Trial Outcomes & Findings for Long-term Safety of Once-daily Hydrocodone Bitartrate (HYD) Tablets For Moderate to Severe Chronic Nonmalignant and Nonneuropathic Pain. Includes a 24-week Extension Period. (NCT NCT01400139)

Last Updated: 2020-03-10

Results Overview

Safety assessments included AEs, clinical laboratory test results, vital sign measurements, ECG findings, and audiology assessments.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

922 participants

Primary outcome timeframe

Up to 84 weeks

Results posted on

2020-03-10

Participant Flow

Core study: First subject first visit: 22-July-2011; Last subject last visit: 26-August-2013. Extension period: First subject first visit: 24-April-2013; Last subject last visit of 24-February-2014. The Core and Extension studies were conducted at medical/research sites in the United States.

Subjects with moderate to severe, chronic nonmalignant and non-neuropathic pain.

Participant milestones

Participant milestones
Measure	Hydrocodone Bitartrate (HYD) Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily
HYD Core Study STARTED	922
HYD Core Study COMPLETED	410
HYD Core Study NOT COMPLETED	512
HYD Extension Period STARTED	106
HYD Extension Period COMPLETED	83
HYD Extension Period NOT COMPLETED	23

Reasons for withdrawal

Reasons for withdrawal
Measure	Hydrocodone Bitartrate (HYD) Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily
HYD Core Study Adverse Event	210
HYD Core Study Lack of Efficacy	59
HYD Core Study Withdrawal by Subject	114
HYD Core Study Lost to Follow-up	39
HYD Core Study Confirmed or suspected diversion	20
HYD Core Study Administrative	56
HYD Core Study Did not qualify for Maintenance Period	14
HYD Extension Period Adverse Event	8
HYD Extension Period Withdrawal by Subject	5
HYD Extension Period Administrative	10

Baseline Characteristics

Long-term Safety of Once-daily Hydrocodone Bitartrate (HYD) Tablets For Moderate to Severe Chronic Nonmalignant and Nonneuropathic Pain. Includes a 24-week Extension Period.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	HYD Core Study n=922 Participants Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily
Age, Continuous	51.8 years STANDARD_DEVIATION 12.53 • n=5 Participants
Sex: Female, Male Female	526 Participants n=5 Participants
Sex: Female, Male Male	396 Participants n=5 Participants
Race/Ethnicity, Customized White	761 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	141 participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	2 participants n=5 Participants
Race/Ethnicity, Customized Asian	8 participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	4 participants n=5 Participants
Race/Ethnicity, Customized Other	6 participants n=5 Participants
Screening Baseline Pain Over the Last 24 Hours	6.4 units on a scale STANDARD_DEVIATION 1.60 • n=5 Participants

PRIMARY outcome

Timeframe: Up to 84 weeks

Population: The Core Study safety population (N=922) was defined as the group of subjects who received at least 1 dose of study drug during the study. The Extension Period safety population (N=106) was the group of core study safety population subjects who entered the extension period and received at least 1 dose of study drug in the extension period.

Safety assessments included AEs, clinical laboratory test results, vital sign measurements, ECG findings, and audiology assessments.

Outcome measures

Outcome measures
Measure	HYD Core Study n=922 Participants Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily	HYD Extension Period n=106 Participants Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily
The Number of Participants With Adverse Events as a Measure of Safety Serious adverse events	80 participants	6 participants
The Number of Participants With Adverse Events as a Measure of Safety All other adverse events in ≥ 5% of patients	586 participants	0 participants

PRIMARY outcome

Timeframe: Core study: from start to end of maintenance period (up to 52 weeks); Extension study: from start of maintenance to end of extension (up to 76 weeks)

Population: The Core Study population analyzed (N=727) was the group of subjects who received at least 1 dose of study drug during the maintenance period. The Extension Period population analyzed (N=106) was the group of core study safety population subjects who entered the extension period and received at least 1 dose of study drug in the extension period.

"Average pain over the last 24 hours" score (on an 11-point numerical rating scale where 0 = no pain and 10 = pain as bad as you can imagine).

Outcome measures

Outcome measures
Measure	HYD Core Study n=727 Participants Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily	HYD Extension Period n=106 Participants Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily
Daily "Average Pain Over the Last 24 Hours"	3.6 units on a scale Standard Deviation 1.80	3.8 units on a scale Standard Deviation 1.73

SECONDARY outcome

Timeframe: Week 12

Population: The Core Study population analyzed was the group of subjects who received at least 1 dose of study drug during the maintenance period and provided data. Data were not collected for this outcome measure during the Extension Period.

"Pain right now" scores were collected using an 11-point scale where 0 = no pain and 10 = pain as bad as you can imagine. The "pain right now" scores were only collected during the Core Study. "Pain right now" scores were not assessed during the Extension Period.

Outcome measures

Outcome measures
Measure	HYD Core Study n=723 Participants Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily	HYD Extension Period Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily
"Pain Right Now" Score	3.46 units on a scale Standard Error 0.071	—

SECONDARY outcome

Timeframe: Baseline and up to 52 weeks in the Core Study maintenance period, and up to 24 weeks in the Extension Period

Population: The Core Study population analyzed was the group of subjects who received at least 1 dose of study drug during the maintenance period and provided data. The Extension Period safety population was the group of core study safety population subjects who entered the extension and received at least 1 dose of study drug in the extension period.

The MOS Sleep-R is a brief, self-administered 12-item assessment designed to measure key aspects of sleep. It includes a sleep problems index II and 6 subscale scores - sleep disturbance, sleep adequacy, daytime somnolence, snoring, awaken short of breath or with headache, and quantity of sleep. For each individual and time of assessment, quantity of sleep was recorded as the number of hours slept per night. The number of hours it took the subject to fall asleep per night was categorized 1, 2, 3, 4, or 5 corresponding to 0 through 15, 16 through 30, 31 through 45, 46 through 60, or more than 60 minutes, respectively. The other scales were recorded as 1 = all of the time, 2 = most of the time, 3 = some of the time, 4 = a little of the time, or 5 = none of the time. A higher value indicates a better score, therefore a positive change from baseline indicates a better sleep pattern and a negative change from baseline indicates a worsening in sleep pattern.

Outcome measures

Outcome measures
Measure	HYD Core Study n=718 Participants Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily	HYD Extension Period n=106 Participants Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily
Medical Outcomes Study (MOS) Sleep Scale - Revised (MOS Sleep-R) Change from Baseline in Sleep Disturbance	4.69 units on a scale Standard Deviation 8.276	3.65 units on a scale Standard Deviation 7.993
Medical Outcomes Study (MOS) Sleep Scale - Revised (MOS Sleep-R) Change from Baseline in Sleep Adequacy	3.29 units on a scale Standard Deviation 8.959	2.94 units on a scale Standard Deviation 8.264
Medical Outcomes Study (MOS) Sleep Scale - Revised (MOS Sleep-R) Change from Baseline in Daytime Somnolence	0.57 units on a scale Standard Deviation 8.469	0.89 units on a scale Standard Deviation 8.418
Medical Outcomes Study (MOS) Sleep Scale - Revised (MOS Sleep-R) Change from Baseline in Snoring	1.28 units on a scale Standard Deviation 6.839	1.77 units on a scale Standard Deviation 6.960
Medical Outcomes Study (MOS) Sleep Scale - Revised (MOS Sleep-R) Change from Baseline in Shortness of Breath	1.46 units on a scale Standard Deviation 9.788	3.46 units on a scale Standard Deviation 10.109
Medical Outcomes Study (MOS) Sleep Scale - Revised (MOS Sleep-R) Change from Baseline in Quantity of Sleep	0.29 units on a scale Standard Deviation 1.413	0.17 units on a scale Standard Deviation 1.189
Medical Outcomes Study (MOS) Sleep Scale - Revised (MOS Sleep-R) Change from Baseline in Sleep Problem Index II	4.04 units on a scale Standard Deviation 8.530	3.70 units on a scale Standard Deviation 8.248

SECONDARY outcome

Timeframe: Up to 52 weeks in the Core Study maintenance period, and up to 24 weeks in the Extension Period

The BPI-SF assessed the severity of pain and interference of pain on daily functions. It consists of 9 sections denoted by Q1 to Q8 and Q9A to Q9G according to their order in the questionnaire, that measure pain location, intensity, pain treatment, and functional interference of pain on mood and every day activities. Scores ranged from 0 (none) to 10 (worst as can be). Four of the items (questions 3 to 6) assess severity of pain and 7 items (questions 9A to 9G) assess interference of pain. The pain interference subscale score was determined by calculating the mean of responses to Q9A - Q9G \[Q9A (general activity), Q9B (mood),Q9C (walking), Q9D (working), Q9E (relations with others), Q9F (sleep), and Q9G (enjoyment of life)\] and the severity of pain subscale score was determined by calculating the mean of responses to Q3 - Q6 \[Q3 (worst pain in last 24 hours), Q4 (least pain in last 24 hours), Q5 (average pain), and Q6 ("pain right now")\]. A lower score indicates lower pain.

Outcome measures

Outcome measures
Measure	HYD Core Study n=721 Participants Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily	HYD Extension Period n=106 Participants Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily
Brief Pain Inventory Short Form (BPI-SF) General Activity (Q9A)	3.24 units on a scale Standard Deviation 2.205	3.27 units on a scale Standard Deviation 2.063
Brief Pain Inventory Short Form (BPI-SF) Mood (Q9B)	2.23 units on a scale Standard Deviation 2.094	1.90 units on a scale Standard Deviation 1.825
Brief Pain Inventory Short Form (BPI-SF) Walking Ability (Q9C)	3.07 units on a scale Standard Deviation 2.402	2.98 units on a scale Standard Deviation 2.298
Brief Pain Inventory Short Form (BPI-SF) Normal Work (Q9D)	3.22 units on a scale Standard Deviation 2.346	3.21 units on a scale Standard Deviation 2.212
Brief Pain Inventory Short Form (BPI-SF) Relations with Others (Q9E)	1.63 units on a scale Standard Deviation 1.934	1.34 units on a scale Standard Deviation 1.620
Brief Pain Inventory Short Form (BPI-SF) Sleep (Q9F)	2.63 units on a scale Standard Deviation 2.258	2.43 units on a scale Standard Deviation 1.931
Brief Pain Inventory Short Form (BPI-SF) Enjoyment of Life (Q9G)	2.55 units on a scale Standard Deviation 2.312	2.23 units on a scale Standard Deviation 2.086
Brief Pain Inventory Short Form (BPI-SF) BPI - Pain Interference Subscale Score	2.65 units on a scale Standard Deviation 2.011	2.48 units on a scale Standard Deviation 1.783
Brief Pain Inventory Short Form (BPI-SF) Worst Pain - Last 24 Hours (Q3)	4.52 units on a scale Standard Deviation 1.966	4.71 units on a scale Standard Deviation 1.875
Brief Pain Inventory Short Form (BPI-SF) Least Pain - Last 24 Hours (Q4)	2.88 units on a scale Standard Deviation 1.741	2.90 units on a scale Standard Deviation 1.494
Brief Pain Inventory Short Form (BPI-SF) Average Pain (Q5)	3.67 units on a scale Standard Deviation 1.703	3.72 units on a scale Standard Deviation 1.560
Brief Pain Inventory Short Form (BPI-SF) Pain Right Now (Q6)	3.39 units on a scale Standard Deviation 1.846	3.49 units on a scale Standard Deviation 1.606
Brief Pain Inventory Short Form (BPI-SF) BPI - Severity of Pain Subscale Score	3.62 units on a scale Standard Deviation 1.730	3.71 units on a scale Standard Deviation 1.562

SECONDARY outcome

Timeframe: Up to 52 weeks in the Core Study maintenance period, and up to 24 weeks in the Extension Period

Population: The Core Study population analyzed was the group of subjects who received at least 1 dose of study drug during the maintenance period and provided data. The Extension Period safety population was the group of core study safety population subjects who entered the extension period and received at least 1 dose of study drug in the extension period.

The SF-36 is a generic health survey with 36 items that measure functional health and well-being from the subject's perspective. The 36 questions are grouped into 11 sections. Some of the sections consist of multiple questions. The survey is summarized into 8 dimensions/scales: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. From the 8 health dimensions, physical component summary, and mental component summary measures are derived. Scores on each scale ranged from 0 to 100; a higher score indicates a better perception of health.

Outcome measures

Outcome measures
Measure	HYD Core Study n=717 Participants Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily	HYD Extension Period n=106 Participants Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily
Medical Outcomes Study 36-item Short Form (SF-36) Physical Functioning	40.61 units on a scale Standard Deviation 9.709	41.93 units on a scale Standard Deviation 9.258
Medical Outcomes Study 36-item Short Form (SF-36) Role Physical	43.27 units on a scale Standard Deviation 8.585	43.78 units on a scale Standard Deviation 8.545
Medical Outcomes Study 36-item Short Form (SF-36) Bodily Pain	42.54 units on a scale Standard Deviation 6.859	43.05 units on a scale Standard Deviation 6.608
Medical Outcomes Study 36-item Short Form (SF-36) General Health	49.28 units on a scale Standard Deviation 9.979	49.18 units on a scale Standard Deviation 10.498
Medical Outcomes Study 36-item Short Form (SF-36) Vitality	49.77 units on a scale Standard Deviation 9.473	50.45 units on a scale Standard Deviation 9.109
Medical Outcomes Study 36-item Short Form (SF-36) Social Functioning	49.44 units on a scale Standard Deviation 7.992	50.55 units on a scale Standard Deviation 7.055
Medical Outcomes Study 36-item Short Form (SF-36) Role Emotional	50.63 units on a scale Standard Deviation 7.570	51.60 units on a scale Standard Deviation 7.109
Medical Outcomes Study 36-item Short Form (SF-36) Mental Health	52.75 units on a scale Standard Deviation 8.060	52.93 units on a scale Standard Deviation 8.199
Medical Outcomes Study 36-item Short Form (SF-36) Physical Component Summary	40.38 units on a scale Standard Deviation 8.962	41.04 units on a scale Standard Deviation 8.809
Medical Outcomes Study 36-item Short Form (SF-36) Mental Component Summary	55.13 units on a scale Standard Deviation 8.638	55.68 units on a scale Standard Deviation 8.506

SECONDARY outcome

Timeframe: At Week 52 in the Core Study maintenance period and at Week 24 in the Extension Period

Population: The Core Study population analyzed was the group of subjects who received at least 1 dose of study drug during the study. The Extension Period safety population was the group of core study safety population subjects who entered the extension period and received at least 1 dose of study drug in the extension period.

The PGIC is an ordinal scale of global evaluation that assesses the change in overall status relative to the start of the study. The scale has only 1 item that measures global change of overall status (improvement or worsening) by the subject on a 7-point scale (Very much improved, Much improved, Minimally improved, No change, Minimally worse, Much worse, Very much worse.

Outcome measures

Outcome measures
Measure	HYD Core Study n=773 Participants Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily	HYD Extension Period n=105 Participants Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily
Patient Global Impression of Change (PGIC) Much improved	276 participants	55 participants
Patient Global Impression of Change (PGIC) Very much improved	132 participants	21 participants
Patient Global Impression of Change (PGIC) Minimally improved	164 participants	17 participants
Patient Global Impression of Change (PGIC) No change	121 participants	9 participants
Patient Global Impression of Change (PGIC) Minimally worse	47 participants	2 participants
Patient Global Impression of Change (PGIC) Much worse	29 participants	1 participants
Patient Global Impression of Change (PGIC) Very much worse	4 participants	0 participants

SECONDARY outcome

Timeframe: At Week 52 or upon early discontinuation at or before Week 4 in the Core Study maintenance period

Population: The Core Study population analyzed was the group of subjects who received at least 1 dose of study drug during the maintenance period and provided data.

The TSQ is a self-administered questionnaire that consists of 2 parts. Part I has 6 questions (Q1 to Q6) that ask the subject to rate the experience with use of the study drug in comparison to the prestudy pain medication regarding ease of use, convenience, frequency, pain control, and overall satisfaction. Each question was rated on a scale from 1 (extremely satisfied) to 6 (extremely dissatisfied): Q1=Satisfaction with study drug; Q2=Ease of study drug use to treat pain; Q3=Convenience of study drug to treat pain; Q4=Overall drug satisfaction managing pain; Q5=Satisfaction with frequency of use; Q6=Ease of planning study drug use. The number of subjects with each category (1-6) of response for each individual question (Q1-Q6) was summarized for subjects who entered the core study maintenance period and responded to each question. TSQ - Part I was not administered in the extension period.

Outcome measures

Outcome measures
Measure	HYD Core Study n=728 Participants Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily	HYD Extension Period Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily
Treatment Satisfaction Questionnaire (TSQ) - Part I Q1: Satisfaction - extremely satisfied	140 participants	—
Treatment Satisfaction Questionnaire (TSQ) - Part I Q1: very satisfied	220 participants	—
Treatment Satisfaction Questionnaire (TSQ) - Part I Q1: satisfied	181 participants	—
Treatment Satisfaction Questionnaire (TSQ) - Part I Q1: dissatisfied	38 participants	—
Treatment Satisfaction Questionnaire (TSQ) - Part I Q1: very dissatisfied	8 participants	—
Treatment Satisfaction Questionnaire (TSQ) - Part I Q1: extremely dissatisfied	6 participants	—
Treatment Satisfaction Questionnaire (TSQ) - Part I Q2: Ease of study drug use - extremely easy	253 participants	—
Treatment Satisfaction Questionnaire (TSQ) - Part I Q2: very easy	209 participants	—
Treatment Satisfaction Questionnaire (TSQ) - Part I Q2: easy	110 participants	—
Treatment Satisfaction Questionnaire (TSQ) - Part I Q2: difficult	15 participants	—
Treatment Satisfaction Questionnaire (TSQ) - Part I Q2: very difficult	4 participants	—
Treatment Satisfaction Questionnaire (TSQ) - Part I Q2: extremely difficult	2 participants	—
Treatment Satisfaction Questionnaire (TSQ) - Part I Q3: Convenience of study drug-extremely convenient	266 participants	—
Treatment Satisfaction Questionnaire (TSQ) - Part I Q3: very convenient	196 participants	—
Treatment Satisfaction Questionnaire (TSQ) - Part I Q3: convenient	118 participants	—
Treatment Satisfaction Questionnaire (TSQ) - Part I Q3: inconvenient	8 participants	—
Treatment Satisfaction Questionnaire (TSQ) - Part I Q3: very inconvenient	4 participants	—
Treatment Satisfaction Questionnaire (TSQ) - Part I Q3: extremely inconvenient	1 participants	—
Treatment Satisfaction Questionnaire (TSQ) - Part I Q4: Overall drug satisfaction- extremely satisfied	141 participants	—
Treatment Satisfaction Questionnaire (TSQ) - Part I Q4: very satisfied	200 participants	—
Treatment Satisfaction Questionnaire (TSQ) - Part I Q4: satisfied	195 participants	—
Treatment Satisfaction Questionnaire (TSQ) - Part I Q4: dissatisfied	44 participants	—
Treatment Satisfaction Questionnaire (TSQ) - Part I Q4: very dissatisfied	6 participants	—
Treatment Satisfaction Questionnaire (TSQ) - Part I Q4: extremely dissatisfied	7 participants	—
Treatment Satisfaction Questionnaire (TSQ) - Part I Q5: Satisfaction use frequency-extremely satisfied	265 participants	—
Treatment Satisfaction Questionnaire (TSQ) - Part I Q5: very satisfied	169 participants	—
Treatment Satisfaction Questionnaire (TSQ) - Part I Q5: satisfied	139 participants	—
Treatment Satisfaction Questionnaire (TSQ) - Part I Q5: dissatisfied	14 participants	—
Treatment Satisfaction Questionnaire (TSQ) - Part I Q5: very dissatisfied	4 participants	—
Treatment Satisfaction Questionnaire (TSQ) - Part I Q5: extremely dissatisfied	2 participants	—
Treatment Satisfaction Questionnaire (TSQ) - Part I Q6: Ease of planning use - extremely easy	284 participants	—
Treatment Satisfaction Questionnaire (TSQ) - Part I Q6: very easy	189 participants	—
Treatment Satisfaction Questionnaire (TSQ) - Part I Q6: easy	106 participants	—
Treatment Satisfaction Questionnaire (TSQ) - Part I Q6: difficult	11 participants	—
Treatment Satisfaction Questionnaire (TSQ) - Part I Q6: very difficult	1 participants	—
Treatment Satisfaction Questionnaire (TSQ) - Part I Q6: extremely difficult	2 participants	—

SECONDARY outcome

Timeframe: At Week 52 or upon early discontinuation at or before Week 4 in maintenance and at Week 24 in extension

Population: The Core Study population analyzed was the group of subjects who received at least 1 dose of study drug during the maintenance period and provided data. The Extension Period safety population was the group of core study safety population subjects who entered the extension period and received at least 1 dose of study drug in the extension period.

The TSQ is a self-administered questionnaire that consists of 2 parts. Part II has 2 questions that measure the subject's willingness to continue the use of study drug as pain medication (Q1), and to recommend the study drug to someone else (Q2). Question 1 consists of 6 categories of response rated on a scale from 1 (very willing to continue) to 6 (very unwilling to continue): 1=Very willing to continue; 2=Willing to continue; 3=Somewhat willing to continue; 4=Somewhat unwilling to continue; 5=Unwilling to continue; 6=Very unwilling to continue. Question 2 consists of 3 categories of response: 1=yes; 2=no; 3=undecided. The number of subjects with each category of response for each individual question was summarized for subjects completing the core study maintenance period and for those enrolled in the extension period.

Outcome measures

Outcome measures
Measure	HYD Core Study n=728 Participants Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily	HYD Extension Period n=106 Participants Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily
Treatment Satisfaction Questionnaire (TSQ) - Part II Q1:Willingness to continue study drug-very willing	281 participants	51 participants
Treatment Satisfaction Questionnaire (TSQ) - Part II Q1: willing to continue	141 participants	29 participants
Treatment Satisfaction Questionnaire (TSQ) - Part II Q1: somewhat willing to continue	53 participants	18 participants
Treatment Satisfaction Questionnaire (TSQ) - Part II Q1: somewhat unwilling to continue	29 participants	4 participants
Treatment Satisfaction Questionnaire (TSQ) - Part II Q1: unwilling to continue	79 participants	3 participants
Treatment Satisfaction Questionnaire (TSQ) - Part II Q1: very unwilling to continue	53 participants	0 participants
Treatment Satisfaction Questionnaire (TSQ) - Part II Q2: Recommend study drug for pain - yes	546 participants	90 participants
Treatment Satisfaction Questionnaire (TSQ) - Part II Q2: no	36 participants	4 participants
Treatment Satisfaction Questionnaire (TSQ) - Part II Q2: undecided	54 participants	11 participants

Adverse Events

HYD Core Study

Serious events: 80 serious events

Other events: 586 other events

Deaths: 0 deaths

HYD Extension Period

Serious events: 6 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	HYD Core Study n=922 participants at risk Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily	HYD Extension Period n=106 participants at risk Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily
Gastrointestinal disorders Nausea	23.6% 218/922 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion: up to 84 weeks. AEs were learned of through spontaneous reports and/or subject interview, or observed during physical examinations or other safety assessments. Ongoing AEs were followed until resolution or 30 days after last study drug dose. Serious AEs up to 30 days after last study drug dose or last visit were followed until AE or sequelae resolved/stabilized.	0.00% 0/106 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion: up to 84 weeks. AEs were learned of through spontaneous reports and/or subject interview, or observed during physical examinations or other safety assessments. Ongoing AEs were followed until resolution or 30 days after last study drug dose. Serious AEs up to 30 days after last study drug dose or last visit were followed until AE or sequelae resolved/stabilized.
Gastrointestinal disorders Constipation	20.9% 193/922 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion: up to 84 weeks. AEs were learned of through spontaneous reports and/or subject interview, or observed during physical examinations or other safety assessments. Ongoing AEs were followed until resolution or 30 days after last study drug dose. Serious AEs up to 30 days after last study drug dose or last visit were followed until AE or sequelae resolved/stabilized.	0.00% 0/106 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion: up to 84 weeks. AEs were learned of through spontaneous reports and/or subject interview, or observed during physical examinations or other safety assessments. Ongoing AEs were followed until resolution or 30 days after last study drug dose. Serious AEs up to 30 days after last study drug dose or last visit were followed until AE or sequelae resolved/stabilized.
Gastrointestinal disorders Vomiting	10.8% 100/922 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion: up to 84 weeks. AEs were learned of through spontaneous reports and/or subject interview, or observed during physical examinations or other safety assessments. Ongoing AEs were followed until resolution or 30 days after last study drug dose. Serious AEs up to 30 days after last study drug dose or last visit were followed until AE or sequelae resolved/stabilized.	0.00% 0/106 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion: up to 84 weeks. AEs were learned of through spontaneous reports and/or subject interview, or observed during physical examinations or other safety assessments. Ongoing AEs were followed until resolution or 30 days after last study drug dose. Serious AEs up to 30 days after last study drug dose or last visit were followed until AE or sequelae resolved/stabilized.
Gastrointestinal disorders Diarrhoea	6.1% 56/922 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion: up to 84 weeks. AEs were learned of through spontaneous reports and/or subject interview, or observed during physical examinations or other safety assessments. Ongoing AEs were followed until resolution or 30 days after last study drug dose. Serious AEs up to 30 days after last study drug dose or last visit were followed until AE or sequelae resolved/stabilized.	0.00% 0/106 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion: up to 84 weeks. AEs were learned of through spontaneous reports and/or subject interview, or observed during physical examinations or other safety assessments. Ongoing AEs were followed until resolution or 30 days after last study drug dose. Serious AEs up to 30 days after last study drug dose or last visit were followed until AE or sequelae resolved/stabilized.
General disorders Fatigue	7.7% 71/922 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion: up to 84 weeks. AEs were learned of through spontaneous reports and/or subject interview, or observed during physical examinations or other safety assessments. Ongoing AEs were followed until resolution or 30 days after last study drug dose. Serious AEs up to 30 days after last study drug dose or last visit were followed until AE or sequelae resolved/stabilized.	0.00% 0/106 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion: up to 84 weeks. AEs were learned of through spontaneous reports and/or subject interview, or observed during physical examinations or other safety assessments. Ongoing AEs were followed until resolution or 30 days after last study drug dose. Serious AEs up to 30 days after last study drug dose or last visit were followed until AE or sequelae resolved/stabilized.
Infections and infestations Upper respiratory tract infection	7.9% 73/922 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion: up to 84 weeks. AEs were learned of through spontaneous reports and/or subject interview, or observed during physical examinations or other safety assessments. Ongoing AEs were followed until resolution or 30 days after last study drug dose. Serious AEs up to 30 days after last study drug dose or last visit were followed until AE or sequelae resolved/stabilized.	0.00% 0/106 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion: up to 84 weeks. AEs were learned of through spontaneous reports and/or subject interview, or observed during physical examinations or other safety assessments. Ongoing AEs were followed until resolution or 30 days after last study drug dose. Serious AEs up to 30 days after last study drug dose or last visit were followed until AE or sequelae resolved/stabilized.
Infections and infestations Sinusitis	5.4% 50/922 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion: up to 84 weeks. AEs were learned of through spontaneous reports and/or subject interview, or observed during physical examinations or other safety assessments. Ongoing AEs were followed until resolution or 30 days after last study drug dose. Serious AEs up to 30 days after last study drug dose or last visit were followed until AE or sequelae resolved/stabilized.	0.00% 0/106 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion: up to 84 weeks. AEs were learned of through spontaneous reports and/or subject interview, or observed during physical examinations or other safety assessments. Ongoing AEs were followed until resolution or 30 days after last study drug dose. Serious AEs up to 30 days after last study drug dose or last visit were followed until AE or sequelae resolved/stabilized.
Infections and infestations Nasopharyngitis	5.1% 47/922 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion: up to 84 weeks. AEs were learned of through spontaneous reports and/or subject interview, or observed during physical examinations or other safety assessments. Ongoing AEs were followed until resolution or 30 days after last study drug dose. Serious AEs up to 30 days after last study drug dose or last visit were followed until AE or sequelae resolved/stabilized.	0.00% 0/106 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion: up to 84 weeks. AEs were learned of through spontaneous reports and/or subject interview, or observed during physical examinations or other safety assessments. Ongoing AEs were followed until resolution or 30 days after last study drug dose. Serious AEs up to 30 days after last study drug dose or last visit were followed until AE or sequelae resolved/stabilized.
Infections and infestations Urinary tract infection	5.1% 47/922 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion: up to 84 weeks. AEs were learned of through spontaneous reports and/or subject interview, or observed during physical examinations or other safety assessments. Ongoing AEs were followed until resolution or 30 days after last study drug dose. Serious AEs up to 30 days after last study drug dose or last visit were followed until AE or sequelae resolved/stabilized.	0.00% 0/106 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion: up to 84 weeks. AEs were learned of through spontaneous reports and/or subject interview, or observed during physical examinations or other safety assessments. Ongoing AEs were followed until resolution or 30 days after last study drug dose. Serious AEs up to 30 days after last study drug dose or last visit were followed until AE or sequelae resolved/stabilized.
Nervous system disorders Dizziness	11.5% 106/922 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion: up to 84 weeks. AEs were learned of through spontaneous reports and/or subject interview, or observed during physical examinations or other safety assessments. Ongoing AEs were followed until resolution or 30 days after last study drug dose. Serious AEs up to 30 days after last study drug dose or last visit were followed until AE or sequelae resolved/stabilized.	0.00% 0/106 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion: up to 84 weeks. AEs were learned of through spontaneous reports and/or subject interview, or observed during physical examinations or other safety assessments. Ongoing AEs were followed until resolution or 30 days after last study drug dose. Serious AEs up to 30 days after last study drug dose or last visit were followed until AE or sequelae resolved/stabilized.
Nervous system disorders Somnolence	11.3% 104/922 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion: up to 84 weeks. AEs were learned of through spontaneous reports and/or subject interview, or observed during physical examinations or other safety assessments. Ongoing AEs were followed until resolution or 30 days after last study drug dose. Serious AEs up to 30 days after last study drug dose or last visit were followed until AE or sequelae resolved/stabilized.	0.00% 0/106 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion: up to 84 weeks. AEs were learned of through spontaneous reports and/or subject interview, or observed during physical examinations or other safety assessments. Ongoing AEs were followed until resolution or 30 days after last study drug dose. Serious AEs up to 30 days after last study drug dose or last visit were followed until AE or sequelae resolved/stabilized.
Nervous system disorders Headache	9.2% 85/922 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion: up to 84 weeks. AEs were learned of through spontaneous reports and/or subject interview, or observed during physical examinations or other safety assessments. Ongoing AEs were followed until resolution or 30 days after last study drug dose. Serious AEs up to 30 days after last study drug dose or last visit were followed until AE or sequelae resolved/stabilized.	0.00% 0/106 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion: up to 84 weeks. AEs were learned of through spontaneous reports and/or subject interview, or observed during physical examinations or other safety assessments. Ongoing AEs were followed until resolution or 30 days after last study drug dose. Serious AEs up to 30 days after last study drug dose or last visit were followed until AE or sequelae resolved/stabilized.
Psychiatric disorders Insomnia	6.2% 57/922 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion: up to 84 weeks. AEs were learned of through spontaneous reports and/or subject interview, or observed during physical examinations or other safety assessments. Ongoing AEs were followed until resolution or 30 days after last study drug dose. Serious AEs up to 30 days after last study drug dose or last visit were followed until AE or sequelae resolved/stabilized.	0.00% 0/106 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion: up to 84 weeks. AEs were learned of through spontaneous reports and/or subject interview, or observed during physical examinations or other safety assessments. Ongoing AEs were followed until resolution or 30 days after last study drug dose. Serious AEs up to 30 days after last study drug dose or last visit were followed until AE or sequelae resolved/stabilized.
Skin and subcutaneous tissue disorders Pruritus	5.6% 52/922 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion: up to 84 weeks. AEs were learned of through spontaneous reports and/or subject interview, or observed during physical examinations or other safety assessments. Ongoing AEs were followed until resolution or 30 days after last study drug dose. Serious AEs up to 30 days after last study drug dose or last visit were followed until AE or sequelae resolved/stabilized.	0.00% 0/106 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion: up to 84 weeks. AEs were learned of through spontaneous reports and/or subject interview, or observed during physical examinations or other safety assessments. Ongoing AEs were followed until resolution or 30 days after last study drug dose. Serious AEs up to 30 days after last study drug dose or last visit were followed until AE or sequelae resolved/stabilized.

Additional Information

Clinical Leader

Purdue Pharma L.P.

Phone: 800-733-1333

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60