Trial Outcomes & Findings for Oxycodone DETERx™ Versus Placebo in Chronic Low Back Pain (CLBP) (NCT NCT01685684)

NCT ID: NCT01685684

Last Updated: 2020-10-19

Results Overview

The PI-NRS is an 11-point numerical rating scale ranging from 0 (no pain) to 10 (worst possible pain).

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 740 participants
• Primary outcome timeframe: Randomized Baseline through Week 12
• Results posted on: 2020-10-19

Participant Flow

The titration (i.e., enrichment) phase of the study was designed to titrate patients to a dose of Oxycodone DETERx that balanced pain control and tolerability to ensure that only patients who experienced a substantial reduction from the screening pain assessment and who can tolerate side effects continue into the Double-blind Maintenance Phase.

Participant milestones

Measure	Oxycodone DETERx (Titration Phase) Achieve a stable Oxycodone DETERx dose of 40-160 mg total daily dose.	Oxycodone DETERx (Double-blind Maintenance Phase) Oxycodone DETERx: 40-160 mg total daily dose of oxycodone DETERx, divided into 2 doses, q12h	Placebo (Double-blind Maintenance Phase) Placebo: Placebo, divided into 2 doses, q12h
Titration Phase STARTED	740	0	0
Titration Phase COMPLETED	389	0	0
Titration Phase NOT COMPLETED	351	0	0
Double-blind Maintenance Phase STARTED	0	193	196
Double-blind Maintenance Phase COMPLETED	0	122	100
Double-blind Maintenance Phase NOT COMPLETED	0	71	96

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Oxycodone DETERx™ Versus Placebo in Chronic Low Back Pain (CLBP)

Baseline characteristics by cohort

Measure	Oxycodone DETERx (Double-blind Maintenance Phase) n=193 Participants	Placebo (Double-blind Maintenance Phase) n=196 Participants	Total n=389 Participants Total of all reporting groups
Age, Continuous	49.2 years STANDARD_DEVIATION 13.31 • n=5 Participants	49.9 years STANDARD_DEVIATION 12.56 • n=7 Participants	49.5 years STANDARD_DEVIATION 12.93 • n=5 Participants
Sex: Female, Male Female	103 Participants n=5 Participants	103 Participants n=7 Participants	206 Participants n=5 Participants
Sex: Female, Male Male	90 Participants n=5 Participants	93 Participants n=7 Participants	183 Participants n=5 Participants
Pain Intensity-Numeric Rating Scale (PI-NRS)	3.0 units on a scale STANDARD_DEVIATION 1.04 • n=5 Participants	2.9 units on a scale STANDARD_DEVIATION 0.97 • n=7 Participants	2.9 units on a scale STANDARD_DEVIATION 1.00 • n=5 Participants

PRIMARY outcome

Timeframe: Randomized Baseline through Week 12

Population: One subject is missing all Average Weekly Pain Scores after Screening in the Oxycodone DETERx treatment group. This subject has been excluded from the analysis.

The PI-NRS is an 11-point numerical rating scale ranging from 0 (no pain) to 10 (worst possible pain).

Outcome measures

Measure	Oxycodone DETERx (Double-blind Maintenance Phase) n=192 Participants	Placebo (Double-blind Maintenance Phase) n=196 Participants
Change in Average Pain Intensity Measured by the Change in Pain Intensity-Numeric Rating Scale (PI-NRS) Scores From Randomization Baseline to Week 12 of the Double-blind Maintenance Phase	0.29 units on a scale Standard Error 0.146	1.85 units on a scale Standard Error 0.223

SECONDARY outcome

Timeframe: Randomization Baseline through Week 12

Survival analysis. Measure type indicated as 'Number' below represents 25% quartile, given that the median was not reached. These data are consistent with subject completion in the Participant Flow module.

Outcome measures

Measure	Oxycodone DETERx (Double-blind Maintenance Phase) n=193 Participants	Placebo (Double-blind Maintenance Phase) n=196 Participants
Time-to-exit From the Study for All Causes	58.0 Days Interval 37.0 to 78.0	35.0 Days Interval 29.0 to 38.0

SECONDARY outcome

Timeframe: Screening Baseline through Week 12

Includes the cumulative distribution of subjects with an improvement in pain intensity, as measured on an 11-point PI-NRS scale, and the proportion of responders with at least 30% and at least 50% reduction in pain intensity.

Outcome measures

Measure	Oxycodone DETERx (Double-blind Maintenance Phase) n=193 Participants	Placebo (Double-blind Maintenance Phase) n=196 Participants
Percent Reduction in Pain Intensity for Responders Subjects with 30% Improvement	95 participants	65 participants
Percent Reduction in Pain Intensity for Responders Subjects with 50% Improvement	74 participants	48 participants

SECONDARY outcome

Timeframe: Randomization Baseline and weekly through Week 12

Weekly pain intensity scores were calculated based on averaged daily pain intensity scores (PI-NRS). Increases to the weekly change in pain intensity, correspond to increases in the PI-NRS scores (i.e. more pain).

Outcome measures

Measure	Oxycodone DETERx (Double-blind Maintenance Phase) n=193 Participants	Placebo (Double-blind Maintenance Phase) n=196 Participants
Weekly Changes in Pain Intensity Week 7	0.1 units on a scale Standard Deviation 1.35	0.7 units on a scale Standard Deviation 2.00
Weekly Changes in Pain Intensity Week 8	0.0 units on a scale Standard Deviation 1.29	0.8 units on a scale Standard Deviation 2.06
Weekly Changes in Pain Intensity Week 10	0.2 units on a scale Standard Deviation 1.55	0.7 units on a scale Standard Deviation 2.20
Weekly Changes in Pain Intensity Week 11	0.2 units on a scale Standard Deviation 1.62	0.8 units on a scale Standard Deviation 2.23
Weekly Changes in Pain Intensity Week 1	0.1 units on a scale Standard Deviation 0.85	0.3 units on a scale Standard Deviation 1.17
Weekly Changes in Pain Intensity Week 2	0.0 units on a scale Standard Deviation 1.05	0.4 units on a scale Standard Deviation 1.46
Weekly Changes in Pain Intensity Week 3	0.1 units on a scale Standard Deviation 1.14	0.5 units on a scale Standard Deviation 1.78
Weekly Changes in Pain Intensity Week 4	0.1 units on a scale Standard Deviation 1.25	0.8 units on a scale Standard Deviation 1.86
Weekly Changes in Pain Intensity Week 5	0.2 units on a scale Standard Deviation 1.41	0.7 units on a scale Standard Deviation 1.86
Weekly Changes in Pain Intensity Week 6	0.2 units on a scale Standard Deviation 1.45	0.7 units on a scale Standard Deviation 1.95
Weekly Changes in Pain Intensity Week 9	0.1 units on a scale Standard Deviation 1.59	0.7 units on a scale Standard Deviation 2.15
Weekly Changes in Pain Intensity Week 12	0.3 units on a scale Standard Deviation 1.54	0.8 units on a scale Standard Deviation 2.29

SECONDARY outcome

Timeframe: Randomization Baseline through Week 12

Evaluation of the total amount of rescue medication used (number of doses per day, number of doses per week, and total number of doses while on-study)

Outcome measures

Measure	Oxycodone DETERx (Double-blind Maintenance Phase) n=193 Participants	Placebo (Double-blind Maintenance Phase) n=196 Participants
Rescue Medication Usage by Dose Doses per Day	0.15 doses Standard Deviation 0.297	0.23 doses Standard Deviation 0.458
Rescue Medication Usage by Dose Doses per Week	1.04 doses Standard Deviation 2.081	1.60 doses Standard Deviation 3.206
Rescue Medication Usage by Dose Total Number of Doses	8.0 doses Standard Deviation 16.38	11.2 doses Standard Deviation 31.55

SECONDARY outcome

Timeframe: Randomization Baseline through Week 12

Evaluation of the total amount of rescue medication used (by milligrams of dosage per day, dosage per week, and total dosage while on-study)

Outcome measures

Measure	Oxycodone DETERx (Double-blind Maintenance Phase) n=193 Participants	Placebo (Double-blind Maintenance Phase) n=196 Participants
Rescue Medication Use by Dosage Dosage per Day	144.63 milligrams Standard Deviation 289.472	189.32 milligrams Standard Deviation 317.605
Rescue Medication Use by Dosage Dosage per Week	1012.39 milligrams Standard Deviation 2026.298	1325.27 milligrams Standard Deviation 2223.231
Rescue Medication Use by Dosage Total Dosage	7873.1 milligrams Standard Deviation 16665.70	9028.1 milligrams Standard Deviation 20441.67

SECONDARY outcome

Timeframe: Screening Baseline through Week 12

The PGIC scale is a self-reported assessment that assesses a subject's impression of his/her change in activity limitations, symptoms, emotions, and the overall quality of life as they relate to his/her painful condition. The 7-point PGIC assessment includes "very much improved", "improved", "a little improved", "no change", "a little worse", "worse", and "very much worse".

Outcome measures

Measure	Oxycodone DETERx (Double-blind Maintenance Phase) n=122 Participants	Placebo (Double-blind Maintenance Phase) n=100 Participants
Patient Global Impression of Change (PGIC) Worse	2 participants	1 participants
Patient Global Impression of Change (PGIC) Very Much Improved	36 participants	17 participants
Patient Global Impression of Change (PGIC) Improved	52 participants	39 participants
Patient Global Impression of Change (PGIC) A Little Improved	23 participants	26 participants
Patient Global Impression of Change (PGIC) No Change	9 participants	12 participants
Patient Global Impression of Change (PGIC) A Little Worse	0 participants	4 participants
Patient Global Impression of Change (PGIC) Very Much Worse	0 participants	1 participants

SECONDARY outcome

Timeframe: Randomization Baseline through Week 12

Short Form 12 Question Health Survey version 2 (SF-12v2) is a self-report survey designed to measure general quality of life from the subject's point of view. The survey includes eight domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. Physical (PCS) and mental component scores (MCS) are also calculated. Positive values indicate improvement from randomization baseline to Week 12.

Outcome measures

Measure	Oxycodone DETERx (Double-blind Maintenance Phase) n=193 Participants	Placebo (Double-blind Maintenance Phase) n=196 Participants
Changes in Quality of Life Physical Component Score	7.524 units on a scale Standard Error 10.1327	3.622 units on a scale Standard Error 9.4290
Changes in Quality of Life Mental Component Score	-2.554 units on a scale Standard Error 10.4145	0.674 units on a scale Standard Error 11.1676
Changes in Quality of Life Physical Functioning	0.6 units on a scale Standard Error 1.35	0.5 units on a scale Standard Error 1.00
Changes in Quality of Life Role Physical	1.2 units on a scale Standard Error 2.35	0.6 units on a scale Standard Error 2.16
Changes in Quality of Life Bodily Pain	0.7 units on a scale Standard Error 1.16	0.4 units on a scale Standard Error 1.29
Changes in Quality of Life General Health	0.28 units on a scale Standard Error 0.784	0.22 units on a scale Standard Error 0.789

SECONDARY outcome

Timeframe: Randomization Baseline and Week 12

Population: The RMDQ was analyzed and presented as a change from Randomization Baseline to Week 12. Subjects' scores from Early Discontinuation visits were not included in this analysis.

The Roland Morris Disability Questionnaire (RMDQ) is a self-administered questionnaire designed to assess physical disability caused by lower back pain. The RMDQ contains 24 sentences that subjects used to describe themselves when they have back pain. The RMDQ score is the total number of items checked which is from a minimum of 0 to a maximum of 24; the greater the score the grater the physical disability due to lower back pain.

Outcome measures

Measure	Oxycodone DETERx (Double-blind Maintenance Phase) n=109 Participants	Placebo (Double-blind Maintenance Phase) n=90 Participants
Change in Level of Physical Disability Using the Roland Morris Disability Questionnaire (RMDQ)	0.4 units on a scale Standard Deviation 4.83	0.7 units on a scale Standard Deviation 5.32

Adverse Events

Screening

Serious events: 2 serious events

Other events: 0 other events

Deaths: 0 deaths

Oxycodone DETERx (Titration Phase)

Serious events: 8 serious events

Other events: 531 other events

Deaths: 0 deaths

Oxycodone DETERx (Double-blind Maintenance Phase)

Serious events: 2 serious events

Other events: 60 other events

Deaths: 0 deaths

Placebo (Double-blind Maintenance Phase)

Serious events: 2 serious events

Other events: 39 other events

Deaths: 0 deaths

Serious adverse events

Measure	Screening n=1297 participants at risk Serious Adverse Event (SAE) collection started during screening.	Oxycodone DETERx (Titration Phase) n=740 participants at risk	Oxycodone DETERx (Double-blind Maintenance Phase) n=193 participants at risk	Placebo (Double-blind Maintenance Phase) n=196 participants at risk
Cardiac disorders Sinus Bradycardia	0.08% 1/1297 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	0.00% 0/740 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	0.00% 0/193 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	0.00% 0/196 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.
Cardiac disorders Angina unstable	0.00% 0/1297 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	0.14% 1/740 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	0.00% 0/193 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	0.00% 0/196 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.
Gastrointestinal disorders Colitis ischaemic	0.00% 0/1297 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	0.14% 1/740 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	0.00% 0/193 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	0.00% 0/196 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/1297 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	0.14% 1/740 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	0.00% 0/193 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	0.00% 0/196 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.
General disorders Sudden cardiac death	0.00% 0/1297 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	0.14% 1/740 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	0.00% 0/193 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	0.00% 0/196 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.
General disorders Non-cardiac chest pain	0.00% 0/1297 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	0.00% 0/740 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	0.00% 0/193 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	0.51% 1/196 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.
Infections and infestations Pneumonia	0.00% 0/1297 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	0.14% 1/740 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	0.00% 0/193 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	0.00% 0/196 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.
Infections and infestations Atypical pneumonia	0.00% 0/1297 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	0.00% 0/740 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	0.52% 1/193 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	0.00% 0/196 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pituitary tumour benign	0.00% 0/1297 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	0.14% 1/740 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	0.00% 0/193 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	0.00% 0/196 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign hydatidiform mole	0.00% 0/1297 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	0.00% 0/740 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	0.00% 0/193 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	0.51% 1/196 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.
Psychiatric disorders Suicidal ideation	0.00% 0/1297 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	0.14% 1/740 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	0.00% 0/193 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	0.00% 0/196 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.
Respiratory, thoracic and mediastinal disorders Emphysema	0.08% 1/1297 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	0.00% 0/740 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	0.00% 0/193 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	0.00% 0/196 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/1297 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	0.14% 1/740 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	0.52% 1/193 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	0.00% 0/196 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.

Other adverse events

Measure	Screening n=1297 participants at risk Serious Adverse Event (SAE) collection started during screening.	Oxycodone DETERx (Titration Phase) n=740 participants at risk	Oxycodone DETERx (Double-blind Maintenance Phase) n=193 participants at risk	Placebo (Double-blind Maintenance Phase) n=196 participants at risk
Gastrointestinal disorders Nausea	— 0/0 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	16.6% 123/740 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	10.9% 21/193 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	4.6% 9/196 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.
Nervous system disorders Headache	— 0/0 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	13.9% 103/740 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	6.2% 12/193 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	11.7% 23/196 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.
Gastrointestinal disorders Constipation	— 0/0 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	13.0% 96/740 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	5.2% 10/193 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	0.51% 1/196 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.
Nervous system disorders Somnolence	— 0/0 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	8.8% 65/740 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	0.52% 1/193 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	0.00% 0/196 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.
Skin and subcutaneous tissue disorders Pruritus	— 0/0 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	7.4% 55/740 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	2.6% 5/193 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	1.5% 3/196 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.
Gastrointestinal disorders Vomiting	— 0/0 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	6.4% 47/740 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	4.1% 8/193 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	1.5% 3/196 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.
Nervous system disorders Dizziness	— 0/0 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	5.7% 42/740 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	1.6% 3/193 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.	0.00% 0/196 • Adverse events (AEs) were collected from the time of first dose with study drug to the End-of-Study Visit/Early Discontinuation Visit. All AEs that were ongoing at the subject's last study visit were to be followed until resolution or for 30 days after the subject's last study drug dose, whichever came first. Serious adverse events (SAEs) were collected from informed consent until 30 days post last dose. If the Investigator became aware of an SAE within 30 days after the subject's last study drug dose, or through the last study visit, the SAE was to be reported. All SAEs, including those ongoing at End-of-Study/Early Discontinuation, were followed until resolution or until the outcome became chronically stable, or if no additional information could be obtained after unsuccessful contact attempts.

Additional Information

Clinical Scientist

Collegium Pharmaceutical

Phone: +1.781.232.0764

Email: clinicaltrials@collegiumpharma.com

Results disclosure agreements

• Principal investigator is a sponsor employee If a joint manuscript has not been submitted for publication within twelve (12) months of completion or termination of the study, the PI is free to publish separately, upon provision of any proposed publication or manuscript to the Sponsor at least sixty (60) days before it is submitted or otherwise disclosed.
• Publication restrictions are in place

Restriction type: OTHER