A long-term, open-label safety study of single-entity hydrocodone bitartrate extended release for the treatment of moderate to severe chronic pain

Figures & data

Figure 1 Disposition of patients in the study.

Notes: Noncompliance includes subjects unable to account for 100% of the HC-ER or rescue medication. Protocol violations include subjects who failed to achieve a stable dose of HC-ER during the C/T phase.
Abbreviations: HC-ER, hydrocodone bitartrate extended release; C/T, conversion/titration; AE, adverse event.

Table 1 Demographic and clinical characteristics at screening for patients who entered the C/T and maintenance phases

	C/T phase	Maintenance phase
N	638	424
Age, years
Mean ± SD	50.9±10.9	50.7±11.0
Range	20–75	20–75
Sex, n (%)
Female	360 (56.4)	239 (56.4)
Race, n (%)
White	518 (81.2)	337 (79.5)
African American	107 (16.8)	77 (18.2)
Asian	1 (0.2)	1 (0.2)
American Indian or Alaskan native	3 (0.5)	2 (0.5)
Other	9 (1.4)	7 (1.7)
Average pain score
Mean ± SD	6.4±1.7	6.4±1.8
Range	1–10	1–10
Pain type,a n (%)
Chronic low back pain	299 (46.9)	198 (46.7)
Osteoarthritis	133 (20.8)	97 (22.9)
Fibromyalgia	55 (8.6)	25 (5.9)
Neuropathic pain	28 (4.4)	18 (4.2)
Rheumatoid arthritis	14 (2.2)	8 (1.9)
Diabetic neuropathy	5 (0.8)	3 (0.7)
Cancer-related pain	1 (0.2)	1 (0.2)
Otherb	210 (32.9)	139 (32.8)

Notes: Data are n (%) or mean ± SD.

a Individual subjects could have had more than one underlying condition

b includes various nonneuropathic and musculoskeletal pain types.

Abbreviations: C/T, conversion/titration; SD, standard deviation.

Figure 2 HC-ER dose over time during the maintenance phase.

Notes: The × and horizontal line indicate mean and median daily dose, respectively. The rectangle and whiskers indicate the 25th and 75th quartiles and 1.5 times interquartile range, respectively. The open squares are outliers.
Abbreviation: HC-ER, hydrocodone bitartrate extended release.

Table 2 Number (%) of patients with treatment-emergent adverse events for patients who entered the C/T and maintenance phases

	C/T phase			Maintenance phase
	Subjects who entered the maintenance phase	Subjects who did not enter the maintenance phase	Total
N	424	214	638	424
Overall
At least one AE	242 (57.1)	162 (75.7)	404 (63.3)	354 (83.5)
At least one drug-related AE	147 (34.7)	93 (43.5)	240 (37.6)	130 (30.7)
At least one serious AE	6 (1.4)	10 (4.7)	16 (2.5)	51 (12.0)
At least one drug-related serious AE	0	1 (0.5)	1 (0.2)	2 (0.5)
AE leading to discontinuation	7 (1.7)a	59 (27.6)	66 (10.3)	34 (8.0)
Serious AE leading to discontinuation	0	5 (2.3)	5 (0.8)	8 (1.9)
Drug-related serious AE leading to discontinuation	6 (1.4)a	45 (21.0)	51 (8.0)	0
Death	0	0	0	4 (0.9)b
Adverse events in ≥5% of subjects in either phase
Constipation	54 (12.7)	18 (8.4)	72 (11.3)	53 (12.5)
Back pain	4 (0.9)	5 (2.3)	9 (1.4)	47 (11.1)
Nausea	36 (8.5)	32 (15.0)	68 (10.7)	42 (9.9)
Vomiting	10 (2.4)	16 (7.5)	26 (4.1)	41 (9.7)
Arthralgia	4 (0.9)	5 (2.3)	9 (1.4)	33 (7.8)
Headache	32 (7.5)	16 (7.5)	48 (7.5)	29 (6.8)
Urinary tract infection	3 (0.7)	3 (1.4)	6 (0.9)	28 (6.6)
Fall	3 (0.7)	5 (2.3)	8 (1.3)	25 (5.9)
Upper respiratory tract infection	6 (1.4)	1 (0.5)	7 (1.1)	25 (5.9)
Nasopharyngitis	10 (2.4)	1 (0.5)	11 (1.7)	24 (5.7)
Anxiety	5 (1.2)	3 (1.4)	8 (1.2)	23 (5.4)
Sinusitis	6 (1.4)	3 (1.4)	9 (1.4)	23 (5.4)
Insomnia	13 (3.1)	11 (5.1)	24 (3.8)	21 (5.0)
Somnolence	31 (7.3)	18 (8.4)	49 (7.7)	18 (4.2)

Notes:

a AEs that led to discontinuation were attributed to the study phase in which the event began (eg, seven subjects discontinued in the maintenance phase due to an AE that began in the C/T phase)

b four subjects died: one stage IV non-small-cell lung cancer, one atherosclerotic coronary artery disease, one suicide via carbon monoxide poisoning (history of depression), and one influenza-like illness due to mixed drug toxicity (oxycodone, methadone, benzodiazepines, and trace HC). A fifth subject committed suicide 13 months after the study ended by mixed drug combination (hydromorphone, HC, dihydrocodeine, trazodone, and ethanol).

Abbreviations: C/T, conversion/titration; AE, adverse event; HC, hydrocodone.

Figure 3 Mean average pain score from screening to the end of the study for patients who entered the maintenance phase.

Notes: The last point (day 337) also includes early termination. Error bars show standard deviation. Dotted and dashed vertical lines indicate screening and the start of the maintenance phase, respectively.
Abbreviation: C/T, conversion/titration.

Table 3 HADS and ODI scores of patients who entered the maintenance phase

	Value at the start of the C/T phase	Change from the start of the C/T phase to the end of the
		C/T phase	Maintenance phase
n	424	423	392
HADS total score, mean ± SD
Anxiety	6.68±2.95	−0.89±2.80	−0.85±3.69
Depression	5.54±3.31	−1.28±3.24	−0.71±3.86
ODI, %, mean ± SD
Disability	41.2±14.9	−10.2±13.4	−6.8±14.5

Note: End of the maintenance phase includes early termination.

Abbreviations: HADS, Hospital Anxiety and Depression Scale; ODI, Oswestry Disability Index; C/T, conversion/titration; SD, standard deviation.