Trial Outcomes & Findings for Study to Evaluate the Analgesic Efficacy and Safety of Hydrocodone Bitartrate/Acetaminophen Immediate-Release Tablets in Participants With Moderate to Severe Pain Following Bunionectomy (NCT NCT02487108)

NCT ID: NCT02487108

Last Updated: 2022-03-31

Results Overview

The SPID48 was calculated as the time-weighted sum of pain intensity difference (PID) at each time point over 48 hours. The SPID48 was based on the NPRS-11, which is an 11-point Likert-type scale in which 0 means no pain and 10 means the most intense pain imaginable. Least square (LS) mean was calculated using an analysis of covariance (ANCOVA) with treatment and center as factors and the baseline pain intensity score as a covariate. Multiple imputation method was used to handle missing data.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 569 participants
• Primary outcome timeframe: 48 hours
• Results posted on: 2022-03-31

Participant Flow

Participant milestones

Measure	Placebo Participants received placebo matched to TV46763 (hydrocodone bitartrate/acetaminophen) immediate release (IR) tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 5.0 mg/325 mg Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 5.0 milligrams (mg)/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 7.5 mg/325 mg Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 7.5 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 10.0 mg/325 mg Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 10.0 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.
Overall Study STARTED	142	142	143	142
Overall Study Received at Least 1 Dose of Study Drug	142	142	141	142
Overall Study COMPLETED	126	126	117	131
Overall Study NOT COMPLETED	16	16	26	11

Reasons for withdrawal

Measure	Placebo Participants received placebo matched to TV46763 (hydrocodone bitartrate/acetaminophen) immediate release (IR) tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 5.0 mg/325 mg Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 5.0 milligrams (mg)/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 7.5 mg/325 mg Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 7.5 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 10.0 mg/325 mg Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 10.0 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.
Overall Study Adverse Event	1	6	12	6
Overall Study Withdrawal by Subject	8	5	5	0
Overall Study Non-compliance to study medication	3	2	5	4
Overall Study Protocol Violation	1	1	2	0
Overall Study Non-compliance to study procedures	0	0	0	1
Overall Study Other than specified	3	2	2	0

Baseline Characteristics

Study to Evaluate the Analgesic Efficacy and Safety of Hydrocodone Bitartrate/Acetaminophen Immediate-Release Tablets in Participants With Moderate to Severe Pain Following Bunionectomy

Baseline characteristics by cohort

Measure	Placebo n=142 Participants Participants received placebo matched to TV46763 (hydrocodone bitartrate/acetaminophen) IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 5.0 mg/325 mg n=142 Participants Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 5.0 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 7.5 mg/325 mg n=143 Participants Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 7.5 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 10.0 mg/325 mg n=142 Participants Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 10.0 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	Total n=569 Participants Total of all reporting groups
Age, Continuous	47.5 years STANDARD_DEVIATION 14.39 • n=93 Participants	45.8 years STANDARD_DEVIATION 14.45 • n=4 Participants	44.9 years STANDARD_DEVIATION 13.87 • n=27 Participants	46.2 years STANDARD_DEVIATION 13.94 • n=483 Participants	46.1 years STANDARD_DEVIATION 14.16 • n=36 Participants
Sex: Female, Male Female	119 Participants n=93 Participants	124 Participants n=4 Participants	125 Participants n=27 Participants	113 Participants n=483 Participants	481 Participants n=36 Participants
Sex: Female, Male Male	23 Participants n=93 Participants	18 Participants n=4 Participants	18 Participants n=27 Participants	29 Participants n=483 Participants	88 Participants n=36 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	40 Participants n=93 Participants	35 Participants n=4 Participants	49 Participants n=27 Participants	47 Participants n=483 Participants	171 Participants n=36 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	102 Participants n=93 Participants	107 Participants n=4 Participants	94 Participants n=27 Participants	94 Participants n=483 Participants	397 Participants n=36 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants	1 Participants n=36 Participants
Race/Ethnicity, Customized White	111 Participants n=93 Participants	102 Participants n=4 Participants	104 Participants n=27 Participants	107 Participants n=483 Participants	424 Participants n=36 Participants
Race/Ethnicity, Customized Black	24 Participants n=93 Participants	30 Participants n=4 Participants	29 Participants n=27 Participants	26 Participants n=483 Participants	109 Participants n=36 Participants
Race/Ethnicity, Customized Asian	4 Participants n=93 Participants	8 Participants n=4 Participants	7 Participants n=27 Participants	5 Participants n=483 Participants	24 Participants n=36 Participants
Race/Ethnicity, Customized American Indian or Alaskan Native	1 Participants n=93 Participants	1 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants	3 Participants n=36 Participants
Race/Ethnicity, Customized Native Hawaiian or Pacific Islander	0 Participants n=93 Participants	1 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants	2 Participants n=36 Participants
Race/Ethnicity, Customized Other	2 Participants n=93 Participants	0 Participants n=4 Participants	3 Participants n=27 Participants	2 Participants n=483 Participants	7 Participants n=36 Participants

PRIMARY outcome

Timeframe: 48 hours

Population: The full analysis set (FAS) included all randomized participants who received at least 1 dose of study drug.

The SPID48 was calculated as the time-weighted sum of pain intensity difference (PID) at each time point over 48 hours. The SPID48 was based on the NPRS-11, which is an 11-point Likert-type scale in which 0 means no pain and 10 means the most intense pain imaginable. Least square (LS) mean was calculated using an analysis of covariance (ANCOVA) with treatment and center as factors and the baseline pain intensity score as a covariate. Multiple imputation method was used to handle missing data.

Outcome measures

Measure	Placebo n=142 Participants Participants received placebo matched to TV46763 (hydrocodone bitartrate/acetaminophen) IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 5.0 mg/325 mg n=142 Participants Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 5.0 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 7.5 mg/325 mg n=141 Participants Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 7.5 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 10.0 mg/325 mg n=142 Participants Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 10.0 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.
Summed Pain Intensity Difference (SPID) Score Calculated Over the First 48 Hours (SPID48) After the First Dose of Study Drug on an 11-Point Numerical Pain Rating Scale (NPRS-11)	76.5 units on a scale Standard Error 6.92	115.4 units on a scale Standard Error 6.92	120.5 units on a scale Standard Error 6.91	129.9 units on a scale Standard Error 6.88

SECONDARY outcome

Timeframe: 0 to 6, 0 to 12, 0 to 24, and 0 to 36 hours

Population: The FAS included all randomized participants who received at least 1 dose of study drug.

The SPID was calculated as the time-weighted sum of PID at each time point over the intervals during the first 36 hours. The SPID was based on the NPRS-11, which is an 11-point Likert-type scale in which 0 means no pain and 10 means the most intense pain imaginable. LS mean was calculated using ANCOVA with treatment and center as factors and the baseline pain intensity score as a covariate. Multiple imputation method was used to handle missing data.

Outcome measures

Measure	Placebo n=142 Participants Participants received placebo matched to TV46763 (hydrocodone bitartrate/acetaminophen) IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 5.0 mg/325 mg n=142 Participants Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 5.0 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 7.5 mg/325 mg n=141 Participants Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 7.5 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 10.0 mg/325 mg n=142 Participants Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 10.0 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.
SPID Scores Over the Intervals During the First 36 Hours Following the First Dose of Study Drug SPID 0-6	3.7 units on a scale Standard Error 0.87	8.3 units on a scale Standard Error 0.87	8.3 units on a scale Standard Error 0.87	9.1 units on a scale Standard Error 0.88
SPID Scores Over the Intervals During the First 36 Hours Following the First Dose of Study Drug SPID 0-12	6.4 units on a scale Standard Error 1.78	15.8 units on a scale Standard Error 1.77	16.5 units on a scale Standard Error 1.76	19.1 units on a scale Standard Error 1.78
SPID Scores Over the Intervals During the First 36 Hours Following the First Dose of Study Drug SPID 0-24	21.1 units on a scale Standard Error 3.55	43.9 units on a scale Standard Error 3.53	44.5 units on a scale Standard Error 3.53	50.9 units on a scale Standard Error 3.53
SPID Scores Over the Intervals During the First 36 Hours Following the First Dose of Study Drug SPID 0-36	44.2 units on a scale Standard Error 5.26	78.2 units on a scale Standard Error 5.26	81.1 units on a scale Standard Error 5.22	88.2 units on a scale Standard Error 5.22

SECONDARY outcome

Timeframe: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, and 6 hours

Population: The FAS included all randomized participants who received at least 1 dose of study drug.

The PID was based on the NPRS-11, which is an 11-point Likert-type scale in which 0 means no pain and 10 means the most intense pain imaginable. PID was calculated at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, and 6 hours after the first dose of study drug. LS mean was calculated using ANCOVA with treatment and center as factors and the baseline pain intensity score as a covariate. Multiple imputation method was used to handle missing data.

Outcome measures

Measure	Placebo n=142 Participants Participants received placebo matched to TV46763 (hydrocodone bitartrate/acetaminophen) IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 5.0 mg/325 mg n=142 Participants Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 5.0 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 7.5 mg/325 mg n=141 Participants Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 7.5 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 10.0 mg/325 mg n=142 Participants Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 10.0 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.
Pain Intensity Difference (PID) Scores 0.25 hour	0.1 units on a scale Standard Error 0.11	0.2 units on a scale Standard Error 0.11	0.1 units on a scale Standard Error 0.11	0.0 units on a scale Standard Error 0.11
Pain Intensity Difference (PID) Scores 0.5 hour	0.5 units on a scale Standard Error 0.15	0.5 units on a scale Standard Error 0.15	0.8 units on a scale Standard Error 0.15	0.5 units on a scale Standard Error 0.15
Pain Intensity Difference (PID) Scores 0.75 hour	0.6 units on a scale Standard Error 0.17	0.9 units on a scale Standard Error 0.17	1.4 units on a scale Standard Error 0.17	1.1 units on a scale Standard Error 0.17
Pain Intensity Difference (PID) Scores 1 hour	0.7 units on a scale Standard Error 0.19	1.4 units on a scale Standard Error 0.19	1.8 units on a scale Standard Error 0.19	1.5 units on a scale Standard Error 0.19
Pain Intensity Difference (PID) Scores 1.5 hours	0.8 units on a scale Standard Error 0.21	1.6 units on a scale Standard Error 0.21	2.2 units on a scale Standard Error 0.21	2.0 units on a scale Standard Error 0.21
Pain Intensity Difference (PID) Scores 2 hours	0.8 units on a scale Standard Error 0.20	1.9 units on a scale Standard Error 0.20	2.2 units on a scale Standard Error 0.20	2.1 units on a scale Standard Error 0.20
Pain Intensity Difference (PID) Scores 3 hours	1.0 units on a scale Standard Error 0.20	1.8 units on a scale Standard Error 0.20	1.7 units on a scale Standard Error 0.20	1.7 units on a scale Standard Error 0.20
Pain Intensity Difference (PID) Scores 4 hours	0.7 units on a scale Standard Error 0.19	1.3 units on a scale Standard Error 0.19	1.0 units on a scale Standard Error 0.19	1.3 units on a scale Standard Error 0.19
Pain Intensity Difference (PID) Scores 5 hours	0.6 units on a scale Standard Error 0.19	1.4 units on a scale Standard Error 0.19	1.2 units on a scale Standard Error 0.19	1.6 units on a scale Standard Error 0.19
Pain Intensity Difference (PID) Scores 6 hours	0.4 units on a scale Standard Error 0.19	1.3 units on a scale Standard Error 0.19	1.3 units on a scale Standard Error 0.19	1.7 units on a scale Standard Error 0.19

SECONDARY outcome

Timeframe: Within 6 hours

Population: The FAS included all randomized participants who received at least 1 dose of study drug.

Time to peak PID after the first dose of study drug but before the second dose of study drug was calculated. Kaplan-Meier method was used to calculate the data. Multiple imputation method was used to handle missing pain intensity scores at scheduled time points.

Outcome measures

Measure	Placebo n=142 Participants Participants received placebo matched to TV46763 (hydrocodone bitartrate/acetaminophen) IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 5.0 mg/325 mg n=142 Participants Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 5.0 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 7.5 mg/325 mg n=141 Participants Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 7.5 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 10.0 mg/325 mg n=142 Participants Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 10.0 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.
Time to Peak PID	3.0 hours Interval 2.02 to 3.03	2.0 hours Interval 1.53 to 2.02	1.53 hours Interval 1.52 to 2.01	2.0 hours Interval 1.53 to 2.02

SECONDARY outcome

Timeframe: 2, 4, 6, 12, 24, and 48 hours

Population: The FAS included all randomized participants who received at least 1 dose of study drug.

Number of participants with a 30% reduction in NPRS-11 scores was reported at 6, 12, 24, and 48 hours after the first dose of study drug.

Outcome measures

Measure	Placebo n=142 Participants Participants received placebo matched to TV46763 (hydrocodone bitartrate/acetaminophen) IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 5.0 mg/325 mg n=142 Participants Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 5.0 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 7.5 mg/325 mg n=141 Participants Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 7.5 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 10.0 mg/325 mg n=142 Participants Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 10.0 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.
Number of Participants With a 30% Reduction in Pain Intensity Measured Using NPRS-11 Scores 2 hours	41 Participants	71 Participants	76 Participants	83 Participants
Number of Participants With a 30% Reduction in Pain Intensity Measured Using NPRS-11 Scores 4 hours	39 Participants	44 Participants	41 Participants	60 Participants
Number of Participants With a 30% Reduction in Pain Intensity Measured Using NPRS-11 Scores 6 hours	32 Participants	56 Participants	51 Participants	66 Participants
Number of Participants With a 30% Reduction in Pain Intensity Measured Using NPRS-11 Scores 12 hours	38 Participants	55 Participants	54 Participants	76 Participants
Number of Participants With a 30% Reduction in Pain Intensity Measured Using NPRS-11 Scores 24 hours	67 Participants	83 Participants	80 Participants	91 Participants
Number of Participants With a 30% Reduction in Pain Intensity Measured Using NPRS-11 Scores 48 hours	86 Participants	96 Participants	92 Participants	100 Participants

SECONDARY outcome

Timeframe: 2, 4, 6, 12, 24, and 48 hours

Population: The FAS included all randomized participants who received at least 1 dose of study drug.

Number of participants with a 50% reduction in NPRS-11 scores was reported at 6, 12, 24, and 48 hours after the first dose of study drug.

Outcome measures

Measure	Placebo n=142 Participants Participants received placebo matched to TV46763 (hydrocodone bitartrate/acetaminophen) IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 5.0 mg/325 mg n=142 Participants Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 5.0 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 7.5 mg/325 mg n=141 Participants Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 7.5 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 10.0 mg/325 mg n=142 Participants Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 10.0 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.
Number of Participants With a 50% Reduction in Pain Intensity Measured Using NPRS-11 Scores 2 hours	27 Participants	52 Participants	63 Participants	63 Participants
Number of Participants With a 50% Reduction in Pain Intensity Measured Using NPRS-11 Scores 4 hours	20 Participants	29 Participants	28 Participants	40 Participants
Number of Participants With a 50% Reduction in Pain Intensity Measured Using NPRS-11 Scores 6 hours	18 Participants	40 Participants	39 Participants	45 Participants
Number of Participants With a 50% Reduction in Pain Intensity Measured Using NPRS-11 Scores 12 hours	22 Participants	33 Participants	31 Participants	52 Participants
Number of Participants With a 50% Reduction in Pain Intensity Measured Using NPRS-11 Scores 24 hours	46 Participants	66 Participants	63 Participants	75 Participants
Number of Participants With a 50% Reduction in Pain Intensity Measured Using NPRS-11 Scores 48 hours	73 Participants	75 Participants	79 Participants	90 Participants

SECONDARY outcome

Timeframe: Day 1

Population: The FAS included all randomized participants who received at least 1 dose of study drug.

Time to perceptible pain relief (PPR) (i.e., onset of pain relief) after the first dose of study drug was calculated using the stopwatch technique. The PPR stopwatch was started immediately after administration of the first dose of study drug (time zero [T0]) and it was given to the participant with the instructions to stop the stopwatch when he or she first perceived pain relief (time to perceptible relief). Kaplan-Meier method was used to calculate the data.

Outcome measures

Measure	Placebo n=142 Participants Participants received placebo matched to TV46763 (hydrocodone bitartrate/acetaminophen) IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 5.0 mg/325 mg n=142 Participants Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 5.0 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 7.5 mg/325 mg n=141 Participants Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 7.5 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 10.0 mg/325 mg n=142 Participants Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 10.0 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.
Time to Onset of Perceptible Pain Relief (PPR)	0.8 hour Interval 0.5 to 1.23	0.5 hour Interval 0.38 to 0.75	0.5 hour Interval 0.47 to 0.68	0.6 hour Interval 0.48 to 0.77

SECONDARY outcome

Timeframe: Day 1

Population: The FAS included all randomized participants who received at least 1 dose of study drug.

Time to meaningful pain relief (MPR) after the first dose of study drug was calculated using the stopwatch technique. The MPR stopwatch was started immediately after administration of the first dose of study drug (time zero [T0]). The stopwatch was given to the participant with the instructions to stop the stopwatch when he or she first experienced meaningful pain relief (time to meaningful relief). Kaplan-Meier method was used to calculate the data.

Outcome measures

Measure	Placebo n=142 Participants Participants received placebo matched to TV46763 (hydrocodone bitartrate/acetaminophen) IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 5.0 mg/325 mg n=142 Participants Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 5.0 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 7.5 mg/325 mg n=141 Participants Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 7.5 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 10.0 mg/325 mg n=142 Participants Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 10.0 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.
Time to Onset of Meaningful Pain Relief (MPR)	NA hour Due to smaller number of participants with an event, median and upper and lower limit of 95% confidence interval (CI) could not be calculated.	1.9 hour Interval 1.43 to 3.02	1.3 hour Interval 1.0 to 2.22	1.8 hour Interval 1.25 to Due to smaller number of participants with an event, upper limit of 95% CI could not be calculated.

SECONDARY outcome

Timeframe: 6, 12, 24, and 48 hours

Population: The FAS included all randomized participants who received at least 1 dose of study drug.

Total rescue medication (oral nonprescription ibuprofen) use (number of tablets used) over 6, 12, 24, and 48 hours after the first dose of study drug was calculated.

Outcome measures

Measure	Placebo n=142 Participants Participants received placebo matched to TV46763 (hydrocodone bitartrate/acetaminophen) IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 5.0 mg/325 mg n=142 Participants Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 5.0 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 7.5 mg/325 mg n=141 Participants Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 7.5 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 10.0 mg/325 mg n=142 Participants Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 10.0 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.
Total Rescue Medication Use (Number of Tablets Used) Total rescue medication use over 6 hours	1.2 tablets Standard Error 0.07	0.8 tablets Standard Error 0.07	0.7 tablets Standard Error 0.07	0.6 tablets Standard Error 0.07
Total Rescue Medication Use (Number of Tablets Used) Total rescue medication use over 12 hours	2.0 tablets Standard Error 0.10	1.4 tablets Standard Error 0.10	1.4 tablets Standard Error 0.10	1.1 tablets Standard Error 0.10
Total Rescue Medication Use (Number of Tablets Used) Total rescue medication use over 24 hours	3.0 tablets Standard Error 0.13	2.1 tablets Standard Error 0.13	1.9 tablets Standard Error 0.13	1.6 tablets Standard Error 0.13
Total Rescue Medication Use (Number of Tablets Used) Total rescue medication use over 48 hours	4.4 tablets Standard Error 0.22	2.9 tablets Standard Error 0.21	2.6 tablets Standard Error 0.21	2.1 tablets Standard Error 0.22

SECONDARY outcome

Timeframe: 6, 12, 24, and 48 hours

Population: The FAS included all randomized participants who received at least 1 dose of study drug.

Number of participants taking rescue medication (oral nonprescription ibuprofen) over 6, 12, 24, and 48 hours after the first dose of study drug were calculated.

Outcome measures

Measure	Placebo n=142 Participants Participants received placebo matched to TV46763 (hydrocodone bitartrate/acetaminophen) IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 5.0 mg/325 mg n=142 Participants Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 5.0 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 7.5 mg/325 mg n=141 Participants Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 7.5 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 10.0 mg/325 mg n=142 Participants Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 10.0 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.
Number of Participants Taking Rescue Medication Rescue medication use over 6 hours	101 Participants	76 Participants	74 Participants	62 Participants
Number of Participants Taking Rescue Medication Rescue medication use over 12 hours	124 Participants	96 Participants	98 Participants	84 Participants
Number of Participants Taking Rescue Medication Rescue medication use over 24 hours	132 Participants	101 Participants	107 Participants	93 Participants
Number of Participants Taking Rescue Medication Rescue medication use over 48 hours	132 Participants	106 Participants	110 Participants	99 Participants

SECONDARY outcome

Timeframe: Day 1 up to Day 13

Population: The safety analysis set included all randomized participants who received at least 1 dose of study drug.

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'.

Outcome measures

Measure	Placebo n=142 Participants Participants received placebo matched to TV46763 (hydrocodone bitartrate/acetaminophen) IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 5.0 mg/325 mg n=142 Participants Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 5.0 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 7.5 mg/325 mg n=141 Participants Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 7.5 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 10.0 mg/325 mg n=142 Participants Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 10.0 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.
Number of Participants With Adverse Events (AEs)	56 Participants	79 Participants	87 Participants	106 Participants

Adverse Events

Placebo

Serious events: 2 serious events

Other events: 33 other events

Deaths: 0 deaths

TV-46763 5.0 mg/325 mg

Serious events: 1 serious events

Other events: 66 other events

Deaths: 0 deaths

TV-46763 7.5 mg/325 mg

Serious events: 0 serious events

Other events: 80 other events

Deaths: 0 deaths

TV-46763 10.0 mg/325 mg

Serious events: 0 serious events

Other events: 98 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=142 participants at risk Participants received placebo matched to TV46763 (hydrocodone bitartrate/acetaminophen) IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 5.0 mg/325 mg n=142 participants at risk Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 5.0 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 7.5 mg/325 mg n=141 participants at risk Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 7.5 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 10.0 mg/325 mg n=142 participants at risk Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 10.0 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.
Immune system disorders Drug hypersensitivity	0.00% 0/142 • Day 1 up to Day 13 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	0.70% 1/142 • Number of events 1 • Day 1 up to Day 13 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	0.00% 0/141 • Day 1 up to Day 13 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	0.00% 0/142 • Day 1 up to Day 13 The safety analysis set included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Cellulitis	0.70% 1/142 • Number of events 1 • Day 1 up to Day 13 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	0.00% 0/142 • Day 1 up to Day 13 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	0.00% 0/141 • Day 1 up to Day 13 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	0.00% 0/142 • Day 1 up to Day 13 The safety analysis set included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Deep vein thrombosis	0.70% 1/142 • Number of events 1 • Day 1 up to Day 13 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	0.00% 0/142 • Day 1 up to Day 13 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	0.00% 0/141 • Day 1 up to Day 13 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	0.00% 0/142 • Day 1 up to Day 13 The safety analysis set included all randomized participants who received at least 1 dose of study drug.

Other adverse events

Measure	Placebo n=142 participants at risk Participants received placebo matched to TV46763 (hydrocodone bitartrate/acetaminophen) IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 5.0 mg/325 mg n=142 participants at risk Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 5.0 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 7.5 mg/325 mg n=141 participants at risk Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 7.5 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.	TV-46763 10.0 mg/325 mg n=142 participants at risk Participants received TV46763 (hydrocodone bitartrate/acetaminophen) 10.0 mg/325 mg IR tablets for 48 hours (every 4 to 6 hours) on Days 1, 2, and 3 during the inpatient treatment period. Participants continued to take the same treatment daily, every 4 to 6 hours after discharge on Day 3, over a 10-day (±1 day) outpatient treatment period.
Gastrointestinal disorders Constipation	1.4% 2/142 • Number of events 2 • Day 1 up to Day 13 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	18.3% 26/142 • Number of events 26 • Day 1 up to Day 13 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	16.3% 23/141 • Number of events 23 • Day 1 up to Day 13 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	21.1% 30/142 • Number of events 30 • Day 1 up to Day 13 The safety analysis set included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Nausea	7.7% 11/142 • Number of events 12 • Day 1 up to Day 13 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	26.1% 37/142 • Number of events 52 • Day 1 up to Day 13 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	38.3% 54/141 • Number of events 63 • Day 1 up to Day 13 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	47.9% 68/142 • Number of events 96 • Day 1 up to Day 13 The safety analysis set included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Vomiting	2.8% 4/142 • Number of events 4 • Day 1 up to Day 13 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	12.7% 18/142 • Number of events 24 • Day 1 up to Day 13 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	19.1% 27/141 • Number of events 37 • Day 1 up to Day 13 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	25.4% 36/142 • Number of events 67 • Day 1 up to Day 13 The safety analysis set included all randomized participants who received at least 1 dose of study drug.
Investigations Alanine aminotransferase increased	0.70% 1/142 • Number of events 1 • Day 1 up to Day 13 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	6.3% 9/142 • Number of events 9 • Day 1 up to Day 13 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	3.5% 5/141 • Number of events 5 • Day 1 up to Day 13 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	3.5% 5/142 • Number of events 5 • Day 1 up to Day 13 The safety analysis set included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Dizziness	2.1% 3/142 • Number of events 4 • Day 1 up to Day 13 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	7.0% 10/142 • Number of events 13 • Day 1 up to Day 13 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	17.0% 24/141 • Number of events 26 • Day 1 up to Day 13 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	16.2% 23/142 • Number of events 26 • Day 1 up to Day 13 The safety analysis set included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Headache	12.0% 17/142 • Number of events 22 • Day 1 up to Day 13 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	9.2% 13/142 • Number of events 18 • Day 1 up to Day 13 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	9.9% 14/141 • Number of events 16 • Day 1 up to Day 13 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	16.9% 24/142 • Number of events 28 • Day 1 up to Day 13 The safety analysis set included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Somnolence	0.70% 1/142 • Number of events 1 • Day 1 up to Day 13 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	5.6% 8/142 • Number of events 8 • Day 1 up to Day 13 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	5.0% 7/141 • Number of events 7 • Day 1 up to Day 13 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	2.8% 4/142 • Number of events 4 • Day 1 up to Day 13 The safety analysis set included all randomized participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Pruritus	1.4% 2/142 • Number of events 2 • Day 1 up to Day 13 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	1.4% 2/142 • Number of events 3 • Day 1 up to Day 13 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	3.5% 5/141 • Number of events 5 • Day 1 up to Day 13 The safety analysis set included all randomized participants who received at least 1 dose of study drug.	7.0% 10/142 • Number of events 10 • Day 1 up to Day 13 The safety analysis set included all randomized participants who received at least 1 dose of study drug.

Additional Information

Director, Clinical Research

Teva Branded Pharmaceutical Products R&D, Inc.

Phone: 1-888-483-8279

Email: USMedInfo@tevapharm.com

Results disclosure agreements

• Principal investigator is a sponsor employee Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
• Publication restrictions are in place

Restriction type: OTHER