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

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ClinicalTrials.gov Identifier: NCT02284243
Recruitment Status : Completed
First Posted : November 5, 2014
Results First Posted : May 2, 2017
Last Update Posted : May 2, 2017
Sponsor:
Collaborator:
Lotus Clinical Research, LLC
Information provided by (Responsible Party):
Recro Pharma, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Pain, Post-operative
Interventions Drug: Intranasal Dexmedetomidine
Drug: Intranasal Placebo
Enrollment 168
Recruitment Details  
Pre-assignment Details  
Arm/Group Title DEX-IN 50mcg IN Placebo
Hide Arm/Group Description

DEX-IN (Intranasal dexmedetomidine) 50mcg every 6 hours for 48 hours.

Intranasal Dexmedetomidine

IN Placebo every 6 hours for 48 hours.

Intranasal Placebo

Period Title: Overall Study
Started 84 84
Completed 80 81
Not Completed 4 3
Reason Not Completed
Lack of Efficacy             3             3
Adverse Event             1             0
Arm/Group Title DEX-IN 50mcg IN Placebo Total
Hide Arm/Group Description

DEX-IN (Intranasal dexmedetomidine) 50mcg every 6 hours for 48 hours.

Intranasal Dexmedetomidine

IN Placebo every 6 hours for 48 hours.

Intranasal Placebo

Total of all reporting groups
Overall Number of Baseline Participants 84 84 168
Hide Baseline Analysis Population Description
Safety analysis set - All subjects receiving at least one study dose
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 84 participants 84 participants 168 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
82
  97.6%
81
  96.4%
163
  97.0%
>=65 years
2
   2.4%
3
   3.6%
5
   3.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 84 participants 84 participants 168 participants
43.9  (12.37) 44.0  (13.08) 44.0  (12.69)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 84 participants 84 participants 168 participants
Female
79
  94.0%
75
  89.3%
154
  91.7%
Male
5
   6.0%
9
  10.7%
14
   8.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 84 participants 84 participants 168 participants
Hispanic or Latino
33
  39.3%
39
  46.4%
72
  42.9%
Not Hispanic or Latino
51
  60.7%
45
  53.6%
96
  57.1%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 84 participants 84 participants 168 participants
American Indian or Alaska Native
0
   0.0%
3
   3.6%
3
   1.8%
Asian
4
   4.8%
4
   4.8%
8
   4.8%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
20
  23.8%
21
  25.0%
41
  24.4%
White
59
  70.2%
56
  66.7%
115
  68.5%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
1
   1.2%
0
   0.0%
1
   0.6%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 84 participants 84 participants 168 participants
84 84 168
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 84 participants 84 participants 168 participants
26.6  (4.31) 27.4  (4.08) 27.0  (4.20)
Baseline pain intensity score (NPRS)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 84 participants 84 participants 168 participants
6.4  (1.42) 6.7  (1.90) 6.5  (1.68)
[1]
Measure Description: Pain intensity was recorded using a Numeric Rating Scale (Range 0-10) where 0 equates to no pain, and 10 equates to the worst pain imaginable.
1.Primary Outcome
Title Summed Pain Intensity Difference Over the First 48 Hours (SPID48).
Hide Description 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.
Time Frame 48 hours
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population, including all randomized subjects who received at least one study dose
Arm/Group Title DEX-IN 50mcg IN Placebo
Hide Arm/Group Description:

DEX-IN (Intranasal dexmedetomidine) 50mcg every 6 hours for 48 hours.

Intranasal Dexmedetomidine

IN Placebo every 6 hours for 48 hours.

Intranasal Placebo

Overall Number of Participants Analyzed 84 84
Mean (Standard Deviation)
Unit of Measure: units on a scale
-2328.2  (5746.724) -548.90  (5819.373)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DEX-IN 50mcg, IN Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0180
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
2.Secondary Outcome
Title SPID at Various Other Time Points
Hide Description 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.
Time Frame Up to 48 Hours
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population, including all randomized subjects who received at least one study dose
Arm/Group Title DEX-IN 50mcg IN Placebo
Hide Arm/Group Description:

DEX-IN (Intranasal dexmedetomidine) 50mcg every 6 hours for 48 hours.

Intranasal Dexmedetomidine

IN Placebo every 6 hours for 48 hours.

Intranasal Placebo

Overall Number of Participants Analyzed 84 84
Mean (Standard Deviation)
Unit of Measure: units on a scale
SPID 0-6 -346.57  (579.0378) -120.46  (590.7313)
SPID 0-12 -568.89  (1213.410) -151.93  (1263.656)
SPID 0-24 -1043.2  (2553.890) -239.07  (2717.394)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DEX-IN 50mcg, IN Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments Applies to SPID 0-6, SPID 0-12, and SPID 0-24
Method ANCOVA
Comments [Not Specified]
3.Secondary Outcome
Title Time to Perceptible and Meaningful Pain Relief
Hide Description 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.
Time Frame 6 hours
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population, including all randomized subjects who received at least one study dose
Arm/Group Title DEX-IN 50mcg IN Placebo
Hide Arm/Group Description:

DEX-IN (Intranasal dexmedetomidine) 50mcg every 6 hours for 48 hours.

Intranasal Dexmedetomidine

IN Placebo every 6 hours for 48 hours.

Intranasal Placebo

Overall Number of Participants Analyzed 84 84
Median (95% Confidence Interval)
Unit of Measure: minutes
Time to perceptible pain relief
18.39
(15.50 to 25.68)
33.0
(18.18 to 85.33)
Time to meaningful pain relief
79.32
(55.25 to 151.88)
NA [1] 
(NA to NA)
[1]
Sufficient number of subjects did not achieve endpoint for analysis
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DEX-IN 50mcg, IN Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments Applies to perceptible and meaningful pain relief
Method Log Rank
Comments [Not Specified]
4.Secondary Outcome
Title Number of Subjects With Significant Pain Improvement Following the First Study Dose.
Hide Description [Not Specified]
Time Frame 6 hours
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population, including all randomized subjects who received at least one study dose
Arm/Group Title DEX-IN 50mcg IN Placebo
Hide Arm/Group Description:

DEX-IN (Intranasal dexmedetomidine) 50mcg every 6 hours for 48 hours.

Intranasal Dexmedetomidine

IN Placebo every 6 hours for 48 hours.

Intranasal Placebo

Overall Number of Participants Analyzed 84 84
Measure Type: Number
Unit of Measure: participants
≥30% reduction in pain 26 15
≥50% reduction in pain 9 2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DEX-IN 50mcg, IN Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments Applies to ≥30% and ≥50% reduction in pain
Method Cochran-Mantel-Haenszel
Comments Test for general association stratified by site
5.Secondary Outcome
Title Use of Rescue Medication (Oral Opioids)
Hide Description Number of subjects requiring rescue medication (Oral opioids) within 48 hours after first study dose
Time Frame 48 hours
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population, including all randomized subjects who received at least one study dose
Arm/Group Title DEX-IN 50mcg IN Placebo
Hide Arm/Group Description:

DEX-IN (Intranasal dexmedetomidine) 50mcg every 6 hours for 48 hours.

Intranasal Dexmedetomidine

IN Placebo every 6 hours for 48 hours.

Intranasal Placebo

Overall Number of Participants Analyzed 84 84
Measure Type: Number
Unit of Measure: participants
66 76
6.Secondary Outcome
Title Time to First Rescue Medication Use
Hide Description 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.
Time Frame 48 hours
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population, including all randomized subjects who received at least one study dose
Arm/Group Title DEX-IN 50mcg IN Placebo
Hide Arm/Group Description:

DEX-IN (Intranasal dexmedetomidine) 50mcg every 6 hours for 48 hours.

Intranasal Dexmedetomidine

IN Placebo every 6 hours for 48 hours.

Intranasal Placebo

Overall Number of Participants Analyzed 84 84
Median (95% Confidence Interval)
Unit of Measure: hours
4.94
(4.03 to 7.85)
2.68
(1.42 to 3.47)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DEX-IN 50mcg, IN Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0009
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
7.Secondary Outcome
Title Number of Subjects With Complete Protection From PONV
Hide Description [Not Specified]
Time Frame 24 hours
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population, including all randomized subjects who received at least one study dose
Arm/Group Title DEX-IN 50mcg IN Placebo
Hide Arm/Group Description:

DEX-IN (Intranasal dexmedetomidine) 50mcg every 6 hours for 48 hours.

Intranasal Dexmedetomidine

IN Placebo every 6 hours for 48 hours.

Intranasal Placebo

Overall Number of Participants Analyzed 84 84
Measure Type: Number
Unit of Measure: participants
72 70
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DEX-IN 50mcg, IN Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7718
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Time Frame 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.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title DEX-IN 50mcg IN Placebo
Hide Arm/Group Description

DEX-IN (Intranasal dexmedetomidine) 50mcg every 6 hours for 48 hours.

Intranasal Dexmedetomidine

IN Placebo every 6 hours for 48 hours.

Intranasal Placebo

All-Cause Mortality
DEX-IN 50mcg IN Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
DEX-IN 50mcg IN Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/84 (1.19%)      0/84 (0.00%)    
Vascular disorders     
Hypotension * 1  1/84 (1.19%)  1 0/84 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 17.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
DEX-IN 50mcg IN Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   51/84 (60.71%)      36/84 (42.86%)    
Cardiac disorders     
Bradycardia * 1  3/84 (3.57%)  3 0/84 (0.00%)  0
Gastrointestinal disorders     
Constipation * 1  1/84 (1.19%)  1 2/84 (2.38%)  2
Nausea * 1  13/84 (15.48%)  14 14/84 (16.67%)  15
Vomiting * 1  4/84 (4.76%)  5 6/84 (7.14%)  6
Injury, poisoning and procedural complications     
Incision Site Erythema * 1  0/84 (0.00%)  0 2/84 (2.38%)  2
Investigations     
Blood Pressure Decreased * 1  22/84 (26.19%)  22 3/84 (3.57%)  3
Nervous system disorders     
Dizziness * 1  3/84 (3.57%)  3 1/84 (1.19%)  1
Headache * 1  6/84 (7.14%)  6 4/84 (4.76%)  4
Respiratory, thoracic and mediastinal disorders     
Epistaxis * 1  2/84 (2.38%)  2 3/84 (3.57%)  3
Nasal Congestion * 1  4/84 (4.76%)  4 1/84 (1.19%)  1
Nasal Discomfort * 1  7/84 (8.33%)  7 2/84 (2.38%)  2
Nasal Dryness * 1  4/84 (4.76%)  4 3/84 (3.57%)  3
Nasal Inflammation * 1  1/84 (1.19%)  1 3/84 (3.57%)  3
Nasal Obstruction * 1  3/84 (3.57%)  3 2/84 (2.38%)  2
Rhinorrhoea * 1  0/84 (0.00%)  0 4/84 (4.76%)  4
Upper-Airway Cough Syndrome * 1  2/84 (2.38%)  2 0/84 (0.00%)  0
Vascular disorders     
Hypotension * 1  2/84 (2.38%)  3 0/84 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 17.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
Discussion and/or publication of data generated is not permitted without the prior written consent of the sponsor.
Results Point of Contact
Name/Title: Randall Mack
Organization: Recro Pharma
Phone: 484-395-2470 ext 2406
Responsible Party: Recro Pharma, Inc.
ClinicalTrials.gov Identifier: NCT02284243     History of Changes
Other Study ID Numbers: REC-14-013
First Submitted: November 3, 2014
First Posted: November 5, 2014
Results First Submitted: January 16, 2017
Results First Posted: May 2, 2017
Last Update Posted: May 2, 2017