Dental Pain
Conditions
Brief summary
The present study is proposed to evaluate the efficacy and safety of single doses of Diclofenac HPBCD subcutaneous (s.c.) (25 mg/1 ml and 50 mg/1 ml) in the treatment of acute moderate-to-severe pain after dental impaction surgery.
Interventions
DRUGDiclofenac HPBCD
1 single injection at day of dental surgical extraction
OTHERPlacebo s.c.
1 single injection at day of dental surgical extraction
Sponsors
IBSA Institut Biochimique SA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Patients undergoing surgical extraction of a single fully or partially impacted mandibular 3rd molar requiring bone removal. * Patients experiencing moderate to severe post-operative pain within 6 hours from end of surgery. * Pre-operative laboratory tests in the reference ranges or without clinically significant abnormalities as judged by the Investigator.
Exclusion criteria
* Surgery performed under general anaesthesia, or sedation. * Complications occurring during the surgical procedure or in the period before randomisation as judged by the investigator. * Acute local or systemic infection at the time of surgery that could confound the post-surgical evaluation. * Patients with clinical signs of gastritis, gastro-duodenal ulcer, GI bleeding. Other GI disturbances or disease that in the opinion of the investigator could be negatively affected by the administration of NSAIDs. * Clinical signs or history of coagulation disorders that could be negatively affected by NSAIDs administration. * Hepatic or renal impairment. * Patients with significant cardiac impairment, history of cerebrovascular disease, history or peripheral arterial disease, uncontrolled hypertension. * Hypersensitivity to diclofenac or other NSAIDs or to one of the study medication components. * Patients under chronic treatment with topical or systemic analgesics/NSAIDs. * Patients under treatment with any medication that may affect the treatment efficacy evaluation. * Patients under treatment with any medication whose concomitant use may be susceptible to interactions with diclofenac or may affect safety.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain Intensity Difference (PID) on a 0-100 VAS | at 1.5 hours after treatment administration | Pain intensity difference (PID) was derived by subtracting each pain intensity score (PI) from the baseline PI score (t0), where PI was assigned by the patient on a 0-100 mm VAS (from 0 = no pain to 100 = worst pain imaginable). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PID | at 15 minutes post-dose. | Pain intensity difference (PID) was derived by subtracting each pain intensity score (PI) from the baseline PI score (t0), where PI was assigned by the patient on a 0-100 mm VAS (from 0 = no pain to 100 = worst pain imaginable). |
Countries
Poland, United Kingdom
Participant flow
Recruitment details
Patients already scheduled for the surgical extraction of a single fully or partially impacted mandibular 3rd molar underwent a screening visit within 30 days from the scheduled date of surgery.
Pre-assignment details
Patients under treatment with other analgesics, Major or minor tranquillizers, Muscle relaxant, Antihistamines, MAO inhibitors or corticosteroids had to undergo a wash out period prior to inclusion in the study.
Participants by arm
| Arm | Count |
|---|---|
| Diclofenac HPBCD s.c. 25mg/ml Diclofenac HPBCD : 1 single injection at day of dental surgical extraction | 77 |
| Diclofenac HPBCD s.c. 50mg/ml Diclofenac HPBCD : 1 single injection at day of dental surgical extraction | 76 |
| Diclofenac HPBCD s.c. 75mg/ml Diclofenac HPBCD : 1 single injection at day of dental surgical extraction | 78 |
| Placebo s.c. (1ml) Placebo s.c. : 1 single injection at day of dental surgical extraction | 75 |
| Total | 306 |
Baseline characteristics
| Characteristic | Placebo s.c. (1ml) | Total | Diclofenac HPBCD s.c. 25mg/ml | Diclofenac HPBCD s.c. 50mg/ml | Diclofenac HPBCD s.c. 75mg/ml |
|---|---|---|---|---|---|
| Age Continuous | 31.9 years STANDARD_DEVIATION 11.3 | 30.56 years STANDARD_DEVIATION 9.79 | 30.7 years STANDARD_DEVIATION 10.3 | 29.5 years STANDARD_DEVIATION 8.68 | 30.2 years STANDARD_DEVIATION 8.76 |
| Sex: Female, Male Female | 44 Participants | 184 Participants | 46 Participants | 48 Participants | 46 Participants |
| Sex: Female, Male Male | 31 Participants | 122 Participants | 31 Participants | 28 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 77 | 3 / 76 | 5 / 78 | 5 / 75 |
| serious Total, serious adverse events | 0 / 77 | 1 / 76 | 0 / 78 | 0 / 75 |
Outcome results
Primary
Pain Intensity Difference (PID) on a 0-100 VAS
Pain intensity difference (PID) was derived by subtracting each pain intensity score (PI) from the baseline PI score (t0), where PI was assigned by the patient on a 0-100 mm VAS (from 0 = no pain to 100 = worst pain imaginable).
Time frame: at 1.5 hours after treatment administration
Population: The reported number of analized participants were included in the ITT which was defined as all randomized patients who received the study medication and with at least one post-baseline efficacy evaluation within 1.5 hours post-dose (primary endpoint);
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Diclofenac HPBCD s.c. 25mg/ml | Pain Intensity Difference (PID) on a 0-100 VAS | 36.5 mm |
| Diclofenac HPBCD s.c. 50mg/ml | Pain Intensity Difference (PID) on a 0-100 VAS | 37.3 mm |
| Diclofenac HPBCD s.c. 75mg/ml | Pain Intensity Difference (PID) on a 0-100 VAS | 37.7 mm |
| Placebo s.c. (1ml) | Pain Intensity Difference (PID) on a 0-100 VAS | 12.3 mm |
Comparison: The sample size calculation was based on a hypothesis of superiority of diclofenac HPBCD s.c. 25mg/ml and 50 mg/ml compared to Placebo with regard to the primary efficacy variable (PID at 1.5 hours following drug administration).~A sample size of 60 in each group had 95% power to detect a difference between diclofenac HPBCD s.c. 25 mg/ml and placebo in means of 15 mm, assuming that the common standard deviation was 22.5 and using a two group t-test with a 0.05 two-sided significance level.p-value: <0.001ANCOVA
p-value: 0.00195% CI: [18.4, 31.7]ANCOVA
Primary
Pain Intensity Difference (PID) on a 0-100 VAS
Pain intensity difference (PID) was derived by subtracting each pain intensity score (PI) from the baseline PI score (t0), where PI was assigned by the patient on a 0-100 mm VAS (from 0 = no pain to 100 = worst pain imaginable).
Time frame: at 1.5 hours after treatment administration
Population: The reported number of analized participants were included in the ITT which was defined as all randomized patients who received the study medication and with at least one post-baseline efficacy evaluation within 1.5 hours post-dose (primary endpoint);
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Diclofenac HPBCD s.c. 25mg/ml | Pain Intensity Difference (PID) on a 0-100 VAS | 36.5 mm |
| Diclofenac HPBCD s.c. 50mg/ml | Pain Intensity Difference (PID) on a 0-100 VAS | 37.3 mm |
| Diclofenac HPBCD s.c. 75mg/ml | Pain Intensity Difference (PID) on a 0-100 VAS | 37.7 mm |
| Placebo s.c. (1ml) | Pain Intensity Difference (PID) on a 0-100 VAS | 12.3 mm |
Comparison: The sample size calculation was based on a hypothesis of superiority of diclofenac HPBCD s.c. 25mg/ml and 50 mg/ml compared to Placebo with regard to the primary efficacy variable (PID at 1.5 hours following drug administration).~A sample size of 60 in each group had 95% power to detect a difference between diclofenac HPBCD s.c. 25 mg/ml and placebo in means of 15 mm, assuming that the common standard deviation was 22.5 and using a two group t-test with a 0.05 two-sided significance level.p-value: <0.00195% CI: [17.6, 30.8]ANCOVA
Comparison: The sample size calculation was based on a hypothesis of superiority of diclofenac HPBCD s.c. 25mg/ml and 50 mg/ml compared to Placebo with regard to the primary efficacy variable (PID at 1.5 hours following drug administration).~A sample size of 60 in each group had 95% power to detect a difference between diclofenac HPBCD s.c. 25 mg/ml and placebo in means of 15 mm, assuming that the common standard deviation was 22.5 and using a two group t-test with a 0.05 two-sided significance level.p-value: <0.00195% CI: [18.4, 31.7]ANCOVA
Secondary
PID
Pain intensity difference (PID) was derived by subtracting each pain intensity score (PI) from the baseline PI score (t0), where PI was assigned by the patient on a 0-100 mm VAS (from 0 = no pain to 100 = worst pain imaginable).
Time frame: at 30 minutes post-dose.
Population: The reported number of analized participants were included in the ITT which was defined as all randomized patients who received the study medication and with at least one post-baseline efficacy evaluation within 1.5 hours post-dose (primary endpoint);
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Diclofenac HPBCD s.c. 25mg/ml | PID | 15.9 mm | Standard Deviation 16.4 |
| Diclofenac HPBCD s.c. 50mg/ml | PID | 18.5 mm | Standard Deviation 19.5 |
| Diclofenac HPBCD s.c. 75mg/ml | PID | 18.6 mm | Standard Deviation 18.9 |
| Placebo s.c. (1ml) | PID | 4.68 mm | Standard Deviation 17.2 |
Secondary
PID
Pain intensity difference (PID) was derived by subtracting each pain intensity score (PI) from the baseline PI score (t0), where PI was assigned by the patient on a 0-100 mm VAS (from 0 = no pain to 100 = worst pain imaginable).
Time frame: at 45 minutes post-dose.
Population: The reported number of analized participants were included in the ITT which was defined as all randomized patients who received the study medication and with at least one post-baseline efficacy evaluation within 1.5 hours post-dose (primary endpoint);
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Diclofenac HPBCD s.c. 25mg/ml | PID | 24.7 mm | Standard Deviation 17.9 |
| Diclofenac HPBCD s.c. 50mg/ml | PID | 27.5 mm | Standard Deviation 22.1 |
| Diclofenac HPBCD s.c. 75mg/ml | PID | 27.8 mm | Standard Deviation 19 |
| Placebo s.c. (1ml) | PID | 9.00 mm | Standard Deviation 20.9 |
Secondary
PID
Pain intensity difference (PID) was derived by subtracting each pain intensity score (PI) from the baseline PI score (t0), where PI was assigned by the patient on a 0-100 mm VAS (from 0 = no pain to 100 = worst pain imaginable).
Time frame: at 60 minutes post-dose.
Population: The reported number of analized participants were included in the ITT which was defined as all randomized patients who received the study medication and with at least one post-baseline efficacy evaluation within 1.5 hours post-dose (primary endpoint);
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Diclofenac HPBCD s.c. 25mg/ml | PID | 30.7 mm | Standard Deviation 18 |
| Diclofenac HPBCD s.c. 50mg/ml | PID | 34.6 mm | Standard Deviation 23 |
| Diclofenac HPBCD s.c. 75mg/ml | PID | 34.6 mm | Standard Deviation 18.7 |
| Placebo s.c. (1ml) | PID | 15.3 mm | Standard Deviation 24 |
Secondary
PID
Pain intensity difference (PID) was derived by subtracting each pain intensity score (PI) from the baseline PI score (t0), where PI was assigned by the patient on a 0-100 mm VAS (from 0 = no pain to 100 = worst pain imaginable).
Time frame: at 90 minutes post-dose.
Population: The reported number of analized participants were included in the ITT which was defined as all randomized patients who received the study medication and with at least one post-baseline efficacy evaluation within 1.5 hours post-dose (primary endpoint);
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Diclofenac HPBCD s.c. 25mg/ml | PID | 36.2 mm | Standard Deviation 19.2 |
| Diclofenac HPBCD s.c. 50mg/ml | PID | 40.1 mm | Standard Deviation 20.8 |
| Diclofenac HPBCD s.c. 75mg/ml | PID | 39.0 mm | Standard Deviation 18.9 |
| Placebo s.c. (1ml) | PID | 18.0 mm | Standard Deviation 26 |
Secondary
PID
Pain intensity difference (PID) was derived by subtracting each pain intensity score (PI) from the baseline PI score (t0), where PI was assigned by the patient on a 0-100 mm VAS (from 0 = no pain to 100 = worst pain imaginable).
Time frame: at 2 hours post-dose.
Population: The reported number of analized participants were included in the ITT which was defined as all randomized patients who received the study medication and with at least one post-baseline efficacy evaluation within 1.5 hours post-dose (primary endpoint);
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Diclofenac HPBCD s.c. 25mg/ml | PID | 38.8 mm | Standard Deviation 19.1 |
| Diclofenac HPBCD s.c. 50mg/ml | PID | 43.9 mm | Standard Deviation 20.4 |
| Diclofenac HPBCD s.c. 75mg/ml | PID | 42.5 mm | Standard Deviation 18.2 |
| Placebo s.c. (1ml) | PID | 26.5 mm | Standard Deviation 25.1 |
Secondary
PID
Pain intensity difference (PID) was derived by subtracting each pain intensity score (PI) from the baseline PI score (t0), where PI was assigned by the patient on a 0-100 mm VAS (from 0 = no pain to 100 = worst pain imaginable).
Time frame: at 3 hours post-dose.
Population: The reported number of analized participants were included in the ITT which was defined as all randomized patients who received the study medication and with at least one post-baseline efficacy evaluation within 1.5 hours post-dose (primary endpoint);
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Diclofenac HPBCD s.c. 25mg/ml | PID | 41.2 mm | Standard Deviation 20 |
| Diclofenac HPBCD s.c. 50mg/ml | PID | 45.5 mm | Standard Deviation 21 |
| Diclofenac HPBCD s.c. 75mg/ml | PID | 45.6 mm | Standard Deviation 19.2 |
| Placebo s.c. (1ml) | PID | 25.3 mm | Standard Deviation 26.8 |
Secondary
PID
Pain intensity difference (PID) was derived by subtracting each pain intensity score (PI) from the baseline PI score (t0), where PI was assigned by the patient on a 0-100 mm VAS (from 0 = no pain to 100 = worst pain imaginable).
Time frame: at 4 hours post-dose.
Population: The reported number of analized participants were included in the ITT which was defined as all randomized patients who received the study medication and with at least one post-baseline efficacy evaluation within 1.5 hours post-dose (primary endpoint);
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Diclofenac HPBCD s.c. 25mg/ml | PID | 38.1 mm | Standard Deviation 21.2 |
| Diclofenac HPBCD s.c. 50mg/ml | PID | 46.3 mm | Standard Deviation 21.8 |
| Diclofenac HPBCD s.c. 75mg/ml | PID | 48.0 mm | Standard Deviation 18.6 |
| Placebo s.c. (1ml) | PID | 29.1 mm | Standard Deviation 26.8 |
Secondary
PID
Pain intensity difference (PID) was derived by subtracting each pain intensity score (PI) from the baseline PI score (t0), where PI was assigned by the patient on a 0-100 mm VAS (from 0 = no pain to 100 = worst pain imaginable).
Time frame: at 5 hours post-dose.
Population: The reported number of analized participants were included in the ITT which was defined as all randomized patients who received the study medication and with at least one post-baseline efficacy evaluation within 1.5 hours post-dose (primary endpoint);
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Diclofenac HPBCD s.c. 25mg/ml | PID | 37.5 mm | Standard Deviation 20.9 |
| Diclofenac HPBCD s.c. 50mg/ml | PID | 42.2 mm | Standard Deviation 23.8 |
| Diclofenac HPBCD s.c. 75mg/ml | PID | 45.6 mm | Standard Deviation 18.3 |
| Placebo s.c. (1ml) | PID | 31.8 mm | Standard Deviation 22 |
Secondary
PID
Pain intensity difference (PID) was derived by subtracting each pain intensity score (PI) from the baseline PI score (t0), where PI was assigned by the patient on a 0-100 mm VAS (from 0 = no pain to 100 = worst pain imaginable).
Time frame: at 6 hours post-dose.
Population: The reported number of analized participants were included in the ITT which was defined as all randomized patients who received the study medication and with at least one post-baseline efficacy evaluation within 1.5 hours post-dose (primary endpoint);
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Diclofenac HPBCD s.c. 25mg/ml | PID | 41.5 mm | Standard Deviation 19.8 |
| Diclofenac HPBCD s.c. 50mg/ml | PID | 40.9 mm | Standard Deviation 23.4 |
| Diclofenac HPBCD s.c. 75mg/ml | PID | 41.7 mm | Standard Deviation 22.4 |
| Placebo s.c. (1ml) | PID | 36.5 mm | Standard Deviation 14.6 |
Secondary
PID
Pain intensity difference (PID) was derived by subtracting each pain intensity score (PI) from the baseline PI score (t0), where PI was assigned by the patient on a 0-100 mm VAS (from 0 = no pain to 100 = worst pain imaginable).
Time frame: at 7 hours post-dose.
Population: The reported number of analized participants were included in the ITT which was defined as all randomized patients who received the study medication and with at least one post-baseline efficacy evaluation within 1.5 hours post-dose (primary endpoint);
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Diclofenac HPBCD s.c. 25mg/ml | PID | 43.2 mm | Standard Deviation 17.9 |
| Diclofenac HPBCD s.c. 50mg/ml | PID | 41.6 mm | Standard Deviation 24.3 |
| Diclofenac HPBCD s.c. 75mg/ml | PID | 43.0 mm | Standard Deviation 19.2 |
| Placebo s.c. (1ml) | PID | 39.1 mm | Standard Deviation 13.5 |
Secondary
PID
Pain intensity difference (PID) was derived by subtracting each pain intensity score (PI) from the baseline PI score (t0), where PI was assigned by the patient on a 0-100 mm VAS (from 0 = no pain to 100 = worst pain imaginable).
Time frame: at 8 hours post-dose.
Population: The reported number of analized participants were included in the ITT which was defined as all randomized patients who received the study medication and with at least one post-baseline efficacy evaluation within 1.5 hours post-dose (primary endpoint);
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Diclofenac HPBCD s.c. 25mg/ml | PID | 45.0 mm | Standard Deviation 15.7 |
| Diclofenac HPBCD s.c. 50mg/ml | PID | 43.8 mm | Standard Deviation 25.2 |
| Diclofenac HPBCD s.c. 75mg/ml | PID | 43.6 mm | Standard Deviation 17.5 |
| Placebo s.c. (1ml) | PID | 37.0 mm | Standard Deviation 14.3 |
Secondary
PID
Pain intensity difference (PID) was derived by subtracting each pain intensity score (PI) from the baseline PI score (t0), where PI was assigned by the patient on a 0-100 mm VAS (from 0 = no pain to 100 = worst pain imaginable).
Time frame: at 15 minutes post-dose.
Population: The reported number of analized participants were included in the ITT which was defined as all randomized patients who received the study medication and with at least one post-baseline efficacy evaluation within 1.5 hours post-dose (primary endpoint);
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Diclofenac HPBCD s.c. 25mg/ml | PID | 8.39 mm | Standard Deviation 14.1 |
| Diclofenac HPBCD s.c. 50mg/ml | PID | 8.28 mm | Standard Deviation 13.7 |
| Diclofenac HPBCD s.c. 75mg/ml | PID | 9.46 mm | Standard Deviation 15.7 |
| Placebo s.c. (1ml) | PID | 1.59 mm | Standard Deviation 11.3 |