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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1179-2333 | Other Identifier | World Health Organization | |
| KF8001-01 | Registry Identifier | RNEC (Mexico) |
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| Name | Class |
|---|---|
| Grünenthal, S.A. | INDUSTRY |
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This study evaluated a new drug fixed-dose combination tablet (FDC) called tramadol/diclofenac at two different strengths (fixed doses of 25 milligrams [mg] of tramadol and of diclofenac or of 50 mg each). Tramadol and diclofenac each relieve pain, but they do so by different mechanisms. They were used alone as comparator drug in this study. Both are marketed drugs and are standard treatment for acute pain, including wisdom tooth removal.
The purpose of this study was to demonstrate that the FDC of Tramadol and Diclofenac 50/50 has superior analgesic effect than the monotherapies and that the FDC of Tramadol and Diclofenac 25/25 has non-inferior analgesic effect than the monotherapies. There was an Enrollment Period, a blinded Treatment Period, and a Follow-up Period. Previously used analgesic medication was washed out for at least 24 hours before surgery. The Treatment Period starts on Day 1 with dental surgery and treatment allocation. Treatment was started within 4 hours after the end of surgery if the participant's pain intensity had reached at least 5 points on the 11-point numerical rating scale (NRS). Each participant received 3 doses of one of the four treatments within 24 hours. One fourth of the participants received the fixed-dose combination tablet at a low dose, one fourth at the higher dose, one fourth received 50 mg of the comparator tramadol alone, and one fourth 50 mg of the comparator diclofenac alone.
The first 2 doses of the investigational medicinal product (IMP) were taken at the site, the last dose in an out-patient setting. Participants returned to the site at 24 hours after the first dose. A Follow-up Period included a final visit at the site or a phone call on Day 14 to assess the participant's safety.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tramadol/Diclofenac 50/50 | Experimental | 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. |
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| Tramadol/Diclofenac 25/25 | Experimental | 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. |
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| Tramadol 50 | Active Comparator | 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. |
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| Diclofenac 50 | Active Comparator | 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tramadol/Diclofenac 50/50 | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Pain Relief Expressed as Total Pain Relief (TOTPAR) Over the 4 Hours Post-dose Period (TOTPAR4) | 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. | Up to 4 hours after first dose |
| Measure | Description | Time Frame |
|---|---|---|
| Total Pain Relief at 6 Hours Post-dose (TOTPAR6) | 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. |
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Inclusion Criteria:
Exclusion Criteria at Enrollment:
Findings in the medical record, vital signs, and/or physical examination demonstrating abnormal conditions of participant's general state of health preventing his/her participation in the clinical study according to the investigator's opinion.
Participant unable to speak, read, or write in Spanish language.
Clinical laboratory parameters exceed the pre-defined alert ranges (i.e., 1 standard deviation above or below the upper/lower limit of the normal ranges).
Known hypersensitivity to the IMPs, the anesthetic to be used during surgery, or to the rescue medication (ibuprofen, ketorolac).
Known alcohol or drug abuse in the last 6 months or any history of seizures. Alcohol abuse is defined as the consumption of more than 3 ounces (about 90 milliliters) of liquor or spirits or 18 ounces (about 530 milliliters) of beer per day, for 5 consecutive days during the 6-month period. Drug abuse is defined as the use of any recreational drug for 5 consecutive days during the 6 month period.
Participants who take analgesic medication for chronic pain, monoamine oxidase inhibitors, tricyclic antidepressants, neuroleptics, or other drugs that reduce the seizure threshold within 4 weeks of enrollment.
Pregnant or lactating women.
Participants who received systemic corticosteroids or opioid analgesics less than 2 weeks before surgery.
Participants with molars linked to the mandibular canal.
Participants requiring immediate dental procedures other than third and fourth molars extraction,
Exclusion Criteria at the Allocation Visit:
Participant received a long-acting non-steroidal anti-inflammatory drug within 24 hours or 5 times the elimination half-life of that drug prior to surgery, whatever the longer.
Participant received any analgesic medication other than short-acting pre-operative or intra-operative anesthetic agents within 24 hours before taking IMPs.
Participant received more than 300 mg of lidocaine in total.
Participant received any analgesic medication other than the IMPs immediately after the oral surgical procedure was completed.
Baseline pain intensity of the participant after oral surgical procedure remains below 5 points on the 11-point NRS.
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| Name | Affiliation | Role |
|---|---|---|
| Grünenthal Study Director | Grünenthal GmbH | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Private Clinic | Zapopan | Jalisco | CP 45030 | Mexico | ||
| Private Clinic |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| Background | 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 |
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Information available on the Grünenthal Group Web Site (see URL below for details).
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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).
The first participant was enrolled on 26 August 2017.
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| ID | Title | Description |
|---|---|---|
| FG000 | Tramadol/Diclofenac 50/50 | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Oct 19, 2017 | Apr 12, 2019 |
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This study used double-blind and double-dummy methods to guarantee the blinding of all personnel involved in the study. Participants, investigators, and all persons involved in the conduct, data management, and analysis of the study were fully blinded to the participant's treatment.
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| Tramadol/Diclofenac 25/25 | Drug | 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. |
|
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| Tramadol 50 | Drug | 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. |
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| Diclofenac 50 | Drug | 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. |
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| Up to 6 hours after first dose |
| Total Pain Relief at 8 Hours Post-dose (TOTPAR8) | 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. | Up to 8 hours after first dose |
| Summed Pain Intensity Difference (SPID) at 4, 6, 8, and 24 Hours Post-dose | 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]). | Baseline; up to 24 hours after first dose |
| Time to Achieve a 50 Percent Reduction in Baseline Pain (Pain at Least Half Gone) | 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. | Up to 24 hours after first dose |
| Time to Onset of First Perceptible Pain Relief | 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. | Up to 8 hours after first dose |
| Time to Onset of Meaningful Pain Relief | Participants used a second stopwatch to document the time between first IMP dose and when they felt their pain relief was meaningful to them. | Up to 8 hours after first dose |
| Time to Intake of First Rescue Medication Dose | The time from first IMP dose to first dose of rescue medication (ibuprofen or ketorolac), if needed, within 24 hours post-dose was calculated. | First dose to 24 hours after first dose |
| Subject's Global Evaluation of the Treatment | Participants documented their overall impression of the analgesic efficacy of the IMPs on a 5-point Likert scale from Excellent (4) to Poor (0). | 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 |
| Incidence and Type of Adverse Events | 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. | Day 1 to Day 14 |
| Monterrey |
| Nuevo León |
| CP 64000 |
| Mexico |
| Private Clinic | Monterrey | Nuevo León | CP 64718 | Mexico |
| Private Clinic | Aguascalientes | CP 20230 | Mexico |
| Private Clinic | Chihuahua City | CP 31203 | Mexico |
| Private Clinic | León | CP 37160 | Mexico |
| Private Clinic | Puebla City | CP 72160 | Mexico |
| University | San Luis Potosí City | CP 78290 | Mexico |
| FG001 | Tramadol/Diclofenac 25/25 | 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. |
| FG002 | Tramadol 50 | 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. |
| FG003 | Diclofenac 50 | 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. |
| Safety Set |
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| COMPLETED |
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| NOT COMPLETED |
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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)
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| ID | Title | Description |
|---|---|---|
| BG000 | Tramadol/Diclofenac 50/50 | 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. |
| BG001 | Tramadol/Diclofenac 25/25 | 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. |
| BG002 | Tramadol 50 | 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. |
| BG003 | Diclofenac 50 | 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. |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Mean | Full Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Body mass index (BMI) | Mean | Standard Deviation | kg/m^2 |
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| Baseline pain intensity categorized | 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. | Count of Participants | Participants |
| ||||||||||
| Baseline pain intensity 11-point NRS | 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. | One participant (Tramadol/Diclofenac 25/25) from the Safety Set had no efficacy assessments and was not included in the Full Analysis Set. | Mean | Standard Deviation | units on a scale |
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| Number of molars extracted | Count of Participants | Participants |
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| Duration of surgery, minutes | Mean | Standard Deviation | minutes |
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| Lidocaine used during surgery, mg | Mean | Standard Deviation | mg |
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| End of surgery to first dose of IMP, hours | Mean | Standard Deviation | hours |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Pain Relief Expressed as Total Pain Relief (TOTPAR) Over the 4 Hours Post-dose Period (TOTPAR4) | 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. | Full Analysis Set | Posted | Least Squares Mean | 95% Confidence Interval | units on a scale | Up to 4 hours after first dose |
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| Secondary | Total Pain Relief at 6 Hours Post-dose (TOTPAR6) | 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. | Full Analysis Set | Posted | Least Squares Mean | 95% Confidence Interval | units on a scale | Up to 6 hours after first dose |
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| Secondary | Total Pain Relief at 8 Hours Post-dose (TOTPAR8) | 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. | Full Analysis Set | Posted | Least Squares Mean | 95% Confidence Interval | units on a scale | Up to 8 hours after first dose |
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| Secondary | Summed Pain Intensity Difference (SPID) at 4, 6, 8, and 24 Hours Post-dose | 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]). | Full Analysis Set | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline; up to 24 hours after first dose |
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| Secondary | Time to Achieve a 50 Percent Reduction in Baseline Pain (Pain at Least Half Gone) | 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. | Full Analysis Set | Posted | Mean | Standard Deviation | hours | Up to 24 hours after first dose |
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| Secondary | Time to Onset of First Perceptible Pain Relief | 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. | Full Analysis Set | Posted | Mean | Standard Deviation | hours | Up to 8 hours after first dose |
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| Secondary | Time to Onset of Meaningful Pain Relief | Participants used a second stopwatch to document the time between first IMP dose and when they felt their pain relief was meaningful to them. | Full Analysis Set | Posted | Mean | Standard Deviation | hours | Up to 8 hours after first dose |
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| Secondary | Time to Intake of First Rescue Medication Dose | The time from first IMP dose to first dose of rescue medication (ibuprofen or ketorolac), if needed, within 24 hours post-dose was calculated. | Full Analysis Set | Posted | Mean | Standard Deviation | hours | First dose to 24 hours after first dose |
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| Secondary | Subject's Global Evaluation of the Treatment | Participants documented their overall impression of the analgesic efficacy of the IMPs on a 5-point Likert scale from Excellent (4) to Poor (0). | Full Analysis Set | Posted | Count of Participants | Participants | 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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| Secondary | Incidence and Type of Adverse Events | 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. | Safety Set | Posted | Number | participants | Day 1 to Day 14 |
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Day 1 to Day 14
Sites were instructed not to report dental pain as an AE until 24 hours after the first dose of IMP.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Tramadol/Diclofenac 50/50 | 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. | 0 | 208 | 0 | 208 | 96 | 208 |
| EG001 | Tramadol/Diclofenac 25/25 | 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. | 0 | 205 | 1 | 205 | 62 | 205 |
| EG002 | Tramadol 50 | 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. | 0 | 206 | 0 | 206 | 105 | 206 |
| EG003 | Diclofenac 50 | 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. | 0 | 207 | 0 | 207 | 48 | 207 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Seizure | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Palpitations | Cardiac disorders | MedDRA 19.0 | Systematic Assessment |
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| Ear pain | Ear and labyrinth disorders | MedDRA 19.0 | Systematic Assessment |
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| Tinnitus | Ear and labyrinth disorders | MedDRA 19.0 | Systematic Assessment |
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| Vertigo | Ear and labyrinth disorders | MedDRA 19.0 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Dysphagia | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Gastritis | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Gingival pain | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Hypoaesthesia oral | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Oral pain | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Chills | General disorders | MedDRA 19.0 | Systematic Assessment |
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| Face oedema | General disorders | MedDRA 19.0 | Systematic Assessment |
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| Inflammation | General disorders | MedDRA 19.0 | Systematic Assessment |
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| Malaise | General disorders | MedDRA 19.0 | Systematic Assessment |
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| Pain | General disorders | MedDRA 19.0 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 19.0 | Systematic Assessment |
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| Alveolar osteitis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
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| Gingivitis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
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| Infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
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| Post procedural infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
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| Tonsillitis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Tooth abscess | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA 19.0 | Systematic Assessment |
| |
| Post procedural contusion | Injury, poisoning and procedural complications | MedDRA 19.0 | Systematic Assessment |
| |
| Post procedural haemorrhage | Injury, poisoning and procedural complications | MedDRA 19.0 | Systematic Assessment |
| |
| Post procedural inflammation | Injury, poisoning and procedural complications | MedDRA 19.0 | Systematic Assessment |
| |
| Post procedural swelling | Injury, poisoning and procedural complications | MedDRA 19.0 | Systematic Assessment |
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| Procedural pain | Injury, poisoning and procedural complications | MedDRA 19.0 | Systematic Assessment |
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| Wound dehiscence | Injury, poisoning and procedural complications | MedDRA 19.0 | Systematic Assessment |
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| Pain in jaw | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Temporomandibular joint syndrome | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Trismus | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
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| Dysgeusia | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
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| Hypoaesthesia | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
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| Paraesthesia | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
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| Syncope | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
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| Tremor | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA 19.0 | Systematic Assessment |
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| Hallucination | Psychiatric disorders | MedDRA 19.0 | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Haematoma | Vascular disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Orthostatic hypotension | Vascular disorders | MedDRA 19.0 | Systematic Assessment |
|
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Trial Helpdesk | Grünenthal GmbH | +49 241 569 | 3223 | clinical-trials@grunenthal.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 19, 2018 | Apr 15, 2019 | SAP_001.pdf |
| ID | Term |
|---|---|
| D059787 | Acute Pain |
| D014098 | Toothache |
| ID | Term |
|---|---|
| D010146 | Pain |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D014076 | Tooth Diseases |
| D009057 | Stomatognathic Diseases |
| D005157 | Facial Pain |
Not provided
Not provided
| ID | Term |
|---|---|
| D014147 | Tramadol |
| D004008 | Diclofenac |
| ID | Term |
|---|---|
| D003511 | Cyclohexanols |
| D000441 | Hexanols |
| D005233 | Fatty Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D004123 | Dimethylamines |
| D008744 | Methylamines |
| D000588 | Amines |
| D008055 | Lipids |
| D010648 | Phenylacetates |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
Not provided
Not provided
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| Bonferroni-Holm procedure used for determining the statistical significance of the results. | ANCOVA | ANCOVA model with treatment, baseline pain intensity, and site as covariates. | <0.0001 | Mean Difference (Final Values) | -4.5 | 2-Sided | 95 | -5.2 | -3.8 | LS means, 95% CIs, and pairwise CIs and p-values comparing the combination treatment arm to the monotherapy arm. | Superiority |
| Bonferroni-Holm procedure used for determining the statistical significance of the results. The planned test was a test for non-inferiority. | ANCOVA | ANCOVA model with treatment, baseline pain intensity, and site as covariates. | <0.0001 | Mean Difference (Final Values) | -3.2 | 2-Sided | 95 | -3.9 | -2.5 | LS means, 95% CIs, and pairwise CIs and p-values comparing the combination treatment arm to the monotherapy arm. | Superiority |
| Bonferroni-Holm procedure used for determining the statistical significance of the results. The planned test was a test for non-inferiority. | ANCOVA | ANCOVA model with treatment, baseline pain intensity, and site as covariates. | <0.0001 | Mean Difference (Final Values) | -2.8 | 2-Sided | 95 | -3.5 | -2.1 | LS means, 95% CIs, and pairwise CIs and p-values comparing the combination treatment arm to the monotherapy arm. | Superiority |
| OG002 | Tramadol 50 | 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. |
| OG003 | Diclofenac 50 | 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. |
|
|
| OG002 | Tramadol 50 | 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. |
| OG003 | Diclofenac 50 | 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. |
|
|
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. |
| OG002 | Tramadol 50 | 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. |
| OG003 | Diclofenac 50 | 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. |
|
|
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. |
| OG003 | Diclofenac 50 | 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. |
|
|
| OG003 | Diclofenac 50 | 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. |
|
|
| OG003 | Diclofenac 50 | 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. |
|
|
| OG003 | Diclofenac 50 | 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. |
|
|
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. |
| OG003 | Diclofenac 50 | 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. |
|
|
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. |
| OG003 | Diclofenac 50 | 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. |
|
|
| Fair |
|
| Good |
|
| Very Good |
|
| Excellent |
|
| Title | Measurements |
|---|---|
| Poor |
|
| Fair |
|
| Good |
|
| Very Good |
|
| Excellent |
|