Trial Outcomes & Findings for Abuse Potential of Orally Administered Crushed Embeda Compared to Crushed Controlled-Release Morphine and Placebo in Non-Dependent Recreational Opioid Users (NCT NCT01380093)
NCT ID: NCT01380093
Last Updated: 2012-05-31
Results Overview
Drug liking assesses the degree that a participant likes a drug effect at the time the question is being asked (that is, at the moment). It is scored using a 100 millimeter (mm) bipolar visual analogue scale (VAS) anchored in the center with a neutral anchor of "neither like nor dislike" (score of 50 mm), on the left with "strong disliking" (score of 0 mm) and on the right with "strong liking" (score of 100 mm). AUE (0-2) = Area under the effect versus time curve from time 0 to 2 hours (hrs) (0-2).
COMPLETED
PHASE1
80 participants
0.5, 1, 1.5 and 2 hrs post-dose
2012-05-31
Participant Flow
Participant milestones
| Measure |
Naloxone
Naloxone hydrochloride 0.2 milligram (mg) intravenously (IV) followed by additional 0.6 mg naloxone hydrochloride IV, each dose followed by an assessment for signs of withdrawal. Participants in this group were assigned to either morphine then placebo or placebo then morphine in the drug discrimination phase of the study.
|
Morphine Then Placebo
Single dose of morphine sulfate 120 mg solution orally on Day 1 followed by single dose of matching placebo solution orally on Day 2. Participants in this group were assigned to morphine, placebo and EMBEDA in either of the 6 sequences in the treatment phase of the study.
|
Placebo Then Morphine
Single dose of matching placebo solution orally on Day 1 followed by single dose of morphine sulfate 120 mg solution orally on Day 2. Participants in this group were assigned to morphine, placebo and EMBEDA in either of the 6 sequences in the treatment phase of the study.
|
Placebo Then EMBEDA Then Morphine
Single dose of matching placebo solution orally in first intervention period; followed by single dose of solution of EMBEDA extended release (ER) capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in second intervention period; then single dose of solution of morphine sulfate (MS Contin) controlled release (CR) tablet 120 mg orally in third intervention period. A washout period of at least 4 days (not exceeding 14 days) was maintained between each intervention period.
|
EMBEDA Then Morphine Then Placebo
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in first intervention period; followed by single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in second intervention period; then single dose of matching placebo solution orally in third intervention period. A washout period of at least 4 days (not exceeding 14 days) was maintained between each intervention period.
|
Morphine Then Placebo Then EMBEDA
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in first intervention period; followed by single dose of matching placebo solution orally in second intervention period; then single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in third intervention period. A washout period of at least 4 days (not exceeding 14 days) was maintained between each intervention period.
|
Morphine Then EMBEDA Then Placebo
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in first intervention period; followed by single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in second intervention period; then single dose of matching placebo solution orally in third intervention period. A washout period of at least 4 days (not exceeding 14 days) was maintained between each intervention period.
|
Placebo Then Morphine Then EMBEDA
Single dose of matching placebo solution orally in first intervention period; followed by single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in second intervention period; then single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in third intervention period. A washout period of at least 4 days (not exceeding 14 days) was maintained between each intervention period.
|
EMBEDA Then Placebo Then Morphine
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in first intervention period; followed by single dose of matching placebo solution orally in second intervention period; then single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in third intervention period. A washout period of at least 4 days (not exceeding 14 days) was maintained between each intervention period.
|
|---|---|---|---|---|---|---|---|---|---|
|
Naloxone Challenge Phase
STARTED
|
80
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Naloxone Challenge Phase
TREATED
|
59
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Naloxone Challenge Phase
COMPLETED
|
59
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Naloxone Challenge Phase
NOT COMPLETED
|
21
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Drug Discrimination Phase: Day 1
STARTED
|
0
|
30
|
29
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Drug Discrimination Phase: Day 1
COMPLETED
|
0
|
29
|
29
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Drug Discrimination Phase: Day 1
NOT COMPLETED
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Drug Discrimination Phase: Day 2
STARTED
|
0
|
29
|
29
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Drug Discrimination Phase: Day 2
COMPLETED
|
0
|
20
|
16
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Drug Discrimination Phase: Day 2
NOT COMPLETED
|
0
|
9
|
13
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Treatment Phase: First Intervention
STARTED
|
0
|
0
|
0
|
6
|
6
|
6
|
6
|
6
|
6
|
|
Treatment Phase: First Intervention
COMPLETED
|
0
|
0
|
0
|
6
|
6
|
6
|
6
|
6
|
6
|
|
Treatment Phase: First Intervention
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Treatment Phase: Washout Period
STARTED
|
0
|
0
|
0
|
5
|
6
|
6
|
6
|
6
|
6
|
|
Treatment Phase: Washout Period
COMPLETED
|
0
|
0
|
0
|
5
|
6
|
6
|
6
|
6
|
6
|
|
Treatment Phase: Washout Period
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Treatment Phase: Second Intervention
STARTED
|
0
|
0
|
0
|
6
|
6
|
6
|
6
|
6
|
6
|
|
Treatment Phase: Second Intervention
COMPLETED
|
0
|
0
|
0
|
5
|
6
|
6
|
6
|
6
|
6
|
|
Treatment Phase: Second Intervention
NOT COMPLETED
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
|
Treatment Phase: Third Intervention
STARTED
|
0
|
0
|
0
|
5
|
6
|
6
|
6
|
6
|
6
|
|
Treatment Phase: Third Intervention
COMPLETED
|
0
|
0
|
0
|
5
|
6
|
6
|
6
|
6
|
4
|
|
Treatment Phase: Third Intervention
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
2
|
Reasons for withdrawal
| Measure |
Naloxone
Naloxone hydrochloride 0.2 milligram (mg) intravenously (IV) followed by additional 0.6 mg naloxone hydrochloride IV, each dose followed by an assessment for signs of withdrawal. Participants in this group were assigned to either morphine then placebo or placebo then morphine in the drug discrimination phase of the study.
|
Morphine Then Placebo
Single dose of morphine sulfate 120 mg solution orally on Day 1 followed by single dose of matching placebo solution orally on Day 2. Participants in this group were assigned to morphine, placebo and EMBEDA in either of the 6 sequences in the treatment phase of the study.
|
Placebo Then Morphine
Single dose of matching placebo solution orally on Day 1 followed by single dose of morphine sulfate 120 mg solution orally on Day 2. Participants in this group were assigned to morphine, placebo and EMBEDA in either of the 6 sequences in the treatment phase of the study.
|
Placebo Then EMBEDA Then Morphine
Single dose of matching placebo solution orally in first intervention period; followed by single dose of solution of EMBEDA extended release (ER) capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in second intervention period; then single dose of solution of morphine sulfate (MS Contin) controlled release (CR) tablet 120 mg orally in third intervention period. A washout period of at least 4 days (not exceeding 14 days) was maintained between each intervention period.
|
EMBEDA Then Morphine Then Placebo
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in first intervention period; followed by single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in second intervention period; then single dose of matching placebo solution orally in third intervention period. A washout period of at least 4 days (not exceeding 14 days) was maintained between each intervention period.
|
Morphine Then Placebo Then EMBEDA
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in first intervention period; followed by single dose of matching placebo solution orally in second intervention period; then single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in third intervention period. A washout period of at least 4 days (not exceeding 14 days) was maintained between each intervention period.
|
Morphine Then EMBEDA Then Placebo
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in first intervention period; followed by single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in second intervention period; then single dose of matching placebo solution orally in third intervention period. A washout period of at least 4 days (not exceeding 14 days) was maintained between each intervention period.
|
Placebo Then Morphine Then EMBEDA
Single dose of matching placebo solution orally in first intervention period; followed by single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in second intervention period; then single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in third intervention period. A washout period of at least 4 days (not exceeding 14 days) was maintained between each intervention period.
|
EMBEDA Then Placebo Then Morphine
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in first intervention period; followed by single dose of matching placebo solution orally in second intervention period; then single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in third intervention period. A washout period of at least 4 days (not exceeding 14 days) was maintained between each intervention period.
|
|---|---|---|---|---|---|---|---|---|---|
|
Naloxone Challenge Phase
Screen failures
|
21
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Drug Discrimination Phase: Day 1
Discrimination failure
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Drug Discrimination Phase: Day 2
Physician Decision
|
0
|
3
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Drug Discrimination Phase: Day 2
Withdrawal by Subject
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Drug Discrimination Phase: Day 2
Discrimination failure
|
0
|
4
|
9
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Drug Discrimination Phase: Day 2
Positive urine drug screen
|
0
|
1
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Drug Discrimination Phase: Day 2
Backup participant
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Drug Discrimination Phase: Day 2
Sponsor decision
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Treatment Phase: Second Intervention
Other
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
|
Treatment Phase: Third Intervention
Non-compliance
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
|
Treatment Phase: Third Intervention
Other
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
Baseline Characteristics
Abuse Potential of Orally Administered Crushed Embeda Compared to Crushed Controlled-Release Morphine and Placebo in Non-Dependent Recreational Opioid Users
Baseline characteristics by cohort
| Measure |
Entire Study Population
n=80 Participants
Includes all participants enrolled in the study.
|
|---|---|
|
Age Continuous
|
24.7 years
STANDARD_DEVIATION 4.52 • n=93 Participants
|
|
Sex: Female, Male
Female
|
17 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
63 Participants
n=93 Participants
|
PRIMARY outcome
Timeframe: 0.5, 1, 1.5 and 2 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose pharmacodynamic (PD) data from each period and did not have major protocol violations.
Drug liking assesses the degree that a participant likes a drug effect at the time the question is being asked (that is, at the moment). It is scored using a 100 millimeter (mm) bipolar visual analogue scale (VAS) anchored in the center with a neutral anchor of "neither like nor dislike" (score of 50 mm), on the left with "strong disliking" (score of 0 mm) and on the right with "strong liking" (score of 100 mm). AUE (0-2) = Area under the effect versus time curve from time 0 to 2 hours (hrs) (0-2).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Drug Liking: Area Under Effect Curve (AUE) From 0-2 Hours
|
88.3 hrs*mm
Standard Deviation 4.41 • Interval 83.6 to 93.6
|
100.3 hrs*mm
Standard Deviation 12.29 • Interval 95.5 to 105.5
|
124.7 hrs*mm
Standard Deviation 22.70 • Interval 120.4 to 130.4
|
PRIMARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Drug liking assesses the degree that a participant likes a drug effect at the time the question is being asked (that is, at the moment). It is scored using a 100 mm bipolar VAS anchored in the center with a neutral anchor of "neither like nor dislike" (score of 50 mm), on the left with "strong disliking" (score of 0 mm) and on the right with "strong liking" (score of 100 mm). Emax = Maximum observed score.
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Drug Liking: Peak Effect (Emax)
|
51.6 mm
Standard Deviation 4.21 • Interval 48.3 to 55.1
|
65.2 mm
Standard Deviation 11.21 • Interval 61.7 to 68.6
|
80.6 mm
Standard Deviation 13.09 • Interval 77.4 to 84.3
|
PRIMARY outcome
Timeframe: 0.5, 1, 1.5 and 2 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
High VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-2) = Area under the effect versus time curve from time 0 to 2 hrs (0-2).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
High: Area Under Effect Curve (AUE) From 0-2 Hours
|
2.0 hrs*mm
Standard Deviation 7.34 • Interval -6.3 to 11.5
|
26.9 hrs*mm
Standard Deviation 27.72 • Interval 18.3 to 36.0
|
77.5 hrs*mm
Standard Deviation 34.40 • Interval 69.4 to 87.2
|
PRIMARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
High VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score.
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
High: Peak Effect (Emax)
|
1.8 mm
Standard Deviation 5.73 • Interval -3.7 to 8.1
|
29.2 mm
Standard Deviation 20.72 • Interval 23.6 to 35.3
|
64.1 mm
Standard Deviation 18.85 • Interval 58.5 to 70.2
|
SECONDARY outcome
Timeframe: 0.5 and 1 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Drug liking assesses the degree that a participant likes a drug effect at the time the question is being asked (that is, at the moment). It is scored using a 100 mm bipolar VAS anchored in the center with a neutral anchor of "neither like nor dislike" (score of 50 mm), on the left with "strong disliking" (score of 0 mm) and on the right with "strong liking" (score of 100 mm). AUE (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Drug Liking: Area Under Effect Curve (AUE) From 0-1 Hour
|
37.8 hrs*mm
Standard Deviation 1.82 • Interval 35.7 to 40.2
|
43.1 hrs*mm
Standard Deviation 6.11 • Interval 40.9 to 45.4
|
51.8 hrs*mm
Standard Deviation 10.12 • Interval 49.8 to 54.3
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3 and 4 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Drug liking assesses the degree that a participant likes a drug effect at the time the question is being asked (that is, at the moment). It is scored using a 100 mm bipolar VAS anchored in the center with a neutral anchor of "neither like nor dislike" (score of 50 mm), on the left with "strong disliking" (score of 0 mm) and on the right with "strong liking" (score of 100 mm). AUE (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Drug Liking: Area Under Effect Curve (AUE) From 0-4 Hours
|
188.6 hrs*mm
Standard Deviation 7.56 • Interval 179.1 to 199.1
|
217.9 hrs*mm
Standard Deviation 24.72 • Interval 208.1 to 228.2
|
265.6 hrs*mm
Standard Deviation 44.44 • Interval 256.9 to 276.9
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Drug liking assesses the degree that a participant likes a drug effect at the time the question is being asked (that is, at the moment). It is scored using a 100 mm bipolar VAS anchored in the center with a neutral anchor of "neither like nor dislike" (score of 50 mm), on the left with "strong disliking" (score of 0 mm) and on the right with "strong liking" (score of 100 mm). AUE (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Drug Liking: Area Under Effect Curve (AUE) From 0-8 Hours
|
390.3 hrs*mm
Standard Deviation 15.19 • Interval 368.4 to 411.1
|
447.3 hrs*mm
Standard Deviation 60.82 • Interval 424.9 to 467.6
|
514.4 hrs*mm
Standard Deviation 87.10 • Interval 493.4 to 536.2
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Drug liking assesses the degree that a participant likes a drug effect at the time the question is being asked (that is, at the moment). It is scored using a 100 mm bipolar VAS anchored in the center with a neutral anchor of "neither like nor dislike" (score of 50 mm), on the left with "strong disliking" (score of 0 mm) and on the right with "strong liking" (score of 100 mm). AUE (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Drug Liking: Area Under Effect Curve (AUE) From 0-12 Hours
|
591.0 hrs*mm
Standard Deviation 20.36 • Interval 560.2 to 619.4
|
658.2 hrs*mm
Standard Deviation 81.77 • Interval 626.7 to 685.9
|
732.9 hrs*mm
Standard Deviation 122.81 • Interval 702.7 to 761.9
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Drug liking assesses the degree that a participant likes a drug effect at the time the question is being asked (that is, at the moment). It is scored using a 100 mm bipolar VAS anchored in the center with a neutral anchor of "neither like nor dislike" (score of 50 mm), on the left with "strong disliking" (score of 0 mm) and on the right with "strong liking" (score of 100 mm). AUE (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Drug Liking: Area Under Effect Curve (AUE) From 0-24 Hours
|
1192.1 hrs*mm
Standard Deviation 29.73 • Interval 1150.1 to 1230.7
|
1263.0 hrs*mm
Standard Deviation 101.88 • Interval 1220.0 to 1300.5
|
1348.2 hrs*mm
Standard Deviation 174.53 • Interval 1306.1 to 1386.8
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Drug liking assesses the degree that a participant likes a drug effect at the time the question is being asked (that is, at the moment). It is scored using a 100 mm bipolar VAS anchored in the center with a neutral anchor of "neither like nor dislike" (score of 50 mm), on the left with "strong disliking" (score of 0 mm) and on the right with "strong liking" (score of 100 mm). TEmax = Time to maximum observed score.
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Drug Liking: Time to Maximum (Peak) Effect (TEmax)
|
5.8 hrs
Standard Deviation 6.83 • Interval 3.8 to 7.5
|
4.8 hrs
Standard Deviation 5.74 • Interval 2.8 to 6.5
|
2.7 hrs
Standard Deviation 2.63 • Interval 0.7 to 4.5
|
SECONDARY outcome
Timeframe: 0.5 and 1 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
High VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
High: Area Under Effect Curve (AUE) From 0-1 Hour
|
0.9 hrs*mm
Standard Deviation 2.87 • Interval -2.9 to 5.2
|
10.3 hrs*mm
Standard Deviation 12.26 • Interval 6.3 to 14.5
|
25.5 hrs*mm
Standard Deviation 16.26 • Interval 21.7 to 29.9
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3 and 4 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
High VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
High: Area Under Effect Curve (AUE) From 0-4 Hours
|
3.4 hrs*mm
Standard Deviation 13.28 • Interval -12.5 to 21.9
|
63.6 hrs*mm
Standard Deviation 53.04 • Interval 47.2 to 81.7
|
178.9 hrs*mm
Standard Deviation 64.56 • Interval 163.2 to 197.8
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
High VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
High: Area Under Effect Curve (AUE) From 0-8 Hours
|
6.5 hrs*mm
Standard Deviation 23.15 • Interval -23.1 to 39.2
|
129.5 hrs*mm
Standard Deviation 101.43 • Interval 99.4 to 161.6
|
330.5 hrs*mm
Standard Deviation 109.02 • Interval 301.5 to 363.8
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
High VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
High: Area Under Effect Curve (AUE) From 0-12 Hours
|
8.1 hrs*mm
Standard Deviation 28.80 • Interval 0.0 to 49.8
|
160.7 hrs*mm
Standard Deviation 129.72 • Interval 121.5 to 201.7
|
412.3 hrs*mm
Standard Deviation 142.08 • Interval 374.4 to 454.8
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
High VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
High: Area Under Effect Curve (AUE) From 0-24 Hours
|
10.7 hrs*mm
Standard Deviation 35.41 • Interval -39.6 to 65.1
|
180.3 hrs*mm
Standard Deviation 149.07 • Interval 129.0 to 233.8
|
485.4 hrs*mm
Standard Deviation 204.51 • Interval 435.7 to 540.6
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
High VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score.
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
High: Time to Maximum (Peak) Effect (TEmax)
|
0.8 hrs
Standard Deviation 0.99 • Interval 0.1 to 1.3
|
2.7 hrs
Standard Deviation 1.94 • Interval 2.1 to 3.3
|
2.5 hrs
Standard Deviation 1.94 • Interval 1.9 to 3.1
|
SECONDARY outcome
Timeframe: 0.5 and 1 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Good effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Good Effects: Area Under Effect Curve (AUE) From 0-1 Hour
|
0.8 hrs*mm
Standard Deviation 2.47 • Interval -3.5 to 5.5
|
12.2 hrs*mm
Standard Deviation 13.74 • Interval 7.8 to 16.7
|
27.2 hrs*mm
Standard Deviation 17.64 • Interval 23.0 to 32.0
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5 and 2 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Good effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-2) = Area under the effect versus time curve from time 0 to 2 hrs (0-2).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Good Effects: Area Under Effect Curve (AUE) From 0-2 Hours
|
1.8 hrs*mm
Standard Deviation 6.69 • Interval -7.4 to 12.2
|
30.4 hrs*mm
Standard Deviation 29.84 • Interval 20.9 to 40.5
|
77.4 hrs*mm
Standard Deviation 38.39 • Interval 68.6 to 88.2
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3 and 4 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Good effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Good Effects: Area Under Effect Curve (AUE) From 0-4 Hours
|
3.1 hrs*mm
Standard Deviation 12.35 • Interval -14.8 to 23.5
|
70.5 hrs*mm
Standard Deviation 58.34 • Interval 52.2 to 90.5
|
178.5 hrs*mm
Standard Deviation 73.28 • Interval 161.4 to 199.7
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Good effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Good Effects: Area Under Effect Curve (AUE) From 0-8 Hours
|
6.2 hrs*mm
Standard Deviation 22.44 • Interval -28.8 to 42.5
|
141.2 hrs*mm
Standard Deviation 120.31 • Interval 105.9 to 177.2
|
330.0 hrs*mm
Standard Deviation 122.85 • Interval 296.6 to 368.0
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Good effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Good Effects: Area Under Effect Curve (AUE) From 0-12 Hours
|
7.8 hrs*mm
Standard Deviation 28.24 • Interval 0.0 to 53.9
|
174.6 hrs*mm
Standard Deviation 153.23 • Interval 129.0 to 220.4
|
417.4 hrs*mm
Standard Deviation 158.39 • Interval 373.8 to 465.4
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Good effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Good Effects: Area Under Effect Curve (AUE) From 0-24 Hours
|
10.2 hrs*mm
Standard Deviation 34.73 • Interval -47.8 to 70.1
|
196.0 hrs*mm
Standard Deviation 176.48 • Interval 137.4 to 255.3
|
503.8 hrs*mm
Standard Deviation 223.88 • Interval 447.3 to 565.4
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Good effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score.
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Good Effects: Peak Effect (Emax)
|
1.8 mm
Standard Deviation 5.38 • Interval -4.6 to 8.6
|
32.6 mm
Standard Deviation 23.74 • Interval 26.2 to 39.4
|
63.0 mm
Standard Deviation 20.71 • Interval 56.7 to 69.9
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Good effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score.
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Good Effects: Time to Maximum (Peak) Effect (TEmax)
|
0.7 hrs
Standard Deviation 0.99 • Interval 0.0 to 1.4
|
2.5 hrs
Standard Deviation 2.13 • Interval 1.8 to 3.3
|
2.6 hrs
Standard Deviation 2.47 • Interval 1.9 to 3.3
|
SECONDARY outcome
Timeframe: 0.5 and 1 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Any effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Any Effects: Area Under Effect Curve (AUE) From 0-1 Hour
|
0.8 hrs*mm
Standard Deviation 2.23 • Interval -2.8 to 4.9
|
9.8 hrs*mm
Standard Deviation 12.17 • Interval 6.0 to 13.7
|
22.6 hrs*mm
Standard Deviation 14.89 • Interval 19.0 to 26.7
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5 and 2 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Any effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-2) = Area under the effect versus time curve from time 0 to 2 hrs (0-2).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Any Effects: Area Under Effect Curve (AUE) From 0-2 Hours
|
1.8 hrs*mm
Standard Deviation 6.41 • Interval -6.2 to 11.3
|
26.7 hrs*mm
Standard Deviation 28.59 • Interval 18.4 to 35.9
|
71.5 hrs*mm
Standard Deviation 33.15 • Interval 63.7 to 81.2
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3 and 4 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Any effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Any Effects: Area Under Effect Curve (AUE) From 0-4 Hours
|
3.2 hrs*mm
Standard Deviation 11.95 • Interval -12.2 to 21.8
|
63.8 hrs*mm
Standard Deviation 54.35 • Interval 47.9 to 81.9
|
172.2 hrs*mm
Standard Deviation 62.60 • Interval 156.9 to 191.0
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Any effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Any Effects: Area Under Effect Curve (AUE) From 0-8 Hours
|
6.4 hrs*mm
Standard Deviation 22.45 • Interval -21.4 to 38.4
|
125.6 hrs*mm
Standard Deviation 94.76 • Interval 97.3 to 157.1
|
331.8 hrs*mm
Standard Deviation 105.57 • Interval 304.3 to 364.2
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Any effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Any Effects: Area Under Effect Curve (AUE) From 0-12 Hours
|
7.8 hrs*mm
Standard Deviation 27.85 • Interval 0.0 to 48.2
|
155.4 hrs*mm
Standard Deviation 117.10 • Interval 119.3 to 195.2
|
422.5 hrs*mm
Standard Deviation 136.00 • Interval 387.5 to 463.4
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Any effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Any Effects: Area Under Effect Curve (AUE) From 0-24 Hours
|
10.2 hrs*mm
Standard Deviation 33.80 • Interval -36.0 to 62.7
|
176.4 hrs*mm
Standard Deviation 130.79 • Interval 129.6 to 228.3
|
510.8 hrs*mm
Standard Deviation 194.67 • Interval 465.6 to 564.4
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Any effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score.
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Any Effects: Peak Effect (Emax)
|
1.9 mm
Standard Deviation 5.35 • Interval -3.3 to 8.1
|
28.7 mm
Standard Deviation 20.03 • Interval 23.3 to 34.8
|
62.4 mm
Standard Deviation 18.59 • Interval 57.1 to 68.5
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Any effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score.
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Any Effects: Time to Maximum (Peak) Effect (TEmax)
|
0.8 hrs
Standard Deviation 0.99 • Interval 0.1 to 1.4
|
3.1 hrs
Standard Deviation 2.34 • Interval 2.5 to 3.8
|
2.8 hrs
Standard Deviation 2.03 • Interval 2.0 to 3.4
|
SECONDARY outcome
Timeframe: 0.5 and 1 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Bad effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Bad Effects: Area Under Effect Curve (AUE) From 0-1 Hour
|
0.3 hrs*mm
Standard Deviation 0.92 • Interval -0.4 to 1.1
|
0.6 hrs*mm
Standard Deviation 1.24 • Interval -0.1 to 1.4
|
1.5 hrs*mm
Standard Deviation 3.70 • Interval 0.9 to 2.4
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5 and 2 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Bad effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-2) = Area under the effect versus time curve from time 0 to 2 hrs (0-2).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Bad Effects: Area Under Effect Curve (AUE) From 0-2 Hours
|
0.5 hrs*mm
Standard Deviation 1.65 • Interval -1.9 to 3.5
|
2.6 hrs*mm
Standard Deviation 4.40 • Interval 0.2 to 5.5
|
7.4 hrs*mm
Standard Deviation 12.50 • Interval 5.1 to 10.4
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3 and 4 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Bad effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Bad Effects: Area Under Effect Curve (AUE) From 0-4 Hours
|
0.9 hrs*mm
Standard Deviation 3.20 • Interval -6.0 to 9.3
|
7.7 hrs*mm
Standard Deviation 13.27 • Interval 0.9 to 16.2
|
27.1 hrs*mm
Standard Deviation 36.06 • Interval 20.3 to 35.6
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Bad effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Bad Effects: Area Under Effect Curve (AUE) From 0-8 Hours
|
1.6 hrs*mm
Standard Deviation 5.84 • Interval -14.0 to 20.9
|
19.7 hrs*mm
Standard Deviation 37.56 • Interval 4.5 to 39.4
|
74.6 hrs*mm
Standard Deviation 80.92 • Interval 59.7 to 94.6
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Bad effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Bad Effects: Area Under Effect Curve (AUE) From 0-12 Hours
|
2.1 hrs*mm
Standard Deviation 7.82 • Interval 0.0 to 30.2
|
28.4 hrs*mm
Standard Deviation 56.67 • Interval 6.4 to 57.1
|
110.3 hrs*mm
Standard Deviation 116.60 • Interval 89.2 to 140.0
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Bad effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Bad Effects: Area Under Effect Curve (AUE) From 0-24 Hours
|
3.6 hrs*mm
Standard Deviation 13.62 • Interval -27.7 to 41.7
|
36.8 hrs*mm
Standard Deviation 76.50 • Interval 6.2 to 75.6
|
147.2 hrs*mm
Standard Deviation 157.74 • Interval 118.1 to 187.6
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Bad effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score.
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Bad Effects: Peak Effect (Emax)
|
0.6 mm
Standard Deviation 1.60 • Interval -3.4 to 5.4
|
6.6 mm
Standard Deviation 10.30 • Interval 2.6 to 11.4
|
20.1 mm
Standard Deviation 18.98 • Interval 16.3 to 25.1
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Bad effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score.
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Bad Effects: Time to Maximum (Peak) Effect (TEmax)
|
0.9 hrs
Standard Deviation 1.60 • Interval 0.1 to 1.9
|
2.2 hrs
Standard Deviation 2.38 • Interval 1.4 to 3.2
|
4.5 hrs
Standard Deviation 3.56 • Interval 3.7 to 5.5
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5 and 1 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Nausea VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Nausea: Area Under Effect Curve (AUE) From 0-1 Hour
|
0.4 hrs*mm
Standard Deviation 1.28 • Interval 0.0 to 1.0
|
0.5 hrs*mm
Standard Deviation 1.16 • Interval 0.0 to 1.1
|
0.8 hrs*mm
Standard Deviation 2.25 • Interval 0.3 to 1.4
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5 and 2 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Nausea VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-2) = Area under the effect versus time curve from time 0 to 2 hrs (0-2).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Nausea: Area Under Effect Curve (AUE) From 0-2 Hours
|
0.7 hrs*mm
Standard Deviation 1.73 • Interval -0.9 to 2.7
|
2.1 hrs*mm
Standard Deviation 4.12 • Interval 0.4 to 4.1
|
3.7 hrs*mm
Standard Deviation 8.14 • Interval 2.1 to 5.8
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3 and 4 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Nausea VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Nausea: Area Under Effect Curve (AUE) From 0-4 Hours
|
1.0 hrs*mm
Standard Deviation 2.78 • Interval -4.1 to 7.4
|
5.5 hrs*mm
Standard Deviation 11.30 • Interval 0.5 to 11.9
|
15.3 hrs*mm
Standard Deviation 26.61 • Interval 10.3 to 21.8
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Nausea VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Nausea: Area Under Effect Curve (AUE) From 0-8 Hours
|
1.6 hrs*mm
Standard Deviation 5.17 • Interval -12.2 to 20.4
|
16.5 hrs*mm
Standard Deviation 39.86 • Interval 2.8 to 35.3
|
47.1 hrs*mm
Standard Deviation 75.02 • Interval 34.3 to 66.8
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Nausea VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Nausea: Area Under Effect Curve (AUE) From 0-12 Hours
|
2.2 hrs*mm
Standard Deviation 7.42 • Interval 0.0 to 31.5
|
25.2 hrs*mm
Standard Deviation 61.13 • Interval 3.7 to 54.8
|
76.9 hrs*mm
Standard Deviation 119.64 • Interval 57.3 to 108.4
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Nausea VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Nausea: Area Under Effect Curve (AUE) From 0-24 Hours
|
3.8 hrs*mm
Standard Deviation 13.69 • Interval -26.9 to 44.4
|
35.3 hrs*mm
Standard Deviation 76.53 • Interval 5.0 to 76.3
|
108.3 hrs*mm
Standard Deviation 171.22 • Interval 80.7 to 152.1
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Nausea VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score.
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Nausea: Peak Effect (Emax)
|
0.8 mm
Standard Deviation 2.41 • Interval -2.5 to 5.3
|
5.2 mm
Standard Deviation 10.41 • Interval 1.8 to 9.6
|
14.9 mm
Standard Deviation 17.14 • Interval 11.8 to 19.6
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Nausea VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score.
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Nausea: Time to Maximum (Peak) Effect (TEmax)
|
1.4 hrs
Standard Deviation 4.17 • Interval 0.0 to 2.9
|
2.5 hrs
Standard Deviation 4.69 • Interval 1.1 to 4.0
|
4.3 hrs
Standard Deviation 3.52 • Interval 2.9 to 5.8
|
SECONDARY outcome
Timeframe: 0.5 and 1 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Feel sick VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour
|
0.3 hrs*mm
Standard Deviation 1.09 • Interval -0.3 to 1.2
|
0.3 hrs*mm
Standard Deviation 0.86 • Interval -0.3 to 1.1
|
1.0 hrs*mm
Standard Deviation 3.50 • Interval 0.4 to 1.9
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5 and 2 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Feel sick VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-2) = Area under the effect versus time curve from time 0 to 2 hrs (0-2).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Feel Sick: Area Under Effect Curve (AUE) From 0-2 Hours
|
0.6 hrs*mm
Standard Deviation 1.75 • Interval -1.3 to 3.1
|
1.7 hrs*mm
Standard Deviation 4.25 • Interval -0.3 to 4.1
|
4.2 hrs*mm
Standard Deviation 10.19 • Interval 2.3 to 6.7
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3 and 4 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Feel sick VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Feel Sick: Area Under Effect Curve (AUE) From 0-4 Hours
|
1.0 hrs*mm
Standard Deviation 3.22 • Interval -4.5 to 8.0
|
5.2 hrs*mm
Standard Deviation 12.28 • Interval -0.3 to 12.2
|
16.1 hrs*mm
Standard Deviation 28.88 • Interval 10.6 to 23.2
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Feel sick VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Feel Sick: Area Under Effect Curve (AUE) From 0-8 Hours
|
1.7 hrs*mm
Standard Deviation 6.27
|
14.8 hrs*mm
Standard Deviation 35.83
|
50.7 hrs*mm
Standard Deviation 72.35
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Feel sick VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Feel Sick: Area Under Effect Curve (AUE) From 0-12 Hours
|
2.3 hrs*mm
Standard Deviation 8.53
|
22.5 hrs*mm
Standard Deviation 54.79
|
80.9 hrs*mm
Standard Deviation 113.22
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Feel sick VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Feel Sick: Area Under Effect Curve (AUE) From 0-24 Hours
|
3.9 hrs*mm
Standard Deviation 14.72
|
31.1 hrs*mm
Standard Deviation 73.35
|
112.8 hrs*mm
Standard Deviation 160.44
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Feel sick VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score.
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Feel Sick: Peak Effect (Emax)
|
0.7 mm
Standard Deviation 1.96
|
4.9 mm
Standard Deviation 11.06
|
16.4 mm
Standard Deviation 17.38
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Feel sick VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score.
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Feel Sick: Time to Maximum (Peak) Effect (TEmax)
|
0.9 hrs
Standard Deviation 2.00
|
1.8 hrs
Standard Deviation 2.77
|
4.3 hrs
Standard Deviation 3.45
|
SECONDARY outcome
Timeframe: 0.5 and 1 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Sleepy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-1) = Area under the effect versus time curve from time 0 to 1 hr(0-1).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour
|
0.4 hrs*mm
Standard Deviation 1.30
|
2.4 hrs*mm
Standard Deviation 6.57
|
3.6 hrs*mm
Standard Deviation 5.13
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5 and 2 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Sleepy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-2) = Area under the effect versus time curve from time 0 to 2 hrs (0-2).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Sleepy: Area Under Effect Curve (AUE) From 0-2 Hours
|
0.7 hrs*mm
Standard Deviation 1.91
|
9.1 hrs*mm
Standard Deviation 12.63
|
21.3 hrs*mm
Standard Deviation 21.28
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3 and 4 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Sleepy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Sleepy: Area Under Effect Curve (AUE) From 0-4 Hours
|
1.7 hrs*mm
Standard Deviation 4.31
|
35.9 hrs*mm
Standard Deviation 38.78
|
74.2 hrs*mm
Standard Deviation 61.41
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Sleepy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Sleepy: Area Under Effect Curve (AUE) From 0-8 Hours
|
4.2 hrs*mm
Standard Deviation 10.15
|
97.6 hrs*mm
Standard Deviation 103.13
|
199.2 hrs*mm
Standard Deviation 141.96
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Sleepy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Sleepy: Area Under Effect Curve (AUE) From 0-12 Hours
|
5.3 hrs*mm
Standard Deviation 13.05
|
138.5 hrs*mm
Standard Deviation 140.93
|
287.5 hrs*mm
Standard Deviation 196.29
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Sleepy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Sleepy: Area Under Effect Curve (AUE) From 0-24 Hours
|
7.6 hrs*mm
Standard Deviation 21.06
|
175.5 hrs*mm
Standard Deviation 175.65
|
378.7 hrs*mm
Standard Deviation 267.76
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Sleepy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score.
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Sleepy: Peak Effect (Emax)
|
1.5 mm
Standard Deviation 3.71
|
27.1 mm
Standard Deviation 22.75
|
43.9 mm
Standard Deviation 21.93
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Sleepy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score.
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Sleepy: Time to Maximum (Peak) Effect (TEmax)
|
1.1 hrs
Standard Deviation 2.20
|
4.0 hrs
Standard Deviation 2.94
|
5.3 hrs
Standard Deviation 2.81
|
SECONDARY outcome
Timeframe: 0.5 and 1 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Dizzy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour
|
0.4 hrs*mm
Standard Deviation 1.28
|
0.9 hrs*mm
Standard Deviation 2.41
|
3.0 hrs*mm
Standard Deviation 5.73
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5 and 2 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Dizzy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-2) = Area under the effect versus time curve from time 0 to 2 hrs (0-2).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Dizzy: Area Under Effect Curve (AUE) From 0-2 Hours
|
0.6 hrs*mm
Standard Deviation 1.70
|
2.8 hrs*mm
Standard Deviation 6.26
|
9.9 hrs*mm
Standard Deviation 15.14
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3 and 4 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Dizzy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Dizzy: Area Under Effect Curve (AUE) From 0-4 Hours
|
1.0 hrs*mm
Standard Deviation 2.93
|
9.5 hrs*mm
Standard Deviation 21.81
|
26.1 hrs*mm
Standard Deviation 41.05
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Dizzy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Dizzy: Area Under Effect Curve (AUE) From 0-8 Hours
|
1.7 hrs*mm
Standard Deviation 5.93
|
20.9 hrs*mm
Standard Deviation 51.17
|
56.7 hrs*mm
Standard Deviation 87.00
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Dizzy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Dizzy: Area Under Effect Curve (AUE) From 0-12 Hours
|
2.4 hrs*mm
Standard Deviation 8.68
|
27.4 hrs*mm
Standard Deviation 66.65
|
71.4 hrs*mm
Standard Deviation 111.82
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Dizzy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Dizzy: Area Under Effect Curve (AUE) From 0-24 Hours
|
4.0 hrs*mm
Standard Deviation 14.73
|
36.0 hrs*mm
Standard Deviation 82.99
|
85.5 hrs*mm
Standard Deviation 135.09
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Dizzy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score.
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Dizzy: Peak Effect (Emax)
|
0.7 mm
Standard Deviation 2.45
|
5.5 mm
Standard Deviation 11.18
|
13.7 mm
Standard Deviation 17.66
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Dizzy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score.
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Dizzy: Time to Maximum (Peak) Effect (TEmax)
|
0.5 hrs
Standard Deviation 0.09
|
2.0 hrs
Standard Deviation 2.57
|
2.4 hrs
Standard Deviation 2.60
|
SECONDARY outcome
Timeframe: 24 hrs post dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Overall drug liking VAS assesses the participant's global perception of drug liking (that is, effects over the whole course of the drug experience including any carryover effects). A 100 mm VAS is used to assess response based on a score ranging from 0 mm to 100 mm (0 mm = "strong disliking", 50 mm= "neither like nor dislike", and 100 mm= "strong liking").
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Overall Drug Liking Effect at 24 Hours
|
50.6 mm
Standard Deviation 3.06
|
58.8 mm
Standard Deviation 17.68
|
69.8 mm
Standard Deviation 20.23
|
SECONDARY outcome
Timeframe: 24 hrs post dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Take drug again VAS is a subjective assessment of the degree to which a participant would desire to take the drug again if given the opportunity. It is presented on a 100 mm VAS with score ranging from 0 mm to 100 mm (score of 0 mm = "definitely would not", 50 mm = "do not care", and 100 mm = "definitely would").
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Take Drug Again Effect at 24 Hours
|
49.8 mm
Standard Deviation 4.41
|
58.0 mm
Standard Deviation 21.90
|
70.6 mm
Standard Deviation 24.53
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5 and 1 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Pupillometry assessments measured change in pupil size (miosis) as an indicator of opioid pharmacological properties. The same eye for each participant was used for all measurements during the study. Participants had the size of their pupil measured (in mm) using a pupillometer. Measurements were made in a dimly lit (mesopic) room with controlled lighting conditions. AUE (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour
|
0.0 hrs*mm
Standard Deviation 0.40
|
-0.5 hrs*mm
Standard Deviation 0.38
|
-1.2 hrs*mm
Standard Deviation 0.60
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5 and 2 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Pupillometry assessments measured change in pupil size (miosis) as an indicator of opioid pharmacological properties. The same eye for each participant was used for all measurements during the study. Participants had the size of their pupil measured (in mm) using a pupillometer. Measurements were made in a dimly lit (mesopic) room with controlled lighting conditions. AUE (0-2) = Area under the effect versus time curve from time 0 to 2 hrs (0-2).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Pupillometry: Area Under Effect Curve (AUE) From 0-2 Hours
|
0.0 hrs*mm
Standard Deviation 0.87
|
-1.7 hrs*mm
Standard Deviation 1.07
|
-4.1 hrs*mm
Standard Deviation 1.31
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3 and 4 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Pupillometry assessments measured change in pupil size (miosis) as an indicator of opioid pharmacological properties. The same eye for each participant was used for all measurements during the study. Participants had the size of their pupil measured (in mm) using a pupillometer. Measurements were made in a dimly lit (mesopic) room with controlled lighting conditions. AUE (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Pupillometry: Area Under Effect Curve (AUE) From 0-4 Hours
|
-0.1 hrs*mm
Standard Deviation 1.67
|
-5.4 hrs*mm
Standard Deviation 2.29
|
-10.3 hrs*mm
Standard Deviation 2.58
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Pupillometry assessments measured change in pupil size (miosis) as an indicator of opioid pharmacological properties. The same eye for each participant was used for all measurements during the study. Participants had the size of their pupil measured (in mm) using a pupillometer. Measurements were made in a dimly lit (mesopic) room with controlled lighting conditions. AUE (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Pupillometry: Area Under Effect Curve (AUE) From 0-8 Hours
|
0.0 hrs*mm
Standard Deviation 3.25
|
-13.8 hrs*mm
Standard Deviation 4.36
|
-22.5 hrs*mm
Standard Deviation 5.35
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Pupillometry assessments measured change in pupil size (miosis) as an indicator of opioid pharmacological properties. The same eye for each participant was used for all measurements during the study. Participants had the size of their pupil measured (in mm) using a pupillometer. Measurements were made in a dimly lit (mesopic) room with controlled lighting conditions. AUE (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Pupillometry: Area Under Effect Curve (AUE) From 0-12 Hours
|
0.7 hrs*mm
Standard Deviation 4.78
|
-20.8 hrs*mm
Standard Deviation 6.80
|
-32.6 hrs*mm
Standard Deviation 7.95
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Pupillometry assessments measured change in pupil size (miosis) as an indicator of opioid pharmacological properties. The same eye for each participant was used for all measurements during the study. Participants had the size of their pupil measured (in mm) using a pupillometer. Measurements were made in a dimly lit (mesopic) room with controlled lighting conditions. AUE (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24).
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Pupillometry: Area Under Effect Curve (AUE) From 0-24 Hours
|
3.5 hrs*mm
Standard Deviation 9.19
|
-34.2 hrs*mm
Standard Deviation 13.96
|
-51.8 hrs*mm
Standard Deviation 15.26
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Pupillometry assessments measured change in pupil size (miosis) as an indicator of opioid pharmacological properties. The same eye for each participant was used for all measurements during the study. Participants had the size of their pupil measured (in mm) using a pupillometer. Measurements were made in a dimly lit (mesopic) room with controlled lighting conditions. Emax = Smallest post-dose pupil size.
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Pupillometry: Peak Effect (Emax)
|
5.6 mm
Standard Deviation 0.76
|
3.9 mm
Standard Deviation 0.71
|
2.8 mm
Standard Deviation 0.74
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dosePopulation: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
Pupillometry assessments measured change in pupil size (miosis) as an indicator of opioid pharmacological properties. The same eye for each participant was used for all measurements during the study. Participants had the size of their pupil measured (in mm) using a pupillometer. Measurements were made in a dimly lit (mesopic) room with controlled lighting conditions. TEmax = Time to smallest post-dose pupil size.
Outcome measures
| Measure |
Placebo
n=33 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
n=33 Participants
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Pupillometry: Time to Maximum (Peak) Effect (TEmax)
|
4.8 hrs
Standard Deviation 6.83
|
5.6 hrs
Standard Deviation 2.26
|
3.2 hrs
Standard Deviation 1.64
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dosePopulation: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
Outcome measures
| Measure |
Placebo
n=35 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Morphine
|
0.9 hrs
Standard Deviation 0.48
|
0.7 hrs
Standard Deviation 0.25
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dosePopulation: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
Outcome measures
| Measure |
Placebo
n=35 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Morphine
|
79308.6 picogram/milliliter (pg/mL)
Standard Deviation 31555.86
|
103621 picogram/milliliter (pg/mL)
Standard Deviation 34005.3
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5 and 1 hrs post-dosePopulation: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
AUC (0-1) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-1).
Outcome measures
| Measure |
Placebo
n=35 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-1)] of Morphine
|
52644.9 hrs*pg/mL
Standard Deviation 19951.60
|
67920.1 hrs*pg/mL
Standard Deviation 24702.80
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5 and 2 hrs post-dosePopulation: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
AUC (0-2) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-2).
Outcome measures
| Measure |
Placebo
n=35 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-2)] of Morphine
|
112989 hrs*pg/mL
Standard Deviation 33784.6
|
129721 hrs*pg/mL
Standard Deviation 39670.7
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3 and 4 hrs post-dosePopulation: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
AUC (0-4) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-4).
Outcome measures
| Measure |
Placebo
n=35 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-4)] of Morphine
|
197745 hrs*pg/mL
Standard Deviation 54807.4
|
199442 hrs*pg/mL
Standard Deviation 60559.8
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dosePopulation: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
AUC (0-8) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-8).
Outcome measures
| Measure |
Placebo
n=35 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-8)] of Morphine
|
269743 hrs*pg/mL
Standard Deviation 77664.5
|
263270 hrs*pg/mL
Standard Deviation 76706.0
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dosePopulation: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
AUC (0-12) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-12).
Outcome measures
| Measure |
Placebo
n=35 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-12)] of Morphine
|
303428 hrs*pg/mL
Standard Deviation 86669.9
|
288324 hrs*pg/mL
Standard Deviation 81697.4
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dosePopulation: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
AUC (0-24) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-24).
Outcome measures
| Measure |
Placebo
n=35 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)] of Morphine
|
376260 hrs*pg/mL
Standard Deviation 104635.5
|
335357 hrs*pg/mL
Standard Deviation 91242.6
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dosePopulation: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).
Outcome measures
| Measure |
Placebo
n=35 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
n=33 Participants
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Morphine
|
551755 hrs*pg/mL
Standard Deviation 476987.0
|
369270 hrs*pg/mL
Standard Deviation 98821.5
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dosePopulation: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
Outcome measures
| Measure |
Placebo
n=35 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Naltrexone
|
0.8 hrs
Standard Deviation 0.32
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dosePopulation: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
Outcome measures
| Measure |
Placebo
n=35 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Naltrexone
|
978.83 pg/mL
Standard Deviation 713.748
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5 and 1 hrs post-dosePopulation: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
AUC (0-1) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-1).
Outcome measures
| Measure |
Placebo
n=35 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-1)] of Naltrexone
|
619.24 hrs*pg/mL
Standard Deviation 441.602
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5 and 2 hrs post-dosePopulation: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
AUC (0-2) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-2).
Outcome measures
| Measure |
Placebo
n=35 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-2)] of Naltrexone
|
1270.91 hrs*pg/mL
Standard Deviation 700.063
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3 and 4 hrs post-dosePopulation: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
AUC (0-4) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-4).
Outcome measures
| Measure |
Placebo
n=35 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-4)] of Naltrexone
|
2018.23 hrs*pg/mL
Standard Deviation 1000.217
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dosePopulation: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
AUC (0-8) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-8).
Outcome measures
| Measure |
Placebo
n=35 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-8)] of Naltrexone
|
2577.19 hrs*pg/mL
Standard Deviation 1228.398
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dosePopulation: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
AUC (0-12) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-12).
Outcome measures
| Measure |
Placebo
n=35 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-12)] of Naltrexone
|
2813.34 hrs*pg/mL
Standard Deviation 1337.306
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dosePopulation: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
AUC (0-24) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-24).
Outcome measures
| Measure |
Placebo
n=35 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)] of Naltrexone
|
3159.91 hrs*pg/mL
Standard Deviation 1522.915
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dosePopulation: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).
Outcome measures
| Measure |
Placebo
n=35 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Naltrexone
|
3320.90 hrs*pg/mL
Standard Deviation 1616.514
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dosePopulation: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
Outcome measures
| Measure |
Placebo
n=35 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Naltrexone Metabolite (6-beta-naltrexol)
|
1.0 hrs
Standard Deviation 0.61
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dosePopulation: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
Outcome measures
| Measure |
Placebo
n=35 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Naltrexone Metabolite (6-beta-naltrexol)
|
6226.3 pg/mL
Standard Deviation 2158.29
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5 and 1 hrs post-dosePopulation: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
AUC (0-1) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-1).
Outcome measures
| Measure |
Placebo
n=35 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-1)] of Naltrexone Metabolite (6-beta-naltrexol)
|
3934.5 hrs*pg/mL
Standard Deviation 1529.66
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5 and 2 hrs post-dosePopulation: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
AUC (0-2) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-2).
Outcome measures
| Measure |
Placebo
n=35 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-2)] of Naltrexone Metabolite (6-beta-naltrexol)
|
8916.1 hrs*pg/mL
Standard Deviation 2747.62
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3 and 4 hrs post-dosePopulation: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
AUC (0-4) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-4).
Outcome measures
| Measure |
Placebo
n=35 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-4)] of Naltrexone Metabolite (6-beta-naltrexol)
|
16532.5 hrs*pg/mL
Standard Deviation 4351.58
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dosePopulation: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
AUC (0-8) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-8).
Outcome measures
| Measure |
Placebo
n=35 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-8)] of Naltrexone Metabolite (6-beta-naltrexol)
|
26634.5 hrs*pg/mL
Standard Deviation 6167.97
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dosePopulation: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
AUC (0-12) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-12).
Outcome measures
| Measure |
Placebo
n=35 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-12)] of Naltrexone Metabolite (6-beta-naltrexol)
|
33324.9 hrs*pg/mL
Standard Deviation 7309.76
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dosePopulation: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
AUC (0-24) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-24).
Outcome measures
| Measure |
Placebo
n=35 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)] of Naltrexone Metabolite (6-beta-naltrexol)
|
47809.1 hrs*pg/mL
Standard Deviation 10184.33
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dosePopulation: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).
Outcome measures
| Measure |
Placebo
n=35 Participants
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|
|
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Naltrexone Metabolite (6-beta-naltrexol)
|
74931.5 hrs*pg/mL
Standard Deviation 25580.10
|
—
|
—
|
Adverse Events
Naloxone (Naloxone Challenge Phase)
Placebo (Drug Discrimination Phase)
Morphine (Drug Discrimination Phase)
Placebo (Treatment Phase)
EMBEDA (Treatment Phase)
Morphine (Treatment Phase)
Serious adverse events
| Measure |
Naloxone (Naloxone Challenge Phase)
n=59 participants at risk
Naloxone hydrochloride 0.2 mg IV followed by additional 0.6 mg naloxone hydrochloride IV, each dose followed by an assessment for signs of withdrawal.
|
Placebo (Drug Discrimination Phase)
n=58 participants at risk
Single dose of matching placebo solution orally on Day 1 or 2.
|
Morphine (Drug Discrimination Phase)
n=59 participants at risk
Single dose of morphine sulfate 120 mg solution orally on Day 1 or 2.
|
Placebo (Treatment Phase)
n=36 participants at risk
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA (Treatment Phase)
n=35 participants at risk
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine (Treatment Phase)
n=33 participants at risk
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|---|---|---|
|
Psychiatric disorders
Bipolar Disorder
|
0.00%
0/59
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
0.00%
0/58
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
0.00%
0/59
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
0.00%
0/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
2.9%
1/35
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
0.00%
0/33
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Psychiatric disorders
Schizoaffective Disorder
|
0.00%
0/59
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
0.00%
0/58
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
0.00%
0/59
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
0.00%
0/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
2.9%
1/35
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
0.00%
0/33
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
Other adverse events
| Measure |
Naloxone (Naloxone Challenge Phase)
n=59 participants at risk
Naloxone hydrochloride 0.2 mg IV followed by additional 0.6 mg naloxone hydrochloride IV, each dose followed by an assessment for signs of withdrawal.
|
Placebo (Drug Discrimination Phase)
n=58 participants at risk
Single dose of matching placebo solution orally on Day 1 or 2.
|
Morphine (Drug Discrimination Phase)
n=59 participants at risk
Single dose of morphine sulfate 120 mg solution orally on Day 1 or 2.
|
Placebo (Treatment Phase)
n=36 participants at risk
Single dose of matching placebo solution orally in either of the first to third intervention periods.
|
EMBEDA (Treatment Phase)
n=35 participants at risk
Single dose of solution of EMBEDA ER capsule containing 120 mg morphine sulfate and 4.8 mg naltrexone hydrochloride orally in either of the first to third intervention periods.
|
Morphine (Treatment Phase)
n=33 participants at risk
Single dose of solution of morphine sulfate (MS Contin) CR tablet 120 mg orally in either of the first to third intervention periods.
|
|---|---|---|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/59
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
0.00%
0/58
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
61.0%
36/59
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
2.8%
1/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
8.6%
3/35
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
45.5%
15/33
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/59
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
0.00%
0/58
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
45.8%
27/59
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
0.00%
0/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
0.00%
0/35
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
42.4%
14/33
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Nervous system disorders
Dizziness
|
0.00%
0/59
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
0.00%
0/58
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
18.6%
11/59
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
0.00%
0/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
5.7%
2/35
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
18.2%
6/33
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Nervous system disorders
Somnolence
|
0.00%
0/59
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
0.00%
0/58
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
16.9%
10/59
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
0.00%
0/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
11.4%
4/35
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
9.1%
3/33
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Nervous system disorders
Headache
|
0.00%
0/59
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
1.7%
1/58
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
6.8%
4/59
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
2.8%
1/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
0.00%
0/35
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
6.1%
2/33
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/59
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
0.00%
0/58
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
40.7%
24/59
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
0.00%
0/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
5.7%
2/35
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
36.4%
12/33
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Skin and subcutaneous tissue disorders
Pruritus generalised
|
0.00%
0/59
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
0.00%
0/58
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
8.5%
5/59
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
0.00%
0/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
5.7%
2/35
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
9.1%
3/33
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
General disorders
Pain
|
0.00%
0/59
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
0.00%
0/58
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
5.1%
3/59
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
0.00%
0/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
0.00%
0/35
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
0.00%
0/33
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
0.00%
0/59
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
0.00%
0/58
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
0.00%
0/59
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
0.00%
0/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
0.00%
0/35
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
15.2%
5/33
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
- Publication restrictions are in place
Restriction type: OTHER