Safety and Efficacy of COV795 in Moderate to Severe Post-Operative Bunionectomy Pain With an Open-label Extension

A Phase 3 Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Evaluation of the Safety and Analgesic Efficacy of COV795 in Moderate to Severe Post-Operative Bunionectomy Pain Followed by an Open-Label Extension

The primary objective of this study is to show the effectiveness of repeated doses of COV795 versus placebo, using the summed pain intensity difference over the first 48 hours in subjects with acute moderate to severe pain following bunionectomy.

Study Overview

• Status: Completed
• Conditions: Pain, Postoperative; Bunion
• Intervention / Treatment: Drug: COV795; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 329
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Bakersfield, California, United States, 93311
      • Trovare Clinical Research, Inc.
    • Pasedena, California, United States, 91105
      • Lotus Clinical Research, LLC
  • Maryland
    • Pasadena, Maryland, United States, 21122
      • Chesapeake Research Group, LLC
  • Texas
    • San Antonio, Texas, United States, 78229
      • Endeavor Clinical Trials, PA
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • Jean Brown Research, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

1. Complete the informed consent process as documented by signed informed consent form(s).
2. Be in generally good health.
3. Be 18 to 75 years of age, inclusively at the time of screening.
4. Be scheduled for a primary unilateral first metatarsal bunionectomy (with no collateral procedures).
5. Have a body mass index ≤33 kg/m2.
6. Female subjects are eligible only if not pregnant, not lactating, not planning to become pregnant for the duration of the study, surgically sterile or at least two years postmenopausal, or practicing an acceptable form of birth control for at least 2 months
7. Male subjects must be sterile or commit to the use of a reliable method of birth control
8. Be classified as Physical status 1 (PS-1) to PS-2 by the American Society of Anesthetists (ASA) Physical Status Classification System.
9. Be willing to complete the pain evaluations and return to the clinic as scheduled.

Exclusion Criteria

1. Have an uncontrolled medical condition, serious intercurrent illness, clinically significant general health condition, or extenuating circumstance that may significantly decrease study compliance or otherwise preclude their participation in the study.
2. Have a clinically significant abnormal electrocardiogram (ECG) at screening
3. Have had any type of gastric bypass surgery or have a gastric band.
4. Have previous abdominal surgery within the past year or history of abdominal adhesions, known or suspected paralytic ileus.
5. Have a history of any medical condition that would alter the absorption, distribution, metabolism or excretion of COV795
6. Have a history of severe bronchial asthma, hypercarbia, or hypoxia
7. Have a clinically significant abnormality on their clinical laboratory values
8. Have Addison's disease, benign prostatic hyperplasia, or kidney disease
9. Have donated blood or blood components within 3 months prior to the screening visit.
10. Have a known allergy or hypersensitivity to any opioid analgesics, anesthetics, acetaminophen, Non-steroid anti-inflammatory drugs (NSAIDs).
11. Have a history of intolerance to short term opioid use.
12. Unwilling to discontinue certain prohibited medications within the allotted time before surgery and throughout the duration of the study. Have taken certain drugs within the indicated times before surgery.
13. Have a history of substance or alcohol abuse and/or a positive result on drug screening.
14. Have a positive test for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) at the screening visit.
15. Have dysphagia and/or cannot swallow study medication whole.
16. Have a history of migraine or frequent headaches, seizures, or are currently taking anticonvulsants.
17. Have previously participated in a clinical trial using COV795 or had a bunionectomy in the last 3 months.
18. Received any investigational drugs or devices within 4 weeks prior to the screening visit.
19. Other criteria as specified in the trial protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; 2 tablets taken every 12 hours
Experimental: COV795	Drug: COV795; 2 tablets taken every 12 hours; Other Names: MNK795

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SPID48 (Summed Pain Intensity Difference)	Pain intensity (PI) is measured using the 11-point (0-10) Numeric Pain Rating Scale (NPRS) score. PID is the arithmetic difference in NPRS score at the time point of interest from the baseline score. SPID48 is the sum of time-weighted PID scores measured 22 times over the 48 hour assessment period, with a total score ranging from -480 (worst) to 480 (best). A higher SPID value indicates greater pain relief.	48 hours

Collaborators and Investigators

• Sponsor: Mallinckrodt

Publications and helpful links

General Publications

• Singla N, Barrett T, Sisk L, Kostenbader K, Young J. Assessment of the safety and efficacy of extended-release oxycodone/acetaminophen, for 14 days postsurgery. Curr Med Res Opin. 2014 Dec;30(12):2571-8. doi: 10.1185/03007995.2014.957824. Epub 2014 Oct 13.
• Singla N, Barrett T, Sisk L, Kostenbader K, Young J, Giuliani M. A randomized, double-blind, placebo-controlled study of the efficacy and safety of MNK-795, a dual-layer, biphasic, immediate-release and extended-release combination analgesic for acute pain. Curr Med Res Opin. 2014 Mar;30(3):349-59. doi: 10.1185/03007995.2013.876979. Epub 2014 Jan 10.

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: November 28, 2011
• First Submitted That Met QC Criteria: November 30, 2011
• First Posted (Estimate): December 2, 2011

Study Record Updates

• Last Update Posted (Estimate): October 21, 2016
• Last Update Submitted That Met QC Criteria: September 8, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: Bunionectomy; Moderate Post-Operative Pain; Severe Post-Operative Pain
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative
• Other Study ID Numbers: COV15000182