Trial Outcomes & Findings for Safety and Efficacy of COV795 in Moderate to Severe Post-Operative Bunionectomy Pain With an Open-label Extension (NCT NCT01484652)

Last Updated: 2016-10-21

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

329 participants

Primary outcome timeframe

48 hours

Results posted on

2016-10-21

Participant Flow

Participant milestones

Participant milestones
Measure	COV795 2 tablets taken every 12 hours at Hour 0, 12, 24, and 36; total of 4 doses	Placebo 2 tablets taken every 12 hours at Hour 0, 12, 24, and 36; total of 4 doses
Overall Study STARTED	166	163
Overall Study COMPLETED	151	142
Overall Study NOT COMPLETED	15	21

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	COV795 n=166 Participants 2 tablets taken every 12 hours	Placebo n=163 Participants 2 tablets taken every 12 hours	Total n=329 Participants Total of all reporting groups
Age, Continuous	42.3 years STANDARD_DEVIATION 13.17 • n=5 Participants	44.6 years STANDARD_DEVIATION 14.14 • n=7 Participants	43.4 years STANDARD_DEVIATION 13.69 • n=5 Participants
Sex: Female, Male Female	145 Participants n=5 Participants	135 Participants n=7 Participants	280 Participants n=5 Participants
Sex: Female, Male Male	21 Participants n=5 Participants	28 Participants n=7 Participants	49 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Asian	13 Participants n=5 Participants	11 Participants n=7 Participants	24 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	51 Participants n=5 Participants	47 Participants n=7 Participants	98 Participants n=5 Participants
Race (NIH/OMB) White	98 Participants n=5 Participants	103 Participants n=7 Participants	201 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	38 Participants n=5 Participants	44 Participants n=7 Participants	82 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	128 Participants n=5 Participants	119 Participants n=7 Participants	247 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 48 hours

Population: 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.

Outcome measures

Outcome measures
Measure	COV795 n=150 Participants 2 tablets taken every 12 hours	Placebo n=153 Participants 2 tablets taken every 12 hours
SPID48 (Summed Pain Intensity Difference)	114.9 scores on a scale Standard Error 7.64	66.9 scores on a scale Standard Error 7.6

Adverse Events

COV795

Serious events: 3 serious events

Other events: 89 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 35 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	COV795 n=166 participants at risk；n=235 participants at risk 2 tablets taken every 12 hours	Placebo n=163 participants at risk；n=94 participants at risk 2 tablets taken every 12 hours
Gastrointestinal disorders Gastrooesophageal reflux disease	0.43% 1/235 • 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. 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.	0.00% 0/94 • 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. 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.
Immune system disorders Allergic reaction	0.00% 0/235 • 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. 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.	1.1% 1/94 • 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. 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.
Vascular disorders Deep vein thrombosis	0.43% 1/235 • 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. 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.	0.00% 0/94 • 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. 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.
Investigations Pregnancy test urine positive	0.43% 1/235 • 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. 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.	0.00% 0/94 • 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. 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.

Other adverse events

Additional Information

Lawrence Hill

Mallinckrodt Pharmaceuticals

Phone: 908-238-6370

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	COV795 n=166 participants at risk；n=235 participants at risk 2 tablets taken every 12 hours	Placebo n=163 participants at risk；n=94 participants at risk 2 tablets taken every 12 hours
Gastrointestinal disorders Constipation	4.2% 7/166 • 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. 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.	3.1% 5/163 • 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. 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.
Gastrointestinal disorders Dry mouth	0.60% 1/166 • 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. 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.	1.2% 2/163 • 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. 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.
Gastrointestinal disorders Nausea	30.7% 51/166 • 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. 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.	5.5% 9/163 • 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. 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.
Gastrointestinal disorders Vomiting	9.0% 15/166 • 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. 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.	0.00% 0/163 • 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. 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.
General disorders Edema peripheral	1.2% 2/166 • 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. 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.	0.00% 0/163 • 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. 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.
Injury, poisoning and procedural complications Excoriation	1.2% 2/166 • 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. 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.	0.00% 0/163 • 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. 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.
Nervous system disorders Dizziness	13.3% 22/166 • 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. 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.	1.2% 2/163 • 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. 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.
Nervous system disorders Headache	9.6% 16/166 • 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. 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.	4.9% 8/163 • 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. 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.
Nervous system disorders Hypoaesthesia	0.60% 1/166 • 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. 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.	1.2% 2/163 • 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. 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.
Nervous system disorders Somnolence	3.6% 6/166 • 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. 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.	0.61% 1/163 • 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. 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.
Renal and urinary disorders Dysuria	1.2% 2/166 • 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. 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.	0.00% 0/163 • 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. 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.
Skin and subcutaneous tissue disorders Blister	1.2% 2/166 • 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. 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.	0.61% 1/163 • 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. 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.
Skin and subcutaneous tissue disorders Erythema	1.2% 2/166 • 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. 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.	0.00% 0/163 • 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. 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.
Skin and subcutaneous tissue disorders Pruritus generalized	1.2% 2/166 • 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. 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.	0.00% 0/163 • 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. 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.
Skin and subcutaneous tissue disorders Rash	1.8% 3/166 • 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. 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.	1.2% 2/163 • 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. 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.
Vascular disorders Hot flush	1.2% 2/166 • 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. 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.	0.61% 1/163 • 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. 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.
Skin and subcutaneous tissue disorders Pruritus	1.8% 3/166 • 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. 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.	1.8% 3/163 • 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. 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.