Trial Outcomes & Findings for Efficacy, Tolerability, Safety, and Pharmacokinetic Study of DFN-15 (NCT NCT03554772)

Last Updated: 2021-01-22

Results Overview

The primary endpoint is the Summed Pain Intensity Difference over the first 6 hours (SPID6) after dosing compared between DFN-15 and placebo. Pain intensity (P) will be measured at timepoints of 15, 30, and 45 minutes and 1, 1.5, 2, 3, 4, 5 and 6, hours after baseline ,using 11-point Pain Intensity Numerical Rating Scale (NPRS). Zero (0) equals no pain and Ten (10) equals worst pain imaginable. SPID6 is created by summing the time weighted pain intensity differences (PID) scores using the area under the PID curve methodology. All SPID calculations will be performed using the standard trapezoidal rule SPIDx =∑\_(i=0)\^x▒((〖PID〗\_i+〖PID〗\_(i+1))/2) \* (T\_(i+1)- T\_i ) Where: PID\_i = P\_i - PBL (Pain score at time i and Pain score at Baseline), and (T\_i+1 - T\_i) is the Time difference in minutes between time i and time i+1. Therefore, SPID6 values may theoretically range between a maximum score of 0 ( no improvement) and a minimum score of -3525 (best improvement)

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

120 participants

Primary outcome timeframe

6 hours post dose

Results posted on

2021-01-22

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Single dose containing 0 mg of celecoxib in 10 ml solution Placebo: Oral Solution	DFN-15 (Celecoxib Oral Solution) 62.5 mg Single dose containing 62.5 mg of celecoxib in 10 ml solution DFN-15 (Celecoxib Oral Solution) 62.5 mg: Oral Solution	DFN-15 (Celecoxib Oral Solution) 125 mg Single dose containing 125 mg of celecoxib in 10 ml solution DFN-15 (Celecoxib Oral Solution) 125 mg: Oral Solution	DFN-15 (Celecoxib Oral Solution) 250 mg Single dose containing 250 mg of celecoxib in 10 ml solution DFN-15 (Celecoxib Oral Solution) 250 mg: Oral Solution
Overall Study STARTED	30	30	29	31
Overall Study Completed Treatment Period (8 Hours Post Dose)	30	30	29	31
Overall Study COMPLETED	30	30	29	29
Overall Study NOT COMPLETED	0	0	0	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Single dose containing 0 mg of celecoxib in 10 ml solution Placebo: Oral Solution	DFN-15 (Celecoxib Oral Solution) 62.5 mg Single dose containing 62.5 mg of celecoxib in 10 ml solution DFN-15 (Celecoxib Oral Solution) 62.5 mg: Oral Solution	DFN-15 (Celecoxib Oral Solution) 125 mg Single dose containing 125 mg of celecoxib in 10 ml solution DFN-15 (Celecoxib Oral Solution) 125 mg: Oral Solution	DFN-15 (Celecoxib Oral Solution) 250 mg Single dose containing 250 mg of celecoxib in 10 ml solution DFN-15 (Celecoxib Oral Solution) 250 mg: Oral Solution
Overall Study Lost to Follow-up	0	0	0	2

Baseline Characteristics

Efficacy, Tolerability, Safety, and Pharmacokinetic Study of DFN-15

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=30 Participants Single dose containing 0 mg of celecoxib in 10 ml solution Placebo: Oral Solution	DFN-15 (Celecoxib Oral Solution) 62.5 mg n=30 Participants Single dose containing 62.5 mg of celecoxib in 10 ml solution DFN-15 (Celecoxib Oral Solution) 62.5 mg: Oral Solution	DFN-15 (Celecoxib Oral Solution) 125 mg n=29 Participants Single dose containing 125 mg of celecoxib in 10 ml solution DFN-15 (Celecoxib Oral Solution) 125 mg: Oral Solution	DFN-15 (Celecoxib Oral Solution) 250 mg n=31 Participants Single dose containing 250 mg of celecoxib in 10 ml solution DFN-15 (Celecoxib Oral Solution) 250 mg: Oral Solution	Total n=120 Participants Total of all reporting groups
Age, Continuous	19.9 years STANDARD_DEVIATION 2.70 • n=5 Participants	19.6 years STANDARD_DEVIATION 2.45 • n=7 Participants	19.2 years STANDARD_DEVIATION 1.64 • n=5 Participants	20.5 years STANDARD_DEVIATION 2.45 • n=4 Participants	19.8 years STANDARD_DEVIATION 2.37 • n=21 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	14 Participants n=7 Participants	17 Participants n=5 Participants	13 Participants n=4 Participants	60 Participants n=21 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	16 Participants n=7 Participants	12 Participants n=5 Participants	18 Participants n=4 Participants	60 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=5 Participants	6 Participants n=7 Participants	4 Participants n=5 Participants	7 Participants n=4 Participants	23 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	24 Participants n=5 Participants	24 Participants n=7 Participants	25 Participants n=5 Participants	24 Participants n=4 Participants	97 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) White	28 Participants n=5 Participants	26 Participants n=7 Participants	22 Participants n=5 Participants	28 Participants n=4 Participants	104 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	4 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	5 Participants n=21 Participants
BMI	26.4 kg/ m^2 STANDARD_DEVIATION 4.15 • n=5 Participants	27.1 kg/ m^2 STANDARD_DEVIATION 5.03 • n=7 Participants	25.1 kg/ m^2 STANDARD_DEVIATION 4.11 • n=5 Participants	24.4 kg/ m^2 STANDARD_DEVIATION 4.41 • n=4 Participants	25.8 kg/ m^2 STANDARD_DEVIATION 4.51 • n=21 Participants
Qualifying Baseline Categorical Pain Score 0 = No Pain	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Qualifying Baseline Categorical Pain Score 1= Mild Pain	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Qualifying Baseline Categorical Pain Score 2= Moderate Pain	8 Participants n=5 Participants	13 Participants n=7 Participants	11 Participants n=5 Participants	12 Participants n=4 Participants	44 Participants n=21 Participants
Qualifying Baseline Categorical Pain Score 3= Severe Pain	22 Participants n=5 Participants	17 Participants n=7 Participants	18 Participants n=5 Participants	19 Participants n=4 Participants	76 Participants n=21 Participants

PRIMARY outcome

Timeframe: 6 hours post dose

Population: mITT Population : defined as all randomized subjects who received study drug and recorded at least one post-dosing PI score

Outcome measures

Outcome measures
Measure	Placebo n=30 Participants Single dose containing 0 mg of celecoxib in 10 ml solution Placebo: Oral Solution	DFN-15 (Celecoxib Oral Solution) 62.5 mg n=30 Participants Single dose containing 62.5 mg of celecoxib in 10 ml solution DFN-15 (Celecoxib Oral Solution) 62.5 mg: Oral Solution	DFN-15 (Celecoxib Oral Solution) 125 mg n=29 Participants Single dose containing 125 mg of celecoxib in 10 ml solution DFN-15 (Celecoxib Oral Solution) 125 mg: Oral Solution	DFN-15 (Celecoxib Oral Solution) 250 mg n=31 Participants Single dose containing 250 mg of celecoxib in 10 ml solution DFN-15 (Celecoxib Oral Solution) 250 mg: Oral Solution
Summed Pain Intensity Difference Over the First Six Hours	-420.2 units on a scale Standard Deviation 716.42	-1101.0 units on a scale Standard Deviation 570.74	-1771.7 units on a scale Standard Deviation 646.10	-1463.5 units on a scale Standard Deviation 727.28

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

DFN-15 (Celecoxib Oral Solution) 62.5 mg

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

DFN-15 (Celecoxib Oral Solution) 125 mg

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

DFN-15 (Celecoxib Oral Solution) 250 mg

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Srinivas Shenoy B.

Dr Reddy's Laboratories, Inc.

Phone: 6099550249

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Other adverse events
Measure	Placebo n=30 participants at risk Single dose containing 0 mg of celecoxib in 10 ml solution Placebo: Oral Solution	DFN-15 (Celecoxib Oral Solution) 62.5 mg n=30 participants at risk Single dose containing 62.5 mg of celecoxib in 10 ml solution DFN-15 (Celecoxib Oral Solution) 62.5 mg: Oral Solution	DFN-15 (Celecoxib Oral Solution) 125 mg n=29 participants at risk Single dose containing 125 mg of celecoxib in 10 ml solution DFN-15 (Celecoxib Oral Solution) 125 mg: Oral Solution	DFN-15 (Celecoxib Oral Solution) 250 mg n=31 participants at risk Single dose containing 250 mg of celecoxib in 10 ml solution DFN-15 (Celecoxib Oral Solution) 250 mg: Oral Solution
Gastrointestinal disorders Nausea	3.3% 1/30 • Number of events 1 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	6.7% 2/30 • Number of events 2 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	3.4% 1/29 • Number of events 1 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	3.2% 1/31 • Number of events 1 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.
Gastrointestinal disorders Vomiting	3.3% 1/30 • Number of events 2 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	3.3% 1/30 • Number of events 1 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	0.00% 0/29 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	3.2% 1/31 • Number of events 1 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.
Investigations Blood Bilirubin Increased	0.00% 0/30 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	3.3% 1/30 • Number of events 1 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	0.00% 0/29 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	6.5% 2/31 • Number of events 2 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.
Investigations Blood Creatinine increased	3.3% 1/30 • Number of events 1 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	0.00% 0/30 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	0.00% 0/29 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	0.00% 0/31 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.
Investigations Blood Urine Present	0.00% 0/30 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	3.3% 1/30 • Number of events 1 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	0.00% 0/29 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	0.00% 0/31 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.
Investigations Cardiac Murmur	0.00% 0/30 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	3.3% 1/30 • Number of events 1 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	0.00% 0/29 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	0.00% 0/31 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.
Investigations Glomerular Filtration Rate decreased	3.3% 1/30 • Number of events 1 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	0.00% 0/30 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	0.00% 0/29 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	0.00% 0/31 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.
Investigations Hematocrit decreased	0.00% 0/30 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	3.3% 1/30 • Number of events 1 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	0.00% 0/29 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	0.00% 0/31 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.
Investigations Hemoglobin decreased	0.00% 0/30 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	3.3% 1/30 • Number of events 1 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	0.00% 0/29 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	0.00% 0/31 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.
Investigations International Normalized Ratio increaed	0.00% 0/30 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	3.3% 1/30 • Number of events 1 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	0.00% 0/29 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	0.00% 0/31 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.
Nervous system disorders Dizziness	3.3% 1/30 • Number of events 1 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	0.00% 0/30 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	3.4% 1/29 • Number of events 2 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	0.00% 0/31 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.
Nervous system disorders Headache	0.00% 0/30 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	3.3% 1/30 • Number of events 1 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	0.00% 0/29 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	0.00% 0/31 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.
Infections and infestations Alveolar Osteitis	3.3% 1/30 • Number of events 1 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	0.00% 0/30 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	3.4% 1/29 • Number of events 1 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	0.00% 0/31 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/30 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	0.00% 0/30 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	0.00% 0/29 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	6.5% 2/31 • Number of events 2 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.
Blood and lymphatic system disorders Coagulopathy	0.00% 0/30 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	0.00% 0/30 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	0.00% 0/29 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	3.2% 1/31 • Number of events 1 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.
Cardiac disorders Wolff-Parkinson-White syndrome	0.00% 0/30 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	0.00% 0/30 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	3.4% 1/29 • Number of events 1 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.	0.00% 0/31 • All AEs, whether volunteered, elicited, or noted on physical examination, and regardless of causality or seriousness, were assessed and recorded in the CRF beginning after administration of study drug through the final follow-up assessment (approximately 7 ± 3 days after the last study drug administration). Additionally, if the investigator became aware of the occurrence of an SAE within 30 days of the last visit, the SAE was reported.