Chronic PainPhase 3NCT01240863
Study to Evaluate the Efficacy and Safety of Hydrocodone Bitartrate Extended-Release Tablets (CEP-33237) for Relief of Moderate to Severe Pain in Patients With Osteoarthritis or Low Back Pain Who Require Opioid Treatment for an Extended Period of Time
A Phase 3 study testing Hydrocodone ER in people with Chronic Pain, run by Teva Branded Pharmaceutical Products R&D, Inc. at 73 sites in United States.
Trial summary
The primary objective of this study is to evaluate efficacy of hydrocodone extended-release (ER) tablets compared with placebo in alleviating moderate to severe pain in patients with osteoarthritis or low back pain as assessed by the weekly Average Pain Intensity (API) at week 12. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Chronic Pain
- What is being tested?
- Hydrocodone ER
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 391 participants
- Where
- 73 sitesUnited States
- Study dates
- Nov 2010to Aug 2011
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The patient is able to speak English and is willing to provide written informed consent, including a written opioid agreement, to participate in this study.
- The patient must be willing and able to successfully self-administer the study drug, comply with study restrictions, complete the electronic diary, and return to the clinic for scheduled study visits as specified in this protocol.
- Women of childbearing potential (not surgically sterile or 2 years postmenopausal), must use a medically accepted method of contraception and must agree to continue use of this method for the duration of the study and for 30 days after participation in the study, and have a negative pregnancy test at screening.
- The patient has pain of at least 3 months' duration associated with osteoarthritis or low back pain.
- The patient reports an average pain intensity score, over the prior 24 hours, of 5 or more on the 11-point numerical rating scale.
- If the patient is receiving physical therapy, biofeedback therapy, acupuncture therapy, or herbal remedies, these therapies must remain unchanged during the study.
- The patient must not participate in other study involving an investigational agent while enrolled into the present study.
Who cannot join
- The patient has known or suspected hypersensitivities, allergies, or other contraindications to any ingredient in the study drug.
- The patient has a recent history (within 5 years) or current evidence of alcohol or other substance abuse with the exception of nicotine or caffeine.
- The patient has medical or psychiatric disease that, in the opinion of the investigator, would compromise collected data.
- The patient is taking a total (ie, around-the-clock plus rescue medication) of more than 135 mg/day of oxycodone, or equivalent, during the 14 days prior to screening.
- The patient has a history of suicidality.
- The patient is expected to have surgery during the study.
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- The patient's primary painful condition under study is related to any source of chronic pain other than osteoarthritis or low back pain.
- The patient is pregnant or lactating.
- The patient has active malignancy.
- The patient has human immunodeficiency virus (HIV).
- In the judgment of the investigator, the patient has any clinically significant deviation from normal in the physical examination and/or clinical laboratory test values.
- The patient has cardiopulmonary disease that would, in the opinion of the investigator, significantly increase the risk of treatment with opioids.
- The patient has participated in a study involving an investigational drug in the previous 30 days.
- The patient has received a monoamine oxidase inhibitor (MAOI) within 14 days before the first treatment with study drug.
- The patient has any other medical condition or is receiving concomitant medication/therapy (e.g., regional nerve block) that would, in the opinion of the investigator, compromise the patient's safety or compliance with the study protocol, or compromise collected data.
- The patient is involved in active litigation in regard to the pain currently being treated.
- The patient has a positive urine drug screen (UDS) that is not medically explainable.
- The investigator feels that the patient is not suitable for the study for any reason.
Trial locations and contacts
73 sites in 1 country.
73 sites in 1 country
United States73 sites
Radiant Research, Inc
Akron, Ohio, 44311
Physician Alliance Research Center
Anaheim, California, 92804
Radiant Research Inc.
Anderson, South Carolina, 29621
Horizon Research Group, LLC
Baton Rouge, Louisiana, 70809
Millennium Pain Center
Bloomington, Illinois, 61701
Beacon Clinical Research, LLC
Brockton, Massachusetts, 02301
Associated Pharmaceutical Research Center, Inc.
Buena Park, California, 90620
Providence Clinical Research
Burbank, California, 91505
Radiant Research, Inc.
Chandler, Arizona, 85225
Medex Healthcare Research, Inc.
Chicago, Illinois, 60603
Sterling Research Group, Ltd.
Cincinnati, Ohio, 45219
Community Research, Inc
Cincinnati, Ohio, 45227
Community Research, Inc
Cincinnati, Ohio, 45245
Clinical Research of West Florida, Inc.
Clearwater, Florida, 33765
Rapid Medical Research
Cleveland, Ohio, 44122
Columbus Clinical Research
Columbus, Ohio, 43213
Community Research
Crestview, Kentucky, 41017
KRK Medical Research
Dallas, Texas, 75230
Radiant Research Dallas
Dallas, Texas, 75231
Renaissance Clinical Research & Hypertension of Texas, PLLC
Dallas, Texas, 75235
Avail Clinical Research, LLC
DeLand, Florida, 32720
Radiant Research, Inc
Denver, Colorado, 80239
Brandywine Clinical Research
Downingtown, Pennsylvania, 19335
Synergy Clinical Research
Escondido, California, 92025
Pain Research of Oregon
Eugene, Oregon, 97401
HealthCare Research
Florissant, Missouri, 63031
Research Center of Fresno, Inc.
Fresno, California, 93726
Greenville Pharmaceutical Research
Greenville, South Carolina, 29615
Radiant Research, Inc
Greer, South Carolina, 29651
Medstar Clinical Research
Houston, Texas, 77083
Rehabilitation Associates of Indiana
Indianapolis, Indiana, 46250
Pacific Coast Pain Management Center
Laguna Hills, California, 92637
South Orange County Surgical Medical Group
Laguna Hills, California, 92653
Clinical Research Center of Nevada
Las Vegas, Nevada, 89104
International Clinical Research, Inc.
Leawood, Kansas, 66211
The Pain Treatment Center of the Bluegrass
Lexington, Kentucky, 40503
Robert M. Karns, MD A Medical Corporation
Los Angeles, California, 90036
Drug Studies America
Marietta, Georgia, 30060
Georgia Institute for Clinical Research, LLC
Marietta, Georgia, 30060
International Research Associates, LLC
Miami, Florida, 33183
Horizon Research Group LLC
Mobile, Alabama, 36608
Better Health Clinical Research, Inc.
Newnan, Georgia, 30265
Trident Institute of Medical Research, LLC
North Charleston, South Carolina, 29406
SP Research
Oklahoma City, Oklahoma, 73112
Meridian Clinical Research
Omaha, Nebraska, 68134
Aspen Clinical Research, LLC
Orem, Utah, 84058
Compass Research
Orlando, Florida, 32806
MidAtlantic Pain Medicine Center
Pikesville, Maryland, 21208
Radiant Research, Inc.
Pinellas Park, Florida, 33781
Gold Coast Research LLC
Plantation, Florida, 33317
Summit Research Network Inc.
Portland, Oregon, 97210
Wake Research Associates
Raleigh, North Carolina, 27612
Lifetree Clinical Research
Salt Lake City, Utah, 84106
Benchmark Research
San Angelo, Texas, 76904
Accelovance, Inc.
San Diego, California, 92108
Radiant Research, Inc.
Santa Rosa, California, 95405
Sarasota Pain Medicine Research LLC
Sarasota, Florida, 34238
Radiant Research, Inc.
Scottsdale, Arizona, 85251
WK River Cities Clinical Research Center
Shreveport, Louisiana, 71105
South Carolina Pharmaceutical Research
Spartanburg, South Carolina, 29303
Medex Healthcare Research Inc.
St Louis, Missouri, 63117
Sundance Clinical Research, LLC
St Louis, Missouri, 63141
DCT-Sugarland, LLC
Sugar Land, Texas, 77478
Clinical Research of West Florida, Inc.
Tampa, Florida, 33603
Tipton Medical and Diagnostic Center
Tipton, Pennsylvania, 16684
AMH Feasterville Family Health Care Center
Trevose, Pennsylvania, 19053
Radiant Research Inc.
Tucson, Arizona, 85710
Bayview Research Group, LLC
Valley Village, California, 91607
Advanced Pain Consultants
Voorhees Township, New Jersey, 08043
Hillcrest Family Health Centers
Waco, Texas, 76710
Omega Medical Research
Warwick, Rhode Island, 02886
Upstate Clinical Research Associates
Williamsville, New York, 14221
Clinical Research Center of Reading
Wyomissing, Pennsylvania, 19610
About this study
Official title: A 12-Week, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Hydrocodone Bitartrate Extended-Release Tablets (CEP-33237) at 15 to 90 mg Every 12 Hours for Relief of Moderate to Severe Pain in Patients With Osteoarthritis or Low Back Pain Who Require Opioid Treatment for an Extended Period of Time
The primary objective of this study is to evaluate efficacy of hydrocodone extended-release (ER) tablets compared with placebo in alleviating moderate to severe pain in patients with osteoarthritis or low back pain as assessed by the weekly Average Pain Intensity (API) at week 12.
Read the detailed description
The study consisted of a screening period of approximately 7 to 14 days, an open label titration period of up to 6 weeks, and a double blind treatment period of 12 weeks.
Participants entered the open label titration period and received hydrocodone ER tablets beginning with 15 mg every 12 hours for 3 to 7 days. The objective of the open label titration period was to find the successful dose of hydrocodone ER tablets that produced stable pain relief (defined as an Average Pain Intensity (API) score of 4 or less on the 11-point numerical rating scale for either 3 consecutive days or 3 out of 5 consecutive days while the patient was maintained on the same dose of study drug for up to 7 days). Patients returned to the study center prior to each dose adjustment.
Participants who met the criterion of a stabilized dose were randomly assigned into the 12 week, double blind, placebo controlled treatment period on the final day of the open label titration period (baseline visit). Patients began treatment with double blind study drug at the effective dose of hydrocodone ER tablets achieved during the titration period or matching placebo. Rescue medication was permitted in addition to the study drug during the double blind treatment period.
- Conditions
- Chronic Pain
- Being tested
- Hydrocodone ER, Placebo
- Keywords
- osteoarthritis, low back pain, Moderate to Severe Pain
- Medical subject headings
- Chronic Pain, Osteoarthritis, Low Back Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hydrocodone ERDrug
Also called CEP-33237, Hydrocodone bitartrate extended-release
During the open-label, titration period, all participants were administered hydrocodone ER tablets at dosages of 15, 30, 45, 60, or 90 mg every 12 hours to identify a dosage deemed successful for managing their pain.
Hydrocodone ER was taken by participants randomized to the hydrocodone ER treatment arm during the double-blind treatment period at the dose level identified during the titration period.
Participants were instructed to take tablets with a glass of water on an empty stomach at least 1 hour before or 2 hours after eating.
PlaceboDrug
Placebo matching the active drug dose identified during the titration period was taken by participants randomized to the placebo treatment arm during the double-blind treatment period.
Participants were instructed to take intervention with a glass of water on an empty stomach at least 1 hour before or 2 hours after eating.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Participants were administered hydrocodone ER tablets at dosages of 15, 30, 45, 60, or 90 mg every 12 hours at the dosage deemed successful for managing their pain during the titration period. During the treatment period, participants were administered placebo tablets every 12 hours that matched the dosage deemed successful for managing their pain during the titration period. A step-wise, double-blind schedule to tamper off active drug was implemented during the first 2 weeks of the 12-week, double-blind, placebo-controlled treatment period to reduce the risk of withdrawal effects in participants randomly assigned to placebo. Receives: Drug: Hydrocodone ER; Drug: Placebo |
| Hydrocodone ER | Experimental | Participants were administered hydrocodone ER tablets at dosages of 15, 30, 45, 60, or 90 mg every 12 hours at the dosage deemed successful for managing their pain during the titration period. During the 12-week, double-blind, placebo-controlled treatment period, participants randomly assigned to hydrocodone ER were administered tablets every 12 hours at the dosage deemed successful for managing their pain during the titration period. Receives: Drug: Hydrocodone ER |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline to Week 12 in Weekly Average Pain Intensity (wAPI)
The primary efficacy variable was the change from baseline to week 12 in the wAPI. The API over the previous 24 hours, based on the 11-point Numerical Rating Scale (NRS 11), was collected daily by e-diary. The Week 12 wAPI scores from the previous 7 days were calculated for each study visit and averaged. The baseline wAPI score was calculated by averaging API scores from 3 to 12 days when the successful dose of hydrocodone extended release was confirmed at the end of the open label titration period, before patients were randomly assigned study drug. In the case of missing week-12 data due to early withdrawal from the study, or excessive rescue medication usage, the wAPI for week 12 was imputed.
The Numeric Rating Scale (NRS-11) is an 11-point scale for patient self-reporting of pain on a Likert-type scale in which 0 is no pain and 10 is the worst pain imaginable. Negative change from baseline values indicate lessening in pain intensity.
Measured: Baseline (end of Open-Label Titration Period), Week 12 of Double-blind Treatment Period
Secondary outcomes (25)
Percentage of Participants Withdrawn From the Study During the Double-Blind Treatment Period By Reason
Percentage of participants who withdrew from the study during the double-blind treatment period. Withdrawal is due to any cause, including lack of efficacy.
Measured: Day 1 to Week 12 of the double-blind treatment period
Kaplan-Meier Estimates for Time to Discontinuation From the Study
Kaplan-Meier estimates for time to discontinuation from the study (due to any cause) was calculated as the number of days since participants were randomly assigned to study drug treatment, ie, the difference between the date the participants withdrew and the date participants were randomly assigned to study drug treatment. The censoring flag was set to 0 if a participant was withdrawn from study drug treatment early and was set to 1 if the participant completed the 12 week treatment period. Censoring time was calculated as the difference of treatment completion date (ie, date of last study drug administration) and date participant was randomly assigned to study drug treatment.
Measured: Day 1 to Week 12 of the double-blind treatment period
Participants With a Weekly Average Pain Intensity (wAPI) Increase From Baseline Exceeding 33%
The API over the previous 24 hours, based on the 11-point Numerical Rating Scale (NRS 11), was collected daily by e-diary. The wAPI scores from the previous 7 days were calculated for each study visit and averaged. The baseline wAPI score was calculated by averaging API scores from 3 to 12 days when the successful dose of hydrocodone extended release was confirmed at the end of the open label titration period, before patients were randomly assigned study drug.
The Numeric Rating Scale (NRS-11) is an 11-point scale for patient self-reporting of pain on a Likert-type scale in which 0 is no pain and 10 is the worst pain imaginable.
Measured: Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, and 12 of the Double-blind treatment period
Participants With a Weekly Average Pain Intensity (wAPI) Increase From Baseline Exceeding 50%
The API over the previous 24 hours, based on the 11-point Numerical Rating Scale (NRS 11), was collected daily by e-diary. The wAPI scores from the previous 7 days were calculated for each study visit and averaged. The baseline wAPI score was calculated by averaging API scores from 3 to 12 days when the successful dose of hydrocodone extended release was confirmed at the end of the open label titration period, before patients were randomly assigned study drug.
The Numeric Rating Scale (NRS-11) is an 11-point scale for patient self-reporting of pain on a Likert-type scale in which 0 is no pain and 10 is the worst pain imaginable.
Measured: Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, and 12 of the Double-blind treatment period
Weekly Average Pain Intensity (wAPI) Scores During the Double-blind Treatment Period
The API over the previous 24 hours, based on the 11-point Numerical Rating Scale (NRS 11), was collected daily by e-diary. The wAPI scores from the previous 7 days were calculated for each study visit and averaged. The baseline wAPI score was calculated by averaging API scores from 3 to 12 days when the successful dose of hydrocodone extended release was confirmed at the end of the open label titration period, before patients were randomly assigned study drug.
The Numeric Rating Scale (NRS-11) is an 11-point scale for patient self-reporting of pain on a Likert-type scale in which 0 is no pain and 10 is the worst pain imaginable.
Measured: Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, and 12 of the Double-blind treatment period
Weekly Average Worst Pain Intensity (WPI) Scores During the Double-blind Treatment Period
The WPI was recorded by the patient in the e-diary daily throughout the study, based on the Numeric Rating Scale (NRS-11). Participants were asked to select the number that best described their WPI over the previous 24 hours. Values were averaged for each week.
The Numeric Rating Scale (NRS-11) is an 11-point scale for patient self-reporting of pain on a Likert-type scale in which 0 is no pain and 10 is the worst pain imaginable.
Measured: Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, and 12 of the Double-blind treatment period
Clinician Assessment of Patient Function (CAPF) at Week 4
Clinicians assessed participants across 5 dimensions:
- Patients general activities
- Patients walking ability
- Patients ability to work/perform activities of daily living
- Patients relationships with others
- Patients enjoyment of life
Assessments are rated on a 7-point scale, in which 1 is very much worsened and 7 is very much improved since the start of the study.
Measured: Week 4 of the Double-blind Treatment Period
Clinician Assessment of Patient Function (CAPF) at Week 8
Clinicians assessed participants across 5 dimensions:
- Patients general activities
- Patients walking ability
- Patients ability to work/perform activities of daily living
- Patients relationships with others
- Patients enjoyment of life
Assessments are rated on a 7-point scale, in which 1 is very much worsened and 7 is very much improved since the start of the study.
Measured: Week 8 of the Double-blind Treatment Period
Clinician Assessment of Patient Function (CAPF) at Week 12
Clinicians assessed participants across 5 dimensions:
- Patients general activities
- Patients walking ability
- Patients ability to work/perform activities of daily living
- Patients relationships with others
- Patients enjoyment of life
Assessments are rated on a 7-point scale, in which 1 is very much worsened and 7 is very much improved since the start of the study.
Measured: Week 12 of the Double-blind Treatment Period
Clinician Assessment of Patient Function (CAPF) at Endpoint
Clinicians assessed participants across 5 dimensions:
- Patients general activities
- Patients walking ability
- Patients ability to work/perform activities of daily living
- Patients relationships with others
- Patients enjoyment of life
Assessments are rated on a 7-point scale, in which 1 is very much worsened and 7 is very much improved since the start of the study.
Endpoint values are the last observed postbaseline data.
Measured: Endpoint of the Double-blind Treatment Period (up to week 12)
Patient Assessment of Function (PAF) at Week 4
The PAF is a self-administered questionnaire used to measure patients' assessment of their own ability to function in normal activities. Answers to the 7 questions were rated on a 7 point scale in which 1 was very much worsened and 7 were very much improved since the start of the study.
The seven functional areas are:
- ability to go to work
- ability to perform at work (includes both work outside the home and housework)
- ability to walk
- ability to exercise
- ability to participate in social events
- ability to have sex
- ability to enjoy life
Measured: Week 4 of the Double-blind Treatment Period
Patient Assessment of Function (PAF) at Week 8
The PAF is a self-administered questionnaire used to measure patients' assessment of their own ability to function in normal activities. Answers to the 7 questions were rated on a 7 point scale in which 1 was very much worsened and 7 were very much improved since the start of the study.
The seven functional areas are:
- ability to go to work
- ability to perform at work (includes both work outside the home and housework)
- ability to walk
- ability to exercise
- ability to participate in social events
- ability to have sex
- ability to enjoy life
Measured: Week 8 of the Double-blind Treatment Period
Patient Assessment of Function (PAF) at Week 12
The PAF is a self-administered questionnaire used to measure patients' assessment of their own ability to function in normal activities. Answers to the 7 questions were rated on a 7 point scale in which 1 was very much worsened and 7 were very much improved since the start of the study.
The seven functional areas are:
- ability to go to work
- ability to perform at work (includes both work outside the home and housework)
- ability to walk
- ability to exercise
- ability to participate in social events
- ability to have sex
- ability to enjoy life
Measured: Week 12 of the Double-blind Treatment Period
Patient Assessment of Function (PAF) at Endpoint
The PAF is a self-administered questionnaire used to measure patients' assessment of their own ability to function in normal activities. Answers to the 7 questions were rated on a 7 point scale in which 1 was very much worsened and 7 were very much improved since the start of the study.
The seven functional areas are:
- ability to go to work
- ability to perform at work (includes both work outside the home and housework)
- ability to walk
- ability to exercise
- ability to participate in social events
- ability to have sex
- ability to enjoy life
Endpoint values are the last observed postbaseline data.
Measured: Endpoint of the Double-blind Treatment Period (up to week 12)
Clinician Global Impression of Severity (CGI-S) of Illness Scores During the Double-blind Treatment Period
The CGI-S is a clinician-rated scale that assesses the severity of the patient's pain condition and response to the treatment. Severity of illness, as related to moderate to severe pain, consists of the following 7 categories:
- 1 normal-shows no sign of illness,
- 2 borderline ill,
- 3 mildly (slightly) ill,
- 4 moderately ill,
- 5 markedly ill,
- 6 severely ill, and
- 7 among the most extremely ill (Guy 1976).
The clinician assesses the severity of the patient's condition, based on the clinician's total clinical experience with patients with this condition, in response to treatment.
Endpoint values are the last observed postbaseline data.
Measured: Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, and 12 of the Double-blind treatment period
Short-Form Health Survey (SF-36) Physical and Mental Component Summary Scores at Baseline, Week 12 and Endpoint
SF-36 is a generic 36-item questionnaire measuring health-related quality of life (HRQL) covering 2 summary measures: physical component summary (PCS) and mental component summary (MCS). The SF-36 consists of 8 subscales. The PCS is represented by 4 subscales: physical function, role limitations due to physical problems, pain, and general health perception. The MCS is represented by 4 subscales: vitality, social function, role limitations due to emotional problems, and mental health. Participants self-report on items in a subscale that have between 2-6 choices per item using Likert-type responses (e.g. none of the time, some of the time, etc.). PCS and MCS scores are constructed as a T-score with a mean of 50 and standard deviation of 10 and no minimum or maximum score; higher scores indicate better health status.
Measured: Baseline (end of Open-Label Titration Period), Week 12 and Endpoint (last visit up to week 12) of the Double-blind treatment period
Brief Pain Inventory - Short Form (BPI-SF) Pain Interference Mean Score During the Double-Blind Treatment Period
For pain interference, the BPI-SF used numerical scales to measure how much pain had interfered with 7 daily activities, including general activity, walking, work, mood, enjoyment of life, relations with others, and sleep in the past 24 hours. The scale used an 11 point Likert scale; range: 0 [does not interfere] to 10 [completely interferes]. BPI pain interference was typically scored as the mean of the 7 interference items. This mean could be used if at least 4 of 7 items had been completed on a given administration.
Measured: Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, 12 and Endpoint (last visit up to week 12) of the Double-blind treatment period
Participants With Adverse Events
An adverse event (AE) was defined in the protocol as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an inability to carry out usual activities. Relation of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes.
Measured: Day 1 up to Day 52 in Open-Label Titration; Day 1 up to Day 128 in Double-Blind Treatment period
Participants With Potentially Clinically Significant Abnormal Vital Signs Values During the Double-Blind Treatment Period
Data represents participants with potentially clinically significant (PCS) vital sign values.
Significance criteria
- Pulse - high: >=120 and increase of >= 15 beats/minute from baseline
- Pulse - low: <=50 and decrease of >=15 beats/minute
- Systolic blood pressure - high: >=180 and increase >=20 mmHg
- Systolic blood pressure - low: <=90 and decrease >=20 mmHg
- Diastolic blood pressure - high: >=105 and increase of >=15 mmHg
- Diastolic blood pressure - low: <=50 and decrease of >=15 mmHg
Measured: Day 1 up to Day 128 in Double-Blind Treatment period
Participants With Potentially Clinically Significant Abnormal Laboratory Values During the Double-Blind Treatment Period
Data represents participants with potentially clinically significant abnormal serum chemistry, hematology and urinalysis values.
Significance criteria:
- Blood urea nitrogen: >=10.71 mmol/L
- Uric acid: M>=625, F>=506 μmol/L
- Hemoglobin: M<=115, F<=95 g/dL
- Hematocrit: M<0.37, F<0.32 %
- Urinalysis: blood (hemoglobin) and total protein: >=2 unit increase from baseline
Measured: Day 1 up to Day 128 in Double-Blind Treatment period
Subjective Opiate Withdrawal Scales (SOWS) Scores During the Double-Blind Treatment Period
The results of the SOWS were collected in the e-diary daily during the first 4 weeks of the double blind treatment period and then during clinic visits at weeks 8 and 12 or early termination. The SOWS was a self administered questionnaire used to measure a participant's signs and symptoms of withdrawal from opiates. The scale contained 16 symptoms (eg, my nose is running; I feel restless), the participant rated the intensity on a scale of 0 (not at all) to 4 (extremely) for a total score of 0-64. The daily total score for the first 4 weeks was the largest score observed during the time period preceding that visit. For example, the week 1 score for each participant was the largest total score on any day between baseline and the night before the week 1 visit; the week 4 score for each participant was the largest score observed between the week 2 visit and the night before the week 4 visit.
Measured: Weeks 1, 2, 4, 8, 12 and Endpoint (last visit up to Week 12) of the Double-blind treatment period
Clinical Opiate Withdrawal Scales (COWS) Scores During the Double-Blind Treatment Period
The COWS was a clinician rated scale used to measure a participant's signs and symptoms of withdrawal from opiates, with ratings based only on apparent relationship to withdrawal. The COWS was performed at day 0 and weeks 1, 2, 4, 8, and 12 (double blind treatment period) or early termination. The scale contained 11 signs/symptoms whose intensity the clinician rated on a scale of 0 to 4 or 5.
A total score was calculated as the sum of the responses to the 11 signs/symptoms for a total range of 0-48. Withdrawal severity was classified, based on the total score, as follows:
- 0 to 4=normal
- 5 to 12=mild
- 13 to 24=moderate
- 25 to 36=moderately severe
- >36=severe
Measured: Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, 12 and Endpoint (last visit up to Week 12) of the Double-blind treatment period
Addiction Behavior Checklist (ABC) Total Scores During Both the Open-Label Titration and Double-Blind Treatment Periods
The ABC was a clinician rated scale that consisted of a brief (20 item) questionnaire designed to track behaviors characteristic of addiction related to prescription opioid medications in chronic pain populations. Items were focused on observable behaviors noted both during and between clinic visits. Each affirmative response was counted as one point, and points were added to calculate the total score, consequently resulting in scores ranging from 0 to 20 (0=no addiction-related behaviors seen and higher scores indicating an increasing number of addition-related behaviors seen).
The ABC was to be performed at visits 2 and 7 (beginning and end of Open-label Titration period) and weeks 1, 4, 8, and 12 (Double-blind Treatment period) or early termination.
Measured: Baseline for Open-Label Titration period, Baseline for Double-Blind Treatment period (which is also the end of the Open-Label Titration period), Weeks 1, 4, 8, 12, and Endpoint (last visit up to Week 12) of the Double-blind Treatment period
Current Opioid Misuse Measures (COMM) Total Scores During Both the Open-Label Titration and Double-Blind Treatment Periods
The COMM was a clinician rated scale developed as a brief self report measure of current aberrant drug-related behavior for patients with chronic pain who were already on long term opioid therapy. A total score was calculated as the sum of the 17 questions. The total score ranged from 0 to 68. A score of 0 indicates no aberrant drug-related behaviors were seen. Patients with a total score of 9 or greater were classified as exhibiting aberrant drug-related behavior.
The COMM was to be performed at visits 2 and 7 (beginning and end of Open-label Titration period) and weeks 1, 4, 8, and 12 (Double-blind Treatment period) or early termination.
Measured: Baseline for Open-Label Titration period, Baseline for Double-Blind Treatment period (which is also the end of the Open-Label Titration period), Weeks 1, 4, 8, 12, and Endpoint (last visit up to Week 12) of the Double-blind Treatment period
Change From Baseline to Endpoint in the Double-Blind Treatment Phase in Electrocardiogram (ECG) Parameters
A 12-lead ECG was conducted at baseline and the last visit during the double-blind treatment period (week 12, or early termination).
Measured: Baseline (end of Open-Label Titration Period), Endpoint (last visit up to Week 12) of the Double-blind treatment period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2010 (estimated)
- Study startNov 2010
- Primary completionAug 2011
- Study completionAug 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic PainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 391 participants (actual)
Sponsor and investigators
- Lead sponsor
- Teva Branded Pharmaceutical Products R&D, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Sponsor's Medical Expert, MD, Study director, Cephalon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01240863
- Sponsor's protocol ID
- C33237/3079
- Status last verified
- Jun 2017
- First submitted
- 10 Nov 2010
- Last updated
- 5 Jun 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A 12-Week, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Hydrocodone Bitartrate Extended-Release Tablets (CEP-33237) at 15 to 90 mg Every 12 Hours for Relief of Moderate to Severe Pain in Patients With Osteoarthritis or Low Back Pain Who Require Opioid Treatment for an Extended Period of Time
- ClinicalTrials.gov ID
- NCT01240863
- Acronym / sponsor ID
- C33237/3079
- Conditions
- Chronic Pain
- Keywords
- osteoarthritis, low back pain, Moderate to Severe Pain
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 391 participants (actual)
- Lead sponsor
- Teva Branded Pharmaceutical Products R&D, Inc.Industry (pharma, biotech, devices)
- Study start
- Nov 2010
- Primary completion
- Aug 2011 (actual)
- Study completion
- Aug 2011 (actual)
- First posted
- 15 Nov 2010 (estimated)
- Results
- Posted 5 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study is to evaluate efficacy of hydrocodone extended-release (ER) tablets compared with placebo in alleviating moderate to severe pain in patients with osteoarthritis or low back pain as assessed by the weekly Average Pain Intensity (API) at week 12.
Detailed description
The study consisted of a screening period of approximately 7 to 14 days, an open label titration period of up to 6 weeks, and a double blind treatment period of 12 weeks.
Participants entered the open label titration period and received hydrocodone ER tablets beginning with 15 mg every 12 hours for 3 to 7 days. The objective of the open label titration period was to find the successful dose of hydrocodone ER tablets that produced stable pain relief (defined as an Average Pain Intensity (API) score of 4 or less on the 11-point numerical rating scale for either 3 consecutive days or 3 out of 5 consecutive days while the patient was maintained on the same dose of study drug for up to 7 days). Patients returned to the study center prior to each dose adjustment.
Participants who met the criterion of a stabilized dose were randomly assigned into the 12 week, double blind, placebo controlled treatment period on the final day of the open label titration period (baseline visit). Patients began treatment with double blind study drug at the effective dose of hydrocodone ER tablets achieved during the titration period or matching placebo. Rescue medication was permitted in addition to the study drug during the double blind treatment period.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Hydrocodone ER, Drug: PlaceboParticipants were administered hydrocodone ER tablets at dosages of 15, 30, 45, 60, or 90 mg every 12 hours at the dosage deemed successful for managing their pain during the titration period. During the treatment period, participants were administered placebo tablets every 12 hours that matched the dosage deemed successful for managing their pain during the titration period. A step-wise, double-blind schedule to tamper off active drug was implemented during the first 2 weeks of the 12-week, double-blind, placebo-controlled treatment period to reduce the risk of withdrawal effects in participants randomly assigned to placebo. |
| Hydrocodone ER | Experimental | Drug: Hydrocodone ERParticipants were administered hydrocodone ER tablets at dosages of 15, 30, 45, 60, or 90 mg every 12 hours at the dosage deemed successful for managing their pain during the titration period. During the 12-week, double-blind, placebo-controlled treatment period, participants randomly assigned to hydrocodone ER were administered tablets every 12 hours at the dosage deemed successful for managing their pain during the titration period. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- The patient is able to speak English and is willing to provide written informed consent, including a written opioid agreement, to participate in this study.
- The patient must be willing and able to successfully self-administer the study drug, comply with study restrictions, complete the electronic diary, and return to the clinic for scheduled study visits as specified in this protocol.
- Women of childbearing potential (not surgically sterile or 2 years postmenopausal), must use a medically accepted method of contraception and must agree to continue use of this method for the duration of the study and for 30 days after participation in the study, and have a negative pregnancy test at screening.
- The patient has pain of at least 3 months' duration associated with osteoarthritis or low back pain.
- The patient reports an average pain intensity score, over the prior 24 hours, of 5 or more on the 11-point numerical rating scale.
Key exclusion criteria (18 listed)
- The patient has known or suspected hypersensitivities, allergies, or other contraindications to any ingredient in the study drug.
- The patient has a recent history (within 5 years) or current evidence of alcohol or other substance abuse with the exception of nicotine or caffeine.
- The patient has medical or psychiatric disease that, in the opinion of the investigator, would compromise collected data.
- The patient is taking a total (ie, around-the-clock plus rescue medication) of more than 135 mg/day of oxycodone, or equivalent, during the 14 days prior to screening.
- The patient has a history of suicidality.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hydrocodone ERAlso: CEP-33237, Hydrocodone bitartrate extended-releaseDuring the open-label, titration period, all participants were administered hydrocodone ER tablets at dosages of 15, 30, 45, 60, or 90 mg every 12 hours to identify a dosage deemed successful for managing their pain. Hydrocodone ER was taken by participants randomized to the hydrocodone ER treatment arm during the double-blind treatment period at the dose level identified during the titration period. Participants were instructed to take tablets with a glass of water on an empty stomach at least 1 hour before or 2 hours after eating. | Drug | Hydrocodone ER, Placebo |
| PlaceboPlacebo matching the active drug dose identified during the titration period was taken by participants randomized to the placebo treatment arm during the double-blind treatment period. Participants were instructed to take intervention with a glass of water on an empty stomach at least 1 hour before or 2 hours after eating. | Drug | Placebo |
Primary outcome
Change From Baseline to Week 12 in Weekly Average Pain Intensity (wAPI)
Time frame: Baseline (end of Open-Label Titration Period), Week 12 of Double-blind Treatment Period
The primary efficacy variable was the change from baseline to week 12 in the wAPI. The API over the previous 24 hours, based on the 11-point Numerical Rating Scale (NRS 11), was collected daily by e-diary. The Week 12 wAPI scores from the previous 7 days were calculated for each study visit and averaged. The baseline wAPI score was calculated by averaging API scores from 3 to 12 days when the successful dose of hydrocodone extended release was confirmed at the end of the open label titration period, before patients were randomly assigned study drug. In the case of missing week-12 data due to early withdrawal from the study, or excessive rescue medication usage, the wAPI for week 12 was imputed. The Numeric Rating Scale (NRS-11) is an 11-point scale for patient self-reporting of pain on a Likert-type scale in which 0 is no pain and 10 is the worst pain imaginable. Negative change from baseline values indicate lessening in pain intensity.
25 secondary outcomes
Percentage of Participants Withdrawn From the Study During the Double-Blind Treatment Period By Reason
Time frame: Day 1 to Week 12 of the double-blind treatment period
Kaplan-Meier Estimates for Time to Discontinuation From the Study
Time frame: Day 1 to Week 12 of the double-blind treatment period
Participants With a Weekly Average Pain Intensity (wAPI) Increase From Baseline Exceeding 33%
Time frame: Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, and 12 of the Double-blind treatment period
Participants With a Weekly Average Pain Intensity (wAPI) Increase From Baseline Exceeding 50%
Time frame: Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, and 12 of the Double-blind treatment period
Weekly Average Pain Intensity (wAPI) Scores During the Double-blind Treatment Period
Time frame: Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, and 12 of the Double-blind treatment period
Weekly Average Worst Pain Intensity (WPI) Scores During the Double-blind Treatment Period
Time frame: Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, and 12 of the Double-blind treatment period
Clinician Assessment of Patient Function (CAPF) at Week 4
Time frame: Week 4 of the Double-blind Treatment Period
Clinician Assessment of Patient Function (CAPF) at Week 8
Time frame: Week 8 of the Double-blind Treatment Period
Clinician Assessment of Patient Function (CAPF) at Week 12
Time frame: Week 12 of the Double-blind Treatment Period
Clinician Assessment of Patient Function (CAPF) at Endpoint
Time frame: Endpoint of the Double-blind Treatment Period (up to week 12)
Patient Assessment of Function (PAF) at Week 4
Time frame: Week 4 of the Double-blind Treatment Period
Patient Assessment of Function (PAF) at Week 8
Time frame: Week 8 of the Double-blind Treatment Period
Patient Assessment of Function (PAF) at Week 12
Time frame: Week 12 of the Double-blind Treatment Period
Patient Assessment of Function (PAF) at Endpoint
Time frame: Endpoint of the Double-blind Treatment Period (up to week 12)
Clinician Global Impression of Severity (CGI-S) of Illness Scores During the Double-blind Treatment Period
Time frame: Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, and 12 of the Double-blind treatment period
Short-Form Health Survey (SF-36) Physical and Mental Component Summary Scores at Baseline, Week 12 and Endpoint
Time frame: Baseline (end of Open-Label Titration Period), Week 12 and Endpoint (last visit up to week 12) of the Double-blind treatment period
Brief Pain Inventory - Short Form (BPI-SF) Pain Interference Mean Score During the Double-Blind Treatment Period
Time frame: Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, 12 and Endpoint (last visit up to week 12) of the Double-blind treatment period
Participants With Adverse Events
Time frame: Day 1 up to Day 52 in Open-Label Titration; Day 1 up to Day 128 in Double-Blind Treatment period
Participants With Potentially Clinically Significant Abnormal Vital Signs Values During the Double-Blind Treatment Period
Time frame: Day 1 up to Day 128 in Double-Blind Treatment period
Participants With Potentially Clinically Significant Abnormal Laboratory Values During the Double-Blind Treatment Period
Time frame: Day 1 up to Day 128 in Double-Blind Treatment period
Subjective Opiate Withdrawal Scales (SOWS) Scores During the Double-Blind Treatment Period
Time frame: Weeks 1, 2, 4, 8, 12 and Endpoint (last visit up to Week 12) of the Double-blind treatment period
Clinical Opiate Withdrawal Scales (COWS) Scores During the Double-Blind Treatment Period
Time frame: Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, 12 and Endpoint (last visit up to Week 12) of the Double-blind treatment period
Addiction Behavior Checklist (ABC) Total Scores During Both the Open-Label Titration and Double-Blind Treatment Periods
Time frame: Baseline for Open-Label Titration period, Baseline for Double-Blind Treatment period (which is also the end of the Open-Label Titration period), Weeks 1, 4, 8, 12, and Endpoint (last visit up to Week 12) of the Double-blind Treatment period
Current Opioid Misuse Measures (COMM) Total Scores During Both the Open-Label Titration and Double-Blind Treatment Periods
Time frame: Baseline for Open-Label Titration period, Baseline for Double-Blind Treatment period (which is also the end of the Open-Label Titration period), Weeks 1, 4, 8, 12, and Endpoint (last visit up to Week 12) of the Double-blind Treatment period
Change From Baseline to Endpoint in the Double-Blind Treatment Phase in Electrocardiogram (ECG) Parameters
Time frame: Baseline (end of Open-Label Titration Period), Endpoint (last visit up to Week 12) of the Double-blind treatment period
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sponsor's Medical Expert, MD study director
Cephalon
73 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Hydrocodone ER in people with Chronic Pain, run by Teva Branded Pharmaceutical Products R&D, Inc. at 73 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 73 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline to Week 12 in Weekly Average Pain Intensity (wAPI) (time frame: Baseline (end of Open-Label Titration Period), Week 12 of Double-blind Treatment Period). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jun 2017.