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Trial record 47 of 458 for:    TRAMADOL

Tramadol/Diclofenac Fixed-dose Combination Phase III Trial in Acute Pain After Third Molar Extraction

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ClinicalTrials.gov Identifier: NCT03714672
Recruitment Status : Completed
First Posted : October 22, 2018
Results First Posted : July 24, 2019
Last Update Posted : July 24, 2019
Sponsor:
Collaborator:
Grünenthal, S.A.
Information provided by (Responsible Party):
Grünenthal GmbH

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Acute Pain
Interventions Drug: Tramadol/Diclofenac 50/50
Drug: Tramadol/Diclofenac 25/25
Drug: Tramadol 50
Drug: Diclofenac 50
Enrollment 1151
Recruitment Details The first participant was enrolled on 26 August 2017.
Pre-assignment Details A total of 1151 participants signed an informed consent form, 829 participants were allocated to treatment. Of the 829 allocated participants, 3 were not treated (1 each in the Diclofenac 50, Tramadol 50, and Tramadol/Diclofenac 25/25 treatment arms) and were not included in the Safety Set (N=826).
Arm/Group Title Tramadol/Diclofenac 50/50 Tramadol/Diclofenac 25/25 Tramadol 50 Diclofenac 50
Hide Arm/Group Description

Participants received 3 doses of tramadol hydrochloride/diclofenac sodium 50 mg/50 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Tramadol/Diclofenac 50/50: Each dose comprised 1 fixed-dose combination tablet and 3 placebo tablets or capsules matching the other active treatment groups. Doses were taken 8 hours apart.

Participants received 3 doses of tramadol hydrochloride/diclofenac sodium 25 mg/25 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Tramadol/Diclofenac 25/25: Each dose comprised 1 fixed-dose combination tablet and 3 placebo tablets or capsules matching the other active treatment groups. Doses were taken 8 hours apart.

Participants received 3 doses of tramadol hydrochloride 50 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Tramadol 50: Each dose comprised 1 capsule containing 50 mg tramadol hydrochloride and 3 placebo tablets matching the other active treatment groups. Doses were taken 8 hours apart.

Participants received 3 doses of diclofenac sodium 50 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Diclofenac 50: Each dose comprised 1 tablet containing 50 mg diclofenac sodium and 3 placebo tablets or capsules matching the other active treatment groups. Doses were taken 8 hours apart.

Period Title: Overall Study
Started 209 206 206 208
Safety Set 208 205 206 207
Completed 207 202 202 207
Not Completed 2 4 4 1
Reason Not Completed
Adverse Event             0             0             3             0
Physician Decision             0             1             0             0
Other Reason             1             2             1             1
Lost to Follow-up             1             1             0             0
Arm/Group Title Tramadol/Diclofenac 50/50 Tramadol/Diclofenac 25/25 Tramadol 50 Diclofenac 50 Total
Hide Arm/Group Description

Participants received 3 doses of tramadol hydrochloride/diclofenac sodium 50 mg/50 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Tramadol/Diclofenac 50/50: Each dose comprised 1 fixed-dose combination tablet and 3 placebo tablets or capsules matching the other active treatment groups. Doses were taken 8 hours apart.

Participants received 3 doses of tramadol hydrochloride/diclofenac sodium 25 mg/25 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Tramadol/Diclofenac 25/25: Each dose comprised 1 fixed-dose combination tablet and 3 placebo tablets or capsules matching the other active treatment groups. Doses were taken 8 hours apart.

Participants received 3 doses of tramadol hydrochloride 50 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Tramadol 50: Each dose comprised 1 capsule containing 50 mg tramadol hydrochloride and 3 placebo tablets matching the other active treatment groups. Doses were be taken 8 hours apart.

Participants received 3 doses of diclofenac sodium 50 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction

Diclofenac 50: Each dose comprised 1 tablet containing 50 mg diclofenac sodium and 3 placebo tablets or capsules matching the other active treatment groups. Doses were be taken 8 hours apart.

Total of all reporting groups
Overall Number of Baseline Participants 208 205 206 207 826
Hide Baseline Analysis Population Description
Safety Set (One participant was allocated to Tramadol/Diclofenac 50/50, but received Tramadol 50. The participant was included in the Tramadol 50 arm for the Safety Set as the analyses were conducted according to the treatment received)
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 208 participants 205 participants 206 participants 207 participants 826 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
208
 100.0%
205
 100.0%
206
 100.0%
207
 100.0%
826
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 208 participants 205 participants 206 participants 207 participants 826 participants
22.9
(18 to 41)
24.0
(18 to 50)
23.8
(18 to 41)
23.6
(18 to 56)
23.6
(18 to 56)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 208 participants 205 participants 206 participants 207 participants 826 participants
Female
126
  60.6%
136
  66.3%
132
  64.1%
135
  65.2%
529
  64.0%
Male
82
  39.4%
69
  33.7%
74
  35.9%
72
  34.8%
297
  36.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 208 participants 205 participants 206 participants 207 participants 826 participants
Hispanic or Latino
208
 100.0%
204
  99.5%
206
 100.0%
206
  99.5%
824
  99.8%
Not Hispanic or Latino
0
   0.0%
1
   0.5%
0
   0.0%
1
   0.5%
2
   0.2%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 208 participants 205 participants 206 participants 207 participants 826 participants
American Indian or Alaska Native
0
   0.0%
2
   1.0%
0
   0.0%
1
   0.5%
3
   0.4%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
0
   0.0%
4
   2.0%
4
   1.9%
2
   1.0%
10
   1.2%
More than one race
202
  97.1%
198
  96.6%
200
  97.1%
203
  98.1%
803
  97.2%
Unknown or Not Reported
6
   2.9%
1
   0.5%
2
   1.0%
1
   0.5%
10
   1.2%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Mexico Number Analyzed 208 participants 205 participants 206 participants 207 participants 826 participants
208 205 206 207 826
Body mass index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 208 participants 205 participants 206 participants 207 participants 826 participants
24.5  (4.08) 25.0  (4.39) 25.1  (4.25) 24.5  (4.51) 24.8  (4.31)
Baseline pain intensity categorized   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 208 participants 205 participants 206 participants 207 participants 826 participants
Moderate
88
  42.3%
87
  42.4%
86
  41.7%
81
  39.1%
342
  41.4%
Severe
120
  57.7%
117
  57.1%
120
  58.3%
126
  60.9%
483
  58.5%
None
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Mild
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Missing
0
   0.0%
1
   0.5%
0
   0.0%
0
   0.0%
1
   0.1%
[1]
Measure Description: Measured using an 11-point NRS by answering the following question: "Please rate your pain by selecting the one number that best describes how much pain you have right now." Scores ranged from 0 (no pain) to 10 (pain as bad as you can imagine, and were categorized as None (0), Mild (≥ 1 and < 5), Moderate (≥ 5 and ≤ 6), and Severe (≥ 7). Baseline was the score assessed before the first dose of IMP.
Baseline pain intensity 11-point NRS   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 208 participants 204 participants 206 participants 207 participants 825 participants
7.0  (1.51) 7.0  (1.45) 7.0  (1.45) 7.0  (1.40) 7.0  (1.45)
[1]
Measure Description: Measured using an 11-point NRS by answering the following question: “Please rate your pain by selecting the one number that best describes how much pain you have right now.” Scores ranged from 0 (no pain) to 10 (pain as bad as you can imagine, and were categorized as None (0), Mild (≥ 1 and < 5), Moderate (≥ 5 and ≤ 6), and Severe (≥ 7). Baseline was the score assessed before the first dose of IMP.
[2]
Measure Analysis Population Description: One participant (Tramadol/Diclofenac 25/25) from the Safety Set had no efficacy assessments and was not included in the Full Analysis Set.
Number of molars extracted  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 208 participants 205 participants 206 participants 207 participants 826 participants
Number of molars extracted 3
37
  17.8%
41
  20.0%
42
  20.4%
43
  20.8%
163
  19.7%
Number of molars extracted 4
171
  82.2%
164
  80.0%
164
  79.6%
164
  79.2%
663
  80.3%
Duration of surgery, minutes  
Mean (Standard Deviation)
Unit of measure:  Minutes
Number Analyzed 208 participants 205 participants 206 participants 207 participants 826 participants
33.0  (21.90) 35.0  (21.56) 34.2  (20.25) 32.9  (19.21) 33.8  (20.74)
Lidocaine used during surgery, mg  
Mean (Standard Deviation)
Unit of measure:  Mg
Number Analyzed 208 participants 205 participants 206 participants 207 participants 826 participants
211.1  (44.18) 211.4  (41.13) 211.3  (43.36) 207.7  (42.13) 210.4  (42.67)
End of surgery to first dose of IMP, hours  
Mean (Standard Deviation)
Unit of measure:  Hours
Number Analyzed 208 participants 205 participants 206 participants 207 participants 826 participants
2.2  (0.89) 2.2  (0.83) 2.1  (0.90) 2.1  (0.85) 2.2  (0.87)
1.Primary Outcome
Title Pain Relief Expressed as Total Pain Relief (TOTPAR) Over the 4 Hours Post-dose Period (TOTPAR4)
Hide Description Pain relief was assessed by the participant at defined time points after the first IMP dose using a 5-point verbal rating scale (VRS) with categories 0 (none), 1 (a little), 2 (some), 3 (a lot), or 4 (complete). Total Pain Relief (TOTPAR4) is a time-weighted summary measure of the total area under the pain relief curve that integrates serial assessments of a participant’s pain over the duration of 4 hours after IMP intake. Minimum and maximum values for TOTPAR4 were 0=worst score and 16=best score, a higher score indicates more pain relief.
Time Frame Up to 4 hours after first dose
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Tramadol/Diclofenac 50/50 Tramadol/Diclofenac 25/25 Tramadol 50 Diclofenac 50
Hide Arm/Group Description:

Participants received 3 doses of tramadol hydrochloride/diclofenac sodium 50 mg/50 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Tramadol/Diclofenac 50/50: Each dose comprised 1 fixed-dose combination tablet and 3 placebo tablets or capsules matching the other active treatment groups. Doses were taken 8 hours apart.

Participants received 3 doses of tramadol hydrochloride/diclofenac sodium 25 mg/25 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Tramadol/Diclofenac 25/25: Each dose comprised 1 fixed-dose combination tablet and 3 placebo tablets or capsules matching the other active treatment groups. Doses were taken 8 hours apart.

Participants received 3 doses of tramadol hydrochloride 50 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Tramadol 50: Each dose comprised 1 capsule containing 50 mg tramadol hydrochloride and 3 placebo tablets matching the other active treatment groups. Doses were taken 8 hours apart.

Participants received 3 doses of diclofenac sodium 50 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction

Diclofenac 50: Each dose comprised 1 tablet containing 50 mg diclofenac sodium and 3 placebo tablets or capsules matching the other active treatment groups. Doses were taken 8 hours apart.

Overall Number of Participants Analyzed 209 204 205 207
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
9.9
(9.3 to 10.4)
8.6
(8.0 to 9.1)
5.4
(4.9 to 5.9)
5.8
(5.3 to 6.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tramadol/Diclofenac 50/50, Diclofenac 50
Comments Bonferroni-Holm procedure used for determining the statistical significance of the results.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment, baseline pain intensity, and site as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.1
Confidence Interval (2-Sided) 95%
-4.8 to -3.4
Estimation Comments LS means, 95% CIs, and pairwise CIs and p-values comparing the combination treatment arm to the monotherapy arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Tramadol/Diclofenac 50/50, Tramadol 50
Comments Bonferroni-Holm procedure used for determining the statistical significance of the results.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment, baseline pain intensity, and site as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.5
Confidence Interval (2-Sided) 95%
-5.2 to -3.8
Estimation Comments LS means, 95% CIs, and pairwise CIs and p-values comparing the combination treatment arm to the monotherapy arm.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Tramadol/Diclofenac 25/25, Tramadol 50
Comments Bonferroni-Holm procedure used for determining the statistical significance of the results. The planned test was a test for non-inferiority.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment, baseline pain intensity, and site as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.2
Confidence Interval (2-Sided) 95%
-3.9 to -2.5
Estimation Comments LS means, 95% CIs, and pairwise CIs and p-values comparing the combination treatment arm to the monotherapy arm.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Tramadol/Diclofenac 25/25, Diclofenac 50
Comments Bonferroni-Holm procedure used for determining the statistical significance of the results. The planned test was a test for non-inferiority.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment, baseline pain intensity, and site as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.8
Confidence Interval (2-Sided) 95%
-3.5 to -2.1
Estimation Comments LS means, 95% CIs, and pairwise CIs and p-values comparing the combination treatment arm to the monotherapy arm.
2.Secondary Outcome
Title Total Pain Relief at 6 Hours Post-dose (TOTPAR6)
Hide Description Pain relief was assessed by the participant at defined time points after the first IMP dose using a 5-point VRS with categories 0 (none), 1 (a little), 2 (some), 3 (a lot), or 4 (complete). Total Pain Relief (TOTPAR6) is a time-weighted summary measure of the total area under the pain relief curve that integrates serial assessments of a participant’s pain over the duration of 6 hours after IMP intake. Minimum and maximum values for TOTPAR6 were 0=worst score and 24=best score, a higher score indicates more pain relief.
Time Frame Up to 6 hours after first dose
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Tramadol/Diclofenac 50/50 Tramadol/Diclofenac 25/25 Tramadol 50 Diclofenac 50
Hide Arm/Group Description:

Participants received 3 doses of tramadol hydrochloride/diclofenac sodium 50 mg/50 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Tramadol/Diclofenac 50/50: Each dose comprised 1 fixed-dose combination tablet and 3 placebo tablets or capsules matching the other active treatment groups. Doses were taken 8 hours apart.

Participants received 3 doses of tramadol hydrochloride/diclofenac sodium 25 mg/25 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Tramadol/Diclofenac 25/25: Each dose comprised 1 fixed-dose combination tablet and 3 placebo tablets or capsules matching the other active treatment groups. Doses were taken 8 hours apart.

Participants received 3 doses of tramadol hydrochloride 50 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Tramadol 50: Each dose comprised 1 capsule containing 50 mg tramadol hydrochloride and 3 placebo tablets matching the other active treatment groups. Doses were taken 8 hours apart.

Participants received 3 doses of diclofenac sodium 50 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction

Diclofenac 50: Each dose comprised 1 tablet containing 50 mg diclofenac sodium and 3 placebo tablets or capsules matching the other active treatment groups. Doses were taken 8 hours apart.

Overall Number of Participants Analyzed 209 204 205 207
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
15.2
(14.4 to 16.0)
13.3
(12.5 to 14.2)
9.3
(8.4 to 10.1)
9.8
(9.0 to 10.6)
3.Secondary Outcome
Title Total Pain Relief at 8 Hours Post-dose (TOTPAR8)
Hide Description Pain relief was assessed by the participant at defined time points after the first IMP dose using a 5-point VRS with categories 0 (none), 1 (a little), 2 (some), 3 (a lot), or 4 (complete). Total Pain Relief (TOTPAR8) is a time-weighted summary measure of the total area under the pain relief curve that integrates serial assessments of a participant’s pain over the duration of 8 hours after IMP intake. Minimum and maximum values for TOTPAR8 were 0=worst score and 32=best score, a higher score indicates more pain relief.
Time Frame Up to 8 hours after first dose
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Tramadol/Diclofenac 50/50 Tramadol/Diclofenac 25/25 Tramadol 50 Diclofenac 50
Hide Arm/Group Description:

Participants received 3 doses of tramadol hydrochloride/diclofenac sodium 50 mg/50 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Tramadol/Diclofenac 50/50: Each dose comprised 1 fixed-dose combination tablet and 3 placebo tablets or capsules matching the other active treatment groups. Doses were taken 8 hours apart.

Participants received 3 doses of tramadol hydrochloride/diclofenac sodium 25 mg/25 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Tramadol/Diclofenac 25/25: Each dose comprised 1 fixed-dose combination tablet and 3 placebo tablets or capsules matching the other active treatment groups. Doses were taken 8 hours apart.

Participants received 3 doses of tramadol hydrochloride 50 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Tramadol 50: Each dose comprised 1 capsule containing 50 mg tramadol hydrochloride and 3 placebo tablets matching the other active treatment groups. Doses were taken 8 hours apart.

Participants received 3 doses of diclofenac sodium 50 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Diclofenac 50: Each dose comprised 1 tablet containing 50 mg diclofenac sodium and 3 placebo tablets or capsules matching the other active treatment groups. Doses were taken 8 hours apart.

Overall Number of Participants Analyzed 209 204 205 207
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
20.1
(19.0 to 21.2)
17.8
(16.7 to 18.9)
13.1
(12.0 to 14.2)
13.7
(12.6 to 14.8)
4.Secondary Outcome
Title Summed Pain Intensity Difference (SPID) at 4, 6, 8, and 24 Hours Post-dose
Hide Description Pain intensity was assessed by the participant before and at defined time points after the first IMP dose using an 11-point NRS with anchors at 0 for “no pain” and 10 for “pain as bad as you can imagine”. Pain Intensity Difference (PIDt) was defined as the difference between baseline pain intensity and pain intensity at time point t, and SPID defined as summed PIDt x [time (hours) elapsed since previous observation]. The SPID scores are the sum of the differences at each time point multiplied by the duration in hours since the previous time point. Positive numbers indicate a reduction in pain [maximum=10 at each time point], and negative numbers indicate an increase in pain [minimum=-10 at each time point]. The overall minimum and maximum are -10 and 10 times the number of hours specified (SPID-4=[-40 to 40], SPID-6=[-60 to 60], SPID-8=[-80 to 80], and SPID-24=[-240 to 240]).
Time Frame Baseline; up to 24 hours after first dose
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Tramadol/Diclofenac 50/50 Tramadol/Diclofenac 25/25 Tramadol 50 Diclofenac 50
Hide Arm/Group Description:

Participants received 3 doses of tramadol hydrochloride/diclofenac sodium 50 mg/50 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Tramadol/Diclofenac 50/50: Each dose comprised 1 fixed-dose combination tablet and 3 placebo tablets or capsules matching the other active treatment groups. Doses were taken 8 hours apart.

Participants received 3 doses of tramadol hydrochloride/diclofenac sodium 25 mg/25 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Tramadol/Diclofenac 25/25: Each dose comprised 1 fixed-dose combination tablet and 3 placebo tablets or capsules matching the other active treatment groups. Doses were taken 8 hours apart.

Participants received 3 doses of tramadol hydrochloride 50 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Tramadol 50: Each dose comprised 1 capsule containing 50 mg tramadol hydrochloride and 3 placebo tablets matching the other active treatment groups. Doses were taken 8 hours apart.

Participants received 3 doses of diclofenac sodium 50 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Diclofenac 50: Each dose comprised 1 tablet containing 50 mg diclofenac sodium and 3 placebo tablets or capsules matching the other active treatment groups. Doses were taken 8 hours apart.

Overall Number of Participants Analyzed 209 204 205 207
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
4 Hours 16.24  (0.564) 13.67  (0.576) 6.43  (0.570) 7.72  (0.568)
6 Hours 25.54  (0.836) 21.86  (0.855) 12.89  (0.845) 14.36  (0.843)
8 Hours 33.70  (1.121) 28.90  (1.146) 19.10  (1.133) 20.54  (1.129)
24 Hours 107.15  (3.787) 91.99  (3.873) 71.41  (3.828) 72.08  (3.816)
5.Secondary Outcome
Title Time to Achieve a 50 Percent Reduction in Baseline Pain (Pain at Least Half Gone)
Hide Description Time (hours) when the participant achieved a 50 percent reduction of baseline (starting) pain. It was assessed at defined time points after the first IMP dose using a YES or NO question for pain half gone.
Time Frame Up to 24 hours after first dose
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Full Analysis Set
Arm/Group Title Tramadol/Diclofenac 50/50 Tramadol/Diclofenac 25/25 Tramadol 50 Diclofenac 50
Hide Arm/Group Description:

Participants received 3 doses of tramadol hydrochloride/diclofenac sodium 50 mg/50 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Tramadol/Diclofenac 50/50: Each dose comprised 1 fixed-dose combination tablet and 3 placebo tablets or capsules matching the other active treatment groups. Doses were taken 8 hours apart.

Participants received 3 doses of tramadol hydrochloride/diclofenac sodium 25 mg/25 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Tramadol/Diclofenac 25/25: Each dose comprised 1 fixed-dose combination tablet and 3 placebo tablets or capsules matching the other active treatment groups. Doses were taken 8 hours apart.

Participants received 3 doses of tramadol hydrochloride 50 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Tramadol 50: Each dose comprised 1 capsule containing 50 mg tramadol hydrochloride and 3 placebo tablets matching the other active treatment groups. Doses were taken 8 hours apart.

Participants received 3 doses of diclofenac sodium 50 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction

Diclofenac 50: Each dose comprised 1 tablet containing 50 mg diclofenac sodium and 3 placebo tablets or capsules matching the other active treatment groups. Doses were taken 8 hours apart.

Overall Number of Participants Analyzed 209 204 205 207
Mean (Standard Deviation)
Unit of Measure: hours
1.27  (1.216) 1.73  (2.778) 3.01  (3.731) 2.53  (2.865)
6.Secondary Outcome
Title Time to Onset of First Perceptible Pain Relief
Hide Description Participants used one stopwatch to document the time between first IMP dose and when they begin to feel any pain-relieving effect from the IMP.
Time Frame Up to 8 hours after first dose
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Full Analysis Set
Arm/Group Title Tramadol/Diclofenac 50/50 Tramadol/Diclofenac 25/25 Tramadol 50 Diclofenac 50
Hide Arm/Group Description:

Participants received 3 doses of tramadol hydrochloride/diclofenac sodium 50 mg/50 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Tramadol/Diclofenac 50/50: Each dose comprised 1 fixed-dose combination tablet and 3 placebo tablets or capsules matching the other active treatment groups. Doses were taken 8 hours apart.

Participants received 3 doses of tramadol hydrochloride/diclofenac sodium 25 mg/25 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Tramadol/Diclofenac 25/25: Each dose comprised 1 fixed-dose combination tablet and 3 placebo tablets or capsules matching the other active treatment groups. Doses were taken 8 hours apart.

Participants received 3 doses of tramadol hydrochloride 50 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Tramadol 50: Each dose comprised 1 capsule containing 50 mg tramadol hydrochloride and 3 placebo tablets matching the other active treatment groups. Doses were taken 8 hours apart.

Participants received 3 doses of diclofenac sodium 50 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction

Diclofenac 50: Each dose comprised 1 tablet containing 50 mg diclofenac sodium and 3 placebo tablets or capsules matching the other active treatment groups. Doses were taken 8 hours apart.

Overall Number of Participants Analyzed 209 204 205 207
Mean (Standard Deviation)
Unit of Measure: hours
0.57  (0.483) 0.67  (0.875) 1.07  (1.000) 1.12  (1.151)
7.Secondary Outcome
Title Time to Onset of Meaningful Pain Relief
Hide Description Participants used a second stopwatch to document the time between first IMP dose and when they felt their pain relief was meaningful to them.
Time Frame Up to 8 hours after first dose
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Full Analysis Set
Arm/Group Title Tramadol/Diclofenac 50/50 Tramadol/Diclofenac 25/25 Tramadol 50 Diclofenac 50
Hide Arm/Group Description:

Participants received 3 doses of tramadol hydrochloride/diclofenac sodium 50 mg/50 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Tramadol/Diclofenac 50/50: Each dose comprised 1 fixed-dose combination tablet and 3 placebo tablets or capsules matching the other active treatment groups. Doses were taken 8 hours apart.

Participants received 3 doses of tramadol hydrochloride/diclofenac sodium 25 mg/25 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Tramadol/Diclofenac 25/25: Each dose comprised 1 fixed-dose combination tablet and 3 placebo tablets or capsules matching the other active treatment groups. Doses were taken 8 hours apart.

Participants received 3 doses of tramadol hydrochloride 50 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Tramadol 50: Each dose comprised 1 capsule containing 50 mg tramadol hydrochloride and 3 placebo tablets matching the other active treatment groups. Doses were taken 8 hours apart.

Participants received 3 doses of diclofenac sodium 50 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Diclofenac 50: Each dose comprised 1 tablet containing 50 mg diclofenac sodium and 3 placebo tablets or capsules matching the other active treatment groups. Doses were taken 8 hours apart.

Overall Number of Participants Analyzed 209 204 205 207
Mean (Standard Deviation)
Unit of Measure: hours
1.47  (1.149) 2.04  (1.810) 2.93  (1.895) 2.75  (1.882)
8.Secondary Outcome
Title Time to Intake of First Rescue Medication Dose
Hide Description The time from first IMP dose to first dose of rescue medication (ibuprofen or ketorolac), if needed, within 24 hours post-dose was calculated.
Time Frame First dose to 24 hours after first dose
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Full Analysis Set
Arm/Group Title Tramadol/Diclofenac 50/50 Tramadol/Diclofenac 25/25 Tramadol 50 Diclofenac 50
Hide Arm/Group Description:

Participants received 3 doses of tramadol hydrochloride/diclofenac sodium 50 mg/50 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Tramadol/Diclofenac 50/50: Each dose comprised 1 fixed-dose combination tablet and 3 placebo tablets or capsules matching the other active treatment groups. Doses were taken 8 hours apart.

Participants received 3 doses of tramadol hydrochloride/diclofenac sodium 25 mg/25 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Tramadol/Diclofenac 25/25: Each dose comprised 1 fixed-dose combination tablet and 3 placebo tablets or capsules matching the other active treatment groups. Doses were taken 8 hours apart.

Participants received 3 doses of tramadol hydrochloride 50 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Tramadol 50: Each dose comprised 1 capsule containing 50 mg tramadol hydrochloride and 3 placebo tablets matching the other active treatment groups. Doses were taken 8 hours apart.

Participants received 3 doses of diclofenac sodium 50 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Diclofenac 50: Each dose comprised 1 tablet containing 50 mg diclofenac sodium and 3 placebo tablets or capsules matching the other active treatment groups. Doses were taken 8 hours apart.

Overall Number of Participants Analyzed 209 204 205 207
Mean (Standard Deviation)
Unit of Measure: hours
21.84  (6.222) 20.99  (7.450) 17.37  (9.745) 17.38  (9.646)
9.Secondary Outcome
Title Subject’s Global Evaluation of the Treatment
Hide Description Participants documented their overall impression of the analgesic efficacy of the IMPs on a 5-point Likert scale from Excellent (4) to Poor (0).
Time Frame 8 hours after the first dose of IMP or before first intake of rescue medication (whatever the first) and 24 hours after the first dose of IMPs
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Full Analysis Set
Arm/Group Title Tramadol/Diclofenac 50/50 Tramadol/Diclofenac 25/25 Tramadol 50 Diclofenac 50
Hide Arm/Group Description:

Participants received 3 doses of tramadol hydrochloride/diclofenac sodium 50 mg/50 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Tramadol/Diclofenac 50/50: Each dose comprised 1 fixed-dose combination tablet and 3 placebo tablets or capsules matching the other active treatment groups. Doses were taken 8 hours apart.

Participants received 3 doses of tramadol hydrochloride/diclofenac sodium 25 mg/25 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Tramadol/Diclofenac 25/25: Each dose comprised 1 fixed-dose combination tablet and 3 placebo tablets or capsules matching the other active treatment groups. Doses were taken 8 hours apart.

Participants received 3 doses of tramadol hydrochloride 50 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Tramadol 50: Each dose comprised 1 capsule containing 50 mg tramadol hydrochloride and 3 placebo tablets matching the other active treatment groups. Doses were taken 8 hours apart.

Participants received 3 doses of diclofenac sodium 50 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Diclofenac 50: Each dose comprised 1 tablet containing 50 mg diclofenac sodium and 3 placebo tablets or capsules matching the other active treatment groups. Doses were taken 8 hours apart.

Overall Number of Participants Analyzed 209 204 205 207
Measure Type: Count of Participants
Unit of Measure: Participants
8-Hours Number Analyzed 207 participants 199 participants 197 participants 201 participants
Poor
4
   1.9%
7
   3.5%
28
  14.2%
23
  11.4%
Fair
10
   4.8%
12
   6.0%
30
  15.2%
25
  12.4%
Good
17
   8.2%
33
  16.6%
36
  18.3%
35
  17.4%
Very Good
73
  35.3%
64
  32.2%
52
  26.4%
67
  33.3%
Excellent
103
  49.8%
83
  41.7%
51
  25.9%
51
  25.4%
24-Hours Number Analyzed 208 participants 201 participants 205 participants 206 participants
Poor
3
   1.4%
4
   2.0%
7
   3.4%
7
   3.4%
Fair
4
   1.9%
5
   2.5%
23
  11.2%
13
   6.3%
Good
12
   5.8%
18
   9.0%
34
  16.6%
39
  18.9%
Very Good
57
  27.4%
65
  32.3%
59
  28.8%
67
  32.5%
Excellent
132
  63.5%
109
  54.2%
82
  40.0%
80
  38.8%
10.Secondary Outcome
Title Incidence and Type of Adverse Events
Hide Description The incidence of treatment emergent adverse events (TEAE) reported from first dose (Day 1) to last scheduled contact with the participant on Day 14 was descriptively summarized. Selected TEAEs were events with preferred terms of nausea, vomiting, abdominal pain, gastrointestinal bleeding, dizziness, or hypotension.
Time Frame Day 1 to Day 14
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Safety Set
Arm/Group Title Tramadol/Diclofenac 50/50 Tramadol/Diclofenac 25/25 Tramadol 50 Diclofenac 50
Hide Arm/Group Description:

Participants received 3 doses of tramadol hydrochloride/diclofenac sodium 50 mg/50 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Tramadol/Diclofenac 50/50: Each dose comprised 1 fixed-dose combination tablet and 3 placebo tablets or capsules matching the other active treatment groups. Doses were taken 8 hours apart.

Participants received 3 doses of tramadol hydrochloride/diclofenac sodium 25 mg/25 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Tramadol/Diclofenac 25/25: Each dose comprised 1 fixed-dose combination tablet and 3 placebo tablets or capsules matching the other active treatment groups. Doses were taken 8 hours apart.

Participants received 3 doses of tramadol hydrochloride 50 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Tramadol 50: Each dose comprised 1 capsule containing 50 mg tramadol hydrochloride and 3 placebo tablets matching the other active treatment groups. Doses were taken 8 hours apart.

Participants received 3 doses of diclofenac sodium 50 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Diclofenac 50: Each dose comprised 1 tablet containing 50 mg diclofenac sodium and 3 placebo tablets or capsules matching the other active treatment groups. Doses were taken 8 hours apart.

Overall Number of Participants Analyzed 208 205 206 207
Measure Type: Number
Unit of Measure: participants
TEAE 96 62 105 48
Severe TEAE 6 1 3 2
TEAE related to IMP or rescue medication 49 23 64 10
Serious TEAE 0 1 0 0
TEAE with outcome of death 0 0 0 0
Selected TEAE 68 26 77 13
TEAE leading to dose reduction 0 0 0 0
TEAE leading to dose interruption 1 2 1 0
TEAE leading to IMP withdrawal 2 1 1 0
Dose reduction, interruption, or withdrawal 3 3 2 0
Time Frame Day 1 to Day 14
Adverse Event Reporting Description Sites were instructed not to report dental pain as an AE until 24 hours after the first dose of IMP.
 
Arm/Group Title Tramadol/Diclofenac 50/50 Tramadol/Diclofenac 25/25 Tramadol 50 Diclofenac 50
Hide Arm/Group Description

Participants received 3 doses of tramadol hydrochloride/diclofenac sodium 50 mg/50 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Tramadol/Diclofenac 50/50: Each dose comprised 1 fixed-dose combination tablet and 3 placebo tablets or capsules matching the other active treatment groups. Doses were taken 8 hours apart.

Participants received 3 doses of tramadol hydrochloride/diclofenac sodium 25 mg/25 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Tramadol/Diclofenac 25/25: Each dose comprised 1 fixed-dose combination tablet and 3 placebo tablets or capsules matching the other active treatment groups. Doses were taken 8 hours apart.

Participants received 3 doses of tramadol hydrochloride 50 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Tramadol 50: Each dose comprised 1 capsule containing 50 mg tramadol hydrochloride and 3 placebo tablets matching the other active treatment groups. Doses were taken 8 hours apart.

Participants received 3 doses of diclofenac sodium 50 mg over a 24-hour period if they developed acute moderate to severe pain within 4 hours after third molar extraction.

Diclofenac 50: Each dose comprised 1 tablet containing 50 mg diclofenac sodium and 3 placebo tablets or capsules matching the other active treatment groups. Doses were taken 8 hours apart.

All-Cause Mortality
Tramadol/Diclofenac 50/50 Tramadol/Diclofenac 25/25 Tramadol 50 Diclofenac 50
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/208 (0.00%)      0/205 (0.00%)      0/206 (0.00%)      0/207 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Tramadol/Diclofenac 50/50 Tramadol/Diclofenac 25/25 Tramadol 50 Diclofenac 50
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/208 (0.00%)      1/205 (0.49%)      0/206 (0.00%)      0/207 (0.00%)    
Nervous system disorders         
Seizure  1  0/208 (0.00%)  0 1/205 (0.49%)  1 0/206 (0.00%)  0 0/207 (0.00%)  0
1
Term from vocabulary, MedDRA 19.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Tramadol/Diclofenac 50/50 Tramadol/Diclofenac 25/25 Tramadol 50 Diclofenac 50
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   96/208 (46.15%)      62/205 (30.24%)      105/206 (50.97%)      48/207 (23.19%)    
Cardiac disorders         
Palpitations  1  0/208 (0.00%)  0 1/205 (0.49%)  1 1/206 (0.49%)  1 0/207 (0.00%)  0
Ear and labyrinth disorders         
Ear pain  1  0/208 (0.00%)  0 0/205 (0.00%)  0 1/206 (0.49%)  1 0/207 (0.00%)  0
Tinnitus  1  1/208 (0.48%)  1 0/205 (0.00%)  0 0/206 (0.00%)  0 0/207 (0.00%)  0
Vertigo  1  0/208 (0.00%)  0 0/205 (0.00%)  0 0/206 (0.00%)  0 1/207 (0.48%)  1
Gastrointestinal disorders         
Abdominal pain  1  0/208 (0.00%)  0 0/205 (0.00%)  0 1/206 (0.49%)  1 0/207 (0.00%)  0
Abdominal pain upper  1  1/208 (0.48%)  1 0/205 (0.00%)  0 0/206 (0.00%)  0 0/207 (0.00%)  0
Diarrhoea  1  0/208 (0.00%)  0 1/205 (0.49%)  1 0/206 (0.00%)  0 1/207 (0.48%)  1
Dyspepsia  1  1/208 (0.48%)  1 0/205 (0.00%)  0 2/206 (0.97%)  2 0/207 (0.00%)  0
Dysphagia  1  0/208 (0.00%)  0 0/205 (0.00%)  0 1/206 (0.49%)  1 0/207 (0.00%)  0
Gastritis  1  0/208 (0.00%)  0 0/205 (0.00%)  0 1/206 (0.49%)  1 2/207 (0.97%)  2
Gingival pain  1  0/208 (0.00%)  0 0/205 (0.00%)  0 0/206 (0.00%)  0 1/207 (0.48%)  1
Hypoaesthesia oral  1  0/208 (0.00%)  0 1/205 (0.49%)  1 0/206 (0.00%)  0 0/207 (0.00%)  0
Nausea  1  51/208 (24.52%)  59 15/205 (7.32%)  17 52/206 (25.24%)  62 7/207 (3.38%)  7
Oral pain  1  0/208 (0.00%)  0 3/205 (1.46%)  3 1/206 (0.49%)  1 1/207 (0.48%)  1
Vomiting  1  41/208 (19.71%)  57 12/205 (5.85%)  15 44/206 (21.36%)  75 3/207 (1.45%)  3
General disorders         
Chills  1  1/208 (0.48%)  1 3/205 (1.46%)  3 3/206 (1.46%)  3 1/207 (0.48%)  1
Face oedema  1  0/208 (0.00%)  0 1/205 (0.49%)  1 0/206 (0.00%)  0 0/207 (0.00%)  0
Inflammation  1  0/208 (0.00%)  0 0/205 (0.00%)  0 2/206 (0.97%)  2 0/207 (0.00%)  0
Malaise  1  0/208 (0.00%)  0 0/205 (0.00%)  0 1/206 (0.49%)  1 0/207 (0.00%)  0
Pain  1  0/208 (0.00%)  0 1/205 (0.49%)  1 1/206 (0.49%)  1 2/207 (0.97%)  2
Pyrexia  1  0/208 (0.00%)  0 4/205 (1.95%)  4 6/206 (2.91%)  6 0/207 (0.00%)  0
Infections and infestations         
Alveolar osteitis  1  1/208 (0.48%)  1 0/205 (0.00%)  0 0/206 (0.00%)  0 0/207 (0.00%)  0
Gingivitis  1  0/208 (0.00%)  0 0/205 (0.00%)  0 1/206 (0.49%)  1 1/207 (0.48%)  1
Infection  1  1/208 (0.48%)  1 0/205 (0.00%)  0 0/206 (0.00%)  0 0/207 (0.00%)  0
Nasopharyngitis  1  2/208 (0.96%)  2 1/205 (0.49%)  1 0/206 (0.00%)  0 3/207 (1.45%)  3
Post procedural infection  1  0/208 (0.00%)  0 0/205 (0.00%)  0 0/206 (0.00%)  0 1/207 (0.48%)  1
Tonsillitis  1  0/208 (0.00%)  0 1/205 (0.49%)  1 0/206 (0.00%)  0 0/207 (0.00%)  0
Tooth abscess  1  1/208 (0.48%)  1 0/205 (0.00%)  0 2/206 (0.97%)  2 0/207 (0.00%)  0
Injury, poisoning and procedural complications         
Contusion  1  0/208 (0.00%)  0 1/205 (0.49%)  1 0/206 (0.00%)  0 0/207 (0.00%)  0
Post procedural contusion  1  0/208 (0.00%)  0 0/205 (0.00%)  0 1/206 (0.49%)  1 0/207 (0.00%)  0
Post procedural haemorrhage  1  1/208 (0.48%)  1 0/205 (0.00%)  0 0/206 (0.00%)  0 2/207 (0.97%)  3
Post procedural inflammation  1  2/208 (0.96%)  2 4/205 (1.95%)  4 5/206 (2.43%)  5 3/207 (1.45%)  3
Post procedural swelling  1  0/208 (0.00%)  0 1/205 (0.49%)  1 2/206 (0.97%)  2 0/207 (0.00%)  0
Procedural pain  1  26/208 (12.50%)  26 21/205 (10.24%)  21 24/206 (11.65%)  24 18/207 (8.70%)  18
Wound dehiscence  1  0/208 (0.00%)  0 0/205 (0.00%)  0 0/206 (0.00%)  0 1/207 (0.48%)  1
Musculoskeletal and connective tissue disorders         
Pain in jaw  1  1/208 (0.48%)  1 0/205 (0.00%)  0 1/206 (0.49%)  1 0/207 (0.00%)  0
Temporomandibular joint syndrome  1  1/208 (0.48%)  1 0/205 (0.00%)  0 0/206 (0.00%)  0 0/207 (0.00%)  0
Trismus  1  0/208 (0.00%)  0 1/205 (0.49%)  1 0/206 (0.00%)  0 0/207 (0.00%)  0
Nervous system disorders         
Dizziness  1  25/208 (12.02%)  28 11/205 (5.37%)  11 29/206 (14.08%)  34 6/207 (2.90%)  6
Dysgeusia  1  1/208 (0.48%)  1 0/205 (0.00%)  0 0/206 (0.00%)  0 1/207 (0.48%)  1
Headache  1  10/208 (4.81%)  10 6/205 (2.93%)  6 15/206 (7.28%)  16 7/207 (3.38%)  7
Hypoaesthesia  1  2/208 (0.96%)  3 0/205 (0.00%)  0 1/206 (0.49%)  1 0/207 (0.00%)  0
Paraesthesia  1  0/208 (0.00%)  0 2/205 (0.98%)  2 0/206 (0.00%)  0 0/207 (0.00%)  0
Somnolence  1  3/208 (1.44%)  3 0/205 (0.00%)  0 1/206 (0.49%)  1 0/207 (0.00%)  0
Syncope  1  1/208 (0.48%)  1 0/205 (0.00%)  0 0/206 (0.00%)  0 0/207 (0.00%)  0
Tremor  1  1/208 (0.48%)  1 0/205 (0.00%)  0 0/206 (0.00%)  0 0/207 (0.00%)  0
Psychiatric disorders         
Anxiety  1  0/208 (0.00%)  0 0/205 (0.00%)  0 2/206 (0.97%)  3 0/207 (0.00%)  0
Hallucination  1  1/208 (0.48%)  1 0/205 (0.00%)  0 0/206 (0.00%)  0 0/207 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Dyspnoea  1  1/208 (0.48%)  1 0/205 (0.00%)  0 0/206 (0.00%)  0 0/207 (0.00%)  0
Oropharyngeal pain  1  0/208 (0.00%)  0 1/205 (0.49%)  1 0/206 (0.00%)  0 1/207 (0.48%)  1
Productive cough  1  0/208 (0.00%)  0 0/205 (0.00%)  0 1/206 (0.49%)  1 0/207 (0.00%)  0
Skin and subcutaneous tissue disorders         
Ecchymosis  1  1/208 (0.48%)  1 0/205 (0.00%)  0 0/206 (0.00%)  0 0/207 (0.00%)  0
Hyperhidrosis  1  0/208 (0.00%)  0 1/205 (0.49%)  1 3/206 (1.46%)  6 1/207 (0.48%)  1
Rash  1  0/208 (0.00%)  0 1/205 (0.49%)  1 0/206 (0.00%)  0 0/207 (0.00%)  0
Vascular disorders         
Haematoma  1  0/208 (0.00%)  0 1/205 (0.49%)  1 0/206 (0.00%)  0 0/207 (0.00%)  0
Hypotension  1  1/208 (0.48%)  1 1/205 (0.49%)  1 2/206 (0.97%)  3 0/207 (0.00%)  0
Orthostatic hypotension  1  1/208 (0.48%)  1 0/205 (0.00%)  0 0/206 (0.00%)  0 0/207 (0.00%)  0
1
Term from vocabulary, MedDRA 19.0
Indicates events were collected by systematic assessment
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.
The sponsor reserves the right to review any proposed presentation of the results of this trial before they are submitted for publication or public disclosure. Neither party (e.g., the sponsor, the coordinating investigator) has the right to prohibit publication or public disclosure unless it can be shown to affect possible patent rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Clinical Trial Helpdesk
Organization: Grünenthal GmbH
Phone: +49 241 569 ext 3223
EMail: clinical-trials@grunenthal.com
Publications:
Gay Escoda C, Piñera Penalva M, Velasco Vivancos V, Berini Aytés L. Cordales incluidos. Patología, clínica y tratamiento del tercer molar incluído. In: Gay Escoda C, Berini Aytés L. (eds.). Tratado de Cirugía Bucal. Tomo I. Madrid: Ergón; 2004. p. 355-85
Layout table for additonal information
Responsible Party: Grünenthal GmbH
ClinicalTrials.gov Identifier: NCT03714672     History of Changes
Other Study ID Numbers: KF8001-01
U1111-1179-2333 ( Other Identifier: World Health Organization )
KF8001-01 ( Registry Identifier: RNEC (Mexico) )
First Submitted: October 19, 2018
First Posted: October 22, 2018
Results First Submitted: April 15, 2019
Results First Posted: July 24, 2019
Last Update Posted: July 24, 2019