Trial Outcomes & Findings for Buprenorphine Transdermal Patch in Subjects With Osteoarthritis Pain Requiring Opioids. Includes a 52-Week Safety Extension. (NCT NCT00315458)

NCT ID: NCT00315458

Last Updated: 2012-09-03

Results Overview

For the Run-in and double-blind phases of the study, the focus of this study was changed before unblinding to a safety study due to early termination and having enrolled only 35% of the planned sample size. Therefore, the safety data is presented for the run-in and double-blind and overall exposure to BTDS, which includes the extension phase.

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 107 participants
• Primary outcome timeframe: 483 days
• Results posted on: 2012-09-03

Participant Flow

12-Dec-2003 (First Patient First Visit) 02-Mar-2005 (Last Patient Last Visit of Extension). At the time of early termination, 39 centers had screened subjects, 22 centers had randomized subjects to the double-blind phase.

All subjects (N = 159) in the run-in period received BTDS 5 for the first 3 days, titrated to BTDS 10 or 20, continued stable nonopioid analgesic regimen for osteoarthritis (OA) pain, and took oxycodone immediate-release 5-mg capsules as supplemental analgesic therapy for primary OA pain site. N = 107 completed the run-in and were randomized.

Participant milestones

Measure	Double-blind Placebo Patch Reference Treatment placebo 10 or 20 applied for 7-day wear	Double-blind BTDS 10/20 Test treatments buprenorphine transdermal patch (BTDS) 10 or BTDS 20 applied for 7-day wear	Run-in Period BTDS 5/10/20 All subjects were started on BTDS 5 and titrated to BTDS 10 and 20. Subjects who met the protocol-specified criteria for adequate analgesia were eligible for entry into the double-blind phase. Subjects who could not tolerate at least BTDS 10 were discontinued from the study.	Extension Phase BTDS 5/10/20 Subjects who finished the entire 12-week (84-day) double-blind phase were eligible to participate in the open-label extension phase. Subjects began treatment with BTDS 5 and their doses were titrated to BTDS 10 or BTDS 20 as needed.
Overall Study STARTED	51	56	159	39
Overall Study COMPLETED	48	44	107	10
Overall Study NOT COMPLETED	3	12	52	29

Reasons for withdrawal

Measure	Double-blind Placebo Patch Reference Treatment placebo 10 or 20 applied for 7-day wear	Double-blind BTDS 10/20 Test treatments buprenorphine transdermal patch (BTDS) 10 or BTDS 20 applied for 7-day wear	Run-in Period BTDS 5/10/20 All subjects were started on BTDS 5 and titrated to BTDS 10 and 20. Subjects who met the protocol-specified criteria for adequate analgesia were eligible for entry into the double-blind phase. Subjects who could not tolerate at least BTDS 10 were discontinued from the study.	Extension Phase BTDS 5/10/20 Subjects who finished the entire 12-week (84-day) double-blind phase were eligible to participate in the open-label extension phase. Subjects began treatment with BTDS 5 and their doses were titrated to BTDS 10 or BTDS 20 as needed.
Overall Study Administrative	0	3	8	21
Overall Study Adverse Event	2	4	23	3
Overall Study Lost to Follow-up	1	2	0	2
Overall Study Withdrawal by Subject	0	3	0	2
Overall Study Lack of Efficacy	0	0	20	1
Overall Study Did not qualify	0	0	1	0

Baseline Characteristics

Buprenorphine Transdermal Patch in Subjects With Osteoarthritis Pain Requiring Opioids. Includes a 52-Week Safety Extension.

Baseline characteristics by cohort

Measure	Double-blind Placebo Patch n=51 Participants Reference Treatment placebo 10 or 20 applied for 7-day wear	Double-blind BTDS n=56 Participants Test treatments buprenorphine transdermal patch (BTDS) 10 or BTDS 20 applied for 7-day wear	Total n=107 Participants Total of all reporting groups
Age Continuous	61.2 years STANDARD_DEVIATION 11.36 • n=5 Participants	59.4 years STANDARD_DEVIATION 9.56 • n=7 Participants	60.3 years STANDARD_DEVIATION 10.45 • n=5 Participants
Sex: Female, Male Female	33 Participants n=5 Participants	39 Participants n=7 Participants	72 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	17 Participants n=7 Participants	35 Participants n=5 Participants

PRIMARY outcome

Timeframe: 483 days

Population: The full analysis population consisted of all subjects who were randomized into the double-blind phase and received at least 1 dose of double-blind treatment.

For the Run-in and double-blind phases of the study, the focus of this study was changed before unblinding to a safety study due to early termination and having enrolled only 35% of the planned sample size. Therefore, the safety data is presented for the run-in and double-blind and overall exposure to BTDS, which includes the extension phase.

Outcome measures

Measure	Double-blind Placebo n=51 Participants Reference treatment placebo 10 or 20 applied for 7-day wear	Double-blind BTDS n=56 Participants Test treatment buprenoprhine transdermal patch (BTDS) 10 or BTDS 20 applied for 7-day wear	Run-in Period n=159 Participants All subjects were started on BTDS 5 and titrated to BTDS 10 and 20. Subjects who met the protocol-specified criteria for adequate analgesia were eligible for entry into the double-blind phase. Subjects who could not tolerate at least BTDS 10 were discontinued from the study.	Overall BTDS Exposure n=159 Participants Total number of subjects exposed to BTDS for overall study which includes the core study and extension phase.
Number of Participants With Adverse Events (AEs) as a Measure of Safety Death	0 participants	1 participants	0 participants	1 participants
Number of Participants With Adverse Events (AEs) as a Measure of Safety Serious adverse events	1 participants	2 participants	1 participants	5 participants
Number of Participants With Adverse Events (AEs) as a Measure of Safety All Other Adverse Events in ≥ 4.5% of Subjects	14 participants	22 participants	60 participants	82 participants

Adverse Events

Double-blind Placebo Patch

Serious events: 1 serious events

Other events: 14 other events

Deaths: 0 deaths

Double-blind BTDS 10/20

Serious events: 2 serious events

Other events: 22 other events

Deaths: 0 deaths

Run-in Period

Serious events: 1 serious events

Other events: 60 other events

Deaths: 0 deaths

Overall BTDS Exposure

Serious events: 5 serious events

Other events: 82 other events

Deaths: 0 deaths

Serious adverse events

Measure	Double-blind Placebo Patch n=51 participants at risk Reference Treatment placebo 10 or 20 applied for 7-day wear	Double-blind BTDS 10/20 n=56 participants at risk Test treatment buprenorphine transdermal patch (BTDS) 10 or BTDS 20 applied for 7-day wear	Run-in Period n=159 participants at risk Open-label Run-in period (BTDS 5, 10, or 20) applied for 7-day wear	Overall BTDS Exposure n=159 participants at risk Total number of subjects exposed to BTDS for overall study which includes the core study and extension phase.
Cardiac disorders Acute coronary syndrome	0.00% 0/51 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	0.00% 0/56 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	0.00% 0/159 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	0.63% 1/159 • Number of events 1 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.
Cardiac disorders Acute myocardial infarction - DEATH	0.00% 0/51 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	1.8% 1/56 • Number of events 1 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	0.00% 0/159 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	0.63% 1/159 • Number of events 1 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.
Nervous system disorders Cervical spinal stenosis	0.00% 0/51 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	1.8% 1/56 • Number of events 1 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	0.00% 0/159 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	0.63% 1/159 • Number of events 1 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.
Respiratory, thoracic and mediastinal disorders Acute exacerbation of COPD	0.00% 0/51 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	0.00% 0/56 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	0.63% 1/159 • Number of events 1 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	0.63% 1/159 • Number of events 1 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.
Psychiatric disorders Recurrent Major Depression	0.00% 0/51 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	0.00% 0/56 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	0.00% 0/159 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	0.63% 1/159 • Number of events 1 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.
Psychiatric disorders Confusion	0.00% 0/51 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	0.00% 0/56 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	0.00% 0/159 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	0.63% 1/159 • Number of events 1 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.
Metabolism and nutrition disorders Hypoglycemia	0.00% 0/51 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	0.00% 0/56 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	0.00% 0/159 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	0.63% 1/159 • Number of events 1 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.
Nervous system disorders Near Syncope	0.00% 0/51 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	0.00% 0/56 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	0.00% 0/159 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	0.63% 1/159 • Number of events 1 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/51 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	0.00% 0/56 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	0.00% 0/159 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	0.63% 1/159 • Number of events 1 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.
General disorders Chest Pain	2.0% 1/51 • Number of events 1 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	0.00% 0/56 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	0.00% 0/159 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	0.00% 0/159 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.

Other adverse events

Measure	Double-blind Placebo Patch n=51 participants at risk Reference Treatment placebo 10 or 20 applied for 7-day wear	Double-blind BTDS 10/20 n=56 participants at risk Test treatment buprenorphine transdermal patch (BTDS) 10 or BTDS 20 applied for 7-day wear	Run-in Period n=159 participants at risk Open-label Run-in period (BTDS 5, 10, or 20) applied for 7-day wear	Overall BTDS Exposure n=159 participants at risk Total number of subjects exposed to BTDS for overall study which includes the core study and extension phase.
Gastrointestinal disorders Nausea	7.8% 4/51 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	10.7% 6/56 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	15.7% 25/159 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	20.1% 32/159 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.
Gastrointestinal disorders Constipation	0.00% 0/51 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	7.1% 4/56 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	6.3% 10/159 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	9.4% 15/159 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.
General disorders Application site pruritus	11.8% 6/51 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	12.5% 7/56 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	10.1% 16/159 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	14.5% 23/159 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.
General disorders Application site erythema	5.9% 3/51 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	3.6% 2/56 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	3.8% 6/159 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	5.7% 9/159 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.
General disorders Application site rash	0.00% 0/51 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	10.7% 6/56 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	0.63% 1/159 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	5.0% 8/159 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.
Musculoskeletal and connective tissue disorders Back Pain	3.9% 2/51 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	5.4% 3/56 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	1.3% 2/159 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	3.1% 5/159 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.
Nervous system disorders Headache	9.8% 5/51 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	3.6% 2/56 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	10.1% 16/159 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	13.8% 22/159 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.
Skin and subcutaneous tissue disorders Sweating Increased	0.00% 0/51 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	5.4% 3/56 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	0.63% 1/159 • Number of events 1 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	3.8% 6/159 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.
Nervous system disorders Somnolence	2.0% 1/51 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	0.00% 0/56 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	6.9% 11/159 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	7.5% 12/159 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/51 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	3.6% 2/56 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	1.9% 3/159 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	5.0% 8/159 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.
Nervous system disorders Dizziness	0.00% 0/51 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	3.6% 2/56 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	3.8% 6/159 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.	6.9% 11/159 • Subjects with AEs that were ongoing at subject's last study visit were followed until resolution or 30 days after last visit, whichever came first. AEs reported during 7 days following last visit were followed until resoultion or 30 days after last visit. AEs were learned of through spontaneous reports and subject interview.

Additional Information

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Purdue Pharma L.P.

Phone: 800-733-1333

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60