Efficacy and Safety of Hydrocodone Bitartrate (HYD) in Subjects With Moderate to Severe Chronic Low Back Pain

A Multicenter, Randomized, Double-blind, Placebo-controlled Study With an Open-label Run-in to Assess the Efficacy and Safety of Hydrocodone Bitartrate (HYD) Tablets 20 to 120 mg Once-daily in Subjects With Moderate to Severe Chronic Low Back Pain

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01452529

Enrollment

905

Registered

2011-10-17

Start date

2011-10-31

Completion date

2013-10-31

Last updated

2020-03-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Low Back Pain

Keywords

Pain, Opioid

Brief summary

The primary objective of this study is to evaluate the analgesic efficacy and safety of HYD tablets 20 to 120 mg once-daily dose compared to placebo in subjects with moderate to severe chronic low back pain uncontrolled by their current stable analgesic regimen

Interventions

DRUGHydrocodone bitartrate q24h film-coated tablets

Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily

DRUGPlacebo to match hydrocodone bitartrate q24h tablets

Placebo to match hydrocodone bitartrate q24h film coated tablets 20 - 120 mg once daily

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

include: * Male and female subjects ≥ 18 years of age with moderate to severe, chronic low back pain (lasting several hours daily) as their predominant pain condition for at least 3 months prior to the screening visit; * Subjects whose low back pain is not adequately treated prior to the screening visit with their stable incoming analgesic regimen; * Subjects deemed by the investigator/medically qualified designee (must be MD or DO) to be appropriate candidates for the protocol specified, around the clock HYD therapeutic regimen; * Female subjects who are premenopausal or postmenopausal less than 1 year and who have not had surgical sterilization (ie, tubal ligation, partial or complete hysterectomy) must have a negative serum pregnancy test, be nonlactating, and willing to use adequate and reliable contraception throughout the study (eg, barrier with additional spermicidal foam or jelly, intra-uterine device, hormonal contraception).

Exclusion criteria

include: * Subjects taking \> 100 mg/day oxycodone or equivalent during last 14 days prior to screening visit; * Subjects who cannot or will not agree to completely stop all incoming opioid and nonopioid analgesic medications and other medications used for chronic pain, excluding herbal and nutraceutical medications; * Subjects who cannot or will not agree to stop local regional pain treatments during the study (nerve/plexus blocks or ablation, neurosurgical procedures for pain control, botulinum toxin injections for control of chronic low back pain, steroid injections in the lower back or inhalation analgesia). The subject must not have had a nerve/plexus block within 4 weeks of the screening visit, neuroablation within 6 months of the screening visit, a botulinum toxin injection in the low back region within 3 months of the screening visit, steroid injections in the lower back within 6 weeks of the screening visit, or intravenous or intramuscular steroid injections within 4 weeks of the screening visit; * Subjects who have used any investigational medication within 30 days prior to the first dose of study medication; * Subjects with any history of seizures (subjects with history of pediatric febrile seizures may participate in the study) or increase in intracranial pressure; * Subjects with current uncontrolled depression or other uncontrolled psychiatric disorder (subjects with controlled depression or other psychiatric disorder must be on a stable medication for ≥ 1 month prior to the screening visit to participate in the study); * Subjects with a history of alcohol, medication, or illicit drug abuse or addiction and/or history of opioid abuse or addiction at any time; * Subjects with clinically unstable cardiac disease, including: unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, active myocardial ischemia, or indwelling pacemaker; * Subjects with unstable respiratory disease that, in the opinion of the investigator, precludes entry into this study; * Subjects with evidence of impaired liver function upon entry into the study (laboratory test values ≥ 3 times the upper limit of the laboratory reference (normal) range (ULN) for aspartate transaminase \[AST/SGOT\] or alanine transaminase \[ALT/SGPT\], or values \> 2 times the ULN for alkaline phosphatase), or total bilirubin level \> 1.5 times the ULN or, in the opinion of the investigator/medically qualified designee (must be MD or DO), liver function impairment to the extent that the subject should not participate in this study; * Subjects with evidence of impaired kidney function upon entry into the study (ie, serum creatinine ≥ 2.5 mg/dL); * Subjects with biliary tract disease, hypothyroidism, adrenal cortical insufficiency, or any other medical condition that, in the opinion of the investigator, is inadequately treated and precludes entry into the study; * Subjects who had surgical procedures directed towards the source of chronic low back pain within 6 months of the screening visit or scheduled for surgery of the lower back or any other major surgery during the study conduct period; * Subjects with history of malignancy within past 2 years, with exception of basal cell carcinoma that has been successfully treated; * Subjects with any condition in which opioids are contraindicated, eg, severe respiratory depression with hypoxia and/or hypercapnia, severe chronic obstructive lung disease, cor pulmonale, severe bronchial asthma, or paralytic ileus; * Subjects who are allergic to hydrocodone or who have a history of allergies to other opioids. This does not include subjects who have experienced common opioid side effects (eg, nausea, constipation); * Subjects receiving monoamine oxidase inhibitors (MAOIs) or who have been taking MAOIs within 2 weeks of the screening visit. Other protocol-specific inclusion/

Design outcomes

Primary

Measure	Time frame	Description
Mean Pain Intensity for Average Pain Over the Last 24 Hours Score	Week 12	Mean pain intensity for average pain over the last 24 hours score (on an 11-point numerical rating scale where 0 = no pain and 10 = pain as bad as you can imagine).

Secondary

Measure	Time frame	Description
Medical Outcome Study Sleep Scale - Revised (MOS Sleep-R) - Sleep Disturbance Subscale	Weeks 4, 8, and 12	The MOS Sleep-R is a brief, self-administered 12-item assessment designed to measure key aspects of sleep. It includes a sleep problems index and 6 subscales - sleep disturbance, sleep adequacy, daytime somnolence, snoring, awaken short of breath or with headache, and quantity of sleep. The sleep disturbance subscale comprised the responses to questions 1, 3, 7, and 8 on the assessment. The individual responses for each question were recorded on a 5-point scale with options ranging from 1 - all of the time to 5 - none of the time. Sleep disturbance scores were transformed linearly on a scale of 0-100. A higher value indicates a better score; therefore, a higher score indicates a better sleep pattern.
Patient Global Impression of Change (PGIC)	Week 12	The PGIC is an ordinal scale which assesses the change in overall status relative to the start of the study. The scale has only 1 item, which measures global change of overall status by the subject on a 7-point scale (very much improved, much improved, minimally improved, no change, minimally worse, much worse, very much worse), where 1 = very much improved and 7 = very much worse. The proportion of subjects responding very much improved and much improved was summarized by treatment group.
Responder Analysis for Subjects With a ≥ 30% Reduction in Pain Compared to Baseline	Baseline to Week 12	A subject's response to treatment was defined as the percentage reduction from the screening mean pain score to the mean pain intensity at week 12 of the double-blind period.
Responder Analysis for Subjects With a ≥ 50% Reduction in Pain Compared to Baseline	Baseline to Week 12	A subject's response to treatment was defined as the percentage reduction from the screening mean pain score to the mean pain intensity at week 12 of the double-blind period.

Countries

United States

Participant flow

Recruitment details

First subject first visit: 23-March-2012; Last subject last visit: 03-September-2013. The study was conducted at medical/research sites in the United States.

Pre-assignment details

Subjects with moderate to severe chronic low back pain uncontrolled by their current stable analgesic regimen were included.

Participants by arm

Arm	Count
Hydrocodone Bitartrate Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily	296
Placebo Placebo to match hydrocodone bitartrate once daily tablets Placebo to match hydrocodone bitartrate q24h tablets: Placebo to match hydrocodone bitartrate q24h film coated tablets 20 - 120 mg once daily	292
Total	588

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Double-blind (DB) Period	Administrative	0	11	7
Double-blind (DB) Period	Adverse Event	0	18	11
Double-blind (DB) Period	Confirmed or suspected diversion	0	2	3
Double-blind (DB) Period	Lack of Efficacy	0	16	44
Double-blind (DB) Period	Lost to Follow-up	0	5	3
Double-blind (DB) Period	Withdrawal by Subject	0	15	14
Run-in Period	Administrative	21	0	0
Run-in Period	Adverse Event	96	0	0
Run-in Period	Confirmed or suspected diversion	23	0	0
Run-in Period	Did not qualify for Double-Blind Phase	59	0	0
Run-in Period	Lack of Efficacy	46	0	0
Run-in Period	Lost to Follow-up	19	0	0
Run-in Period	Withdrawal by Subject	49	0	0

Baseline characteristics

Characteristic	Hydrocodone Bitartrate	Placebo	Total
Age, Continuous	49.2 years STANDARD_DEVIATION 13.51	47.9 years STANDARD_DEVIATION 13.23	48.6 years STANDARD_DEVIATION 13.38
Race/Ethnicity, Customized American Indian or Alaska Native	2 participants	1 participants	3 participants
Race/Ethnicity, Customized Asian	25 participants	29 participants	54 participants
Race/Ethnicity, Customized Black or African American	67 participants	51 participants	118 participants
Race/Ethnicity, Customized Other	7 participants	4 participants	11 participants
Race/Ethnicity, Customized White	195 participants	207 participants	402 participants
Screening Baseline Pain Over the Last 24 Hours	7.4 units on a scale STANDARD_DEVIATION 1.13	7.4 units on a scale STANDARD_DEVIATION 1.19	7.4 units on a scale STANDARD_DEVIATION 1.16
Sex: Female, Male Female	172 Participants	166 Participants	338 Participants
Sex: Female, Male Male	124 Participants	126 Participants	250 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	265 / 905	52 / 296	30 / 292
serious Total, serious adverse events	7 / 905	2 / 296	4 / 292

Outcome results

Primary

Mean Pain Intensity for Average Pain Over the Last 24 Hours Score

Mean pain intensity for average pain over the last 24 hours score (on an 11-point numerical rating scale where 0 = no pain and 10 = pain as bad as you can imagine).

Time frame: Week 12