Efficacy and safety of once-daily, extended-release hydrocodone in individuals previously receiving hydrocodone/acetaminophen combination therapy for chronic pain

Figures & data

Table I. Phase III studies: baseline characteristics.

Variable	12-week RCT			Open-label trial with 1-year maintenance treatment
	Placebo (n = 67)	HYD (n = 62)	Total (n = 129)	HYD (n = 269)
Age (years)
Mean (SD)	52.1 (12.96)	55.3 (10.66)	53.6 (11.97)	52.0 (11.94)
Female sex, n (%)	40 (60)	43 (69)	83 (64)	139 (52)
Race, n (%)
White	47 (70)	41 (66)	88 (68)	235 (87)
Black	17 (25)	17 (27)	34 (26)	29 (11)
Asian	3 (4)	1 (2)	4 (3)	4 (1)
Other	0	3 (5)	3 (2)	1 (<1)
BMI (kg/m^2)
Mean (SD)	32.508 (9.16)	32.909 (7.99)	32.701 (8.59)	31.731 (7.82)
Time since diagnosis of primary pain condition (days)
Mean (SD)	131.70 (120.89)	122.27 (115.02)	127.17 (117.74)	130.39 (123.36)
Screening average pain over past 14 days
Mean (SD)	7.1 (1.17)	7.2 (1.40)	7.2 (1.28)	6.4 (1.70)
Baseline average pain over past 24 hours
Mean (SD)	7.28 (1.36)	7.31 (1.14)	7.30 (1.25)	6.28 (1.66)
Dose of hydrocodone/acetaminophen combination tablet at baseline, mg (hydrocodone equivalent dose)	23 (13)	24 (12)	24 (13)	24 (16)

Abbreviations: RCT = Randomized, controlled trial; BMI = Body mass index; HYD = Hysingla™ ER; SD = Standard deviation.

Figure 1. Mean “average pain over the past 24 hours” at week 12 of the 12-week RCT is shown, using the PMM and two sensitivity statistical analysis models (MAR and hybrid LOCF/BOCF).Abbreviations: LSM = Least squares mean; SE = Standard error; PMM = Pattern-mixture model; MAR = Missing at random model; BOCF = Baseline observation carried forward; LOCF = Last observation carried forward; RCT = Randomized controlled trial.

Figure 2. Mean weekly “average pain over the past 24 hours” during the open-label trial is shown.Abbreviations: SE = Standard error; S = Screening; TE = Titration end.

Figure 3. Mean doses of HYD (A) and non-trial opioid analgesics (B) during the open-label trial are shown.Abbreviations: SE = Standard error; S = Screening; TS = Titration start; TE = Titration end.

Figure 4. HYD dose changes during the maintenance period of the 1-year open-label trial are shown.

Table II. Summary of treatment satisfaction questionnaire in the open-label trial with 1-year maintenance treatment.

Items^a	Response^b (n = 194)
	Satisfied n (%)	Dissatisfied n (%)
Satisfaction with study drug	180 (92.8)	14 (7.22)
Overall drug satisfaction in managing pain	175 (90.2)	19 (9.79)
Satisfaction with frequency of use	188 (96.9)	6 (3.09)
	Easy n (%)	Difficult n (%)
Ease of study drug use to treat pain	186 (95.9)	8 (4.12)
Ease of planning study drug use	189 (97.4)	5 (2.58)
	Convenient n (%)	Inconvenient n (%)
Convenience of study drug to treat pain	190 (97.9)	4 (2.06)

^aQuestionnaire asked for rating of these items with HYD in comparison with pretrial hydrocodone/acetaminophen pain medication.

^bThe questionnaire allowed for six unique responses. “Satisfied” combines the response categories of satisfied, very satisfied, and extremely satisfied. “Dissatisfied” combines the response categories of dissatisfied, very dissatisfied, and extremely dissatisfied.

Abbreviations: HYD = Hysingla™ ER.

Table III. Phase III trials: adverse events^a.

MedDRA System Organ Class	Preferred term	12-week RCT		Open-label trial
		Placebo (n = 67) n (%)	HYD (n = 62) n (%)	Titration period (n = 269) n (%)	Maintenance period (1-year) (n = 225^b) n (%)
Death^c		1 (1)	0	0	2 (1)
Any SAE		2 (3)	0	2 (1)	19 (8)
Any TEAE^d		40 (60)	40 (65)	144 (54)	188 (84)
Ear and labyrinth disorders	Tinnitus	0	1 (2)	5 (2)	12 (5)
Gastrointestinal disorders	Constipation	9 (13)	9 (15)	39 (14)	23 (10)
	Nausea	7 (10)	9 (15)	33 (12)	30 (13)
	Vomiting	4 (6)	8 (13)	9 (3)	21 (9)
	Diarrhea	3 (4)	1 (2)	2 (1)	13 (6)
General disorders and administration-site conditions	Fatigue	3 (4)	5 (8)	7 (3)	14 (6)
Infections and infestations	Upper respiratory tract infection	4 (6)	1 (2)	4 (1)	20 (9)
	Nasopharyngitis	3 (4)	1 (2)	4 (1)	18 (8)
	Sinusitis	0	1 (2)	3 (1)	11 (5)
	Gastroenteritis viral	1 (1)	2 (3)	0	11 (5)
	Influenza	1 (1)	3 (5)	2 (1)	8 (4)
Musculoskeletal and connective tissue disorders	Arthralgia	1 (1)	2 (3)	4 (1)	13 (6)
	Back pain	4 (6)	1 (2)	3 (1)	11 (5)
	Musculoskeletal pain	0	0	0	11 (5)
Nervous system disorders	Dizziness	5 (7)	4 (6)	14 (5)	22 (10)
	Headache	2 (3)	6 (10)	14 (5)	18 (8)
	Somnolence	2 (3)	2 (3)	24 (9)	12 (5)
Psychiatric disorders	Insomnia	3 (4)	3 (5)	5 (2)	16 (7)
	Anxiety	1 (1)	0	2 (1)	12 (5)
Skin and subcutaneous tissue disorders	Pruritus	4 (6)	0	7 (3)	0
Vascular disorders	Hypertension	2 (3)	2 (3)	2 (1)	11 (5)

^aThis table includes TEAEs that occurred during the periods shown in ≥5% of patients for any column in the table. Categories are based on MedDRA coding dictionary, version 16.0.

^bOne patient entered the maintenance period but did not receive study drug.

^cAn additional death occurred during the follow-up period of the long-term study. See detail in the Safety and tolerability section.

^dAny TEAE represents the total number of subjects with a TEAE in any of the treatment periods.

Abbreviations: HYD = Hysingla™ ER; MedDRA = Medical Dictionary for Regulatory Activities; RCT = Randomized controlled trial; SAE = Serious adverse event; TEAE = Treatment-emergent adverse event.