Trial Outcomes & Findings for Long-Term Study of Hydrocodone Bitartrate Controlled-release Capsules in Subjects With Chronic Pain (NCT NCT01115569)

Last Updated: 2022-11-09

Results Overview

Numeric Rating Scale (NRS) for Pain (0-10; where 0 = no pain, 10 = worst pain imaginable) recorded up to 54 weeks, starting at screening through end of study. Lower number equals better outcome.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

424 participants

Primary outcome timeframe

1 year

Results posted on

2022-11-09

Participant Flow

Out of 638 subjects treated with Hydrocodone Bitartate Extended Release (HC-ER) capsules in the Conversion/Titration Phase, 214 subjects discontinued early and 424 continued in the Maintenance HC-ER Treatment Phase; 285 subjects completed.

Participant milestones

Participant milestones
Measure	Open-label Hydrocodone Bitartrate Extended Release (HC-ER) Conversion/Titration Phase: HC-ER capsules daily for up to 6 weeks	Open-label Hydrocodone Bitartrate Extended Release Capsules Maintenance HC-ER Treatment Phase: Open-label, all patients fulfilling the protocol Inclusion/Exclusion criteria will receive HC-ER in a flexible dosing regimen. Hydrocodone Bitartrate: Open-Label, Capsule Strengths 10 mg, 20 mg, 30 mg, 40 mg, 50 mg; by mouth (PO) twice a day (BID) for up to 48 weeks
Conversion/Titration Phase STARTED	638	0
Conversion/Titration Phase COMPLETED	424	0
Conversion/Titration Phase NOT COMPLETED	214	0
Maintenance Phase STARTED	0	424
Maintenance Phase COMPLETED	0	285
Maintenance Phase NOT COMPLETED	0	139

Reasons for withdrawal

Reasons for withdrawal
Measure	Open-label Hydrocodone Bitartrate Extended Release (HC-ER) Conversion/Titration Phase: HC-ER capsules daily for up to 6 weeks	Open-label Hydrocodone Bitartrate Extended Release Capsules Maintenance HC-ER Treatment Phase: Open-label, all patients fulfilling the protocol Inclusion/Exclusion criteria will receive HC-ER in a flexible dosing regimen. Hydrocodone Bitartrate: Open-Label, Capsule Strengths 10 mg, 20 mg, 30 mg, 40 mg, 50 mg; by mouth (PO) twice a day (BID) for up to 48 weeks
Conversion/Titration Phase Adverse Event	59	0
Conversion/Titration Phase Lost to Follow-up	3	0
Conversion/Titration Phase Physician Decision	5	0
Conversion/Titration Phase Protocol Violation	68	0
Conversion/Titration Phase Withdrawal by Subject	26	0
Conversion/Titration Phase Non-Compliance with Study Drug	53	0
Maintenance Phase Adverse Event	0	43
Maintenance Phase Lost to Follow-up	0	8
Maintenance Phase Physician Decision	0	3
Maintenance Phase Protocol Violation	0	9
Maintenance Phase Withdrawal by Subject	0	27
Maintenance Phase Non-Compliance with Study Drug	0	48
Maintenance Phase Administrative	0	1

Baseline Characteristics

Long-Term Study of Hydrocodone Bitartrate Controlled-release Capsules in Subjects With Chronic Pain

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Open-label Hydrocodone Bitartate Extended Release (HC-ER) n=638 Participants Conversion/Titration Phase: HC-ER capsules daily for up to 6 weeks
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	572 Participants n=5 Participants
Age, Categorical >=65 years	66 Participants n=5 Participants
Sex: Female, Male Female	360 Participants n=5 Participants
Sex: Female, Male Male	278 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	107 Participants n=5 Participants
Race (NIH/OMB) White	518 Participants n=5 Participants
Race (NIH/OMB) More than one race	9 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	638 participants n=5 Participants

PRIMARY outcome

Timeframe: 1 year

Population: The number of participants for analysis was determined by the safety population. Numeric Rating Scale (NRS) for Pain assessment was used. Measure is mean change in average daily pain intensity. Total number of participants providing end of study pain intensity score = 391.

Numeric Rating Scale (NRS) for Pain (0-10; where 0 = no pain, 10 = worst pain imaginable) recorded up to 54 weeks, starting at screening through end of study. Lower number equals better outcome.

Outcome measures

Outcome measures
Measure	Open-label Hydrocodone Bitartrate Extended Release Capsules n=391 Participants Maintenance HC-ER Treatment Phase: Open-label, all patients fulfilling the protocol Inclusion/Exclusion criteria will receive HC-CR in a flexible dosing regimen. Hydrocodone Bitartrate: Open-Label, Capsule Strengths 10 mg, 20 mg, 30 mg, 40 mg, 50 mg; by mouth (PO) twice a day (BID) for up to 48 weeks
Mean Change in Average Daily Pain	0.921 units on a scale Standard Deviation 2.2

SECONDARY outcome

Timeframe: 1 year

Clinic Numeric Rating Scale (NRS), Brief Pain Inventory (BPI), Oswestry Disability Index, Hospital Anxiety and Depression Scale, Rescue Doses and Subject Global of Medication

Outcome measures

Outcome data not reported

Adverse Events

Conversion/Titration Phase

Serious events: 26 serious events

Other events: 277 other events

Deaths: 0 deaths

Maintenance Treatment Phase

Serious events: 73 serious events

Other events: 298 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Kevin Romanko

Zogenix

Phone: (510) 550-8323

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Serious adverse events
Measure	Conversion/Titration Phase n=638 participants at risk Conversion/Titration Phase: Hydrocodone Bitartrate Extended Release (HC-ER) capsules daily for up to 6 weeks	Maintenance Treatment Phase n=424 participants at risk Maintenance Hydrocodone Bitartrate Extended Release (HC-ER) Treatment Phase: Open-label, all patients fulfilling the protocol Inclusion/Exclusion criteria will receive HC-CR in a flexible dosing regimen. Hydrocodone Bitartrate: Open-Label, Capsule Strengths 10 mg, 20 mg, 30 mg, 40 mg, 50 mg; by mouth (PO) twice a day (BID) for up to 48 weeks
Psychiatric disorders Suicidal attempt	0.00% 0/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	0.24% 1/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Cardiac disorders Arteriosclerosis coronary artery	0.00% 0/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	0.24% 1/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Metabolism and nutrition disorders Dehydration	0.00% 0/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	0.47% 2/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	0.24% 1/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Infections and infestations Cystitis	0.16% 1/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	0.00% 0/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Infections and infestations Enterococcal infection	0.16% 1/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	0.00% 0/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Infections and infestations Gastroenteritis	0.16% 1/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	0.24% 1/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Infections and infestations Pneumonia	0.16% 1/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	0.71% 3/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Infections and infestations Sepsis	0.16% 1/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	0.24% 1/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Infections and infestations Urinary tract infection	0.16% 1/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	0.24% 1/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Infections and infestations Viral infection	0.16% 1/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	0.24% 1/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Cardiac disorders Atrial fibrillation	0.16% 1/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	0.24% 1/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Cardiac disorders Cardiac failure congestive	0.16% 1/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	0.00% 0/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Cardiac disorders Coronary artery disease	0.16% 1/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	0.00% 0/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Cardiac disorders Myocardial infarction	0.16% 1/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	0.00% 0/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
General disorders Non-cardiac chest pain	0.31% 2/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	0.24% 1/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
General disorders Chest pain	0.16% 1/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	0.24% 1/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Gastrointestinal disorders Gastric ulcer	0.16% 1/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	0.00% 0/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Gastrointestinal disorders Retroperitoneal haemorrage	0.16% 1/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	0.00% 0/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Musculoskeletal and connective tissue disorders Osteoarthrtis	0.16% 1/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	0.94% 4/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Musculoskeletal and connective tissue disorders Pain in extremity	0.16% 1/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	0.00% 0/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.16% 1/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	0.00% 0/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.16% 1/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	1.2% 5/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.16% 1/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	0.24% 1/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Investigations Blood potassium decreased	0.16% 1/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	0.00% 0/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Nervous system disorders Lethargy	0.16% 1/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	0.00% 0/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Nervous system disorders Mental impairment	0.16% 1/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	0.24% 1/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Vascular disorders Hypertension	0.16% 1/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	0.00% 0/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Vascular disorders Venous insufficiency	0.16% 1/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	0.00% 0/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Vascular disorders Deep vein thrombosis	0.00% 0/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	0.24% 1/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Infections and infestations Abscess limb	0.00% 0/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	0.24% 1/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Infections and infestations Cellulitis	0.00% 0/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	0.24% 1/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Infections and infestations Diverticulitis	0.00% 0/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	0.24% 1/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Infections and infestations Extradural abscess	0.00% 0/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	0.24% 1/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Infections and infestations Gastroenteritis viral	0.00% 0/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	0.24% 1/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Infections and infestations Influenza	0.00% 0/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	0.24% 1/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Infections and infestations Mastitis	0.00% 0/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	0.24% 1/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Infections and infestations Oesophageal candidiasis	0.00% 0/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	0.24% 1/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Infections and infestations Pathogen resistance	0.00% 0/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	0.24% 1/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Infections and infestations Pneumonia staphylococcal	0.00% 0/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	0.24% 1/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.

Other adverse events
Measure	Conversion/Titration Phase n=638 participants at risk Conversion/Titration Phase: Hydrocodone Bitartrate Extended Release (HC-ER) capsules daily for up to 6 weeks	Maintenance Treatment Phase n=424 participants at risk Maintenance Hydrocodone Bitartrate Extended Release (HC-ER) Treatment Phase: Open-label, all patients fulfilling the protocol Inclusion/Exclusion criteria will receive HC-CR in a flexible dosing regimen. Hydrocodone Bitartrate: Open-Label, Capsule Strengths 10 mg, 20 mg, 30 mg, 40 mg, 50 mg; by mouth (PO) twice a day (BID) for up to 48 weeks
Infections and infestations Bronchitis	1.6% 10/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	4.7% 20/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Infections and infestations Influenza	0.63% 4/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	4.7% 20/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Musculoskeletal and connective tissue disorders Neck pain	0.47% 3/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	4.5% 19/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.63% 4/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	4.2% 18/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Gastrointestinal disorders Constipation	11.3% 72/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	12.5% 53/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Gastrointestinal disorders Nausea	10.7% 68/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	9.9% 42/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Nervous system disorders Somnolence	7.7% 49/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	4.2% 18/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Nervous system disorders Headache	7.5% 48/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	6.8% 29/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Musculoskeletal and connective tissue disorders Back Pain	1.4% 9/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	11.1% 47/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Gastrointestinal disorders Vomiting	4.1% 26/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	9.7% 41/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Musculoskeletal and connective tissue disorders Arthralgia	1.4% 9/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	7.8% 33/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Infections and infestations Urinary tract infection	0.94% 6/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	6.6% 28/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Injury, poisoning and procedural complications Fall	1.3% 8/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	5.9% 25/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Infections and infestations Upper respiratory tract infection	1.1% 7/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	5.9% 25/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Infections and infestations Nasopharyngitis	1.7% 11/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	5.7% 24/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Psychiatric disorders Anxiety	1.3% 8/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	5.4% 23/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Infections and infestations Sinusitis	1.4% 9/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	5.4% 23/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Psychiatric disorders Insomnia	3.8% 24/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	5.0% 21/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
General disorders Fatigue	3.6% 23/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	3.5% 15/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Gastrointestinal disorders Diarrhoea	3.1% 20/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	4.0% 17/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Nervous system disorders Dizziness	2.8% 18/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	3.1% 13/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
General disorders Oedema peripheral	2.2% 14/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	3.3% 14/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Skin and subcutaneous tissue disorders Pruritus allergic	2.0% 13/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	0.00% 0/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Psychiatric disorders Depression	0.94% 6/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	3.8% 16/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Musculoskeletal and connective tissue disorders Muscle spasms	1.7% 11/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	3.8% 16/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
General disorders Pyrexia	1.7% 11/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	3.5% 15/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Injury, poisoning and procedural complications Contusion	0.63% 4/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	3.3% 14/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Musculoskeletal and connective tissue disorders Pain in extremity	1.1% 7/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	3.3% 14/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Injury, poisoning and procedural complications Muscle strain	1.4% 9/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	3.1% 13/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Nervous system disorders Migraine	0.78% 5/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	2.6% 11/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.31% 2/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	2.6% 11/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Infections and infestations Gastroenteritis viral	0.94% 6/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	2.4% 10/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Respiratory, thoracic and mediastinal disorders Cough	0.94% 6/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	2.1% 9/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Nervous system disorders Paraesthesia	0.16% 1/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	2.1% 9/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Infections and infestations Pneumonia	0.47% 3/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	2.1% 9/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Gastrointestinal disorders Toothache	0.31% 2/638 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.	2.1% 9/424 • Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase). Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.