Clinical evaluation of Hysingla ER analgesic efficacy and safety
Randomized, double-blind, placebo-controlled, multicenter, 12-week study to assess efficacy and safety of Hysingla ER 20 mg to 120 mg once-daily in patients with moderate to severe chronic lower back pain1,2
Primary study objective
- To evaluate the analgesic efficacy of once-daily, single-entity Hysingla ER 20 mg to 120 mg tablets compared with placebo in opioid-naïve and opioid-experienced patients with moderate to severe chronic lower back pain
Primary efficacy assessment
- Mean weekly pain intensity score, calculated using the daily diary "average pain over the last 24 hours"* score at Week 12 of the double-blind treatment period
Safety assesment
- Clinical laboratory test results, vital sign measurements, physical examinations, electrocardiogram findings, and adverse events (AEs) including opioid withdrawal
- Opioid withdrawal was defined as AEs of withdrawal as specified by DSM-IV criteria and by the Standardized MedDRA Query (SMQ) subcategory of drug withdrawal
- Clinical Opiate Withdrawal Scale (COWS) and the Modified Subjective Opiate Withdrawal Scale (OWS) were used to assess opioid withdrawal
*"Average pain over the last 24 hours" was measured on an 11‑point numeric rating scale ranging from 0="no pain" to 10="pain as bad as you can imagine."
Study design
Those patients meeting study randomization criteria entered the double-blind, 12-week period randomized to placebo* or Hysingla ER
- To enter the double-blind treatment period, patients had to qualify for randomization criteria, which included:
- For 3 consecutive days prior to randomization, patients had a reduction of ≥2 points to a score of ≤4 on a 0‑10 numeric scale for "average pain over the last 24 hours"
- Patients had acceptable tolerability to Hysingla ER and received the same dose for 7 ± 2 consecutive days before randomization
- Patients were not taking more than the maximum daily dose of supplemental pain medication
*Placebo does not mean that patients had no treatment options for pain. Patients had the option to use supplemental IR oxycodone.
Patient eligibility criteria
Inclusion criteria
Adult patients age 18 years or older with moderate to severe chronic lower back pain lasting at least 3 months1
- Low back pain was required to be related to nonmalignant and nonneuropathic conditions, nonradiating or radiating no further than above the knee
Opioid-naïve* or opioid-experienced patients who were on a stable analgesic regimen and who were not responsive to their current analgesic regimen (i.e., had uncontrolled low back pain)1,2
- Defined as an "average pain over the last 14 days" score of ≥5 at screening, as well as 3 or more "average pain over the last 24 hours" scores of ≥5 during the screening period
- Opioid-experienced patients could not take more than 100 mg per day oxycodone equivalent for 14 days prior to screening
*Opioid-naïve patients were taking less than 5 mg daily of oxycodone equivalent during the 14 days prior to screening.
Exclusion criteria
Medical history of conditions and procedures listed below1
- Inflammatory arthritis; surgical procedures directed toward the source of the chronic low back pain within 6 months of the screening visit, or any major surgery scheduled during the study period; nerve/plexus block within 4 weeks; lumbar steroid injections within 6 weeks; or the presence of significant cardiac, pulmonary, neurologic, hepatic, renal, gastrointestinal, or psychiatric conditions
Dose Titration
Open-label conversion and dose titration period (up to 45 days)
- 905 patients (48% opioid-experienced) entered into an open-label conversion and titration period with Hysingla ER (20 mg to 120 mg) dosed once daily
- Patients discontinued all medications used for chronic pain prior to starting Hysingla ER treatment; optional use of supplemental IR analgesics (oxycodone 5 mg) was permitted up to 2 doses/day
- Patients discontinued for the following reasons: adverse events (10%), failure to achieve protocol-defined reduction in pain score (7%), lack of therapeutic effect (5%), subject's choice (5%), confirmed or suspected diversion (3%), lost to follow-up (2%), and administrative reasons (2%).
Treatment Period
Double-blind treatment period (12 weeks)
588 patients (65%) were randomized at a ratio of 1:1 with their fixed stabilized dose (20 mg to 120 mg; average daily dose: 57 mg) of Hysingla ER (n=296) or matching placebo (n=292)
- Patients met the study randomization criteria of adequate analgesia (pain reduction of at least 2 points to a score of 4 or less on a 0 to 10 numerical rating scale) and acceptable tolerability of Hysingla ER
- Patients in both groups had the option of taking supplemental IR analgesics (oxycodone 5 mg) up to 6 doses per day depending on their randomized Hysingla ER dose
- 439 patients completed the 12-week, double-blind treatment period: 210 who received placebo, and 229 who received Hysingla ER
*"Average pain over the last 24 hours" was measured on an 11‑point Numeric Rating Scale (NRS) ranging from 0="no pain" to 10="pain as bad as you can imagine" during the double-blind period.
