Study to Evaluate the Efficacy and Safety of Hydrocodone... | NCT01240863

NCT01240863

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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.	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.	Drug: Hydrocodone ER

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Hydrocodone ER	Drug	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.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	Baseline (end of Open-Label Titration Period), Week 12 of Double-blind Treatment Period

Secondary Outcomes

Measure	Description	Time Frame
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.	Day 1 to Week 12 of the double-blind treatment period

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

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.
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.

Name	Affiliation	Role
Sponsor's Medical Expert, MD	Cephalon	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Horizon Research Group LLC		Mobile	Alabama	36608	United States
Radiant Research, Inc.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Hydrocodone ER (Open-Label Titration Period)	All enrolled participants entered the open label titration period and received hydrocodone extended release (ER) tablets beginning with 15 mg every 12 hours for 3 to 7 days. Dosages were titrated upward until pain was effectively controlled. If an effective dosage between 15 mg - 90 mg twice a day was not identified within 6 week, the participant was withdrawn.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Placebo (Double-blind 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 tapering schedule 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 patients randomly assigned to placebo.
BG001	Hydrocodone ER (Double-blind Treatment Period)	Participants were administered hydrocodone ER tablets at a dosage deemed successful for managing their pain during the titration period. Dosages of 15, 30, 45, 60, or 90 mg every 12 hours were given for 12 weeks during the double-blind period.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG0000.14± 0.169 OG001-0.22± 0.176

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		ANCOVA	Treatment and stratification (opioid naïve/opioid experienced) factors as the fixed effects; screening and baseline APIs as covariates.	0.134	statistical significance level of 0.05.	Mean Difference (Final Values)	0.35			2-Sided	95	-0.11	0.82			placebo - hydrocodone		Superiority or Other

Secondary

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.

Full analysis set

Posted

Number

percentage of participants

Day 1 to Week 12 of the double-blind treatment period

ID	Title	Description
OG000	Placebo (Double-blind 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 tapering schedule 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 patients randomly assigned to placebo.
OG001	Hydrocodone ER (Double-blind Treatment Period)	Participants were administered hydrocodone ER tablets at a dosage deemed successful for managing their pain during the titration period. Dosages of 15, 30, 45, 60, or 90 mg every 12 hours were given for 12 weeks during the double-blind period.

Units	Counts

Secondary

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.

Full analysis set

Posted

Median

Inter-Quartile Range

days

Day 1 to Week 12 of the double-blind treatment period

ID	Title	Description
OG000	Placebo (Double-blind 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 tapering schedule 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 patients randomly assigned to placebo.
OG001	Hydrocodone ER (Double-blind Treatment Period)	Participants were administered hydrocodone ER tablets at a dosage deemed successful for managing their pain during the titration period. Dosages of 15, 30, 45, 60, or 90 mg every 12 hours were given for 12 weeks during the double-blind period.

Secondary

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.

Full analysis set. Participants contributing to each time point are included in the number analyzed.

Posted

Count of Participants

Participants

Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, and 12 of the Double-blind treatment period

ID	Title	Description
OG000	Placebo (Double-blind 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 tapering schedule 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 patients randomly assigned to placebo.
OG001	Hydrocodone ER (Double-blind Treatment Period)

Secondary

Participants With a Weekly Average Pain Intensity (wAPI) Increase From Baseline Exceeding 50%

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.

Full analysis set. Participants contributing to each time point are included in the number analyzed.

Posted

Count of Participants

Participants

Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, and 12 of the Double-blind treatment period

ID	Title	Description
OG000	Placebo (Double-blind 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 tapering schedule 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 patients randomly assigned to placebo.
OG001	Hydrocodone ER (Double-blind Treatment Period)

Secondary

Weekly Average Pain Intensity (wAPI) Scores During the Double-blind Treatment Period

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.

Full analysis set. Participants contributing to each time point are included in the number analyzed.

Posted

Mean

Standard Deviation

units on a scale

Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, and 12 of the Double-blind treatment period

ID	Title	Description
OG000	Placebo (Double-blind 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 tapering schedule 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 patients randomly assigned to placebo.
OG001	Hydrocodone ER (Double-blind Treatment Period)

Secondary

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.

Full analysis set. Participants contributing to each time point are included in the number analyzed.

Posted

Mean

Standard Deviation

units on a scale

Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, and 12 of the Double-blind treatment period

ID	Title	Description
OG000	Placebo (Double-blind 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 tapering schedule 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 patients randomly assigned to placebo.
OG001	Hydrocodone ER (Double-blind Treatment Period)	Participants were administered hydrocodone ER tablets at a dosage deemed successful for managing their pain during the titration period. Dosages of 15, 30, 45, 60, or 90 mg every 12 hours were given for 12 weeks during the double-blind period.

Secondary

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.

FAS of participants with assessments at the timeframe

Posted

Count of Participants

Participants

Week 4 of the Double-blind Treatment Period

ID	Title	Description
OG000	Placebo (Double-blind 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 tapering schedule 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 patients randomly assigned to placebo.
OG001	Hydrocodone ER (Double-blind Treatment Period)	Participants were administered hydrocodone ER tablets at a dosage deemed successful for managing their pain during the titration period. Dosages of 15, 30, 45, 60, or 90 mg every 12 hours were given for 12 weeks during the double-blind period.

Secondary

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.

FAS of participants with assessments at the timeframe

Posted

Count of Participants

Participants

Week 8 of the Double-blind Treatment Period

ID	Title	Description
OG000	Placebo (Double-blind 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 tapering schedule 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 patients randomly assigned to placebo.
OG001	Hydrocodone ER (Double-blind Treatment Period)	Participants were administered hydrocodone ER tablets at a dosage deemed successful for managing their pain during the titration period. Dosages of 15, 30, 45, 60, or 90 mg every 12 hours were given for 12 weeks during the double-blind period.

Secondary

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.

FAS of participants with assessments at the timeframe

Posted

Count of Participants

Participants

Week 12 of the Double-blind Treatment Period

ID	Title	Description
OG000	Placebo (Double-blind 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 tapering schedule 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 patients randomly assigned to placebo.
OG001	Hydrocodone ER (Double-blind Treatment Period)	Participants were administered hydrocodone ER tablets at a dosage deemed successful for managing their pain during the titration period. Dosages of 15, 30, 45, 60, or 90 mg every 12 hours were given for 12 weeks during the double-blind period.

Secondary

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.

FAS of participants with assessments at the timeframe

Posted

Count of Participants

Participants

Endpoint of the Double-blind Treatment Period (up to week 12)

ID	Title	Description
OG000	Placebo (Double-blind 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 tapering schedule 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 patients randomly assigned to placebo.
OG001	Hydrocodone ER (Double-blind Treatment Period)	Participants were administered hydrocodone ER tablets at a dosage deemed successful for managing their pain during the titration period. Dosages of 15, 30, 45, 60, or 90 mg every 12 hours were given for 12 weeks during the double-blind period.

Secondary

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

Full analysis set. Participants contributing to each time point are included in the number analyzed.

Posted

Count of Participants

Participants

Week 4 of the Double-blind Treatment Period

ID	Title	Description
OG000	Placebo (Double-blind 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 tapering schedule 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 patients randomly assigned to placebo.
OG001	Hydrocodone ER (Double-blind Treatment Period)	Participants were administered hydrocodone ER tablets at a dosage deemed successful for managing their pain during the titration period. Dosages of 15, 30, 45, 60, or 90 mg every 12 hours were given for 12 weeks during the double-blind period.

Secondary

Patient Assessment of Function (PAF) at Week 8

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

Full analysis set. Participants contributing to each time point are included in the number analyzed.

Posted

Count of Participants

Participants

Week 8 of the Double-blind Treatment Period

ID	Title	Description
OG000	Placebo (Double-blind 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 tapering schedule 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 patients randomly assigned to placebo.
OG001	Hydrocodone ER (Double-blind Treatment Period)	Participants were administered hydrocodone ER tablets at a dosage deemed successful for managing their pain during the titration period. Dosages of 15, 30, 45, 60, or 90 mg every 12 hours were given for 12 weeks during the double-blind period.

Secondary

Patient Assessment of Function (PAF) at Week 12

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

Full analysis set. Participants contributing to each time point are included in the number analyzed.

Posted

Count of Participants

Participants

Week 12 of the Double-blind Treatment Period

ID	Title	Description
OG000	Placebo (Double-blind 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 tapering schedule 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 patients randomly assigned to placebo.
OG001	Hydrocodone ER (Double-blind Treatment Period)	Participants were administered hydrocodone ER tablets at a dosage deemed successful for managing their pain during the titration period. Dosages of 15, 30, 45, 60, or 90 mg every 12 hours were given for 12 weeks during the double-blind period.

Secondary

Patient Assessment of Function (PAF) at Endpoint

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.

Full analysis set. Participants contributing to each time point are included in the number analyzed.

Posted

Count of Participants

Participants

Endpoint of the Double-blind Treatment Period (up to week 12)

ID	Title	Description
OG000	Placebo (Double-blind 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 tapering schedule 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 patients randomly assigned to placebo.
OG001	Hydrocodone ER (Double-blind Treatment Period)	Participants were administered hydrocodone ER tablets at a dosage deemed successful for managing their pain during the titration period. Dosages of 15, 30, 45, 60, or 90 mg every 12 hours were given for 12 weeks during the double-blind period.

Secondary

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.

Full analysis set. Participants contributing to each time point are included in the number analyzed.

Posted

Mean

Standard Deviation

units on a scale

Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, and 12 of the Double-blind treatment period

ID	Title	Description
OG000	Placebo (Double-blind 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 tapering schedule 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 patients randomly assigned to placebo.
OG001	Hydrocodone ER (Double-blind Treatment Period)

Secondary

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.

Full analysis set. Participants contributing to each time point are included in the number analyzed.

Posted

Mean

Standard Deviation

units on a scale

Baseline (end of Open-Label Titration Period), Week 12 and Endpoint (last visit up to week 12) of the Double-blind treatment period

ID	Title	Description
OG000	Placebo (Double-blind 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 tapering schedule 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 patients randomly assigned to placebo.

Secondary

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.

Full analysis set. Participants contributing to each time point are included in the number analyzed.

Posted

Mean

Standard Deviation

units on a scale

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

ID	Title	Description
OG000	Placebo (Double-blind 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 tapering schedule 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 patients randomly assigned to placebo.
OG001	Hydrocodone ER (Double-blind Treatment Period)

Secondary

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.

Safety analysis set (Open-Label Titration) and FAS (Double-Blind Treatment)

Posted

Count of Participants

Participants

Day 1 up to Day 52 in Open-Label Titration; Day 1 up to Day 128 in Double-Blind Treatment period

ID	Title	Description
OG000	Open-Label Titration: Opioid Naive	During the open label titration period, all participants received hydrocodone extended release tablets on an open-label basis. Opioid naïve participants (ie, those taking less than 10 mg/day of oxycodone or equivalent, during the 14 days before screening) started at a 15 mg dose of hydrocodone extended release, administered every 12 hours. A decision regarding dose adjustment was made based on whether the criterion of successful dose (ie, dose that produced stable pain relief) was met. In general, dose escalation stepped from 15 mg to 30 mg, 45 mg, 60 mg, and 90 mg every 12 hours until stable pain relief was obtained.

Secondary

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

FAS

Posted

Count of Participants

Participants

Day 1 up to Day 128 in Double-Blind Treatment period

ID	Title	Description
OG000	Placebo (Double-blind 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 tapering schedule 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 patients randomly assigned to placebo.
OG001	Hydrocodone ER (Double-blind Treatment Period)	Participants were administered hydrocodone ER tablets at a dosage deemed successful for managing their pain during the titration period. Dosages of 15, 30, 45, 60, or 90 mg every 12 hours were given for 12 weeks during the double-blind period.

Secondary

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

Full analysis set including participants with laboratory assessments

Posted

Count of Participants

Participants

Day 1 up to Day 128 in Double-Blind Treatment period

ID	Title	Description
OG000	Placebo (Double-blind 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 tapering schedule 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 patients randomly assigned to placebo.
OG001	Hydrocodone ER (Double-blind Treatment Period)	Participants were administered hydrocodone ER tablets at a dosage deemed successful for managing their pain during the titration period. Dosages of 15, 30, 45, 60, or 90 mg every 12 hours were given for 12 weeks during the double-blind period.

Secondary

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.

Full analysis set. Participants contributing to each time point are included in the number analyzed.

Posted

Mean

Standard Deviation

units on a scale

Weeks 1, 2, 4, 8, 12 and Endpoint (last visit up to Week 12) of the Double-blind treatment period

ID	Title	Description
OG000	Placebo (Double-blind 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 tapering schedule 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 patients randomly assigned to placebo.

Secondary

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

Full analysis set. Participants contributing to each time point are included in the number analyzed.

Posted

Mean

Standard Deviation

units on a scale

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

ID	Title	Description
OG000	Placebo (Double-blind 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 tapering schedule 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 patients randomly assigned to placebo.
OG001	Hydrocodone ER (Double-blind Treatment Period)

Secondary

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.

Full analysis set. Participants contributing to each time point are included in the number analyzed.

Posted

Mean

Standard Deviation

units on a scale

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

ID	Title	Description
OG000	Placebo (Double-blind 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 tapering schedule 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 patients randomly assigned to placebo.

Secondary

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.

Full analysis set. Participants contributing to each time point are included in the number analyzed.

Posted

Mean

Standard Deviation

units on a scale

ID	Title	Description
OG000	Placebo (Double-blind 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 tapering schedule 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 patients randomly assigned to placebo.

Secondary

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).

FAS of participants contributing baseline and endpoint data.

Posted

Mean

Standard Deviation

msec

Baseline (end of Open-Label Titration Period), Endpoint (last visit up to Week 12) of the Double-blind treatment period

ID	Title	Description
OG000	Placebo (Double-blind 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 tapering schedule 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 patients randomly assigned to placebo.
OG001	Hydrocodone ER (Double-blind Treatment Period)	Participants were administered hydrocodone ER tablets at a dosage deemed successful for managing their pain during the titration period. Dosages of 15, 30, 45, 60, or 90 mg every 12 hours were given for 12 weeks during the double-blind period.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Hydrocodone ER (Open-Label Titration Period)	All enrolled participants entered the open label titration period and received hydrocodone extended release (ER) tablets beginning with 15 mg every 12 hours for 3 to 7 days. Dosages were titrated upward until pain was effectively controlled. If an effective dosage between 15 mg - 90 mg twice a day was not identified within 6 week, the participant was withdrawn.	2	389	167	389
EG001	Placebo (Double-blind Treatment Period)	Participants were administered placebo tablets twice a day that matched the dosage deemed successful for managing their pain during the titration period. A step wise, double-blind tapering schedule 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 patients randomly assigned to placebo.	3	147	24	147
EG002	Hydrocodone ER (Double-blind Treatment Period)	Participants were administered hydrocodone ER tablets at a dosage deemed successful for managing their pain during the titration period. Dosages of 15, 30, 45, 60, or 90 mg every 12 hours were given for 12 weeks during the double-blind period.	3	146	45	146

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Oesophagitis	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 events0 affected389 at risk EG0010 events0 affected147 at risk EG0021 events1 affected146 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 events0 affected389 at risk EG0010 events0 affected147 at risk EG0022 events1 affected146 at risk
Hernia obstructive	General disorders	MedDRA (13.0)	Systematic Assessment	EG0000 events0 affected389 at risk EG0010 events0 affected147 at risk EG0021 events1 affected146 at risk
Anaphylactic reaction	Immune system disorders	MedDRA (13.0)	Systematic Assessment	EG0000 events0 affected389 at risk EG0010 events0 affected147 at risk EG0021 events1 affected146 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA (13.0)	Systematic Assessment	EG0000 events0 affected389 at risk EG0011 events1 affected147 at risk EG0020 events0 affected146 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (13.0)	Systematic Assessment	EG0000 events0 affected389 at risk EG0012 events1 affected147 at risk EG0020 events0 affected146 at risk
Bladder cancer recurrent	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (13.0)	Systematic Assessment	EG0000 events0 affected389 at risk EG0011 events1 affected147 at risk EG0020 events0 affected146 at risk
Renal failure acute	Renal and urinary disorders	MedDRA (13.0)	Systematic Assessment	EG0001 events1 affected389 at risk EG0010 events0 affected147 at risk EG0020 events0 affected146 at risk
Deep vein thrombosis	Vascular disorders	MedDRA (13.0)	Systematic Assessment	EG0001 events1 affected389 at risk EG0010 events0 affected147 at risk EG0020 events0 affected146 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Constipation	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG00061 events55 affected389 at risk EG0018 events7 affected147 at risk EG00219 events19 affected146 at risk
Nausea	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG00075 events70 affected389 at risk EG00111 events9 affected147 at risk EG00220 events19 affected146 at risk
Vomiting	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG00026 events25 affected389 at risk EG0016 events5 affected147 at risk EG0029 events9 affected146 at risk
Dizziness	Nervous system disorders	MedDRA (13.0)	Systematic Assessment	EG00023 events22 affected389 at risk EG0011 events1 affected147 at risk EG0023 events3 affected146 at risk
Headache	Nervous system disorders	MedDRA (13.0)	Systematic Assessment	EG00050 events43 affected389 at risk EG0018 events8 affected147 at risk EG00213 events10 affected146 at risk
Somnolence	Nervous system disorders	MedDRA (13.0)	Systematic Assessment	EG00051 events45 affected389 at risk EG0011 events1 affected147 at risk EG0023 events3 affected146 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (13.0)	Systematic Assessment	EG00023 events20 affected389 at risk EG0011 events1 affected147 at risk EG0024 events3 affected146 at risk

ID	Term
D059350	Chronic Pain
D010003	Osteoarthritis
D017116	Low Back Pain

ID	Term
D010146	Pain
D009461	Neurologic Manifestations
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms
D001168	Arthritis
D007592	Joint Diseases
D009140	Musculoskeletal Diseases
D012216	Rheumatic Diseases
D001416	Back Pain