Healthy
Conditions
Keywords
bioequivalence study, sertraline 50 mg, capsules vs tablets
Brief summary
This study is designed to determine differences in drug exposure in subjects after being administered 50 mg tablets of sertraline hydrochloride as compared to drug exposure after administering 50 mg capsules of sertraline hydrochloride under fasted (nonfed) conditions.
Interventions
50 mg capsule, single-dose
Sponsors
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male and/or female subjects between the ages of 21 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). * Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight \>45 kg (99 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve From Time Zero to 72 Hours [AUC (0-72)] | Predose and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 36, 48, and 72 hours postdose | AUC (0-72)= Area under the plasma concentration versus time curve from time zero (pre-dose) to 72 hours (0-72). |
| Maximum Observed Plasma Concentration (Cmax) | Predose and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 36, 48, and 72 hours postdose | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | Predose and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 36, 48, and 72 hours postdose | — |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] | Predose and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 36, 48, and 72 hours postdose | 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 - ∞). |
| Residual Area Under the Concentration Time Curve [AUC(Res%)] | Predose and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 36, 48, and 72 hours postdose | AUC(res%) is the residual AUC defined as (AUCinf minus AUClast) divided by AUCinf. AUCinf is the area under the plasma concentration-time curve from time zero extrapolated to infinite time. AUClast is the area under the plasma concentration-time curve from zero to the last measured concentration. |
| Plasma Decay Half-Life (t1/2) | Predose and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 36, 48, and 72 hours postdose | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. |
Countries
Singapore
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population Entire study population receiving Sertraline Hydrochloride 50 mg as either hard gelatin capsule or film-coated tablet | 30 |
| Total | 30 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age, Continuous | 30.4 years STANDARD_DEVIATION 8.6 |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 30 | 13 / 30 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 |
Outcome results
Primary
Area Under the Curve From Time Zero to 72 Hours [AUC (0-72)]
AUC (0-72)= Area under the plasma concentration versus time curve from time zero (pre-dose) to 72 hours (0-72).
Time frame: Predose and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 36, 48, and 72 hours postdose
Population: All participants: all treated participants with at least one sertraline concentration were evaluated for pharmacokinetics.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sertraline 50 mg Hard Gelatin Capsule | Area Under the Curve From Time Zero to 72 Hours [AUC (0-72)] | 419.9 nanogram hour per milliliter (ng*h/mL) | Standard Deviation 147.14 |
| Sertraline 50 mg Film-Coated Tablet | Area Under the Curve From Time Zero to 72 Hours [AUC (0-72)] | 442.1 nanogram hour per milliliter (ng*h/mL) | Standard Deviation 169.2 |
Comparison: Natural log-transformed AUC (0-72) analyzed using a mixed effect model with sequence, period, treatment as fixed effects; subject within sequence as a random effect. Estimates of adjusted mean differences (Test minus Reference) and corresponding 90% confidence intervals (CIs) were obtained from the model. Adjusted mean differences and 90% CIs for differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test divided by Reference) and 90% CIs for the ratios.90% CI: [100.12, 109.83]
Primary
Maximum Observed Plasma Concentration (Cmax)
Time frame: Predose and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 36, 48, and 72 hours postdose
Population: All participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sertraline 50 mg Hard Gelatin Capsule | Maximum Observed Plasma Concentration (Cmax) | 17.96 nanogram per milliliter (ng/mL) | Standard Deviation 5.0438 |
| Sertraline 50 mg Film-Coated Tablet | Maximum Observed Plasma Concentration (Cmax) | 19.03 nanogram per milliliter (ng/mL) | Standard Deviation 6.3319 |
Comparison: Natural log-transformed Cmax analyzed using a mixed effect model with sequence, period, treatment as fixed effects; subject within sequence as a random effect. Estimates of adjusted mean differences (Test minus Reference) and corresponding 90% CIs were obtained from the model. Adjusted mean differences and 90% CIs for differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test divided by Reference) and 90% CIs for the ratios.90% CI: [98.46, 112.69]
Secondary
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: Predose and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 36, 48, and 72 hours postdose
Population: All participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sertraline 50 mg Hard Gelatin Capsule | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] | 471.4 ng*h/mL | Standard Deviation 189.86 |
| Sertraline 50 mg Film-Coated Tablet | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] | 493.8 ng*h/mL | Standard Deviation 204.9 |
Comparison: Natural log-transformed AUC (0-∞) analyzed using a mixed effect model with sequence, period, treatment as fixed effects; subject within sequence as a random effect. Estimates of adjusted mean differences (Test minus Reference) and corresponding 90% CIs were obtained from the model. Adjusted mean differences and 90% CIs for differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test divided by Reference) and 90% CIs for the ratios.90% CI: [100.16, 112.39]
Secondary
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: Predose and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 36, 48, and 72 hours postdose
Population: All participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sertraline 50 mg Hard Gelatin Capsule | Plasma Decay Half-Life (t1/2) | 25.45 hours | Standard Deviation 3.9067 |
| Sertraline 50 mg Film-Coated Tablet | Plasma Decay Half-Life (t1/2) | 25.40 hours | Standard Deviation 3.3831 |
Secondary
Residual Area Under the Concentration Time Curve [AUC(Res%)]
AUC(res%) is the residual AUC defined as (AUCinf minus AUClast) divided by AUCinf. AUCinf is the area under the plasma concentration-time curve from time zero extrapolated to infinite time. AUClast is the area under the plasma concentration-time curve from zero to the last measured concentration.
Time frame: Predose and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 36, 48, and 72 hours postdose
Population: This parameter was not analyzed. It is reported individually for each subject and not analyzed statistically.
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time frame: Predose and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 36, 48, and 72 hours postdose
Population: All participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sertraline 50 mg Hard Gelatin Capsule | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 5.00 hours |
| Sertraline 50 mg Film-Coated Tablet | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 5.00 hours |