NCT04018612

A Study of Acetaminophen for Post Surgical Dental Pain

Completed Phase 2 Results posted Last updated 29 March 2022

What this trial tests

Phase 2 trial testing Acetaminophen in Pain, Postoperative in 110 participants. Completed in 15 August 2019.

Timeline

25 April 2019

Primary endpoint
26 July 2019

15 August 2019

Quick facts

Lead sponsor	Nevakar, Inc.
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	110
Start date	25 April 2019
Primary completion	26 July 2019
Estimated completion	15 August 2019
Sites	1 location across United States

Drugs / interventions tested

• Acetaminophen (Paracetamol) — full drug profile →
• Placebo

Conditions studied

• Pain, Postoperative — all drugs for Pain, Postoperative →
• Dental Pain — all drugs for Dental Pain →

Sponsor

Nevakar, Inc. — full company profile →

Who can join

Adults 17 to 55, any sex, with Pain, Postoperative or Dental Pain. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Sum of Pain Intensity Difference From 0 to 24 Hours (SPID24) Based on the 11 Point Numeric Pain Rating Scale Primary · Baseline (0.0) and 0.5, 0.75, 1, 1.25, 1.75, 2.25 3.25, 4.25, 5.25, 6.25, 7.25, 8.25, 9.25, 10.25, 11.25, 12.25 (± 5 min) and 14.25, 16.25, 18.25, 20.25, 22.25, and 24.25 (± 10 min) hours

Pain Intensity was self-reported over 24 hours, using a pain rating of 0-10 on the Numerical Rating Scale (NRS), with score between 0-10 (0= no pain; 10 = worst imaginable pain). Time weighted sum of pain intensity difference from 0 to 24 hours was reported. Pain Intensity (PI-NPRS) was collected at initiation of Dose 1 (T0) and post dose 0.5, 0.75, 1, 1.25, 1.75, 2.25 3.25, 4.25, 5.25, 6.25, 7.25, 8.25, 9.25, 10.25, 11.25, 12.25 (± 5 min) and 14.25, 16.25, 18.25, 20.25, 22.25, and 24.25 (± 10 min). SPID24 was include all nominal timepoints from T0 to T24.25 hours. SPID is calculated as Σ\[T(i

Group	Value	95% CI
High Dose APAP	-96.80	± 6.369
Low Dose APAP	-100.69	± 6.333
Placebo	-74.96	± 9.055

Sum of Pain Relief From 0 to 24 Hours (TOTPAR24) Based on a 5-point Likert Scale. Primary · Baseline (0.0) and 0.5, 0.75, 1, 1.25, 1.75, 2.25 3.25, 4.25, 5.25, 6.25, 7.25, 8.25, 9.25, 10.25, 11.25, 12.25 (± 5 min) and 14.25, 16.25, 18.25, 20.25, 22.25, and 24.25 (± 10 min) hours

Pain Relief Rating (PR) was scored on a 5-point scale (0=no-, 1=a little-, 2=some-, 3=a lot of-, and 4=complete- PR). PR was collected at initiation of Dose 1 (T0) and post dose 0.5, 0.75, 1, 1.25, 1.75, 2.25 3.25, 4.25, 5.25, 6.25, 7.25, 8.25, 9.25, 10.25, 11.25, 12.25 (± 5 min) and 14.25, 16.25, 18.25, 20.25, 22.25, and 24.25 (± 10 min) hours. TOTPAR24 is calculated as Sum (\[T(i) - T(i-1)\] x (PR(i-1) + PR(i)) / 2), where T(0)=0, T(i) is the actual time, and PR(i) is the pain relief score at time i. and calculated as Σ\[T(i) -T(i-1)\] x \[(PR(i-1) + PR(i))/2\], where T(0)=0, T(i) is the sch

Group	Value	95% CI
High Dose APAP	55.82	± 3.024
Low Dose APAP	55.24	± 3.007
Placebo	43.11	± 4.300

Time to Perceptible Pain Relief Confirmed (FPR-C) After Dose 1 Administration Stratified by Baseline Pain Score of Moderate or Severe for the 3 Treatment Groups Secondary · 0 to 24 Hours

Upon initiation of the infusion of Dose 1, the participants were given stopwatch #1 and asked to press the stopwatch when they first perceived any pain relief (first perceptible pain relief \[FPR\]) ; a record of the time was noted in the participant record. If a participant does not record perceptible pain relief and prematurely discontinued from the study prior to 24 hours, then the participant was censored at time of drop out. If a participant does not record perceptible pain relief prior to taking rescue medication, the participant was censored at 24 hours

Median time to FPR-C (hours)- for moderate baseline categorical pain intensity score

Group	Value	95% CI
High Dose APAP	0.215	0.080 – 1.000
Low Dose APAP	0.160	0.030 – 0.430
Placebo	0.595	0.060 – 24.00

Median time to FPR-C (hours)- for severe baseline categorical pain intensity score

Group	Value	95% CI
High Dose APAP	0.160	0.030 – 24.00
Low Dose APAP	0.220	0.060 – 24.00
Placebo	0.890	0.040 – 24.00

Time to Meaningful Perceptible Relief (MPR) Measure Stratified by Baseline Pain Score of Moderate or Severe for the 3 Treatment Groups Secondary · 0 to 24 Hours

Upon initiation of the infusion of Dose 1, the participants were given a second stopwatch and asked to press the stopwatch if and when they feel any meaningful perceptible relief; a record of the time was noted in the participant record. If a participant does not record perceptible pain relief and was prematurely discontinued from the study prior to 24 hours, then the participant was censored at time of drop out. If a participant does not record perceptible pain relief prior to taking rescue medication, the participant was censored at 24 hours.

Median time to MPR (hours)- for moderate baseline categorical pain intensity score

Group	Value	95% CI
High Dose APAP	0.660	0.250 – 24.00
Low Dose APAP	0.310	0.110 – 24.00
Placebo	NA	NA – NA

Median time to MPR (hours)- for severe baseline categorical pain intensity score

Group	Value	95% CI
High Dose APAP	0.680	0.120 – 24.00
Low Dose APAP	0.870	0.150 – 24.00
Placebo	NA	NA – NA

Patient Global Evaluation of the Study Medication Secondary · 0 to 24 Hours

Patients Global Evaluation was assessed on a scale of 0 (Poor), 1 (Fair), 2 (Good), 3 (Very Good) and 4 (Excellent) at 24.25 hours post-dose 1 or at participant withdrawal (if applicable), whichever occurred first. Least squares mean of the score are reported.

Group	Value	95% CI
High Dose APAP	2.8	± 0.16
Low Dose APAP	2.7	± 0.15
Placebo	2.3	± 0.22

Pain Intensity Difference Rating (PID) at Different Timepoints After Dose 1 Administration Secondary · Baseline (0.0) and 0.5, 0.75, 1, 1.25, 1.75, 2.25 3.25, 4.25, 5.25, 6.25, 7.25, 8.25, 9.25, 10.25, 11.25, 12.25 (± 5 min) and 14.25, 16.25, 18.25, 20.25, 22.25, and 24.25 hours (± 10 min)

Pain Intensity was self-reported over 24 hours, using a pain rating of 0-10 on the Numerical Rating Scale (NRS), with score between 0-10 (0= no pain; 10 = worst imaginable pain). Pain intensity differences were calculated with respect to Baseline at each time point after Dose 1 administration. A baseline assessment was defined as the last non-missing result prior to administration of the first dose of study medication

0.5

Group	Value	95% CI
High Dose APAP	-2.5	± 1.65
Low Dose APAP	-3.1	± 2.01
Placebo	-0.7	± 1.28

0.75

Group	Value	95% CI
High Dose APAP	-3.3	± 1.88
Low Dose APAP	-3.5	± 2.10
Placebo	-0.8	± 1.40

1

Group	Value	95% CI
High Dose APAP	-3.7	± 1.89
Low Dose APAP	-3.8	± 2.12
Placebo	-0.8	± 1.44

1.25

Group	Value	95% CI
High Dose APAP	-3.9	± 2.02
Low Dose APAP	-4.0	± 2.29
Placebo	-0.7	± 1.52

1.75

Group	Value	95% CI
High Dose APAP	-3.9	± 1.97
Low Dose APAP	-3.7	± 2.45
Placebo	-0.7	± 1.59

2.25

Group	Value	95% CI
High Dose APAP	-3.8	± 2.16
Low Dose APAP	-3.6	± 2.44
Placebo	-0.7	± 1.67

3.25

Group	Value	95% CI
High Dose APAP	-3.4	± 2.32
Low Dose APAP	-3.0	± 2.39
Placebo	-0.9	± 1.95

4.25

Group	Value	95% CI
High Dose APAP	-3.4	± 2.40
Low Dose APAP	-2.9	± 2.32
Placebo	-0.9	± 1.97

Pain Intensity Rating at Different Timepoints After Dose 1 Administration Secondary · 0 to 24 hours

Pain intensity is reported using the 11-point Numerical Rating Scale (NRS), with score between 0-10 (0= no pain; 10 = worst imaginable pain).

0.5

Group	Value	95% CI
High Dose APAP	4.8	± 1.83
Low Dose APAP	4.4	± 1.97
Placebo	6.1	± 1.42

0.75

Group	Value	95% CI
High Dose APAP	4.0	± 2.12
Low Dose APAP	4.0	± 1.98
Placebo	6.0	± 1.70

1

Group	Value	95% CI
High Dose APAP	3.6	± 1.98
Low Dose APAP	3.7	± 2.01
Placebo	6.0	± 1.68

1.25

Group	Value	95% CI
High Dose APAP	3.4	± 2.16
Low Dose APAP	3.5	± 2.14
Placebo	6.2	± 1.89

1.75

Group	Value	95% CI
High Dose APAP	3.5	± 2.24
Low Dose APAP	3.8	± 2.33
Placebo	6.2	± 1.94

2.25

Group	Value	95% CI
High Dose APAP	3.6	± 2.40
Low Dose APAP	3.9	± 2.39
Placebo	6.2	± 1.97

3.25

Group	Value	95% CI
High Dose APAP	3.9	± 2.53
Low Dose APAP	4.5	± 2.48
Placebo	6.0	± 2.17

4.25

Group	Value	95% CI
High Dose APAP	4.0	± 2.58
Low Dose APAP	4.6	± 2.33
Placebo	6.0	± 2.21

Pain Relief (PR) Ratings at Each Observation Time After Dose 1 Administration Secondary · 0 to 24 hours

Pain Relief is reported on a 5-Point Categorical Pain Relief Assessment scale: 0 = No Pain Relief, 1 = A Little Pain Relief, 2 = Some Pain Relief, 3 = A Lot of Pain Relief, 4 = Complete Pain Relief.

0.5

Group	Value	95% CI
High Dose APAP	1.7	± 0.95
Low Dose APAP	1.8	± 0.94
Placebo	0.6	± 0.85

0.75

Group	Value	95% CI
High Dose APAP	2.0	± 1.02
Low Dose APAP	2.0	± 0.98
Placebo	0.6	± 0.85

1

Group	Value	95% CI
High Dose APAP	2.1	± 0.93
Low Dose APAP	2.2	± 0.96
Placebo	0.6	± 0.85

1.25

Group	Value	95% CI
High Dose APAP	2.3	± 0.97
Low Dose APAP	2.2	± 0.99
Placebo	0.6	± 0.85

1.75

Group	Value	95% CI
High Dose APAP	2.3	± 0.97
Low Dose APAP	2.0	± 1.07
Placebo	0.6	± 0.90

2.25

Group	Value	95% CI
High Dose APAP	2.2	± 1.09
Low Dose APAP	2.0	± 1.05
Placebo	0.6	± 0.90

3.25

Group	Value	95% CI
High Dose APAP	2.0	± 1.18
Low Dose APAP	1.7	± 1.12
Placebo	0.8	± 1.15

4.25

Group	Value	95% CI
High Dose APAP	2.0	± 1.21
Low Dose APAP	1.6	± 1.12
Placebo	0.7	± 1.08

Time to Treatment Failure Secondary · 0 to 24 Hours

Time to treatment failure is defined as time to first dose of rescue medication after Dose 1 or withdrawal from the study for any reason. If a participant does not take rescue medication or withdraw from the study prior to 24 hours, the participant was censored at 24 hours

Median time to treatment failure- for moderate baseline categorical pain intensity score

Group	Value	95% CI
High Dose APAP	NA	NA – NA
Low Dose APAP	NA	NA – NA
Placebo	3.680	1.100 – 24.00

Median time to treatment failure for severe baseline categorical pain intensity score

Group	Value	95% CI
High Dose APAP	NA	NA – NA
Low Dose APAP	NA	NA – NA
Placebo	1.335	1.030 – 24.00

Mean Change From Baseline to 24 Hours in Vital Signs (Systolic Blood Pressure) Secondary · 0 to 24 hours

Change from Baseline in systolic blood pressure is the value at 24 hours minus value at Baseline. Baseline was defined as the last non-missing result prior to administration of the first dose of study drug. Systolic blood pressure is obtained at screening, prior to surgery and at Hours 4, 8, 12, 16, 20 and 24 following initiation of dose (±10 min).

Group	Value	95% CI
High Dose APAP	1.6	± 10.78
Low Dose APAP	1.0	± 11.39
Placebo	9.2	± 10.99

Mean Change From Baseline to 24 Hours in Vital Signs (Diastolic Blood Pressure) Secondary · 0 to 24 hours

Change from Baseline in diastolic blood pressure is the value at 24 hours minus value at Baseline. Baseline was defined as the last non-missing result prior to administration of the first dose of study drug. Diastolic blood pressure is obtained at screening, prior to surgery and at Hours 4, 8, 12, 16, 20 and 24 following initiation of dose (±10 min)

Group	Value	95% CI
High Dose APAP	-0.2	± 8.82
Low Dose APAP	2.3	± 9.56
Placebo	5.2	± 11.08

Mean Change From Baseline to 24 Hours in Vital Signs (Temperature) Secondary · 0 to 24 hours

Change from Baseline in temperature is the value at 24 hours minus value at Baseline. Baseline was defined as the last non-missing result prior to administration of the first dose of study drug. Temperature is obtained at screening, prior to surgery and at Hours 4, 8, 12, 16, 20 and 24 following initiation of dose (±10 min)

Group	Value	95% CI
High Dose APAP	0.12	± 0.336
Low Dose APAP	0.21	± 0.275
Placebo	0.06	± 0.347

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 7 days (± 2 days). Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

High Dose APAP

Serious: 0/44 (0%)

Deaths: 0/44

Low Dose APAP

Serious: 0/44 (0%)

Deaths: 0/44

Placebo

Serious: 0/22 (0%)

Deaths: 0/22

Other adverse events (13 terms — click to expand)

Reaction	System	High Dose APAP	Low Dose APAP	Placebo
Hyperbilirubinaemia	Hepatobiliary disorders	—	—	—
Tachycardia	Cardiac disorders	—	—	—
Hypoaesthesia oral	Gastrointestinal disorders	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Infusion site extravasation	General disorders	—	—	—
Infusion site haematoma	General disorders	—	—	—
Pyrexia	General disorders	—	—	—
Postoperative wound infection	Infections and infestations	—	—	—
Arthropod bite	Injury, poisoning and procedural complications	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—
Dizziness	Nervous system disorders	—	—	—
Headache	Nervous system disorders	—	—	—
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	—	—	—

Data from ClinicalTrials.gov NCT04018612 adverse events section.

Sponsor's own description

To assess the safety, tolerability, analgesic, efficacy and pharmacokinetics of high dose acetaminophen relative to placebo and low dose acetaminophen relative to placebo over a 24 hour period in patient experiencing moderate to severe pain following the surgical removal of third molar.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.