Depression - Major Depressive Disorder
Conditions
Keywords
DVS SR, healthy, Bioequivalence study
Brief summary
To determine the bioequivalence of 2 tablets of 25 mg sustained release (SR) formulation of DVS and 1 tablet of 50 mg SR formulation of DVS under fed and fast conditions. To investigate the effect of high-fat meal on pharmacokinetics of desvenlafaxine after administration of 50 mg SR formulation of DVS.
Interventions
Two tablets of 25 mg, single administration, under fed condition
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male and female subjects.
Exclusion criteria
* Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-time Profile From Time 0 to 48 Hours (AUC48) | Day 1 of Periods 1, 2, 3, and 4: pre-dose, 0 hour, and 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose | Area under the plasma concentration versus time curve from time zero (pre-dose) to 48 hours post dose; measured as nanograms multiplied by hours divided by milliliters (ng\*hr/mL). |
| Maximum Plasma Concentration (Cmax) | Day 1 of Periods 1, 2, 3, and 4: pre-dose, 0 hour, and 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose | Cmax measured as nanograms divided by milliliters (ng/mL). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | Day 1 of Periods 1, 2, 3, and 4: pre-dose, 0 hour, and 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose | — |
| Terminal Elimination Half-life (t 1/2) | Day 1 of Periods 1, 2, 3, and 4: pre-dose, 0 hour, and 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose | Terminal elimination (plasma decay) half-life is the time measured for the plasma concentration to decrease by one half. |
| Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) | Day 1 of Periods 1, 2, 3, and 4: pre-dose, 0 hour, and 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose | 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 - ∞). |
| Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Time of the Last Quantifiable Concentration (AUClast) | Day 1 of Periods 1, 2, 3, and 4: pre-dose, 0 hour, and 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose | — |
Countries
Belgium
Participant flow
Pre-assignment details
Participants randomized to an open-label treatment sequence beginning in Period 1 with 25 milligrams as 2 tablets (25 mg\*2) in fed state=A; or a 50 mg tablet in fed state=B; or 25 mg\*2 tablets in fasted state=C; or a 50 mg tablet in fasted state=D in a cross-over, 4-period design. Treatment groups sequenced as: ABCD, BADC, CDAB, and DCBA.
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population Participants randomized to 1 of the 4 treatment sequences beginning with DVS SR 25 mg\*2 Fed (A); or DVS SR 50 mg Fed (B); or DVS SR 25 mg\*2 Fasted (C); or DVS SR 50 mg Fasted (D). | 41 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| First Intervention (Period 1) | Adverse Event | 1 | 0 | 0 | 0 |
| Third Intervention (Period 3) | Adverse Event | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age Continuous | 37.6 years STANDARD_DEVIATION 10.6 |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 19 / 41 | 19 / 40 | 19 / 40 | 16 / 39 |
| serious Total, serious adverse events | 0 / 41 | 0 / 40 | 0 / 40 | 0 / 39 |
Outcome results
Primary
Area Under the Plasma Concentration-time Profile From Time 0 to 48 Hours (AUC48)
Area under the plasma concentration versus time curve from time zero (pre-dose) to 48 hours post dose; measured as nanograms multiplied by hours divided by milliliters (ng\*hr/mL).
Time frame: Day 1 of Periods 1, 2, 3, and 4: pre-dose, 0 hour, and 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose
Population: Pharmacokinetic parameter analysis (PK) population: all participants randomized and treated and had at least 1 of the PK parameters of primary interest in at least 1 treatment period. N=number of participants contributing to the mean.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DVS SR 25 mg*2 Fed | Area Under the Plasma Concentration-time Profile From Time 0 to 48 Hours (AUC48) | 2948 ng*hr/mL | Standard Deviation 726.28 |
| DVS SR 50 mg Fed | Area Under the Plasma Concentration-time Profile From Time 0 to 48 Hours (AUC48) | 2966 ng*hr/mL | Standard Deviation 836.52 |
| DVS SR 25 mg*2 Fasted | Area Under the Plasma Concentration-time Profile From Time 0 to 48 Hours (AUC48) | 2632 ng*hr/mL | Standard Deviation 764.41 |
| DVS SR 50 mg Fasted | Area Under the Plasma Concentration-time Profile From Time 0 to 48 Hours (AUC48) | 2777 ng*hr/mL | Standard Deviation 893.35 |
Comparison: DVS SR 25 mg\*2 fasted (test); DVS SR 50 mg fasted (reference).~Natural log transformed AUC48: mixed models analysis with sequence, period, treatment (formulation by food status) as fixed effects and subject within sequence as a random effect.90% CI: [86.94, 105.04]Mixed Models Analysis
Comparison: DVS SR 25 mg\*2 fed (test); DVS SR 50 mg fed (reference).~Natural log transformed AUC48: mixed models analysis with sequence, period, treatment (formulation by food status) as fixed effects and subject within sequence as a random effect.90% CI: [97.17, 105.64]Mixed Models Analysis
Comparison: Food effect DVS SR 50 mg fed (test) versus DVS SR 50 mg fasted (reference).~Natural log transformed AUC48: mixed models analysis with sequence, period, treatment (formulation by food status) as fixed effects and subject within sequence as a random effect.90% CI: [101.1, 117.01]Mixed Models Analysis
Primary
Maximum Plasma Concentration (Cmax)
Cmax measured as nanograms divided by milliliters (ng/mL).
Time frame: Day 1 of Periods 1, 2, 3, and 4: pre-dose, 0 hour, and 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose
Population: PK population; N=number of participants contributing to the mean.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DVS SR 25 mg*2 Fed | Maximum Plasma Concentration (Cmax) | 130.6 ng/mL | Standard Deviation 29.711 |
| DVS SR 50 mg Fed | Maximum Plasma Concentration (Cmax) | 131.0 ng/mL | Standard Deviation 36.308 |
| DVS SR 25 mg*2 Fasted | Maximum Plasma Concentration (Cmax) | 107.3 ng/mL | Standard Deviation 26.773 |
| DVS SR 50 mg Fasted | Maximum Plasma Concentration (Cmax) | 112.1 ng/mL | Standard Deviation 28.51 |
Comparison: DVS SR 25 mg\*2 fasted (test); DVS SR 50 mg fasted (reference).~Natural log transformed Cmax: mixed models analysis with sequence, period, treatment (formulation by food status) as fixed effects and subject within sequence as a random effect.90% CI: [89.37, 101.2]Mixed Models Analysis
Comparison: DVS SR 25 mg\*2 fed (test); DVS SR 50 mg fed (reference).~Natural log transformed Cmax: mixed models analysis with sequence, period, treatment (formulation by food status) as fixed effects and subject within sequence as a random effect.90% CI: [94.66, 108.4]Mixed Models Analysis
Comparison: Food effect DVS SR 50 mg fed (test) versus DVS SR 50 mg fasted (reference).~Natural log transformed Cmax: mixed models analysis with sequence, period, treatment (formulation by food status) as fixed effects and subject within sequence as a random effect.90% CI: [108.59, 122.94]Mixed Models Analysis
Secondary
Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf)
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: Day 1 of Periods 1, 2, 3, and 4: pre-dose, 0 hour, and 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose
Population: PK population; N=number of participants contributing to the mean.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DVS SR 25 mg*2 Fed | Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) | 3171 ng*hr/mL | Standard Deviation 820.37 |
| DVS SR 50 mg Fed | Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) | 3216 ng*hr/mL | Standard Deviation 973.36 |
| DVS SR 25 mg*2 Fasted | Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) | 3008 ng*hr/mL | Standard Deviation 1147.6 |
| DVS SR 50 mg Fasted | Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) | 3052 ng*hr/mL | Standard Deviation 1059.9 |
Secondary
Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Time of the Last Quantifiable Concentration (AUClast)
Time frame: Day 1 of Periods 1, 2, 3, and 4: pre-dose, 0 hour, and 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose
Population: PK population; N=number of participants contributing to the mean.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DVS SR 25 mg*2 Fed | Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Time of the Last Quantifiable Concentration (AUClast) | 2948 ng*hr/mL | Standard Deviation 726.28 |
| DVS SR 50 mg Fed | Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Time of the Last Quantifiable Concentration (AUClast) | 2966 ng*hr/mL | Standard Deviation 836.47 |
| DVS SR 25 mg*2 Fasted | Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Time of the Last Quantifiable Concentration (AUClast) | 2631 ng*hr/mL | Standard Deviation 767.89 |
| DVS SR 50 mg Fasted | Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Time of the Last Quantifiable Concentration (AUClast) | 2778 ng*hr/mL | Standard Deviation 894.03 |
Secondary
Terminal Elimination Half-life (t 1/2)
Terminal elimination (plasma decay) half-life is the time measured for the plasma concentration to decrease by one half.
Time frame: Day 1 of Periods 1, 2, 3, and 4: pre-dose, 0 hour, and 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose
Population: PK population; N=number of participants contributing to the median.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DVS SR 25 mg*2 Fed | Terminal Elimination Half-life (t 1/2) | 10.50 hours | Standard Deviation 2.2478 |
| DVS SR 50 mg Fed | Terminal Elimination Half-life (t 1/2) | 10.72 hours | Standard Deviation 2.8931 |
| DVS SR 25 mg*2 Fasted | Terminal Elimination Half-life (t 1/2) | 12.71 hours | Standard Deviation 6.0106 |
| DVS SR 50 mg Fasted | Terminal Elimination Half-life (t 1/2) | 11.13 hours | Standard Deviation 2.9444 |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time frame: Day 1 of Periods 1, 2, 3, and 4: pre-dose, 0 hour, and 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose
Population: PK population; N=number of participants contributing to the median.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DVS SR 25 mg*2 Fed | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 6.00 hours |
| DVS SR 50 mg Fed | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 8.00 hours |
| DVS SR 25 mg*2 Fasted | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 6.00 hours |
| DVS SR 50 mg Fasted | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 6.00 hours |