Hysingla® ER, a once-daily, single-entity hydrocodone with abuse-deterrent properties in treating chronic nonmalignant and nonneuropathic pain in patients with osteoarthritis

Figures & data

Table 1. Demographic and baseline characteristics of patients with osteoarthritis pain.

Variables	Total N = 307
Age, years (mean ± SD)	55.9 ± 10.8
Sex, n (%) Male Female	135 (44) 172 (56)
Race, n (%) White Black or African-American Native Hawaiian or other Pacific Islander Asian American Indian or Alaska Native Other	244 (79) 57 (19) 0 3 (1) 1 (0) 2 (1)
BMI, kg/m^2 (mean ± SD)	32.7 ± 7.9
Opioid experienced, n (%) Experienced Naïve	181 (59) 126 (41)
Time since first diagnosis of primary pain condition, months (mean ± SD)	127.9 ± 116.1
Baseline pain^a (mean ± SD) Screening average pain score over last 14 days Baseline mean average pain over last 24 h^b	6.7 ± 1.7 6.5 ± 1.6

BMI: body mass index; N: number of patients in the safety population; n: number of patients with data; SD: standard deviation.

Percentages are based on N.

^aPain was recorded on an 11-point numerical rating scale where 0 = no pain and 10 = pain as bad as you can imagine.

^bThe baseline mean ‘average pain over the last 24 h’ was defined as the mean value of the daily ‘average pain over the last 24 h’ scores recorded during the screening period.

Table 2. Summary of patient disposition and reasons for discontinuation.

	Dose titration period (N = 307) n (%)	Maintenance period (N = 261) n (%)	Overall treatment period (N = 307) n (%)
Completed period on HYD	261 (85)	163 (62)	163 (53)
Discontinued study	46 (15)	98 (38)	144 (47)
Reason for discontinuation
Adverse event	26 (8)	42 (16)	68 (22)
Patient’s choice	6 (2)	26 (10)	32 (10)
Lost to follow-up	2 (1)	7 (3)	9 (3)
Lack of therapeutic effect	8 (3)	8 (3)	16 (5)
Confirmed or suspected diversion	1 (0)	4 (2)	5 (2)
Administrative	1 (0)	11 (4)	12 (4)
Did not qualify for maintenance period	2 (1)	NA	2 (1)

HYD: hydrocodone extended release; N: number of patients in the safety population; n: number of patients with data; NA: not applicable.

Table 3. Incidence of opioid-related treatment-emergent adverse events (TEAEs).

MedDRA system organ class Preferred term^a	Total (N = 307) n (%)
Any TEAE	202 (66)
Endocrine disorders	3 (1)
Androgen deficiency	2 (1)
Hypogonadism	1 (0)
Gastrointestinal disorders	144 (47)
Constipation	83 (27)
Nausea	77 (25)
Vomiting	38 (12)
Dry mouth	16 (5)
General disorders and administration-site conditions	40 (13)
Fatigue	29 (9)
Edema peripheral	14 (5)
Injury, poisoning, and procedural complications	11 (4)
Fall	11 (4)
Nervous system disorders	106 (35)
Somnolence	45 (15)
Dizziness	43 (14)
Headache	32 (10)
Sedation	7 (2)
Psychiatric disorders	19 (6)
Insomnia	19 (6)
Skin and subcutaneous tissue disorders	28 (9)
Pruritus	19 (6)
Hyperhidrosis	11 (4)

MedDRA: Medical Dictionary for Regulatory Activities coding dictionary, version 16.0.

^aThis table includes TEAEs occurring during any of the treatment periods; multiple occurrences of the same adverse event in one individual are counted only once.

Table 4. Incidence of treatment-emergent serious adverse events.

MedDRA system organ class Preferred term^a	Total (N = 307) n (%)
Any treatment-emergent adverse event (TEAE)	30 (9.8)
Blood and lymphatic system disorders	3 (1.0)
Anemia	1 (<1.0)
Lymphoid tissue hyperplasia	1 (<1.0)
Spontaneous hematoma	1 (<1.0)
Cardiac disorders	1 (<1.0)
Myocardial ischemia	1 (<1.0)
Palpitations	1 (<1.0)
Gastrointestinal disorders	2 (<1.0)
Gastrointestinal hemorrhage	1 (<1.0)
Esophageal obstruction	1 (<1.0)
General disorders and administration-site conditions	2 (<1.0)
Chest pain	1 (<1.0)
Device dislocation	1 (<1.0)
Infections and infestations	3 (1.0)
Appendicitis	1 (<1.0)
Cellulitis staphylococcal	1 (<1.0)
Diverticulitis	1 (<1.0)
Injury, poisoning, and procedural complications	2 (<1.0)
Fibula fracture	1 (<1.0)
Muscle strain	1 (<1.0)
Metabolism and nutrition disorders	1 (<1.0)
Fluid overload	1 (<1.0)
Musculoskeletal and connective tissue disorders	6 (2.0)
Osteoarthritis	4 (1.3)
Arthralgia	1 (<1.0)
Polyarthritis	1 (<1.0)
Neoplasms benign, malignant, and unspecified (including cysts and polyps)	1 (<1.0)
Malignant neoplasm progression	1 (<1.0)
Nervous system disorders	5 (1.6)
Cerebral infarction	1 (<1.0)
Cerebrovascular accident	1 (<1.0)
Nerve compression	1 (<1.0)
Sedation	1 (<1.0)
Transient ischemic attack	1 (<1.0)
Psychiatric disorders	2 (<1.0)
Drug abuse	2 (<1.0)
Renal and urinary disorders	3 (1.0)
Nephrolithiasis	1 (<1.0)
Renal failure acute	1 (<1.0)
Urinary retention	1 (<1.0)
Reproductive system and breast disorders	1 (<1.0)
Breast hematoma	1 (<1.0)
Respiratory, thoracic, and mediastinal disorders	4 (1.3)
Pulmonary embolism	2 (<1.0)
Asthma	1 (<1.0)
Bronchospasm	1 (<1.0)
Hypoxia	1 (<1.0)
Pulmonary artery thrombosis	1 (<1.0)
Vascular disorders	2 (<1.0)
Arterial occlusive disease	1 (<1.0)
Deep vein thrombosis	1 (<1.0)

MedDRA: Medical Dictionary for Regulatory Activities coding dictionary, version 16.0; N: number of patients in the safety population; n: number of patients with data.

^aThis table includes TEAEs occurring during any of the treatment periods; multiple occurrences of the same adverse event in one individual are counted only once.

Figure 1. Mean ‘Average Pain Over the Last 24 Hours’ score in patients with osteoarthritis-related pain. HYD: hydrocodone bitartrate; OA: osteoarthritis; SE: standard error.

Figure 2. Mean ‘Pain Right Now’ score recorded daily immediately prior to dosing and at 12 hours postdose and mean ‘Average Pain Over the Last 24 Hours’ score during the first 3 months of the maintenance period (dashed line). Error bars represent the standard deviation.

Figure 3. Mean daily dose of HYD and nonstudy opioids during the titration period and the 52-week maintenance period in patients with osteoarthritis-related pain.^a HYD: hydrocodone bitartrate; SE: standard error.

^aOne patient reported unusually high use of nonstudy opioids (162 mg/day) during month 9 of the Maintenance Period. These data have not been included in this figure.

Nonstudy opioid analgesic dosages are given in oxycodone equivalents.

Figure 4. HYD dose adjustments during the maintenance period in patients with osteoarthritis-related pain. HYD: hydrocodone bitartrate.

Table 5. Treatment satisfaction questionnaire.

Question number: category answered	Total (N = 261)
	n (%)
1. Satisfaction with study drug, NP	203
Satisfied to extremely satisfied	189 (93)
Dissatisfied to extremely dissatisfied	14 (7)
2. Ease of study drug use to treat pain, NP	203
Easy to extremely easy	198 (98)
Difficult to extremely difficult	5 (2)
3. Convenience of study drug to treat pain, NP	203
Convenient to extremely convenient	201 (99)
Inconvenient to extremely inconvenient	2 (1)
4. Overall drug satisfaction managing pain, NP	203
Satisfied to extremely satisfied	189 (93)
Dissatisfied to extremely dissatisfied	14 (7)
5. Satisfaction with frequency of use, NP	203
Satisfied to extremely satisfied	202 (100)
Dissatisfied to extremely dissatisfied	1 (0)
6. Ease of planning study drug use, NP	203
Easy to extremely easy	201 (99)
Difficult to extremely difficult	2 (1)

N: number of patients in the safety population entering the maintenance period; n: number of patients with each individual response; NP: number of patients responding to each question in part 1 of the questionnaire.

Percentages are based on NP.