Cancer, Pain
Conditions
Keywords
Breakthrough Pain in Patients with Cancer
Brief summary
The purpose of this study is to evaluate the efficacy of BEMA Fentanyl (Onsolis) at any dose in the management of breakthrough pain in cancer subjects on background opioid therapy. The standard of care for these breakthrough pain episodes is a rapid onset, short acting analgesic with minimal associated sleepiness. Oral morphine, oxycodone and hydromorphone are routinely used, but because of slow and variable oral absorption, the pain control is not the best with these products. Oral transmucosal fentanyl citrate (OTFC) has been used successfully in treating breakthrough pain episodes associated with cancer. OTFC is a lozenge of fentanyl on a stick and is administered by continuously swabbing the interior of the subject's mouth until the product is dissolved (approximately 15 to 30 minutes). The buccal route of administration avoids the delay and variability associated with oral absorption.
Detailed description
This is a randomized, double-blind, placebo controlled, multiple cross-over study. Eligible subjects will be treated with open label BEMA fentanyl over a period of up to two weeks. Doses will be titrated upward, starting at 200 μg, until a dose is identified that produces satisfactory pain relief for at least 2 episodes. Those subjects who identify a dose of BEMA fentanyl that produces satisfactory relief of breakthrough pain episodes will enter the double-blind, placebo controlled period of the trial. They will receive 3 placebo doses and 6 BEMA fentanyl doses in a random sequence per randomization schedule.
Interventions
DRUGBEMA™
BioDelivery Sciences International, Inc. (BDSI) has developed BioErodible MucoAdhesive (BEMA) Fentanyl, an alternative product to OTFC that does not require the subject to continuously paint the inside of the mouth with the dosage form. The BDSI product is a small soluble film that is placed against the mucosal membrane inside the mouth. The mucoadhesive polymers in the film readily adhere to the mucosal membrane (within 5 seconds) when moistened. The components of the film are water soluble, so the entire dosage form dissolves within 30 minutes of application.
DRUGPlacebo
Sponsors
BioDelivery Sciences International
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or non-pregnant and non-lactating female. A female of child-bearing potential is eligible to participate in this study if she is using an acceptable method of birth control. * 18 years or older * Patient must have pain associated with cancer or cancer treatment. * Patient must be on a stable current regimen of oral opioids equivalent to 60 - 1000 mg/day of oral morphine or 50 - 300 µg/hr of transdermal fentanyl (e.g. oxycodone 30 mg, methadone 20 mg, and hydromorphone 7.5 mg). * Regularly experiences 1 - 4 breakthrough pain episodes per day that require additional opioids for pain control * At least partial relief of breakthrough pain by use of opioid therapy * Subject must be able to self-administer the study medication correctly. * Subject must be willing and able to complete the electronic diary card with each pain episode. * Signed consent must be obtained at screening prior to any procedures being performed.
Exclusion criteria
* Psychiatric/cognitive or neurological impairment that would limit the subject's ability to understand or complete the diary * Cardiopulmonary disease that, in the opinion of the investigator, would significantly increase the risk of respiratory depression * Recent history or current evidence of alcohol or other drug substance (licit or illicit) abuse * Rapidly escalating pain that the investigator believes may require an increase in the dosage of background pain medication during the study * Moderate (Grade 3) to severe (Grade 4) mucositis (Subjects with less than moderate mucositis are permitted and must be instructed to not apply the BEMA disc at a site of inflammation.) * Strontium 89 therapy within the previous 6 months * Any other therapy prior to the study that the investigator considers could alter pain or the response to pain medication. * Use of an investigational drug within 4 weeks preceding this study * History of hypersensitivity or intolerance to fentanyl * Regularly more than 4 episodes per day * Eastern Cooperative Oncology Group (ECOG) performance status of 4 or 5 * Subject is pregnant, actively trying to become pregnant, breast feeding or not using adequate contraceptive measures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Summary of Pain Intensity Differences (SPID) | 0-30 minutes | Pain intensity (using an 11-point \[0 = no pain to 10 = worst pain\] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point. The primary endpoint was the Summary of Pain Intensity Differences at 30 minutes after dosing (SPID 30) in ITT population for Onsolis versus placebo during double-blind period of study. SPID was calculated as a weighted sum of the PID of all time points at or before time point of interest.Range of possible SPID values is -10X time point (minutes) to 10X time point (minutes). Higher value indicates a better outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| SPID | 0-5 minutes | Pain intensity (using an 11-point \[0 = no pain to 10 = worst pain\] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point. The primary endpoint was the Summary of Pain Intensity Differences at 30 minutes after dosing (SPID 30) in ITT population for Onsolis versus placebo during double-blind period of study. SPID was calculated as a weighted sum of the PID of all time points at or before time point of interest.Range of possible SPID values is -10X time point (minutes) to 10X time point (minutes). Higher value indicates a better outcome.SPID was calculated as a weighted sum of the pain intensity difference of all time points at or before the time point of interest. |
| PID | 5 minutes after dosing | Pain intensity (using an 11-point \[0 = no pain to 10 = worst pain\] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point. |
| Pain Relief | 5 minutes after dosing | Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief) at 5, 10, 15, 30, 45, and 60 minutes after taking the study medication or until rescue. |
| Total Pain Relief | 5 minutes | Total Pain Relief (TOTPAR) is calculated as the weighted sum of the pain relief (PR) of all time points at or prior to the time point of interest.Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief)compared to baseline (pre-dose) |
| Subject Overall Satisfaction With Study Drug | 60 minutes or at time of rescue medication use | Subjects evaluated their overall satisfaction with study drug at the time rescue medication was consumed or at the 60-minute time point using a 5-point categorical scale (0 = poor, 1 = fair, 2 = good, 3 = very good, and 4 = excellent). |
| Episodes With at Least 50% Decreases in Pain | 15 minutes | Number of episodes where the total pain score has at least a 50% reduction from baseline. |
| Episodes With at Least 33% Decreases in Pain | 15 minutes | Number of episodes where the total pain score has at least a 33% reduction from baseline. |
| Episodes With Complete Pain Relief | 5 minutes | Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief). Percentage of episodes with complete relief per subject is analyzed where a complete pain relief episode is defined as pain relief of value 4 at the specified time point. |
| Rescue Medication Usage | 28 Days | Rescue medication is medication taken if adequate pain relief is not realized within 30 minutes following application of the study drug. Percentage of episodes when rescue medication was used per subject is analyzed. |
| Percentage of Pain Free Episodes | 5 minutes | A pain free episode is one with 0 pain intensity at the specified time point. Percentage of episodes that are pain-free per subject is analyzed. |
Other
| Measure | Time frame | Description |
|---|---|---|
| SPID in Neuropathic Pain Subpopulation | 15 minutes | Pain intensity (using an 11-point \[0 = no pain to 10 = worst pain\] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point. The primary endpoint was the Summary of Pain Intensity Differences at 30 minutes after dosing (SPID 30) in ITT population for Onsolis versus placebo during double-blind period of study. SPID was calculated as a weighted sum of the PID of all time points at or before time point of interest.Range of possible SPID values is -10X time point (minutes) to 10X time point (minutes). Higher value indicates a better outcome. SPID was calculated as a weighted sum of the pain intensity difference of all time points at or before the time point of interest for the Neuropathic pain subpopulation for relevant time points (15, 30, 45, 60 minutes). Neuropathic pain subpopulation is a subset of ITT population who have neuropathic pain at baseline. |
Countries
United States
Participant flow
Recruitment details
24FEB2006 to 14MAR2007
Pre-assignment details
During the open-label titration period, subjects were treated with Onsolis at escalating doses (200, 400, 600, 800, and 1200 μg) over a period of up to two weeks until subjects identified a dose that produced satisfactory pain relief for at least two episodes.
Participants by arm
| Arm | Count |
|---|---|
| Onsolis Includes all subjects and all dose levels | 151 |
| Total | 151 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Double-blind Treatment Period | Adverse Event | 3 |
| Double-blind Treatment Period | Lack of Efficacy | 1 |
| Double-blind Treatment Period | Noncompliance | 4 |
| Double-blind Treatment Period | Withdrawal by Subject | 4 |
| Open-label Titration Period | Adverse Event | 10 |
| Open-label Titration Period | Death | 3 |
| Open-label Titration Period | Lack of Efficacy | 5 |
| Open-label Titration Period | Noncompliance and other | 27 |
| Open-label Titration Period | Protocol Violation | 2 |
| Open-label Titration Period | Withdrawal by Subject | 22 |
Baseline characteristics
| Characteristic | Onsolis |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 47 Participants |
| Age, Categorical Between 18 and 65 years | 104 Participants |
| Age, Continuous | 57.1 years STANDARD_DEVIATION 12.2 |
| Female reproductive status Male | 67 Participants |
| Female reproductive status Post-menopausal | 43 Participants |
| Female reproductive status Potentially able to bear children | 3 Participants |
| Female reproductive status Sterile | 38 Participants |
| Height (inches) | 66.4 Inches STANDARD_DEVIATION 3.86 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 7 Participants |
| Race (NIH/OMB) White | 131 Participants |
| Region of Enrollment United States | 151 participants |
| Sex: Female, Male Female | 85 Participants |
| Sex: Female, Male Male | 66 Participants |
| Weight (pounds) | 160.89 pounds STANDARD_DEVIATION 42.011 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 44 / 151 |
| serious Total, serious adverse events | 23 / 151 |
Outcome results
Primary
Summary of Pain Intensity Differences (SPID)
Pain intensity (using an 11-point \[0 = no pain to 10 = worst pain\] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point. The primary endpoint was the Summary of Pain Intensity Differences at 30 minutes after dosing (SPID 30) in ITT population for Onsolis versus placebo during double-blind period of study. SPID was calculated as a weighted sum of the PID of all time points at or before time point of interest.Range of possible SPID values is -10X time point (minutes) to 10X time point (minutes). Higher value indicates a better outcome.
Time frame: 0-30 minutes
Population: In double-blind period, subjects received 3 doses placebo and 6 doses Onsolis. Mean SPID of Onsolis episodes and mean SPID of placebo episodes are calculated per subject and are used in analysis.Missing data were imputed on an episode-by-episode basis by carrying forward last observed data value (last observation carried forward \[LOCF\]).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | Summary of Pain Intensity Differences (SPID) | 47.9 Score on a scale | Standard Error 3.87 |
| Placebo | Summary of Pain Intensity Differences (SPID) | 38.1 Score on a scale | Standard Error 4.3 |
p-value: 0.00495% CI: [3.31, 16.18]Mixed Models Analysis
Secondary
Episodes With at Least 33% Decreases in Pain
Number of episodes where the total pain score has at least a 33% reduction from baseline.
Time frame: 15 minutes
Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis.~All efficacy analyses were conducted using the intent-to-treat (ITT) population.~Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | Episodes With at Least 33% Decreases in Pain | 26.4 episodes | Standard Error 3.55 |
| Placebo | Episodes With at Least 33% Decreases in Pain | 21.3 episodes | Standard Error 3.66 |
p-value: 0.1Wilcoxon (Mann-Whitney)
Secondary
Episodes With at Least 33% Decreases in Pain
Number of episodes where the total pain score has at least a 33% reduction from baseline.
Time frame: 30 minutes
Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis.~All efficacy analyses were conducted using the intent-to-treat (ITT) population.~Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | Episodes With at Least 33% Decreases in Pain | 47.3 episodes | Standard Error 4.05 |
| Placebo | Episodes With at Least 33% Decreases in Pain | 38.2 episodes | Standard Error 4.45 |
p-value: 0.009Wilcoxon (Mann-Whitney)
Secondary
Episodes With at Least 33% Decreases in Pain
Number of episodes where the total pain score has at least a 50% reduction from baseline.
Time frame: 60 minutes
Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis.~All efficacy analyses were conducted using the intent-to-treat (ITT) population.~Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | Episodes With at Least 33% Decreases in Pain | 64.3 episodes | Standard Error 3.72 |
| Placebo | Episodes With at Least 33% Decreases in Pain | 48.2 episodes | Standard Error 4.51 |
p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
Episodes With at Least 33% Decreases in Pain
Number of episodes where the total pain score has at least a 33% reduction from baseline.
Time frame: 45 minutes
Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis.~All efficacy analyses were conducted using the intent-to-treat (ITT) population.~Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | Episodes With at Least 33% Decreases in Pain | 57.5 episodes | Standard Error 3.93 |
| Placebo | Episodes With at Least 33% Decreases in Pain | 46.5 episodes | Standard Error 4.5 |
p-value: 0.004Wilcoxon (Mann-Whitney)
Secondary
Episodes With at Least 50% Decreases in Pain
Number of episodes where the total pain score has at least a 50% reduction from baseline.
Time frame: 30 minutes
Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis.~All efficacy analyses were conducted using the intent-to-treat (ITT) population.~Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | Episodes With at Least 50% Decreases in Pain | 32.8 episodes | Standard Error 3.78 |
| Placebo | Episodes With at Least 50% Decreases in Pain | 24.1 episodes | Standard Error 3.87 |
p-value: 0.002Wilcoxon (Mann-Whitney)
Secondary
Episodes With at Least 50% Decreases in Pain
Number of episodes where the total pain score has at least a 50% reduction from baseline.
Time frame: 45 minutes
Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis.~All efficacy analyses were conducted using the intent-to-treat (ITT) population.~Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | Episodes With at Least 50% Decreases in Pain | 41.1 episodes | Standard Error 4.11 |
| Placebo | Episodes With at Least 50% Decreases in Pain | 30.5 episodes | Standard Error 4.1 |
p-value: 0.008Wilcoxon (Mann-Whitney)
Secondary
Episodes With at Least 50% Decreases in Pain
Number of episodes where the total pain score has at least a 50% reduction from baseline.
Time frame: 60 minutes
Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis.~All efficacy analyses were conducted using the intent-to-treat (ITT) population.~Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | Episodes With at Least 50% Decreases in Pain | 46.1 episodes | Standard Error 4.17 |
| Placebo | Episodes With at Least 50% Decreases in Pain | 34.0 episodes | Standard Error 4.3 |
p-value: 0.005Wilcoxon (Mann-Whitney)
Secondary
Episodes With at Least 50% Decreases in Pain
Number of episodes where the total pain score has at least a 50% reduction from baseline.
Time frame: 15 minutes
Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis.~All efficacy analyses were conducted using the intent-to-treat (ITT) population.~Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | Episodes With at Least 50% Decreases in Pain | 14.9 episodes | Standard Error 2.81 |
| Placebo | Episodes With at Least 50% Decreases in Pain | 14.7 episodes | Standard Error 3.35 |
p-value: 0.963Wilcoxon (Mann-Whitney)
Secondary
Episodes With Complete Pain Relief
Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief). Percentage of episodes with complete relief per subject is analyzed where a complete pain relief episode is defined as pain relief of value 4 at the specified time point.
Time frame: 45 minutes
Population: All efficacy analyses were conducted using the intent-to-treat (ITT) population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | Episodes With Complete Pain Relief | 9.4 percentage of episodes | Standard Error 2.18 |
| Placebo | Episodes With Complete Pain Relief | 6.4 percentage of episodes | Standard Error 2.27 |
p-value: 0.131Wilcoxon (Mann-Whitney)
Secondary
Episodes With Complete Pain Relief
Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief).Percentage of episodes with complete relief per subject is analyzed where a complete pain relief episode is defined as pain relief of value 4 at the specified time point.
Time frame: 15 minutes
Population: All efficacy analyses were conducted using the intent-to-treat (ITT) population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | Episodes With Complete Pain Relief | 1.7 percentage of episodes | Standard Error 0.83 |
| Placebo | Episodes With Complete Pain Relief | 1.3 percentage of episodes | Standard Error 0.94 |
p-value: 0.75Wilcoxon (Mann-Whitney)
Secondary
Episodes With Complete Pain Relief
Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief).Percentage of episodes with complete relief per subject is analyzed where a complete pain relief episode is defined as pain relief of value 4 at the specified time point.
Time frame: 10 minutes
Population: All efficacy analyses were conducted using the intent-to-treat (ITT) population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | Episodes With Complete Pain Relief | 1.0 percentage of episodes | Standard Error 0.72 |
| Placebo | Episodes With Complete Pain Relief | 0.7 percentage of episodes | Standard Error 0.68 |
p-value: 1Wilcoxon (Mann-Whitney)
Secondary
Episodes With Complete Pain Relief
Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief). Percentage of episodes with complete relief per subject is analyzed where a complete pain relief episode is defined as pain relief of value 4 at the specified time point.
Time frame: 5 minutes
Population: All efficacy analyses were conducted using the intent-to-treat (ITT) population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | Episodes With Complete Pain Relief | 0.7 percentage of episodes | Standard Error 0.66 |
| Placebo | Episodes With Complete Pain Relief | 0.7 percentage of episodes | Standard Error 0.68 |
p-value: 1Wilcoxon (Mann-Whitney)
Secondary
Episodes With Complete Pain Relief
Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief). Percentage of episodes with complete relief per subject is analyzed where a complete pain relief episode is defined as pain relief of value 4 at the specified time point.
Time frame: 60 minutes
Population: All efficacy analyses were conducted using the intent-to-treat (ITT) population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | Episodes With Complete Pain Relief | 12.8 percentage of episodes | Standard Error 2.49 |
| Placebo | Episodes With Complete Pain Relief | 7.2 percentage of episodes | Standard Error 2.4 |
p-value: 0.007Wilcoxon (Mann-Whitney)
Secondary
Episodes With Complete Pain Relief
Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief). Percentage of episodes with complete relief per subject is analyzed where a complete pain relief episode is defined as pain relief of value 4 at the specified time point.
Time frame: 30 minutes
Population: All efficacy analyses were conducted using the intent-to-treat (ITT) population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | Episodes With Complete Pain Relief | 5.4 percentage of episodes | Standard Error 1.63 |
| Placebo | Episodes With Complete Pain Relief | 2.6 percentage of episodes | Standard Error 1.33 |
p-value: 0.032Wilcoxon (Mann-Whitney)
Secondary
Pain Relief
Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief) at 5, 10, 15, 30, 45, and 60 minutes after taking the study medication or until rescue.
Time frame: 5 minutes after dosing
Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis.~All efficacy analyses were conducted using the intent-to-treat (ITT) population.~Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | Pain Relief | 0.4 Scores on a scale | Standard Error 0.04 |
| Placebo | Pain Relief | 0.4 Scores on a scale | Standard Error 0.06 |
p-value: 0.193Wilcoxon (Mann-Whitney)
Secondary
Pain Relief
Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief) at 5, 10, 15, 30, 45, and 60 minutes after taking the study medication or until rescue.
Time frame: 10 minutes after dosing
Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis.~All efficacy analyses were conducted using the intent-to-treat (ITT) population.~Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | Pain Relief | 0.8 Scores on a scale | Standard Error 0.05 |
| Placebo | Pain Relief | 0.7 Scores on a scale | Standard Error 0.06 |
p-value: 0.113Wilcoxon (Mann-Whitney)
Secondary
Pain Relief
Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief) at 5, 10, 15, 30, 45, and 60 minutes after taking the study medication or until rescue.
Time frame: 15 minutes after dosing
Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis.~All efficacy analyses were conducted using the intent-to-treat (ITT) population.~Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | Pain Relief | 1.1 Scores on a scale | Standard Error 0.05 |
| Placebo | Pain Relief | 1.0 Scores on a scale | Standard Error 0.07 |
p-value: 0.192Wilcoxon (Mann-Whitney)
Secondary
Pain Relief
Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief) at 5, 10, 15, 30, 45, and 60 minutes after taking the study medication or until rescue.
Time frame: 30 minutes after dosing
Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis.~All efficacy analyses were conducted using the intent-to-treat (ITT) population.~Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | Pain Relief | 1.7 Scores on a scale | Standard Error 0.05 |
| Placebo | Pain Relief | 1.3 Scores on a scale | Standard Error 0.08 |
p-value: 0.002Wilcoxon (Mann-Whitney)
Secondary
Pain Relief
Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief) at 5, 10, 15, 30, 45, and 60 minutes after taking the study medication or until rescue.
Time frame: 45 minutes after dosing
Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis.~All efficacy analyses were conducted using the intent-to-treat (ITT) population.~Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | Pain Relief | 1.9 Scores on a scale | Standard Error 0.06 |
| Placebo | Pain Relief | 1.5 Scores on a scale | Standard Error 0.09 |
p-value: 0.002Wilcoxon (Mann-Whitney)
Secondary
Pain Relief
Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief) at 5, 10, 15, 30, 45, and 60 minutes after taking the study medication or until rescue.
Time frame: 60 minutes after dosing
Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis.~All efficacy analyses were conducted using the intent-to-treat (ITT) population.~Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | Pain Relief | 2.1 Scores on a scale | Standard Error 0.06 |
| Placebo | Pain Relief | 1.6 Scores on a scale | Standard Error 0.09 |
p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
Percentage of Pain Free Episodes
A pain free episode is one with 0 pain intensity at the specified time point. Percentage of episodes that are pain-free per subject is analyzed.
Time frame: 10 minutes
Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis.~All efficacy analyses were conducted using the intent-to-treat (ITT) population.~Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | Percentage of Pain Free Episodes | 1.0 percentage of episodes | Standard Error 0.72 |
| Placebo | Percentage of Pain Free Episodes | 1.4 percentage of episodes | Standard Error 1.35 |
p-value: 1Wilcoxon (Mann-Whitney)
Secondary
Percentage of Pain Free Episodes
A pain free episode is one with 0 pain intensity at the specified time point. Percentage of episodes that are pain-free per subject is analyzed.
Time frame: 15 minutes
Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis.~All efficacy analyses were conducted using the intent-to-treat (ITT) population.~Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | Percentage of Pain Free Episodes | 2.3 percentage of episodes | Standard Error 1.02 |
| Placebo | Percentage of Pain Free Episodes | 2.0 percentage of episodes | Standard Error 1.48 |
p-value: 0.563Wilcoxon (Mann-Whitney)
Secondary
Percentage of Pain Free Episodes
A pain free episode is one with 0 pain intensity at the specified time point. Percentage of episodes that are pain-free per subject is analyzed.
Time frame: 30 minutes
Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis.~All efficacy analyses were conducted using the intent-to-treat (ITT) population.~Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | Percentage of Pain Free Episodes | 5.3 percentage of episodes | Standard Error 1.57 |
| Placebo | Percentage of Pain Free Episodes | 4.4 percentage of episodes | Standard Error 1.88 |
p-value: 0.498Wilcoxon (Mann-Whitney)
Secondary
Percentage of Pain Free Episodes
A pain free episode is one with 0 pain intensity at the specified time point. Percentage of episodes that are pain-free per subject is analyzed.
Time frame: 45 minutes
Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis.~All efficacy analyses were conducted using the intent-to-treat (ITT) population.~Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | Percentage of Pain Free Episodes | 10.5 percentage of episodes | Standard Error 2.34 |
| Placebo | Percentage of Pain Free Episodes | 6.4 percentage of episodes | Standard Error 2.27 |
p-value: 0.077Wilcoxon (Mann-Whitney)
Secondary
Percentage of Pain Free Episodes
A pain free episode is one with 0 pain intensity at the specified time point. Percentage of episodes that are pain-free per subject is analyzed.
Time frame: 60 minutes
Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis.~All efficacy analyses were conducted using the intent-to-treat (ITT) population.~Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | Percentage of Pain Free Episodes | 14.2 percentage of episodes | Standard Error 2.62 |
| Placebo | Percentage of Pain Free Episodes | 9.6 percentage of episodes | Standard Error 2.9 |
p-value: 0.031Wilcoxon (Mann-Whitney)
Secondary
Percentage of Pain Free Episodes
A pain free episode is one with 0 pain intensity at the specified time point. Percentage of episodes that are pain-free per subject is analyzed.
Time frame: 5 minutes
Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis.~All efficacy analyses were conducted using the intent-to-treat (ITT) population, however, only available data is summarized here.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | Percentage of Pain Free Episodes | 1.0 percentage of episodes | Standard Error 0.73 |
| Placebo | Percentage of Pain Free Episodes | 1.4 percentage of episodes | Standard Error 1.37 |
p-value: 1Wilcoxon (Mann-Whitney)
Secondary
PID
Pain intensity (using an 11-point \[0 = no pain to 10 = worst pain\] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point.
Time frame: 15 minutes after dosing
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | PID | 1.4 Scores on a scale | Standard Error 0.09 |
| Placebo | PID | 1.2 Scores on a scale | Standard Error 0.1 |
p-value: 0.223Wilcoxon (Mann-Whitney)
Secondary
PID
Pain intensity (using an 11-point \[0 = no pain to 10 = worst pain\] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point.
Time frame: 45 minutes after dosing
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | PID | 3.0 Scores on a scale | Standard Error 0.13 |
| Placebo | PID | 2.3 Scores on a scale | Standard Error 0.17 |
p-value: 0.001Wilcoxon (Mann-Whitney)
Secondary
PID
Pain intensity (using an 11-point \[0 = no pain to 10 = worst pain\] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point.
Time frame: 30 minutes after dosing
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | PID | 2.5 Scores on a scale | Standard Error 0.11 |
| Placebo | PID | 1.9 Scores on a scale | Standard Error 0.14 |
p-value: 0.015Wilcoxon (Mann-Whitney)
Secondary
PID
Pain intensity (using an 11-point \[0 = no pain to 10 = worst pain\] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point.
Time frame: 60 minutes after dosing
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | PID | 3.3 Scores on a scale | Standard Error 0.13 |
| Placebo | PID | 2.4 Scores on a scale | Standard Error 0.18 |
p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
PID
Pain intensity (using an 11-point \[0 = no pain to 10 = worst pain\] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point.
Time frame: 10 minutes after dosing
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | PID | 0.8 Scores on a scale | Standard Error 0.07 |
| Placebo | PID | 0.7 Scores on a scale | Standard Error 0.08 |
p-value: 0.458Wilcoxon (Mann-Whitney)
Secondary
PID
Pain intensity (using an 11-point \[0 = no pain to 10 = worst pain\] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point.
Time frame: 5 minutes after dosing
Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis.~All efficacy analyses were conducted using the intent-to-treat (ITT) population.~Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | PID | 0.3 Scores on a scale | Standard Error 0.04 |
| Placebo | PID | 0.3 Scores on a scale | Standard Error 0.06 |
p-value: 0.517Wilcoxon (Mann-Whitney)
Secondary
Rescue Medication Usage
Rescue medication is medication taken if adequate pain relief is not realized within 30 minutes following application of the study drug. Percentage of episodes when rescue medication was used per subject is analyzed.
Time frame: 28 Days
Population: All efficacy analyses were conducted using the intent-to-treat (ITT) population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | Rescue Medication Usage | 30.0 percentage of episodes | Standard Error 3.53 |
| Placebo | Rescue Medication Usage | 44.6 percentage of episodes | Standard Error 4.38 |
p-value: 0.002Wilcoxon (Mann-Whitney)
Secondary
SPID
Pain intensity (using an 11-point \[0 = no pain to 10 = worst pain\] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point. The primary endpoint was the Summary of Pain Intensity Differences at 30 minutes after dosing (SPID 30) in ITT population for Onsolis versus placebo during double-blind period of study. SPID was calculated as a weighted sum of the PID of all time points at or before time point of interest.Range of possible SPID values is -10X time point (minutes) to 10X time point (minutes). Higher value indicates a better outcome.SPID was calculated as a weighted sum of the pain intensity difference of all time points at or before the time point of interest.
Time frame: 0-60 minutes
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | SPID | 138.0 Scores on a scale | Standard Error 9.41 |
| Placebo | SPID | 106.0 Scores on a scale | Standard Error 10.58 |
p-value: <0.00195% CI: [15.85, 48.12]Mixed Models Analysis
Secondary
SPID
Pain intensity (using an 11-point \[0 = no pain to 10 = worst pain\] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point. The primary endpoint was the Summary of Pain Intensity Differences at 30 minutes after dosing (SPID 30) in ITT population for Onsolis versus placebo during double-blind period of study. SPID was calculated as a weighted sum of the PID of all time points at or before time point of interest.Range of possible SPID values is -10X time point (minutes) to 10X time point (minutes). Higher value indicates a better outcome.SPID was calculated as a weighted sum of the pain intensity difference of all time points at or before the time point of interest.
Time frame: 0-45 minutes
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | SPID | 90.5 Scores on a scale | Standard Error 6.63 |
| Placebo | SPID | 70.8 Scores on a scale | Standard Error 7.41 |
p-value: <0.00195% CI: [8.5, 30.86]Mixed Models Analysis
Secondary
SPID
Pain intensity (using an 11-point \[0 = no pain to 10 = worst pain\] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point. The primary endpoint was the Summary of Pain Intensity Differences at 30 minutes after dosing (SPID 30) in ITT population for Onsolis versus placebo during double-blind period of study. SPID was calculated as a weighted sum of the PID of all time points at or before time point of interest.Range of possible SPID values is -10X time point (minutes) to 10X time point (minutes). Higher value indicates a better outcome.SPID was calculated as a weighted sum of the pain intensity difference of all time points at or before the time point of interest.
Time frame: 0-15 minutes
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | SPID | 12.8 Scores on a scale | Standard Error 1.47 |
| Placebo | SPID | 10.4 Scores on a scale | Standard Error 1.61 |
p-value: 0.04795% CI: [0.04, 4.61]Mixed Models Analysis
Secondary
SPID
Pain intensity (using an 11-point \[0 = no pain to 10 = worst pain\] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point. The primary endpoint was the Summary of Pain Intensity Differences at 30 minutes after dosing (SPID 30) in ITT population for Onsolis versus placebo during double-blind period of study. SPID was calculated as a weighted sum of the PID of all time points at or before time point of interest.Range of possible SPID values is -10X time point (minutes) to 10X time point (minutes). Higher value indicates a better outcome.SPID was calculated as a weighted sum of the pain intensity difference of all time points at or before the time point of interest.
Time frame: 0-10 minutes
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | SPID | 5.9 Scores on a scale | Standard Error 0.8 |
| Placebo | SPID | 4.9 Scores on a scale | Standard Error 0.9 |
p-value: 0.17995% CI: [-0.44, 2.33]Mixed Models Analysis
Secondary
SPID
Pain intensity (using an 11-point \[0 = no pain to 10 = worst pain\] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point. The primary endpoint was the Summary of Pain Intensity Differences at 30 minutes after dosing (SPID 30) in ITT population for Onsolis versus placebo during double-blind period of study. SPID was calculated as a weighted sum of the PID of all time points at or before time point of interest.Range of possible SPID values is -10X time point (minutes) to 10X time point (minutes). Higher value indicates a better outcome.SPID was calculated as a weighted sum of the pain intensity difference of all time points at or before the time point of interest.
Time frame: 0-5 minutes
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | SPID | 1.8 Scores on a scale | Standard Error 0.3 |
| Placebo | SPID | 1.5 Scores on a scale | Standard Error 0.36 |
p-value: 0.4495% CI: [-0.4, 0.91]Wilcoxon (Mann-Whitney)
Secondary
Subject Overall Satisfaction With Study Drug
Subjects evaluated their overall satisfaction with study drug at the time rescue medication was consumed or at the 60-minute time point using a 5-point categorical scale (0 = poor, 1 = fair, 2 = good, 3 = very good, and 4 = excellent).
Time frame: 60 minutes or at time of rescue medication use
Population: All efficacy analyses were conducted using the intent-to-treat (ITT) population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | Subject Overall Satisfaction With Study Drug | 2.0 Scores on a scale | Standard Error 0.06 |
| Placebo | Subject Overall Satisfaction With Study Drug | 1.5 Scores on a scale | Standard Error 0.1 |
p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
Total Pain Relief
Total Pain Relief (TOTPAR) is calculated as the weighted sum of the pain relief (PR) of all time points at or prior to the time point of interest. Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief)compared to baseline (pre-dose)
Time frame: 30 minutes
Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis.~All efficacy analyses were conducted using the intent-to-treat (ITT) population.~Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | Total Pain Relief | 36.1 Scores on a scale | Standard Error 1.3 |
| Placebo | Total Pain Relief | 29.5 Scores on a scale | Standard Error 1.79 |
p-value: 0.002Wilcoxon (Mann-Whitney)
Secondary
Total Pain Relief
Total Pain Relief (TOTPAR) is calculated as the weighted sum of the pain relief (PR) of all time points at or prior to the time point of interest. Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief)compared to baseline (pre-dose)
Time frame: 45 minutes
Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis.~All efficacy analyses were conducted using the intent-to-treat (ITT) population.~Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | Total Pain Relief | 64.2 Scores on a scale | Standard Error 2.05 |
| Placebo | Total Pain Relief | 52.3 Scores on a scale | Standard Error 2.93 |
p-value: 0.005Wilcoxon (Mann-Whitney)
Secondary
Total Pain Relief
Total Pain Relief (TOTPAR) is calculated as the weighted sum of the pain relief (PR) of all time points at or prior to the time point of interest. Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief)compared to baseline (pre-dose)
Time frame: 60 minutes
Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis.~All efficacy analyses were conducted using the intent-to-treat (ITT) population.~Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | Total Pain Relief | 94.8 Scores on a scale | Standard Error 2.84 |
| Placebo | Total Pain Relief | 76.0 Scores on a scale | Standard Error 4.16 |
p-value: 0.001Wilcoxon (Mann-Whitney)
Secondary
Total Pain Relief
Total Pain Relief (TOTPAR) is calculated as the weighted sum of the pain relief (PR) of all time points at or prior to the time point of interest. Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief)compared to baseline (pre-dose)
Time frame: 15 minutes
Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis.~All efficacy analyses were conducted using the intent-to-treat (ITT) population.~Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | Total Pain Relief | 11.6 Scores on a scale | Standard Error 0.62 |
| Placebo | Total Pain Relief | 9.8 Scores on a scale | Standard Error 0.82 |
p-value: 0.062Wilcoxon (Mann-Whitney)
Secondary
Total Pain Relief
Total Pain Relief (TOTPAR) is calculated as the weighted sum of the pain relief (PR) of all time points at or prior to the time point of interest. Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief)compared to baseline (pre-dose)
Time frame: 10 minutes
Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis.~All efficacy analyses were conducted using the intent-to-treat (ITT) population.~Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | Total Pain Relief | 6.1 Scores on a scale | Standard Error 0.4 |
| Placebo | Total Pain Relief | 5.2 Scores on a scale | Standard Error 0.54 |
p-value: 0.278Wilcoxon (Mann-Whitney)
Secondary
Total Pain Relief
Total Pain Relief (TOTPAR) is calculated as the weighted sum of the pain relief (PR) of all time points at or prior to the time point of interest.Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief)compared to baseline (pre-dose)
Time frame: 5 minutes
Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis.~All efficacy analyses were conducted using the intent-to-treat (ITT) population.~Last observation carried forward (LOCF) is used to impute missing data or data after rescue medication usage.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | Total Pain Relief | 2.2 Scores on a scale | Standard Error 0.21 |
| Placebo | Total Pain Relief | 1.8 Scores on a scale | Standard Error 0.28 |
p-value: 0.157Wilcoxon (Mann-Whitney)
Other Pre-specified
SPID in Neuropathic Pain Subpopulation
Pain intensity (using an 11-point \[0 = no pain to 10 = worst pain\] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point. The primary endpoint was the Summary of Pain Intensity Differences at 30 minutes after dosing (SPID 30) in ITT population for Onsolis versus placebo during double-blind period of study. SPID was calculated as a weighted sum of the PID of all time points at or before time point of interest.Range of possible SPID values is -10X time point (minutes) to 10X time point (minutes). Higher value indicates a better outcome. SPID was calculated as a weighted sum of the pain intensity difference of all time points at or before the time point of interest for the Neuropathic pain subpopulation for relevant time points (15, 30, 45, 60 minutes). Neuropathic pain subpopulation is a subset of ITT population who have neuropathic pain at baseline.
Time frame: 15 minutes
Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis.~All efficacy analyses were conducted using the intent-to-treat (ITT) population.~Missing data were imputed on an episode-by-episode basis by carrying forward the last observed data value (last observation carried forward \[LOCF\]).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | SPID in Neuropathic Pain Subpopulation | 13.8 Scores on a scale | Standard Error 2.93 |
| Placebo | SPID in Neuropathic Pain Subpopulation | 7.8 Scores on a scale | Standard Error 3.2 |
p-value: 0.02395% CI: [0.92, 11.01]Mixed Models Analysis
Other Pre-specified
SPID in Neuropathic Pain Subpopulation
Pain intensity (using an 11-point \[0 = no pain to 10 = worst pain\] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point. The primary endpoint was the Summary of Pain Intensity Differences at 30 minutes after dosing (SPID 30) in ITT population for Onsolis versus placebo during double-blind period of study. SPID was calculated as a weighted sum of the PID of all time points at or before time point of interest.Range of possible SPID values is -10X time point (minutes) to 10X time point (minutes). Higher value indicates a better outcome. SPID was calculated as a weighted sum of the pain intensity difference of all time points at or before the time point of interest for the Neuropathic pain subpopulation for relevant time points (15, 30, 45, 60 minutes). Neuropathic pain subpopulation is a subset of ITT population who have neuropathic pain at baseline.
Time frame: 30 minutes
Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis.~All efficacy analyses were conducted using the intent-to-treat (ITT) population.~Missing data were imputed on an episode-by-episode basis by carrying forward the last observed data value (last observation carried forward \[LOCF\]).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | SPID in Neuropathic Pain Subpopulation | 51.6 Scores on a scale | Standard Error 8.05 |
| Placebo | SPID in Neuropathic Pain Subpopulation | 31.8 Scores on a scale | Standard Error 8.86 |
p-value: 0.00995% CI: [5.63, 34.04]Mixed Models Analysis
Other Pre-specified
SPID in Neuropathic Pain Subpopulation
Pain intensity (using an 11-point \[0 = no pain to 10 = worst pain\] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point. The primary endpoint was the Summary of Pain Intensity Differences at 30 minutes after dosing (SPID 30) in ITT population for Onsolis versus placebo during double-blind period of study. SPID was calculated as a weighted sum of the PID of all time points at or before time point of interest.Range of possible SPID values is -10X time point (minutes) to 10X time point (minutes). Higher value indicates a better outcome. SPID was calculated as a weighted sum of the pain intensity difference of all time points at or before the time point of interest for the Neuropathic pain subpopulation for relevant time points (15, 30, 45, 60 minutes). Neuropathic pain subpopulation is a subset of ITT population who have neuropathic pain at baseline.
Time frame: 45 minutes
Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis.~All efficacy analyses were conducted using the intent-to-treat (ITT) population.~Missing data were imputed on an episode-by-episode basis by carrying forward the last observed data value (last observation carried forward \[LOCF\]).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | SPID in Neuropathic Pain Subpopulation | 93.0 Scores on a scale | Standard Error 14.09 |
| Placebo | SPID in Neuropathic Pain Subpopulation | 59.7 Scores on a scale | Standard Error 15.63 |
p-value: 0.01295% CI: [8.32, 58.2]Mixed Models Analysis
Other Pre-specified
SPID in Neuropathic Pain Subpopulation
Pain intensity (using an 11-point \[0 = no pain to 10 = worst pain\] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point. The primary endpoint was the Summary of Pain Intensity Differences at 30 minutes after dosing (SPID 30) in ITT population for Onsolis versus placebo during double-blind period of study. SPID was calculated as a weighted sum of the PID of all time points at or before time point of interest.Range of possible SPID values is -10X time point (minutes) to 10X time point (minutes). Higher value indicates a better outcome. SPID was calculated as a weighted sum of the pain intensity difference of all time points at or before the time point of interest for the Neuropathic pain subpopulation for relevant time points (15, 30, 45, 60 minutes). Neuropathic pain subpopulation is a subset of ITT population who have neuropathic pain at baseline.
Time frame: 60 minutes
Population: During the double-blind period, subjects received 3 doses of placebo and 6 doses of Onsolis.~All efficacy analyses were conducted using the intent-to-treat (ITT) population.~Missing data were imputed on an episode-by-episode basis by carrying forward the last observed data value (last observation carried forward \[LOCF\]).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Onsolis | SPID in Neuropathic Pain Subpopulation | 137.8 Scores on a scale | Standard Error 20.19 |
| Placebo | SPID in Neuropathic Pain Subpopulation | 90.9 Scores on a scale | Standard Error 22.53 |
p-value: 0.01595% CI: [10.69, 83.08]Mixed Models Analysis