Trial Outcomes & Findings for Efficacy and Safety of Hydrocodone Bitartrate (HYD) in Subjects With Moderate to Severe Chronic Low Back Pain (NCT NCT01452529)
NCT ID: NCT01452529
Last Updated: 2020-03-10
Results Overview
Mean pain intensity for "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).
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
905 participants
Primary outcome timeframe
Week 12
Results posted on
2020-03-10
Participant Flow
First subject first visit: 23-March-2012; Last subject last visit: 03-September-2013. The study was conducted at medical/research sites in the United States.
Subjects with moderate to severe chronic low back pain uncontrolled by their current stable analgesic regimen were included.
Participant milestones
| Measure |
Open-label Run-in Dose-titration Period Hydrocodone Bitartrate
The open-label run-in dose-titration period was designed to assess subjects qualification for randomization
|
Hydrocodone Bitartrate
Hydrocodone bitartrate (HYD) once daily (q24h) tablets
Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily
|
Placebo
Placebo to match hydrocodone bitartrate once daily tablets
Placebo to match hydrocodone bitartrate q24h tablets: Placebo to match hydrocodone bitartrate q24h film coated tablets 20 - 120 mg once daily
|
|---|---|---|---|
|
Run-in Period
STARTED
|
905
|
0
|
0
|
|
Run-in Period
COMPLETED
|
592
|
0
|
0
|
|
Run-in Period
NOT COMPLETED
|
313
|
0
|
0
|
|
Double-blind (DB) Period
STARTED
|
0
|
296
|
292
|
|
Double-blind (DB) Period
COMPLETED
|
0
|
229
|
210
|
|
Double-blind (DB) Period
NOT COMPLETED
|
0
|
67
|
82
|
Reasons for withdrawal
| Measure |
Open-label Run-in Dose-titration Period Hydrocodone Bitartrate
The open-label run-in dose-titration period was designed to assess subjects qualification for randomization
|
Hydrocodone Bitartrate
Hydrocodone bitartrate (HYD) once daily (q24h) tablets
Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily
|
Placebo
Placebo to match hydrocodone bitartrate once daily tablets
Placebo to match hydrocodone bitartrate q24h tablets: Placebo to match hydrocodone bitartrate q24h film coated tablets 20 - 120 mg once daily
|
|---|---|---|---|
|
Run-in Period
Adverse Event
|
96
|
0
|
0
|
|
Run-in Period
Withdrawal by Subject
|
49
|
0
|
0
|
|
Run-in Period
Lost to Follow-up
|
19
|
0
|
0
|
|
Run-in Period
Lack of Efficacy
|
46
|
0
|
0
|
|
Run-in Period
Confirmed or suspected diversion
|
23
|
0
|
0
|
|
Run-in Period
Administrative
|
21
|
0
|
0
|
|
Run-in Period
Did not qualify for Double-Blind Phase
|
59
|
0
|
0
|
|
Double-blind (DB) Period
Adverse Event
|
0
|
18
|
11
|
|
Double-blind (DB) Period
Withdrawal by Subject
|
0
|
15
|
14
|
|
Double-blind (DB) Period
Lost to Follow-up
|
0
|
5
|
3
|
|
Double-blind (DB) Period
Lack of Efficacy
|
0
|
16
|
44
|
|
Double-blind (DB) Period
Confirmed or suspected diversion
|
0
|
2
|
3
|
|
Double-blind (DB) Period
Administrative
|
0
|
11
|
7
|
Baseline Characteristics
Efficacy and Safety of Hydrocodone Bitartrate (HYD) in Subjects With Moderate to Severe Chronic Low Back Pain
Baseline characteristics by cohort
| Measure |
Placebo
n=292 Participants
Placebo to match hydrocodone bitartrate once daily tablets
Placebo to match hydrocodone bitartrate q24h tablets: Placebo to match hydrocodone bitartrate q24h film coated tablets 20 - 120 mg once daily
|
Total
n=588 Participants
Total of all reporting groups
|
Hydrocodone Bitartrate
n=296 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
|
47.9 years
STANDARD_DEVIATION 13.23 • n=7 Participants
|
48.6 years
STANDARD_DEVIATION 13.38 • n=5 Participants
|
49.2 years
STANDARD_DEVIATION 13.51 • n=5 Participants
|
|
Sex: Female, Male
Female
|
166 Participants
n=7 Participants
|
338 Participants
n=5 Participants
|
172 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
126 Participants
n=7 Participants
|
250 Participants
n=5 Participants
|
124 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
207 participants
n=7 Participants
|
402 participants
n=5 Participants
|
195 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
51 participants
n=7 Participants
|
118 participants
n=5 Participants
|
67 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
29 participants
n=7 Participants
|
54 participants
n=5 Participants
|
25 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
1 participants
n=7 Participants
|
3 participants
n=5 Participants
|
2 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
4 participants
n=7 Participants
|
11 participants
n=5 Participants
|
7 participants
n=5 Participants
|
|
Screening Baseline Pain Over the Last 24 Hours
|
7.4 units on a scale
STANDARD_DEVIATION 1.19 • n=7 Participants
|
7.4 units on a scale
STANDARD_DEVIATION 1.16 • n=5 Participants
|
7.4 units on a scale
STANDARD_DEVIATION 1.13 • n=5 Participants
|
PRIMARY outcome
Timeframe: Week 12Population: The full analysis population (N = 588) was the group of subjects who were randomized and received at least 1 dose of double-blind study drug
Mean pain intensity for "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
| Measure |
Hydrocodone Bitartrate
n=296 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
|
Placebo
n=292 Participants
Placebo to match hydrocodone bitartrate once daily tablets
Placebo to match hydrocodone bitartrate q24h tablets: Placebo to match hydrocodone bitartrate q24h film coated tablets 20 - 120 mg once daily
|
|---|---|---|
|
Mean Pain Intensity for "Average Pain Over the Last 24 Hours" Score
|
3.7 units on a scale
Standard Error 0.13
|
4.2 units on a scale
Standard Error 0.13
|
SECONDARY outcome
Timeframe: Weeks 4, 8, and 12Population: The full analysis population (N = 588) was the group of subjects who were randomized and received at least 1 dose of double-blind study drug
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 and 6 subscales - sleep disturbance, sleep adequacy, daytime somnolence, snoring, awaken short of breath or with headache, and quantity of sleep. The sleep disturbance subscale comprised the responses to questions 1, 3, 7, and 8 on the assessment. The individual responses for each question were recorded on a 5-point scale with options ranging from 1 - "all of the time" to 5 - "none of the time". Sleep disturbance scores were transformed linearly on a scale of 0-100. A higher value indicates a better score; therefore, a higher score indicates a better sleep pattern.
Outcome measures
| Measure |
Hydrocodone Bitartrate
n=296 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
|
Placebo
n=292 Participants
Placebo to match hydrocodone bitartrate once daily tablets
Placebo to match hydrocodone bitartrate q24h tablets: Placebo to match hydrocodone bitartrate q24h film coated tablets 20 - 120 mg once daily
|
|---|---|---|
|
Medical Outcome Study Sleep Scale - Revised (MOS Sleep-R) - Sleep Disturbance Subscale
Screening
|
44.38 units on a scale
Standard Deviation 9.262
|
44.72 units on a scale
Standard Deviation 9.871
|
|
Medical Outcome Study Sleep Scale - Revised (MOS Sleep-R) - Sleep Disturbance Subscale
Week 4
|
50.38 units on a scale
Standard Deviation 8.851
|
50.51 units on a scale
Standard Deviation 9.156
|
|
Medical Outcome Study Sleep Scale - Revised (MOS Sleep-R) - Sleep Disturbance Subscale
Week 8
|
50.16 units on a scale
Standard Deviation 8.879
|
51.16 units on a scale
Standard Deviation 8.781
|
|
Medical Outcome Study Sleep Scale - Revised (MOS Sleep-R) - Sleep Disturbance Subscale
Week 12
|
51.57 units on a scale
Standard Deviation 8.576
|
52.12 units on a scale
Standard Deviation 8.779
|
SECONDARY outcome
Timeframe: Week 12Population: The full analysis population (N = 588) was the group of subjects who were randomized and received at least 1 dose of double-blind study drug
The PGIC is an ordinal scale which assesses the change in overall status relative to the start of the study. The scale has only 1 item, which measures global change of overall status by the subject on a 7-point scale (very much improved, much improved, minimally improved, no change, minimally worse, much worse, very much worse), where 1 = very much improved and 7 = very much worse. The proportion of subjects responding "very much improved" and "much improved" was summarized by treatment group.
Outcome measures
| Measure |
Hydrocodone Bitartrate
n=296 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
|
Placebo
n=292 Participants
Placebo to match hydrocodone bitartrate once daily tablets
Placebo to match hydrocodone bitartrate q24h tablets: Placebo to match hydrocodone bitartrate q24h film coated tablets 20 - 120 mg once daily
|
|---|---|---|
|
Patient Global Impression of Change (PGIC)
Total Subjects Completing PGIC
|
283 Participants
|
267 Participants
|
|
Patient Global Impression of Change (PGIC)
Subjects Responding Very Much or Much Improved
|
173 Participants
|
130 Participants
|
SECONDARY outcome
Timeframe: Baseline to Week 12Population: The full analysis population (N = 588) was the group of subjects who were randomized and received at least 1 dose of double-blind study drug
A subject's response to treatment was defined as the percentage reduction from the screening mean pain score to the mean pain intensity at week 12 of the double-blind period.
Outcome measures
| Measure |
Hydrocodone Bitartrate
n=296 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
|
Placebo
n=292 Participants
Placebo to match hydrocodone bitartrate once daily tablets
Placebo to match hydrocodone bitartrate q24h tablets: Placebo to match hydrocodone bitartrate q24h film coated tablets 20 - 120 mg once daily
|
|---|---|---|
|
Responder Analysis for Subjects With a ≥ 30% Reduction in Pain Compared to Baseline
Number of Subjects Responding
|
285 Participants
|
280 Participants
|
|
Responder Analysis for Subjects With a ≥ 30% Reduction in Pain Compared to Baseline
Number of Subjects with ≥ 30% Reduction in Pain
|
184 Participants
|
147 Participants
|
SECONDARY outcome
Timeframe: Baseline to Week 12Population: The full analysis population (N = 588) was the group of subjects who were randomized and received at least 1 dose of double-blind study drug
A subject's response to treatment was defined as the percentage reduction from the screening mean pain score to the mean pain intensity at week 12 of the double-blind period.
Outcome measures
| Measure |
Hydrocodone Bitartrate
n=296 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
|
Placebo
n=292 Participants
Placebo to match hydrocodone bitartrate once daily tablets
Placebo to match hydrocodone bitartrate q24h tablets: Placebo to match hydrocodone bitartrate q24h film coated tablets 20 - 120 mg once daily
|
|---|---|---|
|
Responder Analysis for Subjects With a ≥ 50% Reduction in Pain Compared to Baseline
Number of Subjects Responding
|
285 Participants
|
280 Participants
|
|
Responder Analysis for Subjects With a ≥ 50% Reduction in Pain Compared to Baseline
Number of Subjects with ≥ 50% Reduction in Pain
|
137 Participants
|
109 Participants
|
Adverse Events
Open-label Run-in Dose-titration Period Hydrocodone Bitartrate
Serious events: 7 serious events
Other events: 265 other events
Deaths: 0 deaths
Hydrocodone Bitartrate
Serious events: 2 serious events
Other events: 52 other events
Deaths: 0 deaths
Placebo
Serious events: 4 serious events
Other events: 30 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Open-label Run-in Dose-titration Period Hydrocodone Bitartrate
n=905 participants at risk
The open-label run-in dose-titration period was designed to assess subjects' qualification for randomization
|
Hydrocodone Bitartrate
n=296 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
|
Placebo
n=292 participants at risk
Placebo to match hydrocodone bitartrate once daily tablets
Placebo to match hydrocodone bitartrate q24h tablets: Placebo to match hydrocodone bitartrate q24h film coated tablets 20 - 120 mg once daily
|
|---|---|---|---|
|
Cardiac disorders
Angina unstable
|
0.11%
1/905 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
0.00%
0/296 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
0.00%
0/292 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/905 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
0.00%
0/296 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
0.34%
1/292 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
|
Endocrine disorders
Hypothyroidism
|
0.00%
0/905 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
0.34%
1/296 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
0.00%
0/292 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
|
Gastrointestinal disorders
Abdominal pain
|
0.11%
1/905 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
0.00%
0/296 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
0.00%
0/292 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
|
Gastrointestinal disorders
Vomiting
|
0.11%
1/905 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
0.00%
0/296 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
0.00%
0/292 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
|
General disorders
Chest pain
|
0.00%
0/905 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
0.34%
1/296 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
0.00%
0/292 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/905 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
0.00%
0/296 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
0.34%
1/292 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
|
Infections and infestations
Lobar pneumonia
|
0.00%
0/905 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
0.00%
0/296 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
0.34%
1/292 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
|
Injury, poisoning and procedural complications
Concussion
|
0.00%
0/905 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
0.00%
0/296 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
0.34%
1/292 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
0.11%
1/905 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
0.00%
0/296 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
0.00%
0/292 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
0.11%
1/905 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
0.00%
0/296 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
0.00%
0/292 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
|
Musculoskeletal and connective tissue disorders
Joint effusion
|
0.11%
1/905 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
0.00%
0/296 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
0.00%
0/292 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/905 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
0.00%
0/296 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
0.34%
1/292 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of lung
|
0.00%
0/905 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
0.00%
0/296 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
0.34%
1/292 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
|
Nervous system disorders
Intracranial aneurysm
|
0.11%
1/905 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
0.00%
0/296 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
0.00%
0/292 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
|
Psychiatric disorders
Drug abuse
|
0.11%
1/905 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
0.00%
0/296 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
0.00%
0/292 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
|
Psychiatric disorders
Major depression
|
0.00%
0/905 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
0.34%
1/296 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
0.00%
0/292 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
|
Reproductive system and breast disorders
Ovarian cyst ruptured
|
0.11%
1/905 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
0.00%
0/296 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
0.00%
0/292 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
|
Respiratory, thoracic and mediastinal disorders
Emphysema
|
0.00%
0/905 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
0.00%
0/296 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
0.34%
1/292 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/905 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
0.00%
0/296 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
0.34%
1/292 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
|
Surgical and medical procedures
Abortion induced
|
0.11%
1/905 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
0.00%
0/296 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
0.00%
0/292 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
Other adverse events
| Measure |
Open-label Run-in Dose-titration Period Hydrocodone Bitartrate
n=905 participants at risk
The open-label run-in dose-titration period was designed to assess subjects' qualification for randomization
|
Hydrocodone Bitartrate
n=296 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
|
Placebo
n=292 participants at risk
Placebo to match hydrocodone bitartrate once daily tablets
Placebo to match hydrocodone bitartrate q24h tablets: Placebo to match hydrocodone bitartrate q24h film coated tablets 20 - 120 mg once daily
|
|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
15.9%
144/905 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
8.1%
24/296 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
5.5%
16/292 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
|
Gastrointestinal disorders
Constipation
|
9.4%
85/905 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
3.4%
10/296 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
2.4%
7/292 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
|
Gastrointestinal disorders
Vomiting
|
7.2%
65/905 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
6.1%
18/296 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
3.1%
9/292 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
|
Nervous system disorders
Dizziness
|
7.1%
64/905 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
3.0%
9/296 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
1.7%
5/292 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
|
Nervous system disorders
Headache
|
6.5%
59/905 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
2.0%
6/296 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
|
1.7%
5/292 • Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or 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