Trial Outcomes & Findings for Placebo-Controlled Evaluation of Intranasal Dexmedetomidine for Postoperative Analgesia Following Bunionectomy Surgery (NCT NCT02284243)

NCT ID: NCT02284243

Last Updated: 2017-05-02

Results Overview

Pain intensity was recorded using a Numeric Pain Rating Scale (Range 0-10) where 0 equates to no pain (better), and 10 equates to the worst pain imaginable (worse). Pain intensity scores were to be recorded at the following time points: 0.25, 0.5, 0.75, 1, 2, 4, and 6 hours post Dose 1. Thereafter pain assessments were to be recorded every 2 hours until 48 hours post Dose 1. Pain intensity differences from baseline were calculated at each time point and a time weighted summed pain intensity difference (SPID) was then calculated. Time weighted SPID calculations were computed by multiplying a weight factor to each score prior to summation. The weight factor at each time point was the time elapsed since the previous observation.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 168 participants
• Primary outcome timeframe: 48 hours
• Results posted on: 2017-05-02

Participant Flow

Participant milestones

Measure	DEX-IN 50mcg DEX-IN (Intranasal dexmedetomidine) 50mcg every 6 hours for 48 hours. Intranasal Dexmedetomidine	IN Placebo IN Placebo every 6 hours for 48 hours. Intranasal Placebo
Overall Study STARTED	84	84
Overall Study COMPLETED	80	81
Overall Study NOT COMPLETED	4	3

Reasons for withdrawal

Measure	DEX-IN 50mcg DEX-IN (Intranasal dexmedetomidine) 50mcg every 6 hours for 48 hours. Intranasal Dexmedetomidine	IN Placebo IN Placebo every 6 hours for 48 hours. Intranasal Placebo
Overall Study Lack of Efficacy	3	3
Overall Study Adverse Event	1	0

Baseline Characteristics

Placebo-Controlled Evaluation of Intranasal Dexmedetomidine for Postoperative Analgesia Following Bunionectomy Surgery

Baseline characteristics by cohort

Measure	DEX-IN 50mcg n=84 Participants DEX-IN (Intranasal dexmedetomidine) 50mcg every 6 hours for 48 hours. Intranasal Dexmedetomidine	IN Placebo n=84 Participants IN Placebo every 6 hours for 48 hours. Intranasal Placebo	Total n=168 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	82 Participants n=5 Participants	81 Participants n=7 Participants	163 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Age, Continuous	43.9 years STANDARD_DEVIATION 12.37 • n=5 Participants	44.0 years STANDARD_DEVIATION 13.08 • n=7 Participants	44.0 years STANDARD_DEVIATION 12.69 • n=5 Participants
Sex: Female, Male Female	79 Participants n=5 Participants	75 Participants n=7 Participants	154 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	9 Participants n=7 Participants	14 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	33 Participants n=5 Participants	39 Participants n=7 Participants	72 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	51 Participants n=5 Participants	45 Participants n=7 Participants	96 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
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	20 Participants n=5 Participants	21 Participants n=7 Participants	41 Participants n=5 Participants
Race (NIH/OMB) White	59 Participants n=5 Participants	56 Participants n=7 Participants	115 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	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	84 participants n=5 Participants	84 participants n=7 Participants	168 participants n=5 Participants
Body Mass Index (BMI)	26.6 kg/m^2 STANDARD_DEVIATION 4.31 • n=5 Participants	27.4 kg/m^2 STANDARD_DEVIATION 4.08 • n=7 Participants	27.0 kg/m^2 STANDARD_DEVIATION 4.20 • n=5 Participants
Baseline pain intensity score (NPRS)	6.4 units on a scale STANDARD_DEVIATION 1.42 • n=5 Participants	6.7 units on a scale STANDARD_DEVIATION 1.90 • n=7 Participants	6.5 units on a scale STANDARD_DEVIATION 1.68 • n=5 Participants

PRIMARY outcome

Timeframe: 48 hours

Population: mITT population, including all randomized subjects who received at least one study dose

Pain intensity was recorded using a Numeric Pain Rating Scale (Range 0-10) where 0 equates to no pain (better), and 10 equates to the worst pain imaginable (worse). Pain intensity scores were to be recorded at the following time points: 0.25, 0.5, 0.75, 1, 2, 4, and 6 hours post Dose 1. Thereafter pain assessments were to be recorded every 2 hours until 48 hours post Dose 1. Pain intensity differences from baseline were calculated at each time point and a time weighted summed pain intensity difference (SPID) was then calculated. Time weighted SPID calculations were computed by multiplying a weight factor to each score prior to summation. The weight factor at each time point was the time elapsed since the previous observation.

Outcome measures

Measure	DEX-IN 50mcg n=84 Participants DEX-IN (Intranasal dexmedetomidine) 50mcg every 6 hours for 48 hours. Intranasal Dexmedetomidine	IN Placebo n=84 Participants IN Placebo every 6 hours for 48 hours. Intranasal Placebo
Summed Pain Intensity Difference Over the First 48 Hours (SPID48).	-2328.2 units on a scale Standard Deviation 5746.724	-548.90 units on a scale Standard Deviation 5819.373

SECONDARY outcome

Timeframe: Up to 48 Hours

Population: mITT population, including all randomized subjects who received at least one study dose

Pain intensity was recorded using a Numeric Pain Rating Scale (Range 0-10) where 0 equates to no pain (better), and 10 equates to the worst pain imaginable (worse). Pain intensity scores were to be recorded at the following time points: 0.25, 0.5, 0.75, 1, 2, 4, and 6 hours post Dose 1. Thereafter pain assessments were to be recorded every 2 hours until 48 hours post Dose 1. Pain intensity differences from baseline were calculated at each time point and a time weighted summed pain intensity difference (SPID) was then calculated. Time weighted SPID calculations were computed by multiplying a weight factor to each score prior to summation. The weight factor at each time point was the time elapsed since the previous observation.

Outcome measures

Measure	DEX-IN 50mcg n=84 Participants DEX-IN (Intranasal dexmedetomidine) 50mcg every 6 hours for 48 hours. Intranasal Dexmedetomidine	IN Placebo n=84 Participants IN Placebo every 6 hours for 48 hours. Intranasal Placebo
SPID at Various Other Time Points SPID 0-6	-346.57 units on a scale Standard Deviation 579.0378	-120.46 units on a scale Standard Deviation 590.7313
SPID at Various Other Time Points SPID 0-12	-568.89 units on a scale Standard Deviation 1213.410	-151.93 units on a scale Standard Deviation 1263.656
SPID at Various Other Time Points SPID 0-24	-1043.2 units on a scale Standard Deviation 2553.890	-239.07 units on a scale Standard Deviation 2717.394

SECONDARY outcome

Timeframe: 6 hours

Population: mITT population, including all randomized subjects who received at least one study dose

Kaplan-Meier analysis of time to perceptible and meaningful pain relief for 50th percentile of subjects. Time to perceptible pain relief and time to meaningful pain relief were measured using the double-stopwatch method. The first stopwatch was given to each subject with the instructions to stop the watch when they first perceive pain relief to occur (time to perceptible relief). Once the first watch was stopped, the second stopwatch was given to the subject with the instructions to stop the watch when they are first experiencing meaningful pain relief (time to meaningful relief). A shorter time to pain relief is better.

Outcome measures

Measure	DEX-IN 50mcg n=84 Participants DEX-IN (Intranasal dexmedetomidine) 50mcg every 6 hours for 48 hours. Intranasal Dexmedetomidine	IN Placebo n=84 Participants IN Placebo every 6 hours for 48 hours. Intranasal Placebo
Time to Perceptible and Meaningful Pain Relief Time to perceptible pain relief	18.39 minutes Interval 15.5 to 25.68	33.0 minutes Interval 18.18 to 85.33
Time to Perceptible and Meaningful Pain Relief Time to meaningful pain relief	79.32 minutes Interval 55.25 to 151.88	NA minutes Sufficient number of subjects did not achieve endpoint for analysis

SECONDARY outcome

Timeframe: 6 hours

Population: mITT population, including all randomized subjects who received at least one study dose

Outcome measures

Measure	DEX-IN 50mcg n=84 Participants DEX-IN (Intranasal dexmedetomidine) 50mcg every 6 hours for 48 hours. Intranasal Dexmedetomidine	IN Placebo n=84 Participants IN Placebo every 6 hours for 48 hours. Intranasal Placebo
Number of Subjects With Significant Pain Improvement Following the First Study Dose. ≥30% reduction in pain	26 participants	15 participants
Number of Subjects With Significant Pain Improvement Following the First Study Dose. ≥50% reduction in pain	9 participants	2 participants

SECONDARY outcome

Timeframe: 48 hours

Population: mITT population, including all randomized subjects who received at least one study dose

Number of subjects requiring rescue medication (Oral opioids) within 48 hours after first study dose

Outcome measures

Measure	DEX-IN 50mcg n=84 Participants DEX-IN (Intranasal dexmedetomidine) 50mcg every 6 hours for 48 hours. Intranasal Dexmedetomidine	IN Placebo n=84 Participants IN Placebo every 6 hours for 48 hours. Intranasal Placebo
Use of Rescue Medication (Oral Opioids)	66 participants	76 participants

SECONDARY outcome

Timeframe: 48 hours

Population: mITT population, including all randomized subjects who received at least one study dose

Kaplan Meier analysis of time to first use of rescue analgesia 50th percentile of subjects. Rescue analgesia (oral oxycodone) was available to subjects with inadequately controlled pain. All doses of rescue analgesia administered were recorded and the time from the first study dose to first rescue analgesia in each subject was evaluated. A longer time to first rescue is better.

Outcome measures

Measure	DEX-IN 50mcg n=84 Participants DEX-IN (Intranasal dexmedetomidine) 50mcg every 6 hours for 48 hours. Intranasal Dexmedetomidine	IN Placebo n=84 Participants IN Placebo every 6 hours for 48 hours. Intranasal Placebo
Time to First Rescue Medication Use	4.94 hours Interval 4.03 to 7.85	2.68 hours Interval 1.42 to 3.47

SECONDARY outcome

Timeframe: 24 hours

Population: mITT population, including all randomized subjects who received at least one study dose

Outcome measures

Measure	DEX-IN 50mcg n=84 Participants DEX-IN (Intranasal dexmedetomidine) 50mcg every 6 hours for 48 hours. Intranasal Dexmedetomidine	IN Placebo n=84 Participants IN Placebo every 6 hours for 48 hours. Intranasal Placebo
Number of Subjects With Complete Protection From PONV	72 participants	70 participants

Adverse Events

DEX-IN 50mcg

Serious events: 1 serious events

Other events: 51 other events

Deaths: 0 deaths

IN Placebo

Serious events: 0 serious events

Other events: 36 other events

Deaths: 0 deaths

Serious adverse events

Measure	DEX-IN 50mcg n=84 participants at risk DEX-IN (Intranasal dexmedetomidine) 50mcg every 6 hours for 48 hours. Intranasal Dexmedetomidine	IN Placebo n=84 participants at risk IN Placebo every 6 hours for 48 hours. Intranasal Placebo
Vascular disorders Hypotension	1.2% 1/84 • Number of events 1 • All AEs were collected through the Day 7 study visit. All SAEs were assessed through the Day 7 visit, but were reported through 30 days of the last study visit if the investigator was made aware of the event.	0.00% 0/84 • All AEs were collected through the Day 7 study visit. All SAEs were assessed through the Day 7 visit, but were reported through 30 days of the last study visit if the investigator was made aware of the event.

Other adverse events

Measure	DEX-IN 50mcg n=84 participants at risk DEX-IN (Intranasal dexmedetomidine) 50mcg every 6 hours for 48 hours. Intranasal Dexmedetomidine	IN Placebo n=84 participants at risk IN Placebo every 6 hours for 48 hours. Intranasal Placebo
Cardiac disorders Bradycardia	3.6% 3/84 • Number of events 3 • All AEs were collected through the Day 7 study visit. All SAEs were assessed through the Day 7 visit, but were reported through 30 days of the last study visit if the investigator was made aware of the event.	0.00% 0/84 • All AEs were collected through the Day 7 study visit. All SAEs were assessed through the Day 7 visit, but were reported through 30 days of the last study visit if the investigator was made aware of the event.
Gastrointestinal disorders Constipation	1.2% 1/84 • Number of events 1 • All AEs were collected through the Day 7 study visit. All SAEs were assessed through the Day 7 visit, but were reported through 30 days of the last study visit if the investigator was made aware of the event.	2.4% 2/84 • Number of events 2 • All AEs were collected through the Day 7 study visit. All SAEs were assessed through the Day 7 visit, but were reported through 30 days of the last study visit if the investigator was made aware of the event.
Gastrointestinal disorders Nausea	15.5% 13/84 • Number of events 14 • All AEs were collected through the Day 7 study visit. All SAEs were assessed through the Day 7 visit, but were reported through 30 days of the last study visit if the investigator was made aware of the event.	16.7% 14/84 • Number of events 15 • All AEs were collected through the Day 7 study visit. All SAEs were assessed through the Day 7 visit, but were reported through 30 days of the last study visit if the investigator was made aware of the event.
Gastrointestinal disorders Vomiting	4.8% 4/84 • Number of events 5 • All AEs were collected through the Day 7 study visit. All SAEs were assessed through the Day 7 visit, but were reported through 30 days of the last study visit if the investigator was made aware of the event.	7.1% 6/84 • Number of events 6 • All AEs were collected through the Day 7 study visit. All SAEs were assessed through the Day 7 visit, but were reported through 30 days of the last study visit if the investigator was made aware of the event.
Injury, poisoning and procedural complications Incision Site Erythema	0.00% 0/84 • All AEs were collected through the Day 7 study visit. All SAEs were assessed through the Day 7 visit, but were reported through 30 days of the last study visit if the investigator was made aware of the event.	2.4% 2/84 • Number of events 2 • All AEs were collected through the Day 7 study visit. All SAEs were assessed through the Day 7 visit, but were reported through 30 days of the last study visit if the investigator was made aware of the event.
Investigations Blood Pressure Decreased	26.2% 22/84 • Number of events 22 • All AEs were collected through the Day 7 study visit. All SAEs were assessed through the Day 7 visit, but were reported through 30 days of the last study visit if the investigator was made aware of the event.	3.6% 3/84 • Number of events 3 • All AEs were collected through the Day 7 study visit. All SAEs were assessed through the Day 7 visit, but were reported through 30 days of the last study visit if the investigator was made aware of the event.
Nervous system disorders Dizziness	3.6% 3/84 • Number of events 3 • All AEs were collected through the Day 7 study visit. All SAEs were assessed through the Day 7 visit, but were reported through 30 days of the last study visit if the investigator was made aware of the event.	1.2% 1/84 • Number of events 1 • All AEs were collected through the Day 7 study visit. All SAEs were assessed through the Day 7 visit, but were reported through 30 days of the last study visit if the investigator was made aware of the event.
Nervous system disorders Headache	7.1% 6/84 • Number of events 6 • All AEs were collected through the Day 7 study visit. All SAEs were assessed through the Day 7 visit, but were reported through 30 days of the last study visit if the investigator was made aware of the event.	4.8% 4/84 • Number of events 4 • All AEs were collected through the Day 7 study visit. All SAEs were assessed through the Day 7 visit, but were reported through 30 days of the last study visit if the investigator was made aware of the event.
Respiratory, thoracic and mediastinal disorders Epistaxis	2.4% 2/84 • Number of events 2 • All AEs were collected through the Day 7 study visit. All SAEs were assessed through the Day 7 visit, but were reported through 30 days of the last study visit if the investigator was made aware of the event.	3.6% 3/84 • Number of events 3 • All AEs were collected through the Day 7 study visit. All SAEs were assessed through the Day 7 visit, but were reported through 30 days of the last study visit if the investigator was made aware of the event.
Respiratory, thoracic and mediastinal disorders Nasal Congestion	4.8% 4/84 • Number of events 4 • All AEs were collected through the Day 7 study visit. All SAEs were assessed through the Day 7 visit, but were reported through 30 days of the last study visit if the investigator was made aware of the event.	1.2% 1/84 • Number of events 1 • All AEs were collected through the Day 7 study visit. All SAEs were assessed through the Day 7 visit, but were reported through 30 days of the last study visit if the investigator was made aware of the event.
Respiratory, thoracic and mediastinal disorders Nasal Discomfort	8.3% 7/84 • Number of events 7 • All AEs were collected through the Day 7 study visit. All SAEs were assessed through the Day 7 visit, but were reported through 30 days of the last study visit if the investigator was made aware of the event.	2.4% 2/84 • Number of events 2 • All AEs were collected through the Day 7 study visit. All SAEs were assessed through the Day 7 visit, but were reported through 30 days of the last study visit if the investigator was made aware of the event.
Respiratory, thoracic and mediastinal disorders Nasal Dryness	4.8% 4/84 • Number of events 4 • All AEs were collected through the Day 7 study visit. All SAEs were assessed through the Day 7 visit, but were reported through 30 days of the last study visit if the investigator was made aware of the event.	3.6% 3/84 • Number of events 3 • All AEs were collected through the Day 7 study visit. All SAEs were assessed through the Day 7 visit, but were reported through 30 days of the last study visit if the investigator was made aware of the event.
Respiratory, thoracic and mediastinal disorders Nasal Inflammation	1.2% 1/84 • Number of events 1 • All AEs were collected through the Day 7 study visit. All SAEs were assessed through the Day 7 visit, but were reported through 30 days of the last study visit if the investigator was made aware of the event.	3.6% 3/84 • Number of events 3 • All AEs were collected through the Day 7 study visit. All SAEs were assessed through the Day 7 visit, but were reported through 30 days of the last study visit if the investigator was made aware of the event.
Respiratory, thoracic and mediastinal disorders Nasal Obstruction	3.6% 3/84 • Number of events 3 • All AEs were collected through the Day 7 study visit. All SAEs were assessed through the Day 7 visit, but were reported through 30 days of the last study visit if the investigator was made aware of the event.	2.4% 2/84 • Number of events 2 • All AEs were collected through the Day 7 study visit. All SAEs were assessed through the Day 7 visit, but were reported through 30 days of the last study visit if the investigator was made aware of the event.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/84 • All AEs were collected through the Day 7 study visit. All SAEs were assessed through the Day 7 visit, but were reported through 30 days of the last study visit if the investigator was made aware of the event.	4.8% 4/84 • Number of events 4 • All AEs were collected through the Day 7 study visit. All SAEs were assessed through the Day 7 visit, but were reported through 30 days of the last study visit if the investigator was made aware of the event.
Respiratory, thoracic and mediastinal disorders Upper-Airway Cough Syndrome	2.4% 2/84 • Number of events 2 • All AEs were collected through the Day 7 study visit. All SAEs were assessed through the Day 7 visit, but were reported through 30 days of the last study visit if the investigator was made aware of the event.	0.00% 0/84 • All AEs were collected through the Day 7 study visit. All SAEs were assessed through the Day 7 visit, but were reported through 30 days of the last study visit if the investigator was made aware of the event.
Vascular disorders Hypotension	2.4% 2/84 • Number of events 3 • All AEs were collected through the Day 7 study visit. All SAEs were assessed through the Day 7 visit, but were reported through 30 days of the last study visit if the investigator was made aware of the event.	0.00% 0/84 • All AEs were collected through the Day 7 study visit. All SAEs were assessed through the Day 7 visit, but were reported through 30 days of the last study visit if the investigator was made aware of the event.

Additional Information

Randall Mack

Recro Pharma

Phone: 484-395-2470

Email: rmack@recropharma.com

Results disclosure agreements

• Principal investigator is a sponsor employee Discussion and/or publication of data generated is not permitted without the prior written consent of the sponsor.
• Publication restrictions are in place

Restriction type: OTHER