Major Depressive Disorder
Conditions
Keywords
Major Depressive Disorder, bupropion XL, Wellbutrin XL
Brief summary
Determine bioequivalence between branded and generic bupropion extended release (XL) products (and between generic products) at steady state in patients with major depressive disorder.
Detailed description
The protocol is a prospective, randomized, double-blinded, crossover study with Major Depressive Disorder (MDD) receiving bupropion HCl 300mg XL (branded or generic). Subjects will be studied in 4 phases for a total of approximately 28 weeks: Phase 1: an approximately 4-week lead-in phase during which participants remain on their existing bupropion product Phases 2 - 4: randomized cross-over phases of approximately 6 weeks on each of the four bupropion study drugs (brand and 3 generics).
Interventions
DRUGBupropion XL 300
Subjects will be studied in 4 phases for a total of approximately 28 weeks: Phase 1: an approximately 4-week lead-in phase during which participants remain on their existing bupropion product Phases 2 - 4: randomized cross-over phases of approximately 6 weeks on each of the four bupropion study drugs (brand and 3 generics).
Sponsors
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Masking description
The randomization table will be generated by the Barnes-Jewish Hospital Investigational Pharmacy. Each subject will be assigned the next available number. Subjects, investigators, and all study team members will be blinded to drug treatment. In the case of dropouts (either subject- or investigator-initiated), subjects will be replaced, to provide the required number of subjects.
Intervention model description
Each participant receives the 4 drugs in sequence (sequence is randomized).
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Each subject must meet all of the following criteria: 1. Adult outpatients age 18-75 years 2. Currently on once daily bupropion HCl 300mg XL (brand or any generic), for a minimum of 4 months 3. Major depressive disorder (MDD), in partial or full remission for at least 4 months, as confirmed by the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID). Spontaneous relapse of depression unrelated to medication changes is less likely - about 5% chance per year - after remission has been maintained for at least 4 months.2 4. Ability to understand and willingness to comply with study procedures, and to provide written informed consent
Exclusion criteria
Subjects will not be enrolled if any of the following criteria exist: 1. Remission from depression not clearly attributed to bupropion treatment 2. Current severe side effects attributable to bupropion 3. Poor adherence to bupropion treatment per patient self- report and history of refill persistence 4. History of active seizure disorder, or seizure treatment within past year 5. History of significant hepatic or renal disease, based on physician assessment 6. Currently taking drugs or natural products known to influence cytochrome P450B6 (CYP2B6) activity 7. Currently taking drugs for hepatitis C or multiple sclerosis, due to their ability to cause depression 8. Dementia or other significant cognitive impairment, per diagnosis or investigative team's assessment 9. Lifetime diagnosis of schizophrenia, schizoaffective or schizophreniform dis-order, delusional disorder, or current psychotic symptoms diagnosed by SCID 10. Abuse of or dependence on alcohol or other substances within the past 6 months as determined by SCID, and confirmed by study physician interview 11. Current suicidal ideation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve (AUC0-24) Ratio for Racemic Bupropion | For 24 hours approximately every 6 weeks | Area under the curve (AUC) generic/Area under the curve (AUC) brand bupropion |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bupropion Subjects will be studied for 28 weeks in a sequential cross-over study:
1. a 4-week lead-in phase during which all participants remain on their existing bupropion product
2. Four randomized cross-over phases of 6 weeks on each of the four bupropion study drugs (brand Wellbutrin 300mg XL, Valeant, Par and Watson 3 generics) | 70 |
| Total | 70 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Phase 1 Current Tx (Non-randomized) | Adverse Event | 1 |
| Phase 1 Current Tx (Non-randomized) | Withdrawal by Subject | 2 |
| Phase 2 (Randomized: 1 Brand, 3 Generic) | Adverse Event | 1 |
| Phase 2 (Randomized: 1 Brand, 3 Generic) | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Bupropion | — |
|---|---|---|
| Age, Continuous | 47 years | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 53 Participants | — |
| Sex: Female, Male Male | 17 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 | 0 / 71 | 0 / 71 | 0 / 71 | 0 / 71 |
| other Total, other adverse events | 0 / 71 | 0 / 71 | 1 / 71 | 0 / 71 |
| serious Total, serious adverse events | 0 / 71 | 0 / 71 | 0 / 71 | 0 / 71 |
Outcome results
Primary
Area Under the Curve (AUC0-24) Ratio for Racemic Bupropion
Area under the curve (AUC) generic/Area under the curve (AUC) brand bupropion
Time frame: For 24 hours approximately every 6 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Valeant Brand Bupropion XL® 300mg | Area Under the Curve (AUC0-24) Ratio for Racemic Bupropion | Erthrohydrobuprion | 2.09 percentage of Brand |
| Valeant Brand Bupropion XL® 300mg | Area Under the Curve (AUC0-24) Ratio for Racemic Bupropion | Bupropion | .84 percentage of Brand |
| Valeant Brand Bupropion XL® 300mg | Area Under the Curve (AUC0-24) Ratio for Racemic Bupropion | Threohydrobupropion | 9.38 percentage of Brand |
| Valeant Brand Bupropion XL® 300mg | Area Under the Curve (AUC0-24) Ratio for Racemic Bupropion | Hydroxybupropion | 20.9 percentage of Brand |
| Par Generic Bupropion XL® 300mg | Area Under the Curve (AUC0-24) Ratio for Racemic Bupropion | Bupropion | .88 percentage of Brand |
| Par Generic Bupropion XL® 300mg | Area Under the Curve (AUC0-24) Ratio for Racemic Bupropion | Threohydrobupropion | 9.05 percentage of Brand |
| Par Generic Bupropion XL® 300mg | Area Under the Curve (AUC0-24) Ratio for Racemic Bupropion | Erthrohydrobuprion | 2.05 percentage of Brand |
| Par Generic Bupropion XL® 300mg | Area Under the Curve (AUC0-24) Ratio for Racemic Bupropion | Hydroxybupropion | 20.9 percentage of Brand |
| Watson Generic Bupropion XL® 300mg | Area Under the Curve (AUC0-24) Ratio for Racemic Bupropion | Hydroxybupropion | 21.8 percentage of Brand |
| Watson Generic Bupropion XL® 300mg | Area Under the Curve (AUC0-24) Ratio for Racemic Bupropion | Bupropion | .83 percentage of Brand |
| Watson Generic Bupropion XL® 300mg | Area Under the Curve (AUC0-24) Ratio for Racemic Bupropion | Erthrohydrobuprion | 1.98 percentage of Brand |
| Watson Generic Bupropion XL® 300mg | Area Under the Curve (AUC0-24) Ratio for Racemic Bupropion | Threohydrobupropion | 8.57 percentage of Brand |
| Mylan Generic Bupropion XL® 300mg | Area Under the Curve (AUC0-24) Ratio for Racemic Bupropion | Threohydrobupropion | 8.78 percentage of Brand |
| Mylan Generic Bupropion XL® 300mg | Area Under the Curve (AUC0-24) Ratio for Racemic Bupropion | Bupropion | .89 percentage of Brand |
| Mylan Generic Bupropion XL® 300mg | Area Under the Curve (AUC0-24) Ratio for Racemic Bupropion | Hydroxybupropion | 21.6 percentage of Brand |
| Mylan Generic Bupropion XL® 300mg | Area Under the Curve (AUC0-24) Ratio for Racemic Bupropion | Erthrohydrobuprion | 2.02 percentage of Brand |
p-value: <0.05ANOVA