Healthy
Conditions
Keywords
diltiazem, angiotrofin, bioequivalence
Brief summary
This study will research the existance of actual bioequivalence between Diltiazem in 60 Mg Tablets As Tilazem 60® Made by Pfizer, S.A. DE C.V., Versus Angiotrofin® 60 Mg Made by Amstrong Laboratorios De Mexico, S.A. DE C.V.
Detailed description
Bioequivalence of this particular drug
Interventions
DRUGTILACEM
At 08:00 hours on day 1, CIF-BIOTEC personnel will start to administer the study drug. Each volunteer will receive a single dose of 60 mg of Diltiazem. The study drugs will be ingested with 250 mL of drinking water. Research Pharmacy personnel will inspect the volunteer's oropharynx to ensure that he/she has swallowed the tablet and record their observations in the corresponding forms.
DRUGANGIOTROFIN
At 08:00 hours on day 1, CIF-BIOTEC Pharmacy personnel will start to administer the study drug. Each volunteer will receive a single dose of 60 mg of Diltiazem. The study drugs will be ingested with 250 mL of drinking water. Research Pharmacy personnel will inspect the volunteer's oropharynx to ensure that he/she has swallowed the tablet and record their observations in the corresponding forms.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male and/or female subjects between the ages of 18 and 55 years, inclusive (Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12-lead ECG and clinical laboratory tests). * Both genders * Body Mass Index (BMI) of 17.5 to 30.5 kg/m2 or ± 10% variation of the ideal weight; and a total body weight \>50 kg (110 lbs).
Exclusion criteria
* Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing). * Any condition possibly affecting drug absorption (eg, gastrectomy). * A positive urine drug screen
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] | 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 24 hours post dose | AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t) |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] | 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 24 hours post dose | AUC (0-∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-∞). It is obtained from AUC (0-t) plus AUC (t-∞). |
| Maximum Observed Plasma Concentration (Cmax) | 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 24 hours post dose | — |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 24 hours post dose | — |
| Plasma Decay Half-Life (t1/2) | 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 24 hours post dose | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. |
Countries
Mexico
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population Includes groups randomized to receive any treatment (Tilazem 60 mg tablet first or Angiotrofin 60 mg tablet first ) | 26 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention Period | Protocol Violation | 0 | 1 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age Continuous | 33.0 Years STANDARD_DEVIATION 10 |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 25 | 13 / 25 |
| serious Total, serious adverse events | 0 / 25 | 0 / 25 |
Outcome results
Primary
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)]
AUC (0-∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-∞). It is obtained from AUC (0-t) plus AUC (t-∞).
Time frame: 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 24 hours post dose
Population: Pharmacokinetic (PK) parameter analysis population included all treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tilazem 60 mg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] | 612.95 ng*hr/mL | Standard Deviation 298.23 |
| Angiotrofin 60 mg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] | 648.68 ng*hr/mL | Standard Deviation 283.73 |
Comparison: Natural-log transformed AUC (0-∞) was analyzed using a mixed effect model with sequence, period, and treatment as fixed effects and participant within sequence as a random effect.90% CI: [83.83, 99.34]
Primary
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]
AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t)
Time frame: 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 24 hours post dose
Population: Pharmacokinetic (PK) parameter analysis population included all treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tilazem 60 mg | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] | 463.41 ng*hr/mL | Standard Deviation 245.03 |
| Angiotrofin 60 mg | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] | 498.87 ng*hr/mL | Standard Deviation 226.07 |
Comparison: Natural-log transformed AUC (0-t) was analyzed using a mixed effect model with sequence, period, and treatment as fixed effects and participant within sequence as a random effect.90% CI: [81.23, 96.75]
Primary
Maximum Observed Plasma Concentration (Cmax)
Time frame: 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 24 hours post dose
Population: PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tilazem 60 mg | Maximum Observed Plasma Concentration (Cmax) | 68.67 ng/mL | Standard Deviation 50.36 |
| Angiotrofin 60 mg | Maximum Observed Plasma Concentration (Cmax) | 79.60 ng/mL | Standard Deviation 44.01 |
Comparison: Natural-log transformed Cmax was analyzed using a mixed effect model with sequence, period, and treatment as fixed effects and participant within sequence as a random effect.90% CI: [67.08, 103.31]
Primary
Plasma Decay Half-Life (t1/2)
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time frame: 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 24 hours post dose
Population: PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tilazem 60 mg | Plasma Decay Half-Life (t1/2) | 12.17 hr | Standard Deviation 5.98 |
| Angiotrofin 60 mg | Plasma Decay Half-Life (t1/2) | 11.71 hr | Standard Deviation 5.55 |
Primary
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time frame: 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 24 hours post dose
Population: PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tilazem 60 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 2.38 hr | Standard Deviation 0.98 |
| Angiotrofin 60 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 2.44 hr | Standard Deviation 1.04 |