Pain
Conditions
Brief summary
This will be a monocentric, single blinded, randomized, single-dose, two-periods, two-sequence, crossover bioequivalence study of two oral formulations in healthy participants under fasting conditions.
Interventions
DRUGMejoral® 500 Tablets
500 mg tablet of paracetamol
DRUGTylenol® Caplets
500 mg tablet of paracetamol
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Understanding of the study procedures, restrictions and willingness to participate as evidenced by voluntary written informed consent * Men and women between 18 to 55 years of age, with good state of health * Participants' body mass index must be between 18.0 and 27.0 * Blood pressure (seated) up to 139 milliliters of mercury (mm/Hg) systolic and up to 89 mm/Hg diastolic, heart rate between 60 and 100 beats per minute and respiratory frequency between 14 and 20 breaths per minute * The laboratory tests: Complete blood count with differential count, Chemical blood of 27 elements, Urinalysis, Non-Reactive Anti-hepatitis B virus (HBV) hepatitis B and Anti-hepatitis C antibodies (HCV) hepatitis C, Non-Reactive Human immunodeficiency virus (HIV) test, Negative Venereal Disease Research Laboratory (VDRL) test with maximum 3 months validity and allowed variation of +/-10% of the normal range * Electrocardiogram (ECG) with no more than three months validity and with no clinically significant findings * Pregnancy test, drug abuse test and alcohol test with negative results at selection visit and approximately 12 h before drug product administration in both study periods
Exclusion criteria
* Participants with some alteration in their vital signs; who fail to comply with the proposed inclusion criteria * Participants with a history of suffering cardiovascular, renal, hepatic, muscle, metabolic, gastrointestinal, neurological problems, endocrine, hematopoietic or any type of anemia, asthma, mental illness or other organic abnormalities. Participants who have had a muscle injury within the 21 days prior to the study * Clinically significant abnormalities in the ECG, dyspepsia, gastritis, esophagitis, gastric or duodenal ulcer; participants who require any drug product other than test product during the course of study * Exposed to inductors or liver enzyme inhibitors or drugs capable of altering urinary pH or any potentially toxic drugs, vitamins, herbal remedies within the 30 days prior to the beginning of the study * Participant hospitalized for any problem during the seven months prior to the study start; received investigational product within 90 days prior to the study * Allergic to any drug product, food or substance, require special diet; positive drug abuse, alcohol, pregnancy test, breast feeding women * Donated or lost 450 milliliter (mL) or more blood within the 60 days prior to the beginning of the study * Participants who have not been recorded in the the Federal Commission for the Protection against Sanitary Risks (COFEPRIS) page * Ingested alcohol, carbonated beverage, products containing xanthines, charcoal grilled nourishment, grapefruit or orange or who have smoked 24 h prior to the beginning of both study periods * Subordination relationship between participants and investigators, an employee of the sponsor or the study site or members of their immediate family
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve From Time Zero to Last Sampling Time [AUC(0-t)] | 2 days | AUC(0-t) of paracetamol was calculated using the trapezoidal rule. Blood samples were taken before the administration of the reference/test product (pre-dose) and at 0.250, 0.333, 0.500, 0.667, 0.833, 1.000, 1.250, 1.500, 1.750, 2.000, 4.000, 6.000, 8.000, 12.000 and 16.000 hours (h) after each period. |
| Area Under the Curve From Time Zero Extrapolated to Infinity [AUC(0-inf)] | 2 days | AUC(0-inf) of paracetamol was calculated using the trapezoidal rule. Blood samples were taken before the administration of the reference/test product (pre-dose) and at 0.250, 0.333, 0.500, 0.667, 0.833, 1.000, 1.250, 1.500, 1.750, 2.000, 4.000, 6.000, 8.000, 12.000 and 16.000 h after each period. |
| Maximum Plasma Concentration (Cmax) | 2 days | Cmax of paracetamol was obtained graphically from the plasma concentration over time profile. Blood samples were taken before the administration of the reference/test product (pre-dose) and at 0.250, 0.333, 0.500, 0.667, 0.833, 1.000, 1.250, 1.500, 1.750, 2.000, 4.000, 6.000, 8.000, 12.000 and 16.000 h after each period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Reach Maximum Plasma Concentration (Tmax) | 2 days | Tmax of paracetamol was obtained graphically from the plasma concentration over time profile. Blood samples were taken before the administration of the reference/test product (pre-dose) and at 0.250, 0.333, 0.500, 0.667, 0.833, 1.000, 1.250, 1.500, 1.750, 2.000, 4.000, 6.000, 8.000, 12.000 and 16.000 h after each period. |
Countries
Mexico
Participant flow
Recruitment details
Recruitment was done in one center in Mexico.
Pre-assignment details
Fifty two participants were screened for this study, out of which 15 participants were considered screening failure, 9 were kept as backup and 28 participants were randomized and all 28 of them completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Overall Participants Total number of participants who were randomized and received treatment. | 28 |
| Total | 28 |
Baseline characteristics
| Characteristic | Overall Participants |
|---|---|
| Age, Continuous | 30.8 Years STANDARD_DEVIATION 10.4 |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 28 | 0 / 28 |
| serious Total, serious adverse events | 0 / 28 | 0 / 28 |
Outcome results
Primary
Area Under the Curve From Time Zero Extrapolated to Infinity [AUC(0-inf)]
AUC(0-inf) of paracetamol was calculated using the trapezoidal rule. Blood samples were taken before the administration of the reference/test product (pre-dose) and at 0.250, 0.333, 0.500, 0.667, 0.833, 1.000, 1.250, 1.500, 1.750, 2.000, 4.000, 6.000, 8.000, 12.000 and 16.000 h after each period.
Time frame: 2 days
Population: One participant had a positive pre-dose sample in the second period of the study, equivalent to 7.74% of their Cmax, therefore, his data was not taken into account in the bioequivalence analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tylenol® Caplets (Reference) | Area Under the Curve From Time Zero Extrapolated to Infinity [AUC(0-inf)] | 15.972 h*μg/mL | Standard Deviation 4.239 |
| Mejoral® 500 Tablets (Test) | Area Under the Curve From Time Zero Extrapolated to Infinity [AUC(0-inf)] | 15.620 h*μg/mL | Standard Deviation 4.681 |
90% CI: [89.826, 102.574]ANOVA
Primary
Area Under the Curve From Time Zero to Last Sampling Time [AUC(0-t)]
AUC(0-t) of paracetamol was calculated using the trapezoidal rule. Blood samples were taken before the administration of the reference/test product (pre-dose) and at 0.250, 0.333, 0.500, 0.667, 0.833, 1.000, 1.250, 1.500, 1.750, 2.000, 4.000, 6.000, 8.000, 12.000 and 16.000 hours (h) after each period.
Time frame: 2 days
Population: One participant had a positive pre-dose sample in the second period of the study, equivalent to 7.74% of their Cmax, therefore, his data was not taken into account in the bioequivalence analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tylenol® Caplets (Reference) | Area Under the Curve From Time Zero to Last Sampling Time [AUC(0-t)] | 15.212 hours*microgram/millilitre (h*μg/mL) | Standard Deviation 4.141 |
| Mejoral® 500 Tablets (Test) | Area Under the Curve From Time Zero to Last Sampling Time [AUC(0-t)] | 14.698 hours*microgram/millilitre (h*μg/mL) | Standard Deviation 4.52 |
90% CI: [88.329, 101.54]ANOVA
Primary
Maximum Plasma Concentration (Cmax)
Cmax of paracetamol was obtained graphically from the plasma concentration over time profile. Blood samples were taken before the administration of the reference/test product (pre-dose) and at 0.250, 0.333, 0.500, 0.667, 0.833, 1.000, 1.250, 1.500, 1.750, 2.000, 4.000, 6.000, 8.000, 12.000 and 16.000 h after each period.
Time frame: 2 days
Population: One participant had a positive pre-dose sample in the second period of the study, equivalent to 7.74% of their Cmax, therefore, his data was not taken into account in the bioequivalence analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tylenol® Caplets (Reference) | Maximum Plasma Concentration (Cmax) | 7.182 micogram per mililitre (μg/mL) | Standard Deviation 2.841 |
| Mejoral® 500 Tablets (Test) | Maximum Plasma Concentration (Cmax) | 8.118 micogram per mililitre (μg/mL) | Standard Deviation 3.938 |
90% CI: [85.151, 132.283]ANOVA
Secondary
Time to Reach Maximum Plasma Concentration (Tmax)
Tmax of paracetamol was obtained graphically from the plasma concentration over time profile. Blood samples were taken before the administration of the reference/test product (pre-dose) and at 0.250, 0.333, 0.500, 0.667, 0.833, 1.000, 1.250, 1.500, 1.750, 2.000, 4.000, 6.000, 8.000, 12.000 and 16.000 h after each period.
Time frame: 2 days
Population: One participant had a positive pre-dose sample in the second period of the study, equivalent to 7.74% of their Cmax, therefore, his data was not taken into account in the bioequivalence analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tylenol® Caplets (Reference) | Time to Reach Maximum Plasma Concentration (Tmax) | 0.719 Hours (h) | Standard Deviation 0.474 |
| Mejoral® 500 Tablets (Test) | Time to Reach Maximum Plasma Concentration (Tmax) | 0.738 Hours (h) | Standard Deviation 0.501 |