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Hydrocodone/Acetaminophen for Acute Pain Following Bunionectomy

Registration Number
NCT01038609
Lead Sponsor
AbbVie (prior sponsor, Abbott)
Brief Summary

The primary purpose of this study was to evaluate analgesic efficacy and safety of hydrocodone/acetaminophen extended release compared to placebo in moderate to severe pain following primary unilateral first metatarsal bunionectomy.

Detailed Description

The bunionectomy was performed under regional anesthesia and propofol sedation. Perioperative anesthesia was standardized for all participants. Upon completion of surgery, designated study personnel ensured continued eligibility per the selection criteria of the protocol.

After an appropriate period of time following bunionectomy, participants who had a pain intensity score of ≥ 40 mm on a 100 mm visual analog scale (VAS) and moderate or severe pain intensity per the categorical pain intensity scale were eligible for randomization, in equal numbers, into 1 of 5 treatment arms. In order to maintain the single-blind nature of the study, all participants were dosed with study drug (active and/or placebo) every 6 hours.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
250
Inclusion Criteria
  • Subjects who were in general good health, experiencing moderate to severe pain following bunionectomy surgery and who were willing to remain confined for approximately 4 days following surgery for study procedures.
Exclusion Criteria
  • Subjects who underwent Base wedge osteotomy and/or Long-Z hart bunionectomy procedures
  • Allergic reaction to study medications
  • Pregnant or breastfeeding females
  • Clinically significant lab abnormalities at screening
  • Positive hepatitis testing at screening
  • Clinically significant or uncontrolled medical disorders or illness at screening
  • Active malignancy or chemotherapy
  • Any history of drug or alcohol abuse/addiction
  • Known or suspected history of human immunodeficiency virus (HIV); requires treatment with monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs) or butyrophenones
  • History of major depressive episode or major psychiatric disorder
  • Current systemic corticosteroid therapy
  • Inability to refrain from smoking during or alcohol during stay at investigative site

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlacebo1 dose of 1 placebo tablet (for hydrocodone/acetaminophen extended release) plus 1 placebo capsule (for morphine extended release), administered once every 12 hours, and 1 dose of 1 placebo tablet (for hydrocodone/acetaminophen extended release), administered once every 6 hours (for a total of 8 doses).
AcetaminophenAcetaminophen1 dose of 1 placebo capsule (for morphine extended release) plus 1 acetaminophen tablet, administered once every 12 hours, and 1 dose of 1 acetaminophen tablet, administered once every 6 hours (for a total of 8 doses).
Morphine Extended ReleaseMorphine Extended Release1 dose of 1 placebo tablet (for hydrocodone/acetaminophen extended release) plus 1 morphine extended release capsule, administered once every 12 hours, and 1 dose of 1 placebo tablet (for hydrocodone/acetaminophen extended release), administered once every 6 hours (for a total of 8 doses).
Morphine Extended Release / AcetaminophenAcetaminophen1 dose of 1 morphine extended release capsule plus 1 acetaminophen tablet, administered once every 12 hours, and 1 dose of 1 acetaminophen tablet, administered once every 6 hours (for a total of 8 doses).
Hydrocodone/Acetaminophen Extended ReleaseHydrocodone/Acetaminophen Extended Release1 dose of 1 hydrocodone/acetaminophen extended release tablet plus 1 placebo capsule (for morphine extended release), administered once every 12 hours, and 1 dose of 1 placebo tablet (for hydrocodone/acetaminophen extended release), administered once every 6 hours (for a total of 8 doses).
Morphine Extended Release / AcetaminophenMorphine Extended Release1 dose of 1 morphine extended release capsule plus 1 acetaminophen tablet, administered once every 12 hours, and 1 dose of 1 acetaminophen tablet, administered once every 6 hours (for a total of 8 doses).
Primary Outcome Measures
NameTimeMethod
Sum of Pain Intensity Difference (SPID) Using the Pain Intensity Visual Analogue Scale (VAS)From time of first study drug administration to 48 hours following first study drug administration

Participants assessed pain intensity on a 100 mm visual analogue scale (VAS) with 0 meaning "no pain" and 100 meaning the "worst pain imaginable". The SPID VAS score for 0 to 48 hours following initial study drug dose measured the cumulative pain intensity difference during treatment with higher mean SPID VAS scores indicating greater improvement from Baseline. The SPID score is a measure of the cumulative pain intensity difference during treatment and the area under the curve was estimated using the linear trapezoidal rule.

Secondary Outcome Measures
NameTimeMethod
Participant's Global Assessment of Study DrugFrom time of first study drug administration to 48 hours following first study drug administration

The participant's overall impression of the study drug was obtained on a 5-point categorical scale: excellent; very good; good; fair; poor.

Participants With Adverse Events (AEs)AEs were recorded from study drug administration until 30 days following discontinuation of study drug (total 32 days); SAEs were recorded from the time informed consent was obtained until 30 days following discontinuation of study drug (total 51 days).

An adverse event (AE) is defined as any untoward medical occurrence in a participant, which does not necessarily have a causal relationship with treatment. If an adverse event meets any of the following criteria, it is considered a serious adverse event (SAE): results in death or is life-threatening, results in admission or prolongation of hospitalization, results in congenital anomaly or persistent or significant disability/incapacity, or is an important medical event requiring medical or surgical intervention to prevent serious outcome. AEs were categorized by severity (mild, moderate, severe) and relationship to treatment (probably, possibly, probably not, not related). Please see Adverse Events section below for more details.

Time to Perceptible and Meaningful Pain ReliefFrom time of first study drug administration to 12 hours following first study drug administration

The median time (minutes) from first perceptible pain relief (onset of pain relief) and time until first meaningful pain relief.

Number of Participants With Vital Signs Values Meeting Potentially Clinically Significant CriteriaAt specified intervals from Screening through 7 days after first dose of study drug

Potentially clinically significant criteria: Systolic blood pressure (BP) ≤90 mm Hg and ≥20 mm Hg decrease (low) or ≥180 mm Hg and ≥20 mm Hg increase (high); Diastolic BP ≤50 mm Hg and ≥15 mm Hg decrease (low) or ≥105 mm Hg and ≥15 mm Hg increase (high). Heart rate ≤50 beats per minute (bpm) and ≥15 bpm decrease (low) or ≥120 bpm and ≥15 bpm increase (high). Respiratory rate \<10 respirations per minute (rpm) (low) or \>24 rpm (high).

TOTPAR (Total Pain Relief)From time of first study drug administration to 48 hours following first study drug administration

TOTPAR was the time-interval weighted sum of pain relief. Pain relief was assessed by participants' responses to how their pain relief was compared with the pain they had just before receiving the first dose of study drug: no relief, a little relief, some relief, a lot of relief, or complete relief. Higher mean TOTPAR scores indicate better pain relief. The TOTPAR score is a measure of the cumulative pain intensity difference during treatment and the area under the curve was estimated using the linear trapezoidal rule.

Number of Participants With Chemistry Values Meeting Potentially Clinically Significant CriteriaAt specified intervals from Screening through 7 days after first dose of study drug

Potentially clinically significant criteria: alanine aminotransferase/aspartate aminotransferase (ALT/AST) ≥3 times upper limit of normal (ULN); calcium ≤1.8 mmol/L.

Trial Locations

Locations (4)

Site Reference ID/Investigator# 26302

🇺🇸

Austin, Texas, United States

Site Reference ID/Investigator# 26223

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Peoria, Arizona, United States

Site Reference ID/Investigator# 26303

🇺🇸

San Marcos, Texas, United States

Site Reference ID/Investigator# 26304

🇺🇸

West Jordan, Utah, United States

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