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

• Sponsor: Mallinckrodt (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01484652
• Collaborator: (none)
• Enrollment: 329
• Locations: 5
• Arms: 2
• Duration (Months): 10
• Patients Per Site: 65.8
• Patients Per Site Per Month: 6.6

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Pain, Postoperative; Bunion	Drug: COV795; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 329 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: Nov 1, 2011
• Actual Primary Completion Date: Aug 1, 2012
• Actual Study Completion Date: Sep 1, 2012

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. SPID48 (Summed Pain Intensity Difference) [48 hours]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Trovare Clinical Research, Inc.	Bakersfield	California	United States	93311
2	Lotus Clinical Research, LLC	Pasedena	California	United States	91105
3	Chesapeake Research Group, LLC	Pasadena	Maryland	United States	21122
4	Endeavor Clinical Trials, PA	San Antonio	Texas	United States	78229
5	Jean Brown Research, Inc.	Salt Lake City	Utah	United States	84124

Sponsors and Collaborators

• Mallinckrodt

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Mallinckrodt
• ClinicalTrials.gov Identifier: NCT01484652
• Other Study ID Numbers: COV15000182
• First Posted: Dec 2, 2011
• Last Update Posted: Oct 21, 2016
• Last Verified: Sep 1, 2016

• Keywords provided by Mallinckrodt: Moderate Post-Operative Pain; Severe Post-Operative Pain; Bunionectomy
• Additional relevant MeSH terms: Pain, Postoperative

Study Results

Participant Flow

Arm/Group Title	COV795	Placebo
Arm/Group Description	2 tablets taken every 12 hours at Hour 0, 12, 24, and 36; total of 4 doses	2 tablets taken every 12 hours at Hour 0, 12, 24, and 36; total of 4 doses
Period Title: Overall Study
STARTED	166	163
COMPLETED	151	142
NOT COMPLETED	15	21

Baseline Characteristics

Arm/Group Title	COV795	Placebo	Total
Arm/Group Description	2 tablets taken every 12 hours	2 tablets taken every 12 hours	Total of all reporting groups
Overall Participants	166	163	329
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.3 (13.17)	44.6 (14.14)	43.4 (13.69)
Sex: Female, Male (Count of Participants)
Female	145 87.3%	135 82.8%	280 85.1%
Male	21 12.7%	28 17.2%	49 14.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	3 1.8%	0 0%	3 0.9%
Asian	13 7.8%	11 6.7%	24 7.3%
Native Hawaiian or Other Pacific Islander	0 0%	1 0.6%	1 0.3%
Black or African American	51 30.7%	47 28.8%	98 29.8%
White	98 59%	103 63.2%	201 61.1%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 0.6%	1 0.6%	2 0.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	38 22.9%	44 27%	82 24.9%
Not Hispanic or Latino	128 77.1%	119 73%	247 75.1%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	SPID48 (Summed Pain Intensity Difference)
Description	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.
Time Frame	48 hours

Outcome Measure Data

Analysis Population Description

The analysis population for the primary outcome measure was the modified intent-to-treat population (mITT). The mITT analysis population includes 303 subjects from Cohort 2. Missing pain intensity difference scores were imputed using a multiple imputation method.

Arm/Group Title	COV795	Placebo
Arm/Group Description	2 tablets taken every 12 hours	2 tablets taken every 12 hours
Measure Participants	150	153
Mean (Standard Error) [scores on a scale]	114.9 (7.64)	66.9 (7.6)

Adverse Events

Time Frame	Serious Adverse Events (SAEs) span the entire study, ie, the double-blind and open-label extension phases. Other Adverse Events reflects data from the double-blind phase of the study.
Adverse Event Reporting Description	Subjects who received at least one dose of COV795 during the double-blind phase or open-label phase are included in the SAE COV795 group summary. Subjects who only received placebo during the entire study are included in the Placebo group summary.
Arm/Group Title	COV795		Placebo
Arm/Group Description	2 tablets taken every 12 hours		2 tablets taken every 12 hours
All Cause Mortality
	COV795		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	COV795		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/235 (1.3%)		1/94 (1.1%)
Gastrointestinal disorders
Gastrooesophageal reflux disease	1/235 (0.4%)		0/94 (0%)
Immune system disorders
Allergic reaction	0/235 (0%)		1/94 (1.1%)
Investigations
Pregnancy test urine positive	1/235 (0.4%)		0/94 (0%)
Vascular disorders
Deep vein thrombosis	1/235 (0.4%)		0/94 (0%)
Other (Not Including Serious) Adverse Events
	COV795		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	89/166 (53.6%)		35/163 (21.5%)
Gastrointestinal disorders
Constipation	7/166 (4.2%)		5/163 (3.1%)
Dry mouth	1/166 (0.6%)		2/163 (1.2%)
Nausea	51/166 (30.7%)		9/163 (5.5%)
Vomiting	15/166 (9%)		0/163 (0%)
General disorders
Edema peripheral	2/166 (1.2%)		0/163 (0%)
Injury, poisoning and procedural complications
Excoriation	2/166 (1.2%)		0/163 (0%)
Nervous system disorders
Dizziness	22/166 (13.3%)		2/163 (1.2%)
Headache	16/166 (9.6%)		8/163 (4.9%)
Hypoaesthesia	1/166 (0.6%)		2/163 (1.2%)
Somnolence	6/166 (3.6%)		1/163 (0.6%)
Renal and urinary disorders
Dysuria	2/166 (1.2%)		0/163 (0%)
Skin and subcutaneous tissue disorders
Blister	2/166 (1.2%)		1/163 (0.6%)
Erythema	2/166 (1.2%)		0/163 (0%)
Pruritus generalized	2/166 (1.2%)		0/163 (0%)
Rash	3/166 (1.8%)		2/163 (1.2%)
Pruritus	3/166 (1.8%)		3/163 (1.8%)
Vascular disorders
Hot flush	2/166 (1.2%)		1/163 (0.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.