Hydrocodone/Acetaminophen for Acute Pain Following Bunionectomy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier:
NCT01038609
First received: December 22, 2009
Last updated: March 10, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Pain
Drug: Hydrocodone/Acetaminophen Extended Release
Drug: Acetaminophen
Drug: Morphine Extended Release
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: A Randomized, Multicenter, Single-Blind Study Comparing Hydrocodone/Acetaminophen Extended Release 10/650, Morphine Extended Release, and Acetaminophen to Placebo in Subjects With Acute Pain Following Bunionectomy

Resource links provided by NLM:


Further study details as provided by AbbVie:

Primary Outcome Measures:
  • Sum of Pain Intensity Difference (SPID) Using the Pain Intensity Visual Analogue Scale (VAS) [ Time Frame: From time of first study drug administration to 48 hours following first study drug administration ] [ Designated as safety issue: No ]
    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:
  • TOTPAR (Total Pain Relief) [ Time Frame: From time of first study drug administration to 48 hours following first study drug administration ] [ Designated as safety issue: No ]
    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.

  • Participant's Global Assessment of Study Drug [ Time Frame: From time of first study drug administration to 48 hours following first study drug administration ] [ Designated as safety issue: No ]
    The participant's overall impression of the study drug was obtained on a 5-point categorical scale: excellent; very good; good; fair; poor.

  • Time to Perceptible and Meaningful Pain Relief [ Time Frame: From time of first study drug administration to 12 hours following first study drug administration ] [ Designated as safety issue: No ]
    The median time (minutes) from first perceptible pain relief (onset of pain relief) and time until first meaningful pain relief.

  • Participants With Adverse Events (AEs) [ Time Frame: 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). ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Vital Signs Values Meeting Potentially Clinically Significant Criteria [ Time Frame: At specified intervals from Screening through 7 days after first dose of study drug ] [ Designated as safety issue: Yes ]
    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).

  • Number of Participants With Chemistry Values Meeting Potentially Clinically Significant Criteria [ Time Frame: At specified intervals from Screening through 7 days after first dose of study drug ] [ Designated as safety issue: Yes ]
    Potentially clinically significant criteria: alanine aminotransferase/aspartate aminotransferase (ALT/AST) ≥3 times upper limit of normal (ULN); calcium ≤1.8 mmol/L.


Enrollment: 250
Study Start Date: December 2009
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
1 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).
Drug: Placebo
Active Comparator: Acetaminophen
1 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).
Drug: Acetaminophen
Other Name: Tylenol
Active Comparator: Morphine Extended Release
1 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).
Drug: Morphine Extended Release
Other Name: Kadian
Active Comparator: Morphine Extended Release / Acetaminophen
1 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).
Drug: Acetaminophen
Other Name: Tylenol
Drug: Morphine Extended Release
Other Name: Kadian
Experimental: Hydrocodone/Acetaminophen Extended Release
1 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).
Drug: Hydrocodone/Acetaminophen Extended Release
Other Name: ABT-712

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01038609

Locations
United States, Arizona
Site Reference ID/Investigator# 26223
Peoria, Arizona, United States, 85381
United States, Texas
Site Reference ID/Investigator# 26302
Austin, Texas, United States, 78705
Site Reference ID/Investigator# 26303
San Marcos, Texas, United States, 78666
United States, Utah
Site Reference ID/Investigator# 26304
West Jordan, Utah, United States, 84088
Sponsors and Collaborators
AbbVie (prior sponsor, Abbott)
Investigators
Study Director: Pedro Quintana Diez, MD AbbVie
  More Information

Additional Information:
No publications provided

Responsible Party: AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier: NCT01038609     History of Changes
Other Study ID Numbers: M12-058
Study First Received: December 22, 2009
Results First Received: November 1, 2013
Last Updated: March 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by AbbVie:
Postoperative Pain

Additional relevant MeSH terms:
Acute Pain
Pain
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Morphine
Hydrocodone
Acetaminophen, hydrocodone drug combination
Oxycodone
Acetaminophen
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Analgesics, Non-Narcotic
Antipyretics
Antitussive Agents
Respiratory System Agents
Anti-Inflammatory Agents, Non-Steroidal
Anti-Inflammatory Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on September 18, 2014