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Caffeine

Phase 3

Postoperative Dental Pain | Small molecule | Pain |Bayer AG|Last Updated: Mar 25, 2025

Success Probability

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLED
Total Trials1
Total Enrollment541

FDA Designations

No designations recorded

Clinical trial landscape

Caffeine · 2 trials · 2 indications

Phase 3 1Phase 2 1
NCT05485805A Study to Learn How Well a Single Dose of the Study Treatment Naproxen Sodium and Caffeine Combined in One Tablet (Fixed-dose Combination) Works to Relieve Pain After Dental Surgeries Compared to the Single Ingredients and to PlaceboPostoperative Dental Pain
COMPLETED541 Analytics
PHASE3COMPLETED
A Study to Learn How Well a Single Dose of the Study Treatment Naproxen Sodium and Caffeine Combined in One Tablet (Fixed-dose Combination) Works to Relieve Pain After Dental Surgeries Compared to the Single Ingredients and to Placebo
Postoperative Dental PainUnlock trial analytics

Study Endpoints

Primary Endpoints

Sum of Pain Intensity Difference (SPID) Over 8 Hours Post-dose
Up to 8 hours post-dose

Pain intensity scale is the Numerical Rating Scale measured from 0 to 10, where 0 indicates no pain and 10 means the wors pain imaginable. Pain intensity Difference (PID) is calculated by subtracting the pain intensity at different time points in the post-dose time point from the pain intensity at baseline. The summed pain intensity difference (SPID) is to be calculated by multiplying the PID score at each post dose time point by the duration (in hours) since the preceding time point and then summing the values over the relevant time period. For SPID (0-8), eight PIDs are summed up, which is minimally 0, if there is no pain relief or maximally 80, if there is very strong pain and significant pain relief.

Sum of Pain Intensity Difference (SPID) Over 8 Hours
Up to 8 hours post dose

Pain intensity is measured using Numerical Rating Scale (from 0 to 10: 0 = no pain, 10 = worst possible pain). For each post dose time point, pain intensity difference (PID) is derived by subtracting the pain intensity at the post dose time point from the baseline intensity score (baseline score - post-baseline score). A positive difference is indicative of improvement. Sum of Pain Intensity Differences (SPIDs) was calculated by multiplying the PID score at each post-dose time point by the duration (in hours) since the preceding time point and then summing these values over the specific time period. SPID over 8 hours ranges from -80 to 80. A higher value indicates a better pain reduction.

Secondary Endpoints

Sum of Pain Intensity Differences From 0 to 2, 4, 6, 12 and 24 Hours Post-dose
from 0 to 2, 4, 6, 12 and 24 hours post-dose
Total Pain Relief (TOTPAR) From 0 to 2, 4, 6, 8, 12 and 24 Hours Post-dose
up to 24 hours post-dose
Time to First Use of Rescue Medication
Up to 24 hours post-dose
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Study Design & Arms

AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Naproxen sodium/caffeine - Dose 1EXPERIMENTALParticipants will receive a single dose of one tablet of naproxen sodium/caffeine plus one tablet of placebo after extraction of third molars.
Naproxen sodium/caffeine - Dose 2EXPERIMENTALParticipants will receive a single dose of two tablets of naproxen sodium/caffeine after extraction of third molars.
Naproxen sodiumEXPERIMENTALParticipants will receive a single dose of one tablet of naproxen sodium plus one tablet of placebo after extraction of third molars.
CaffeineEXPERIMENTALParticipants will receive a single dose of two tablets of caffeine after extraction of third molars.
PlaceboPLACEBO_COMPARATORParticipants will receive a single dose of two tablets of matching placebo after extraction of third molars.
Naproxen sodium/caffeine - Dose 3EXPERIMENTALParticipants received a single dose of one tablet of naproxen sodium/caffeine (low dose/ medium low dose) plus one tablet of placebo after extraction of third molars
Naproxen sodium/caffeine - Dose 4EXPERIMENTALParticipants received a single dose of one tablet of naproxen sodium/caffeine (low dose/ low dose) plus one tablet of placebo after extraction of third molars

Interventions

NameTypeDescription
Naproxen sodium and caffeine (BAY2880376)DRUGTablet, oral use, single dose
Naproxen sodium (Aleve)DRUGTablet, oral use, single dose
CaffeineDRUGTablet, oral use, single dose
PlaceboDRUGTablet, oral use, single dose
Naproxen sodium/Caffeine (BAY2880376)DRUGTablet, oral, single dose
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Eligibility Criteria

Age Range16 Years to N/A
SexALL
Healthy VolunteersYes
Study Sites1

Inclusion Criteria: * Healthy, ambulatory, male or female volunteers 16 years of age or older; * Body mass index (BMI) 18.5 to 35.0 kg/m\^2 inclusive as measured by the National Institutes of Health (NIH) BMI Calculator; * Participants will undergo surgical extraction of three or four third molars,...

Countries:United States
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Frequently asked questions about Caffeine

What is Caffeine used for in postoperative dental pain?

Caffeine is being studied as part of a fixed-dose combination tablet with naproxen sodium for the relief of moderate to severe pain after dental surgeries, including wisdom tooth removal. It is being evaluated in clinical trials for postoperative dental pain and postoperative pain.

Who makes Caffeine?

Caffeine is being developed by Bayer AG, a pharmaceutical company traded on the OTC market under the ticker BAYRY. The company is conducting clinical trials to evaluate caffeine in combination with naproxen sodium for postoperative pain relief.

What phase is Caffeine in?

Caffeine is in clinical development, with a completed Phase 2 trial and a completed Phase 3 trial. It is an investigational combination product and has not been approved for the studied indications based on the available data.

What does Caffeine target?

Caffeine is a small molecule that acts as a central nervous system stimulant. In the studied combination, it is used as an adjuvant to enhance the analgesic effect of naproxen sodium, a nonsteroidal anti-inflammatory drug, for postoperative pain relief.

What clinical trials is Caffeine in?

Caffeine has been studied in two completed clinical trials: NCT04132336, a Phase 2 dose-finding study in patients with moderate to severe pain after wisdom tooth removal, and NCT05485805, a Phase 3 study comparing a fixed-dose combination of naproxen sodium and caffeine to its single ingredients and placebo after dental surgeries.

Is Caffeine the same as a fixed-dose combination with naproxen sodium?

Caffeine is being studied as part of a fixed-dose combination tablet with naproxen sodium. The combination is being evaluated for postoperative dental pain, with the caffeine component intended to enhance pain relief compared to naproxen sodium alone.