.0)	6 (15.4)	5 (12.8)	5 (13.2)
AEs reported in ≥ two subjects
Headache	3 (7.9)	1 (2.5)	3 (7.7)	2 (5.1)	3 (7.9)
Dizziness	1 (2.6)	0	1 (2.6)	0	0
Abdominal pain	1 (2.6)	0	1 (2.6)	0	1 (2.6)
Diarrhea	1 (2.6)	1 (2.5)	0	0	1 (2.6)
Nausea	0	1 (2.5)	1 (2.6)	0	2 (5.3)
Vomiting	0	0	1 (2.6)	0	1 (2.6)
Euphoric mood	0	0	0	2 (5.1)	0
Pyrexia	0	0	2 (5.1)	0	0

AE: Adverse event; ER: Extended release; IR: Immediate release.

Figure 4. Xtampza^® ER microspheres on a kitchen grater.

Note the scale of the kitchen grater relative to the microsphere formulation.

ER: Extended release.