Trial Outcomes & Findings for Study of BEMA™ Fentanyl in the Treatment of Breakthrough Pain in Cancer Subjects (NCT NCT00293033)

NCT ID: NCT00293033

Last Updated: 2019-11-18

Results Overview

Pain intensity (using an 11-point \[0 = no pain to 10 = worst pain\] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point. The primary endpoint was the Summary of Pain Intensity Differences at 30 minutes after dosing (SPID 30) in ITT population for Onsolis versus placebo during double-blind period of study. SPID was calculated as a weighted sum of the PID of all time points at or before time point of interest.Range of possible SPID values is -10X time point (minutes) to 10X time point (minutes). Higher value indicates a better outcome.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 152 participants
• Primary outcome timeframe: 0-30 minutes
• Results posted on: 2019-11-18

Participant Flow

24FEB2006 to 14MAR2007

During the open-label titration period, subjects were treated with Onsolis at escalating doses (200, 400, 600, 800, and 1200 μg) over a period of up to two weeks until subjects identified a dose that produced satisfactory pain relief for at least two episodes.

Participant milestones

Measure	Onsolis Subjects were administered BEMA™ Fentanyl at escalating doses (200, 400, 600, 800, and 1200 μg) in Titration period. During the double-blind period, subjects were randomly assigned to a sequence of active and placebo discs. Each subject acted as his or her own control. For each subject, the sequencing of the placebo and BEMA™ Fentanyl discs was random.
Open-label Titration Period STARTED	151
Open-label Titration Period COMPLETED	82
Open-label Titration Period NOT COMPLETED	69
Double-blind Treatment Period STARTED	82
Double-blind Treatment Period COMPLETED	70
Double-blind Treatment Period NOT COMPLETED	12

Reasons for withdrawal

Measure	Onsolis Subjects were administered BEMA™ Fentanyl at escalating doses (200, 400, 600, 800, and 1200 μg) in Titration period. During the double-blind period, subjects were randomly assigned to a sequence of active and placebo discs. Each subject acted as his or her own control. For each subject, the sequencing of the placebo and BEMA™ Fentanyl discs was random.
Open-label Titration Period Adverse Event	10
Open-label Titration Period Death	3
Open-label Titration Period Lack of Efficacy	5
Open-label Titration Period Protocol Violation	2
Open-label Titration Period Withdrawal by Subject	22
Open-label Titration Period Noncompliance and other	27
Double-blind Treatment Period Adverse Event	3
Double-blind Treatment Period Lack of Efficacy	1
Double-blind Treatment Period Withdrawal by Subject	4
Double-blind Treatment Period Noncompliance	4

Baseline Characteristics

Study of BEMA™ Fentanyl in the Treatment of Breakthrough Pain in Cancer Subjects

Baseline characteristics by cohort

Measure	Onsolis n=151 Participants Includes all subjects and all dose levels
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	104 Participants n=5 Participants
Age, Categorical >=65 years	47 Participants n=5 Participants
Age, Continuous	57.1 years STANDARD_DEVIATION 12.2 • n=5 Participants
Sex: Female, Male Female	85 Participants n=5 Participants
Sex: Female, Male Male	66 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	12 Participants n=5 Participants
Race (NIH/OMB) White	131 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	7 Participants n=5 Participants
Region of Enrollment United States	151 participants n=5 Participants
Female reproductive status Post-menopausal	43 Participants n=5 Participants
Female reproductive status Sterile	38 Participants n=5 Participants
Female reproductive status Potentially able to bear children	3 Participants n=5 Participants
Female reproductive status Male	67 Participants n=5 Participants
Height (inches)	66.4 Inches STANDARD_DEVIATION 3.86 • n=5 Participants
Weight (pounds)	160.89 pounds STANDARD_DEVIATION 42.011 • n=5 Participants

PRIMARY outcome

Timeframe: 0-30 minutes

Population: In double-blind period, subjects received 3 doses placebo and 6 doses Onsolis. Mean SPID of Onsolis episodes and mean SPID of placebo episodes are calculated per subject and are used in analysis.Missing data were imputed on an episode-by-episode basis by carrying forward last observed data value (last observation carried forward \[LOCF\]).

Pain intensity (using an 11-point [0 = no pain to 10 = worst pain] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point. The primary endpoint was the Summary of Pain Intensity Differences at 30 minutes after dosing (SPID 30) in ITT population for Onsolis versus placebo during double-blind period of study. SPID was calculated as a weighted sum of the PID of all time points at or before time point of interest.Range of possible SPID values is

-10X time point (minutes) to 10X time point (minutes). Higher value indicates a better outcome.

Outcome measures

Measure	Onsolis n=394 Breakthrough Pain (BTP) Episodes BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=197 Breakthrough Pain (BTP) Episodes Placebo Disc
Summary of Pain Intensity Differences (SPID)	47.9 Score on a scale Standard Error 3.87	38.1 Score on a scale Standard Error 4.3

SECONDARY outcome

Timeframe: 0-5 minutes

Pain intensity (using an 11-point [0 = no pain to 10 = worst pain] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point. The primary endpoint was the Summary of Pain Intensity Differences at 30 minutes after dosing (SPID 30) in ITT population for Onsolis versus placebo during double-blind period of study. SPID was calculated as a weighted sum of the PID of all time points at or before time point of interest.Range of possible SPID values is -10X time point (minutes) to 10X time point (minutes). Higher value indicates a better outcome.SPID was calculated as a weighted sum of the pain intensity difference of all time points at or before the time point of interest.

Outcome measures

Measure	Onsolis n=361 BTP Episodes BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=176 BTP Episodes Placebo Disc
SPID	1.8 Scores on a scale Standard Error 0.30	1.5 Scores on a scale Standard Error 0.36

SECONDARY outcome

Timeframe: 0-10 minutes

Pain intensity (using an 11-point [0 = no pain to 10 = worst pain] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point. The primary endpoint was the Summary of Pain Intensity Differences at 30 minutes after dosing (SPID 30) in ITT population for Onsolis versus placebo during double-blind period of study. SPID was calculated as a weighted sum of the PID of all time points at or before time point of interest.Range of possible SPID values is -10X time point (minutes) to 10X time point (minutes). Higher value indicates a better outcome.SPID was calculated as a weighted sum of the pain intensity difference of all time points at or before the time point of interest.

Outcome measures

Measure	Onsolis n=379 BTP Episodes BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=184 BTP Episodes Placebo Disc
SPID	5.9 Scores on a scale Standard Error 0.80	4.9 Scores on a scale Standard Error 0.90

SECONDARY outcome

Timeframe: 0-15 minutes

Pain intensity (using an 11-point [0 = no pain to 10 = worst pain] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point. The primary endpoint was the Summary of Pain Intensity Differences at 30 minutes after dosing (SPID 30) in ITT population for Onsolis versus placebo during double-blind period of study. SPID was calculated as a weighted sum of the PID of all time points at or before time point of interest.Range of possible SPID values is -10X time point (minutes) to 10X time point (minutes). Higher value indicates a better outcome.SPID was calculated as a weighted sum of the pain intensity difference of all time points at or before the time point of interest.

Outcome measures

Measure	Onsolis n=382 BTP Episodes BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=194 BTP Episodes Placebo Disc
SPID	12.8 Scores on a scale Standard Error 1.47	10.4 Scores on a scale Standard Error 1.61

SECONDARY outcome

Timeframe: 0-45 minutes

Pain intensity (using an 11-point [0 = no pain to 10 = worst pain] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point. The primary endpoint was the Summary of Pain Intensity Differences at 30 minutes after dosing (SPID 30) in ITT population for Onsolis versus placebo during double-blind period of study. SPID was calculated as a weighted sum of the PID of all time points at or before time point of interest.Range of possible SPID values is -10X time point (minutes) to 10X time point (minutes). Higher value indicates a better outcome.SPID was calculated as a weighted sum of the pain intensity difference of all time points at or before the time point of interest.

Outcome measures

Measure	Onsolis n=382 BTP Episodes BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=194 BTP Episodes Placebo Disc
SPID	90.5 Scores on a scale Standard Error 6.63	70.8 Scores on a scale Standard Error 7.41

SECONDARY outcome

Timeframe: 0-60 minutes

Pain intensity (using an 11-point [0 = no pain to 10 = worst pain] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point. The primary endpoint was the Summary of Pain Intensity Differences at 30 minutes after dosing (SPID 30) in ITT population for Onsolis versus placebo during double-blind period of study. SPID was calculated as a weighted sum of the PID of all time points at or before time point of interest.Range of possible SPID values is -10X time point (minutes) to 10X time point (minutes). Higher value indicates a better outcome.SPID was calculated as a weighted sum of the pain intensity difference of all time points at or before the time point of interest.

Outcome measures

Measure	Onsolis n=382 BTP Episodes BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=194 BTP Episodes Placebo Disc
SPID	138.0 Scores on a scale Standard Error 9.41	106.0 Scores on a scale Standard Error 10.58

SECONDARY outcome

Timeframe: 5 minutes after dosing

Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis. All efficacy analyses were conducted using the intent-to-treat (ITT) population. Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.

Pain intensity (using an 11-point [0 = no pain to 10 = worst pain] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point.

Outcome measures

Measure	Onsolis n=361 BTP Episodes BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=176 BTP Episodes Placebo Disc
PID	0.3 Scores on a scale Standard Error 0.04	0.3 Scores on a scale Standard Error 0.06

SECONDARY outcome

Timeframe: 10 minutes after dosing

Pain intensity (using an 11-point [0 = no pain to 10 = worst pain] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point.

Outcome measures

Measure	Onsolis n=379 BTP Episodes BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=184 BTP Episodes Placebo Disc
PID	0.8 Scores on a scale Standard Error 0.07	0.7 Scores on a scale Standard Error 0.08

SECONDARY outcome

Timeframe: 15 minutes after dosing

Pain intensity (using an 11-point [0 = no pain to 10 = worst pain] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point.

Outcome measures

Measure	Onsolis n=382 BTP Episodes BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=194 BTP Episodes Placebo Disc
PID	1.4 Scores on a scale Standard Error 0.09	1.2 Scores on a scale Standard Error 0.10

SECONDARY outcome

Timeframe: 30 minutes after dosing

Pain intensity (using an 11-point [0 = no pain to 10 = worst pain] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point.

Outcome measures

Measure	Onsolis n=394 BTP Episodes BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=197 BTP Episodes Placebo Disc
PID	2.5 Scores on a scale Standard Error 0.11	1.9 Scores on a scale Standard Error 0.14

SECONDARY outcome

Timeframe: 45 minutes after dosing

Pain intensity (using an 11-point [0 = no pain to 10 = worst pain] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point.

Outcome measures

Measure	Onsolis n=404 BTP Episodes BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=198 BTP Episodes Placebo Disc
PID	3.0 Scores on a scale Standard Error 0.13	2.3 Scores on a scale Standard Error 0.17

SECONDARY outcome

Timeframe: 60 minutes after dosing

Pain intensity (using an 11-point [0 = no pain to 10 = worst pain] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point.

Outcome measures

Measure	Onsolis n=408 BTP Episodes BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=198 BTP Episodes Placebo Disc
PID	3.3 Scores on a scale Standard Error 0.13	2.4 Scores on a scale Standard Error 0.18

SECONDARY outcome

Timeframe: 5 minutes after dosing

Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis. All efficacy analyses were conducted using the intent-to-treat (ITT) population. Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.

Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief) at 5, 10, 15, 30, 45, and 60 minutes after taking the study medication or until rescue.

Outcome measures

Measure	Onsolis n=361 BTP Episodes BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=176 BTP Episodes Placebo Disc
Pain Relief	0.4 Scores on a scale Standard Error 0.04	0.4 Scores on a scale Standard Error 0.06

SECONDARY outcome

Timeframe: 10 minutes after dosing

Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis. All efficacy analyses were conducted using the intent-to-treat (ITT) population. Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.

Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief) at 5, 10, 15, 30, 45, and 60 minutes after taking the study medication or until rescue.

Outcome measures

Measure	Onsolis n=379 BTP Episodes BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=184 BTP Episodes Placebo Disc
Pain Relief	0.8 Scores on a scale Standard Error 0.05	0.7 Scores on a scale Standard Error 0.06

SECONDARY outcome

Timeframe: 15 minutes after dosing

Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis. All efficacy analyses were conducted using the intent-to-treat (ITT) population. Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.

Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief) at 5, 10, 15, 30, 45, and 60 minutes after taking the study medication or until rescue.

Outcome measures

Measure	Onsolis n=382 BTP Episodes BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=194 BTP Episodes Placebo Disc
Pain Relief	1.1 Scores on a scale Standard Error 0.05	1.0 Scores on a scale Standard Error 0.07

SECONDARY outcome

Timeframe: 30 minutes after dosing

Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis. All efficacy analyses were conducted using the intent-to-treat (ITT) population. Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.

Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief) at 5, 10, 15, 30, 45, and 60 minutes after taking the study medication or until rescue.

Outcome measures

Measure	Onsolis n=394 BTP Episodes BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=197 BTP Episodes Placebo Disc
Pain Relief	1.7 Scores on a scale Standard Error 0.05	1.3 Scores on a scale Standard Error 0.08

SECONDARY outcome

Timeframe: 45 minutes after dosing

Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis. All efficacy analyses were conducted using the intent-to-treat (ITT) population. Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.

Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief) at 5, 10, 15, 30, 45, and 60 minutes after taking the study medication or until rescue.

Outcome measures

Measure	Onsolis n=404 BTP Episodes BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=198 BTP Episodes Placebo Disc
Pain Relief	1.9 Scores on a scale Standard Error 0.06	1.5 Scores on a scale Standard Error 0.09

SECONDARY outcome

Timeframe: 60 minutes after dosing

Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis. All efficacy analyses were conducted using the intent-to-treat (ITT) population. Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.

Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief) at 5, 10, 15, 30, 45, and 60 minutes after taking the study medication or until rescue.

Outcome measures

Measure	Onsolis n=409 BTP Episodes BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=198 BTP Episodes Placebo Disc
Pain Relief	2.1 Scores on a scale Standard Error 0.06	1.6 Scores on a scale Standard Error 0.09

SECONDARY outcome

Timeframe: 5 minutes

Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis. All efficacy analyses were conducted using the intent-to-treat (ITT) population. Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.

Total Pain Relief (TOTPAR) is calculated as the weighted sum of the pain relief (PR) of all time points at or prior to the time point of interest.Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief)compared to baseline (pre-dose)

Outcome measures

Measure	Onsolis n=361 BTP Episodes BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=176 BTP Episodes Placebo Disc
Total Pain Relief	2.2 Scores on a scale Standard Error 0.21	1.8 Scores on a scale Standard Error 0.28

SECONDARY outcome

Timeframe: 10 minutes

Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis. All efficacy analyses were conducted using the intent-to-treat (ITT) population. Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.

Total Pain Relief (TOTPAR) is calculated as the weighted sum of the pain relief (PR) of all time points at or prior to the time point of interest. Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief)compared to baseline (pre-dose)

Outcome measures

Measure	Onsolis n=379 BTP Episodes BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=184 BTP Episodes Placebo Disc
Total Pain Relief	6.1 Scores on a scale Standard Error 0.40	5.2 Scores on a scale Standard Error 0.54

SECONDARY outcome

Timeframe: 15 minutes

Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis. All efficacy analyses were conducted using the intent-to-treat (ITT) population. Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.

Total Pain Relief (TOTPAR) is calculated as the weighted sum of the pain relief (PR) of all time points at or prior to the time point of interest. Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief)compared to baseline (pre-dose)

Outcome measures

Measure	Onsolis n=382 BTP Episodes BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=194 BTP Episodes Placebo Disc
Total Pain Relief	11.6 Scores on a scale Standard Error 0.62	9.8 Scores on a scale Standard Error 0.82

SECONDARY outcome

Timeframe: 30 minutes

Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis. All efficacy analyses were conducted using the intent-to-treat (ITT) population. Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.

Total Pain Relief (TOTPAR) is calculated as the weighted sum of the pain relief (PR) of all time points at or prior to the time point of interest. Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief)compared to baseline (pre-dose)

Outcome measures

Measure	Onsolis n=394 BTP Episodes BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=197 BTP Episodes Placebo Disc
Total Pain Relief	36.1 Scores on a scale Standard Error 1.30	29.5 Scores on a scale Standard Error 1.79

SECONDARY outcome

Timeframe: 45 minutes

Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis. All efficacy analyses were conducted using the intent-to-treat (ITT) population. Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.

Total Pain Relief (TOTPAR) is calculated as the weighted sum of the pain relief (PR) of all time points at or prior to the time point of interest. Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief)compared to baseline (pre-dose)

Outcome measures

Measure	Onsolis n=404 BTP Episodes BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=198 BTP Episodes Placebo Disc
Total Pain Relief	64.2 Scores on a scale Standard Error 2.05	52.3 Scores on a scale Standard Error 2.93

SECONDARY outcome

Timeframe: 60 minutes

Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis. All efficacy analyses were conducted using the intent-to-treat (ITT) population. Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.

Total Pain Relief (TOTPAR) is calculated as the weighted sum of the pain relief (PR) of all time points at or prior to the time point of interest. Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief)compared to baseline (pre-dose)

Outcome measures

Measure	Onsolis n=409 BTP Episodes BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=198 BTP Episodes Placebo Disc
Total Pain Relief	94.8 Scores on a scale Standard Error 2.84	76.0 Scores on a scale Standard Error 4.16

SECONDARY outcome

Timeframe: 60 minutes or at time of rescue medication use

Population: All efficacy analyses were conducted using the intent-to-treat (ITT) population.

Subjects evaluated their overall satisfaction with study drug at the time rescue medication was consumed or at the 60-minute time point using a 5-point categorical scale (0 = poor, 1 = fair, 2 = good, 3 = very good, and 4 = excellent).

Outcome measures

Measure	Onsolis n=359 Subject Overall Satisfaction BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=174 Subject Overall Satisfaction Placebo Disc
Subject Overall Satisfaction With Study Drug	2.0 Scores on a scale Standard Error 0.06	1.5 Scores on a scale Standard Error 0.10

SECONDARY outcome

Timeframe: 5 minutes

Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis. All efficacy analyses were conducted using the intent-to-treat (ITT) population, however, only available data is summarized here.

A pain free episode is one with 0 pain intensity at the specified time point. Percentage of episodes that are pain-free per subject is analyzed.

Outcome measures

Measure	Onsolis n=77 Participants BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=74 Participants Placebo Disc
Percentage of Pain Free Episodes	1.0 percentage of episodes Standard Error 0.73	1.4 percentage of episodes Standard Error 1.37

SECONDARY outcome

Timeframe: 10 minutes

Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis. All efficacy analyses were conducted using the intent-to-treat (ITT) population. Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.

A pain free episode is one with 0 pain intensity at the specified time point. Percentage of episodes that are pain-free per subject is analyzed.

Outcome measures

Measure	Onsolis n=77 Participants BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=74 Participants Placebo Disc
Percentage of Pain Free Episodes	1.0 percentage of episodes Standard Error 0.72	1.4 percentage of episodes Standard Error 1.35

SECONDARY outcome

Timeframe: 15 minutes

Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis. All efficacy analyses were conducted using the intent-to-treat (ITT) population. Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.

A pain free episode is one with 0 pain intensity at the specified time point. Percentage of episodes that are pain-free per subject is analyzed.

Outcome measures

Measure	Onsolis n=77 Participants BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=74 Participants Placebo Disc
Percentage of Pain Free Episodes	2.3 percentage of episodes Standard Error 1.02	2.0 percentage of episodes Standard Error 1.48

SECONDARY outcome

Timeframe: 30 minutes

Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis. All efficacy analyses were conducted using the intent-to-treat (ITT) population. Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.

A pain free episode is one with 0 pain intensity at the specified time point. Percentage of episodes that are pain-free per subject is analyzed.

Outcome measures

Measure	Onsolis n=77 Participants BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=76 Participants Placebo Disc
Percentage of Pain Free Episodes	5.3 percentage of episodes Standard Error 1.57	4.4 percentage of episodes Standard Error 1.88

SECONDARY outcome

Timeframe: 45 minutes

Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis. All efficacy analyses were conducted using the intent-to-treat (ITT) population. Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.

A pain free episode is one with 0 pain intensity at the specified time point. Percentage of episodes that are pain-free per subject is analyzed.

Outcome measures

Measure	Onsolis n=77 Participants BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=76 Participants Placebo Disc
Percentage of Pain Free Episodes	10.5 percentage of episodes Standard Error 2.34	6.4 percentage of episodes Standard Error 2.27

SECONDARY outcome

Timeframe: 60 minutes

Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis. All efficacy analyses were conducted using the intent-to-treat (ITT) population. Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.

A pain free episode is one with 0 pain intensity at the specified time point. Percentage of episodes that are pain-free per subject is analyzed.

Outcome measures

Measure	Onsolis n=78 Participants BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=76 Participants Placebo Disc
Percentage of Pain Free Episodes	14.2 percentage of episodes Standard Error 2.62	9.6 percentage of episodes Standard Error 2.90

SECONDARY outcome

Timeframe: 15 minutes

Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis. All efficacy analyses were conducted using the intent-to-treat (ITT) population. Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.

Number of episodes where the total pain score has at least a 50% reduction from baseline.

Outcome measures

Measure	Onsolis n=77 Participants BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=75 Participants Placebo Disc
Episodes With at Least 50% Decreases in Pain	14.9 episodes Standard Error 2.81	14.7 episodes Standard Error 3.35

SECONDARY outcome

Timeframe: 30 minutes

Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis. All efficacy analyses were conducted using the intent-to-treat (ITT) population. Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.

Number of episodes where the total pain score has at least a 50% reduction from baseline.

Outcome measures

Measure	Onsolis n=77 Participants BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=76 Participants Placebo Disc
Episodes With at Least 50% Decreases in Pain	32.8 episodes Standard Error 3.78	24.1 episodes Standard Error 3.87

SECONDARY outcome

Timeframe: 45 minutes

Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis. All efficacy analyses were conducted using the intent-to-treat (ITT) population. Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.

Number of episodes where the total pain score has at least a 50% reduction from baseline.

Outcome measures

Measure	Onsolis n=77 Participants BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=76 Participants Placebo Disc
Episodes With at Least 50% Decreases in Pain	41.1 episodes Standard Error 4.11	30.5 episodes Standard Error 4.10

SECONDARY outcome

Timeframe: 60 minutes

Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis. All efficacy analyses were conducted using the intent-to-treat (ITT) population. Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.

Number of episodes where the total pain score has at least a 50% reduction from baseline.

Outcome measures

Measure	Onsolis n=78 Participants BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=76 Participants Placebo Disc
Episodes With at Least 50% Decreases in Pain	46.1 episodes Standard Error 4.17	34.0 episodes Standard Error 4.30

SECONDARY outcome

Timeframe: 15 minutes

Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis. All efficacy analyses were conducted using the intent-to-treat (ITT) population. Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.

Number of episodes where the total pain score has at least a 33% reduction from baseline.

Outcome measures

Measure	Onsolis n=77 Participants BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=75 Participants Placebo Disc
Episodes With at Least 33% Decreases in Pain	26.4 episodes Standard Error 3.55	21.3 episodes Standard Error 3.66

SECONDARY outcome

Timeframe: 30 minutes

Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis. All efficacy analyses were conducted using the intent-to-treat (ITT) population. Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.

Number of episodes where the total pain score has at least a 33% reduction from baseline.

Outcome measures

Measure	Onsolis n=77 Participants BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=76 Participants Placebo Disc
Episodes With at Least 33% Decreases in Pain	47.3 episodes Standard Error 4.05	38.2 episodes Standard Error 4.45

SECONDARY outcome

Timeframe: 45 minutes

Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis. All efficacy analyses were conducted using the intent-to-treat (ITT) population. Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.

Number of episodes where the total pain score has at least a 33% reduction from baseline.

Outcome measures

Measure	Onsolis n=77 Participants BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=76 Participants Placebo Disc
Episodes With at Least 33% Decreases in Pain	57.5 episodes Standard Error 3.93	46.5 episodes Standard Error 4.50

SECONDARY outcome

Timeframe: 60 minutes

Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis. All efficacy analyses were conducted using the intent-to-treat (ITT) population. Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.

Number of episodes where the total pain score has at least a 50% reduction from baseline.

Outcome measures

Measure	Onsolis n=78 Participants BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=76 Participants Placebo Disc
Episodes With at Least 33% Decreases in Pain	64.3 episodes Standard Error 3.72	48.2 episodes Standard Error 4.51

SECONDARY outcome

Timeframe: 5 minutes

Population: All efficacy analyses were conducted using the intent-to-treat (ITT) population.

Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief). Percentage of episodes with complete relief per subject is analyzed where a complete pain relief episode is defined as pain relief of value 4 at the specified time point.

Outcome measures

Measure	Onsolis n=76 Participants BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=73 Participants Placebo Disc
Episodes With Complete Pain Relief	0.7 percentage of episodes Standard Error 0.66	0.7 percentage of episodes Standard Error 0.68

SECONDARY outcome

Timeframe: 10 minutes

Population: All efficacy analyses were conducted using the intent-to-treat (ITT) population.

Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief).Percentage of episodes with complete relief per subject is analyzed where a complete pain relief episode is defined as pain relief of value 4 at the specified time point.

Outcome measures

Measure	Onsolis n=77 Participants BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=74 Participants Placebo Disc
Episodes With Complete Pain Relief	1.0 percentage of episodes Standard Error 0.72	0.7 percentage of episodes Standard Error 0.68

SECONDARY outcome

Timeframe: 15 minutes

Population: All efficacy analyses were conducted using the intent-to-treat (ITT) population.

Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief).Percentage of episodes with complete relief per subject is analyzed where a complete pain relief episode is defined as pain relief of value 4 at the specified time point.

Outcome measures

Measure	Onsolis n=77 Participants BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=75 Participants Placebo Disc
Episodes With Complete Pain Relief	1.7 percentage of episodes Standard Error 0.83	1.3 percentage of episodes Standard Error 0.94

SECONDARY outcome

Timeframe: 30 minutes

Population: All efficacy analyses were conducted using the intent-to-treat (ITT) population.

Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief). Percentage of episodes with complete relief per subject is analyzed where a complete pain relief episode is defined as pain relief of value 4 at the specified time point.

Outcome measures

Measure	Onsolis n=77 Participants BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=76 Participants Placebo Disc
Episodes With Complete Pain Relief	5.4 percentage of episodes Standard Error 1.63	2.6 percentage of episodes Standard Error 1.33

SECONDARY outcome

Timeframe: 45 minutes

Population: All efficacy analyses were conducted using the intent-to-treat (ITT) population.

Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief). Percentage of episodes with complete relief per subject is analyzed where a complete pain relief episode is defined as pain relief of value 4 at the specified time point.

Outcome measures

Measure	Onsolis n=77 Participants BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=76 Participants Placebo Disc
Episodes With Complete Pain Relief	9.4 percentage of episodes Standard Error 2.18	6.4 percentage of episodes Standard Error 2.27

SECONDARY outcome

Timeframe: 60 minutes

Population: All efficacy analyses were conducted using the intent-to-treat (ITT) population.

Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief). Percentage of episodes with complete relief per subject is analyzed where a complete pain relief episode is defined as pain relief of value 4 at the specified time point.

Outcome measures

Measure	Onsolis n=78 Participants BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=76 Participants Placebo Disc
Episodes With Complete Pain Relief	12.8 percentage of episodes Standard Error 2.49	7.2 percentage of episodes Standard Error 2.40

SECONDARY outcome

Timeframe: 28 Days

Population: All efficacy analyses were conducted using the intent-to-treat (ITT) population.

Rescue medication is medication taken if adequate pain relief is not realized within 30 minutes following application of the study drug. Percentage of episodes when rescue medication was used per subject is analyzed.

Outcome measures

Measure	Onsolis n=79 Participants BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=77 Participants Placebo Disc
Rescue Medication Usage	30.0 percentage of episodes Standard Error 3.53	44.6 percentage of episodes Standard Error 4.38

OTHER_PRE_SPECIFIED outcome

Timeframe: 15 minutes

Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis. All efficacy analyses were conducted using the intent-to-treat (ITT) population. Missing data were imputed on an episode-by-episode basis by carrying forward the last observed data value (last observation carried forward \[LOCF\]).

Pain intensity (using an 11-point [0 = no pain to 10 = worst pain] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point. The primary endpoint was the Summary of Pain Intensity Differences at 30 minutes after dosing (SPID 30) in ITT population for Onsolis versus placebo during double-blind period of study. SPID was calculated as a weighted sum of the PID of all time points at or before time point of interest.Range of possible SPID values is -10X time point (minutes) to 10X time point (minutes). Higher value indicates a better outcome. SPID was calculated as a weighted sum of the pain intensity difference of all time points at or before the time point of interest for the Neuropathic pain subpopulation for relevant time points (15, 30, 45, 60 minutes). Neuropathic pain subpopulation is a subset of ITT population who have neuropathic pain at baseline.

Outcome measures

Measure	Onsolis n=23 Participants BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=22 Participants Placebo Disc
SPID in Neuropathic Pain Subpopulation	13.8 Scores on a scale Standard Error 2.93	7.8 Scores on a scale Standard Error 3.20

OTHER_PRE_SPECIFIED outcome

Timeframe: 30 minutes

Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis. All efficacy analyses were conducted using the intent-to-treat (ITT) population. Missing data were imputed on an episode-by-episode basis by carrying forward the last observed data value (last observation carried forward \[LOCF\]).

Pain intensity (using an 11-point [0 = no pain to 10 = worst pain] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point. The primary endpoint was the Summary of Pain Intensity Differences at 30 minutes after dosing (SPID 30) in ITT population for Onsolis versus placebo during double-blind period of study. SPID was calculated as a weighted sum of the PID of all time points at or before time point of interest.Range of possible SPID values is -10X time point (minutes) to 10X time point (minutes). Higher value indicates a better outcome. SPID was calculated as a weighted sum of the pain intensity difference of all time points at or before the time point of interest for the Neuropathic pain subpopulation for relevant time points (15, 30, 45, 60 minutes). Neuropathic pain subpopulation is a subset of ITT population who have neuropathic pain at baseline.

Outcome measures

Measure	Onsolis n=23 Participants BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=22 Participants Placebo Disc
SPID in Neuropathic Pain Subpopulation	51.6 Scores on a scale Standard Error 8.05	31.8 Scores on a scale Standard Error 8.86

OTHER_PRE_SPECIFIED outcome

Timeframe: 45 minutes

Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis. All efficacy analyses were conducted using the intent-to-treat (ITT) population. Missing data were imputed on an episode-by-episode basis by carrying forward the last observed data value (last observation carried forward \[LOCF\]).

Pain intensity (using an 11-point [0 = no pain to 10 = worst pain] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point. The primary endpoint was the Summary of Pain Intensity Differences at 30 minutes after dosing (SPID 30) in ITT population for Onsolis versus placebo during double-blind period of study. SPID was calculated as a weighted sum of the PID of all time points at or before time point of interest.Range of possible SPID values is -10X time point (minutes) to 10X time point (minutes). Higher value indicates a better outcome. SPID was calculated as a weighted sum of the pain intensity difference of all time points at or before the time point of interest for the Neuropathic pain subpopulation for relevant time points (15, 30, 45, 60 minutes). Neuropathic pain subpopulation is a subset of ITT population who have neuropathic pain at baseline.

Outcome measures

Measure	Onsolis n=23 Participants BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=22 Participants Placebo Disc
SPID in Neuropathic Pain Subpopulation	93.0 Scores on a scale Standard Error 14.09	59.7 Scores on a scale Standard Error 15.63

OTHER_PRE_SPECIFIED outcome

Timeframe: 60 minutes

Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis. All efficacy analyses were conducted using the intent-to-treat (ITT) population. Missing data were imputed on an episode-by-episode basis by carrying forward the last observed data value (last observation carried forward \[LOCF\]).

Pain intensity (using an 11-point [0 = no pain to 10 = worst pain] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point. The primary endpoint was the Summary of Pain Intensity Differences at 30 minutes after dosing (SPID 30) in ITT population for Onsolis versus placebo during double-blind period of study. SPID was calculated as a weighted sum of the PID of all time points at or before time point of interest.Range of possible SPID values is -10X time point (minutes) to 10X time point (minutes). Higher value indicates a better outcome. SPID was calculated as a weighted sum of the pain intensity difference of all time points at or before the time point of interest for the Neuropathic pain subpopulation for relevant time points (15, 30, 45, 60 minutes). Neuropathic pain subpopulation is a subset of ITT population who have neuropathic pain at baseline.

Outcome measures

Measure	Onsolis n=23 Participants BioErodible MucoAdhesive (BEMA) Fentanyl	Placebo n=22 Participants Placebo Disc
SPID in Neuropathic Pain Subpopulation	137.8 Scores on a scale Standard Error 20.19	90.9 Scores on a scale Standard Error 22.53

Adverse Events

Onsolis

Serious events: 23 serious events

Other events: 44 other events

Deaths: 0 deaths

Serious adverse events

Measure	Onsolis n=151 participants at risk All AEs were assigned to BEMA™ Fentanyl (Onsolis). Because of the multiple crossover design and the number of breakthrough pain episodes that usually occur during the day, it was likely that a subject would receive both active and placebo doses within a few hours of each other. Given the proximity of these different treatments, attempts to ascribe individual AEs to one treatment or another would be difficult, therefore, the chosen convention was to consider all AEs as occurring on active medication.
Blood and lymphatic system disorders Splenomegaly	0.66% 1/151 • Number of events 1 • A prior-treatment adverse event (AE) was defined as an AE that began before the first dose of the study drug. A treatment-emergent AE was defined as an AE that began on or after the initial dose of study medication up until the Follow-up Visit on Day 29. At each visit, after the subject had an opportunity to spontaneously mention any problems, the investigator inquired about AEs by asking the following: 1. Have you had any (other) medical problems since your last visit/assessment? 2. Have you taken any new medications, other than those given to you in this study, since your last visit/assessment?
Gastrointestinal disorders Gastrointestinal hemorrhage	0.66% 1/151 • Number of events 1 • A prior-treatment adverse event (AE) was defined as an AE that began before the first dose of the study drug. A treatment-emergent AE was defined as an AE that began on or after the initial dose of study medication up until the Follow-up Visit on Day 29. At each visit, after the subject had an opportunity to spontaneously mention any problems, the investigator inquired about AEs by asking the following: 1. Have you had any (other) medical problems since your last visit/assessment? 2. Have you taken any new medications, other than those given to you in this study, since your last visit/assessment?
Gastrointestinal disorders Hematemesis	0.66% 1/151 • Number of events 1 • A prior-treatment adverse event (AE) was defined as an AE that began before the first dose of the study drug. A treatment-emergent AE was defined as an AE that began on or after the initial dose of study medication up until the Follow-up Visit on Day 29. At each visit, after the subject had an opportunity to spontaneously mention any problems, the investigator inquired about AEs by asking the following: 1. Have you had any (other) medical problems since your last visit/assessment? 2. Have you taken any new medications, other than those given to you in this study, since your last visit/assessment?
Gastrointestinal disorders Intestinal obstruction	0.66% 1/151 • Number of events 1 • A prior-treatment adverse event (AE) was defined as an AE that began before the first dose of the study drug. A treatment-emergent AE was defined as an AE that began on or after the initial dose of study medication up until the Follow-up Visit on Day 29. At each visit, after the subject had an opportunity to spontaneously mention any problems, the investigator inquired about AEs by asking the following: 1. Have you had any (other) medical problems since your last visit/assessment? 2. Have you taken any new medications, other than those given to you in this study, since your last visit/assessment?
Gastrointestinal disorders Esophageal hemorrhage	0.66% 1/151 • Number of events 1 • A prior-treatment adverse event (AE) was defined as an AE that began before the first dose of the study drug. A treatment-emergent AE was defined as an AE that began on or after the initial dose of study medication up until the Follow-up Visit on Day 29. At each visit, after the subject had an opportunity to spontaneously mention any problems, the investigator inquired about AEs by asking the following: 1. Have you had any (other) medical problems since your last visit/assessment? 2. Have you taken any new medications, other than those given to you in this study, since your last visit/assessment?
General disorders Pyrexia	0.66% 1/151 • Number of events 1 • A prior-treatment adverse event (AE) was defined as an AE that began before the first dose of the study drug. A treatment-emergent AE was defined as an AE that began on or after the initial dose of study medication up until the Follow-up Visit on Day 29. At each visit, after the subject had an opportunity to spontaneously mention any problems, the investigator inquired about AEs by asking the following: 1. Have you had any (other) medical problems since your last visit/assessment? 2. Have you taken any new medications, other than those given to you in this study, since your last visit/assessment?
Hepatobiliary disorders Bile duct obstruction	0.66% 1/151 • Number of events 1 • A prior-treatment adverse event (AE) was defined as an AE that began before the first dose of the study drug. A treatment-emergent AE was defined as an AE that began on or after the initial dose of study medication up until the Follow-up Visit on Day 29. At each visit, after the subject had an opportunity to spontaneously mention any problems, the investigator inquired about AEs by asking the following: 1. Have you had any (other) medical problems since your last visit/assessment? 2. Have you taken any new medications, other than those given to you in this study, since your last visit/assessment?
Hepatobiliary disorders Hepatic failure	0.66% 1/151 • Number of events 1 • A prior-treatment adverse event (AE) was defined as an AE that began before the first dose of the study drug. A treatment-emergent AE was defined as an AE that began on or after the initial dose of study medication up until the Follow-up Visit on Day 29. At each visit, after the subject had an opportunity to spontaneously mention any problems, the investigator inquired about AEs by asking the following: 1. Have you had any (other) medical problems since your last visit/assessment? 2. Have you taken any new medications, other than those given to you in this study, since your last visit/assessment?
Infections and infestations Pneumonia	4.0% 6/151 • Number of events 6 • A prior-treatment adverse event (AE) was defined as an AE that began before the first dose of the study drug. A treatment-emergent AE was defined as an AE that began on or after the initial dose of study medication up until the Follow-up Visit on Day 29. At each visit, after the subject had an opportunity to spontaneously mention any problems, the investigator inquired about AEs by asking the following: 1. Have you had any (other) medical problems since your last visit/assessment? 2. Have you taken any new medications, other than those given to you in this study, since your last visit/assessment?
Infections and infestations Sepsis	0.66% 1/151 • Number of events 1 • A prior-treatment adverse event (AE) was defined as an AE that began before the first dose of the study drug. A treatment-emergent AE was defined as an AE that began on or after the initial dose of study medication up until the Follow-up Visit on Day 29. At each visit, after the subject had an opportunity to spontaneously mention any problems, the investigator inquired about AEs by asking the following: 1. Have you had any (other) medical problems since your last visit/assessment? 2. Have you taken any new medications, other than those given to you in this study, since your last visit/assessment?
Metabolism and nutrition disorders Dehydration	1.3% 2/151 • Number of events 2 • A prior-treatment adverse event (AE) was defined as an AE that began before the first dose of the study drug. A treatment-emergent AE was defined as an AE that began on or after the initial dose of study medication up until the Follow-up Visit on Day 29. At each visit, after the subject had an opportunity to spontaneously mention any problems, the investigator inquired about AEs by asking the following: 1. Have you had any (other) medical problems since your last visit/assessment? 2. Have you taken any new medications, other than those given to you in this study, since your last visit/assessment?
Metabolism and nutrition disorders Failure to thrive	0.66% 1/151 • Number of events 1 • A prior-treatment adverse event (AE) was defined as an AE that began before the first dose of the study drug. A treatment-emergent AE was defined as an AE that began on or after the initial dose of study medication up until the Follow-up Visit on Day 29. At each visit, after the subject had an opportunity to spontaneously mention any problems, the investigator inquired about AEs by asking the following: 1. Have you had any (other) medical problems since your last visit/assessment? 2. Have you taken any new medications, other than those given to you in this study, since your last visit/assessment?
Metabolism and nutrition disorders Hypoglycemia	0.66% 1/151 • Number of events 1 • A prior-treatment adverse event (AE) was defined as an AE that began before the first dose of the study drug. A treatment-emergent AE was defined as an AE that began on or after the initial dose of study medication up until the Follow-up Visit on Day 29. At each visit, after the subject had an opportunity to spontaneously mention any problems, the investigator inquired about AEs by asking the following: 1. Have you had any (other) medical problems since your last visit/assessment? 2. Have you taken any new medications, other than those given to you in this study, since your last visit/assessment?
Musculoskeletal and connective tissue disorders Bone pain	0.66% 1/151 • Number of events 1 • A prior-treatment adverse event (AE) was defined as an AE that began before the first dose of the study drug. A treatment-emergent AE was defined as an AE that began on or after the initial dose of study medication up until the Follow-up Visit on Day 29. At each visit, after the subject had an opportunity to spontaneously mention any problems, the investigator inquired about AEs by asking the following: 1. Have you had any (other) medical problems since your last visit/assessment? 2. Have you taken any new medications, other than those given to you in this study, since your last visit/assessment?
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Vaginal cancer recurrent	0.66% 1/151 • Number of events 1 • A prior-treatment adverse event (AE) was defined as an AE that began before the first dose of the study drug. A treatment-emergent AE was defined as an AE that began on or after the initial dose of study medication up until the Follow-up Visit on Day 29. At each visit, after the subject had an opportunity to spontaneously mention any problems, the investigator inquired about AEs by asking the following: 1. Have you had any (other) medical problems since your last visit/assessment? 2. Have you taken any new medications, other than those given to you in this study, since your last visit/assessment?
Nervous system disorders Grand mal convulsion	0.66% 1/151 • Number of events 1 • A prior-treatment adverse event (AE) was defined as an AE that began before the first dose of the study drug. A treatment-emergent AE was defined as an AE that began on or after the initial dose of study medication up until the Follow-up Visit on Day 29. At each visit, after the subject had an opportunity to spontaneously mention any problems, the investigator inquired about AEs by asking the following: 1. Have you had any (other) medical problems since your last visit/assessment? 2. Have you taken any new medications, other than those given to you in this study, since your last visit/assessment?
Psychiatric disorders Confusional state	0.66% 1/151 • Number of events 1 • A prior-treatment adverse event (AE) was defined as an AE that began before the first dose of the study drug. A treatment-emergent AE was defined as an AE that began on or after the initial dose of study medication up until the Follow-up Visit on Day 29. At each visit, after the subject had an opportunity to spontaneously mention any problems, the investigator inquired about AEs by asking the following: 1. Have you had any (other) medical problems since your last visit/assessment? 2. Have you taken any new medications, other than those given to you in this study, since your last visit/assessment?
Renal and urinary disorders Renal failure acute	0.66% 1/151 • Number of events 1 • A prior-treatment adverse event (AE) was defined as an AE that began before the first dose of the study drug. A treatment-emergent AE was defined as an AE that began on or after the initial dose of study medication up until the Follow-up Visit on Day 29. At each visit, after the subject had an opportunity to spontaneously mention any problems, the investigator inquired about AEs by asking the following: 1. Have you had any (other) medical problems since your last visit/assessment? 2. Have you taken any new medications, other than those given to you in this study, since your last visit/assessment?
Respiratory, thoracic and mediastinal disorders Hemoptysis	0.66% 1/151 • Number of events 1 • A prior-treatment adverse event (AE) was defined as an AE that began before the first dose of the study drug. A treatment-emergent AE was defined as an AE that began on or after the initial dose of study medication up until the Follow-up Visit on Day 29. At each visit, after the subject had an opportunity to spontaneously mention any problems, the investigator inquired about AEs by asking the following: 1. Have you had any (other) medical problems since your last visit/assessment? 2. Have you taken any new medications, other than those given to you in this study, since your last visit/assessment?
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.66% 1/151 • Number of events 1 • A prior-treatment adverse event (AE) was defined as an AE that began before the first dose of the study drug. A treatment-emergent AE was defined as an AE that began on or after the initial dose of study medication up until the Follow-up Visit on Day 29. At each visit, after the subject had an opportunity to spontaneously mention any problems, the investigator inquired about AEs by asking the following: 1. Have you had any (other) medical problems since your last visit/assessment? 2. Have you taken any new medications, other than those given to you in this study, since your last visit/assessment?
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.66% 1/151 • Number of events 1 • A prior-treatment adverse event (AE) was defined as an AE that began before the first dose of the study drug. A treatment-emergent AE was defined as an AE that began on or after the initial dose of study medication up until the Follow-up Visit on Day 29. At each visit, after the subject had an opportunity to spontaneously mention any problems, the investigator inquired about AEs by asking the following: 1. Have you had any (other) medical problems since your last visit/assessment? 2. Have you taken any new medications, other than those given to you in this study, since your last visit/assessment?
Vascular disorders Arterial thrombosis limb	0.66% 1/151 • Number of events 1 • A prior-treatment adverse event (AE) was defined as an AE that began before the first dose of the study drug. A treatment-emergent AE was defined as an AE that began on or after the initial dose of study medication up until the Follow-up Visit on Day 29. At each visit, after the subject had an opportunity to spontaneously mention any problems, the investigator inquired about AEs by asking the following: 1. Have you had any (other) medical problems since your last visit/assessment? 2. Have you taken any new medications, other than those given to you in this study, since your last visit/assessment?
Vascular disorders Deep vein thrombosis	0.66% 1/151 • Number of events 1 • A prior-treatment adverse event (AE) was defined as an AE that began before the first dose of the study drug. A treatment-emergent AE was defined as an AE that began on or after the initial dose of study medication up until the Follow-up Visit on Day 29. At each visit, after the subject had an opportunity to spontaneously mention any problems, the investigator inquired about AEs by asking the following: 1. Have you had any (other) medical problems since your last visit/assessment? 2. Have you taken any new medications, other than those given to you in this study, since your last visit/assessment?

Other adverse events

Measure	Onsolis n=151 participants at risk All AEs were assigned to BEMA™ Fentanyl (Onsolis). Because of the multiple crossover design and the number of breakthrough pain episodes that usually occur during the day, it was likely that a subject would receive both active and placebo doses within a few hours of each other. Given the proximity of these different treatments, attempts to ascribe individual AEs to one treatment or another would be difficult, therefore, the chosen convention was to consider all AEs as occurring on active medication.
Gastrointestinal disorders Nausea	13.9% 21/151 • Number of events 21 • A prior-treatment adverse event (AE) was defined as an AE that began before the first dose of the study drug. A treatment-emergent AE was defined as an AE that began on or after the initial dose of study medication up until the Follow-up Visit on Day 29. At each visit, after the subject had an opportunity to spontaneously mention any problems, the investigator inquired about AEs by asking the following: 1. Have you had any (other) medical problems since your last visit/assessment? 2. Have you taken any new medications, other than those given to you in this study, since your last visit/assessment?
Gastrointestinal disorders Vomiting	12.6% 19/151 • Number of events 19 • A prior-treatment adverse event (AE) was defined as an AE that began before the first dose of the study drug. A treatment-emergent AE was defined as an AE that began on or after the initial dose of study medication up until the Follow-up Visit on Day 29. At each visit, after the subject had an opportunity to spontaneously mention any problems, the investigator inquired about AEs by asking the following: 1. Have you had any (other) medical problems since your last visit/assessment? 2. Have you taken any new medications, other than those given to you in this study, since your last visit/assessment?
Metabolism and nutrition disorders Dehydration	4.6% 7/151 • Number of events 7 • A prior-treatment adverse event (AE) was defined as an AE that began before the first dose of the study drug. A treatment-emergent AE was defined as an AE that began on or after the initial dose of study medication up until the Follow-up Visit on Day 29. At each visit, after the subject had an opportunity to spontaneously mention any problems, the investigator inquired about AEs by asking the following: 1. Have you had any (other) medical problems since your last visit/assessment? 2. Have you taken any new medications, other than those given to you in this study, since your last visit/assessment?
Nervous system disorders Somnolence	6.6% 10/151 • Number of events 11 • A prior-treatment adverse event (AE) was defined as an AE that began before the first dose of the study drug. A treatment-emergent AE was defined as an AE that began on or after the initial dose of study medication up until the Follow-up Visit on Day 29. At each visit, after the subject had an opportunity to spontaneously mention any problems, the investigator inquired about AEs by asking the following: 1. Have you had any (other) medical problems since your last visit/assessment? 2. Have you taken any new medications, other than those given to you in this study, since your last visit/assessment?
Nervous system disorders Dizziness	4.6% 7/151 • Number of events 7 • A prior-treatment adverse event (AE) was defined as an AE that began before the first dose of the study drug. A treatment-emergent AE was defined as an AE that began on or after the initial dose of study medication up until the Follow-up Visit on Day 29. At each visit, after the subject had an opportunity to spontaneously mention any problems, the investigator inquired about AEs by asking the following: 1. Have you had any (other) medical problems since your last visit/assessment? 2. Have you taken any new medications, other than those given to you in this study, since your last visit/assessment?

Additional Information

Larry Gever, PharmD, Director, Medical Affairs

Meda Pharmaceuticals Inc.

Phone: 732-564-2400

Email: larry.gever@meda.us

Results disclosure agreements

• Principal investigator is a sponsor employee The oral or written use of study results by the investigator are not permitted without the express written consent from BDSI. All data resulting from this study remain property of BDSI.
• Publication restrictions are in place

Restriction type: OTHER