Chronic Pain
Conditions
Keywords
chronic pain
Brief summary
This Phase 3, multi-center study will evaluate the long-term safety and tolerability of hydrocodone bitartrate controlled release capsule (HC-CR) at daily doses of 40 mg or more in subjects with moderate to severe chronic pain. Long-term maintenance of HC-CR efficacy will be evaluated.
Detailed description
Subjects will go through screening, an open-label conversion and titration phase of up to 6 weeks followed by an open-label treatment phase for up to 48 weeks with a 2 week follow-up period.
Interventions
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
Sponsors
Zogenix, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Subjects must have a diagnosed moderate to severe chronic pain condition treated with around-the-clock opioids for at least the past 3 months or in the Investigator's opinion qualify for around-the-clock opioid therapy for treatment of their pain * Subjects must have been taking opioids at least 5 days/week for the past month at an average daily dose of at least 30 mg hydrocodone * Subjects must be able to complete study procedures and attend clinic visits for 6 to 12 months * Females subjects of childbearing potential must have a negative urine pregnancy test at the Screen Visit, and must consent to use a medically-acceptable method of contraception throughout the entire study period. * Subjects must have had an adequate medical evaluation for the treatment of their underlying painful condition and appropriate primary medical/surgical therapies for the underlying condition * Subjects must voluntarily provide written informed consent
Exclusion criteria
* Any clinically significant condition that would, in the opinion of the investigator, preclude study participation or interfere with the assessment of pain or increase the risk of opioid-related adverse events (AEs) * A medical condition that, in the opinion of the Investigator, would compromise the subject's ability to swallow, absorb, metabolize, or excrete study drug * A surgical procedure for pain within the last 3 months * Uncontrolled blood pressure, i.e., a sitting systolic blood pressure \>180 mm Hg or \<90 mm Hg, and/or a sitting diastolic blood pressure \>120 mm Hg or \<50 mm Hg at Screening * A body mass index (BMI) \> 45 kg/m2 * A hospital anxiety and depression scale (HADS) score of \>12 in either depression or anxiety subscales or an established history of any psychiatric disorder that is poorly controlled * A clinically significant abnormality in clinical chemistry, hematology or urinalysis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Average Daily Pain | 1 year | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maintenance of Efficacy | 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 |
Countries
United States
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Open-label Hydrocodone Bitartate Extended Release (HC-ER) Conversion/Titration Phase: HC-ER capsules daily for up to 6 weeks | 638 |
| Total | 638 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Conversion/Titration Phase | Adverse Event | 59 | 0 |
| Conversion/Titration Phase | Lost to Follow-up | 3 | 0 |
| Conversion/Titration Phase | Non-Compliance with Study Drug | 53 | 0 |
| Conversion/Titration Phase | Physician Decision | 5 | 0 |
| Conversion/Titration Phase | Protocol Violation | 68 | 0 |
| Conversion/Titration Phase | Withdrawal by Subject | 26 | 0 |
| Maintenance Phase | Administrative | 0 | 1 |
| Maintenance Phase | Adverse Event | 0 | 43 |
| Maintenance Phase | Lost to Follow-up | 0 | 8 |
| Maintenance Phase | Non-Compliance with Study Drug | 0 | 48 |
| Maintenance Phase | Physician Decision | 0 | 3 |
| Maintenance Phase | Protocol Violation | 0 | 9 |
| Maintenance Phase | Withdrawal by Subject | 0 | 27 |
Baseline characteristics
| Characteristic | Open-label Hydrocodone Bitartate Extended Release (HC-ER) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 66 Participants |
| Age, Categorical Between 18 and 65 years | 572 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 107 Participants |
| Race (NIH/OMB) More than one race | 9 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 518 Participants |
| Region of Enrollment United States | 638 participants |
| Sex: Female, Male Female | 360 Participants |
| Sex: Female, Male Male | 278 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 277 / 638 | 298 / 424 |
| serious Total, serious adverse events | 26 / 638 | 73 / 424 |
Outcome results
Primary
Mean Change in Average Daily Pain
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open-label Hydrocodone Bitartrate Extended Release Capsules | Mean Change in Average Daily Pain | 0.921 units on a scale | Standard Deviation 2.2 |
Secondary
Maintenance of Efficacy
Clinic Numeric Rating Scale (NRS), Brief Pain Inventory (BPI), Oswestry Disability Index, Hospital Anxiety and Depression Scale, Rescue Doses and Subject Global of Medication
Time frame: 1 year