Postpartum Depression
Conditions
Brief summary
The primary purpose of this study was to evaluate whether the safe-use conditions for administration of brexanolone (ZULRESSO®) can be implemented in a home setting.
Interventions
DRUGZULRESSO®
Intravenous infusion of ZULRESSO®.
Sponsors
Supernus Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Ambulatory female ≥18 years of age. 2. Participant has a current diagnosis of postpartum depression (PPD), as confirmed by the investigator. 3. Participant agrees not to be the primary caregiver of any dependents during the infusion and must be accompanied by another adult (other than the home healthcare provider) during interactions with their child(ren). 4. Participant has no history of sleep apnea or any clinically significant respiratory conditions. 5. Participant agrees to refrain from the use of central nervous system depressants, such as opioids, benzodiazepines, sleep aids and from drinking alcohol during the infusion. 6. Participant is suitable for administration of ZULRESSO® in a home setting, as per the judgement of the investigator. 7. Participant's home is suitable and has necessary provisions for administration of ZULRESSO® and meets the following criteria: * safe environment for the home infusion provider staff. * access to a working telephone. * electricity and grounded electrical outlets. * running water. * access to back-up emergency services (911 service or ambulance availability). * sanitary environment. 8. Participant agrees to stay at home until the end-of-study visit has been completed, except for a medical emergency. 9. Participant must have a negative pregnancy test at screening and on Day 1 prior to the start of the ZULRESSO® infusion.
Exclusion criteria
1. Participant has end stage renal failure. 2. Participant has known allergy to progesterone or allopregnanolone or any excipients in the brexanolone injection. 3. Participant is currently at risk of suicide, as judged by the investigator, or has attempted suicide associated with the current episode of PPD.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With At Least One Treatment-Emergent Adverse Event (TEAE) Leading to Dose Interruption/Discontinuation | Up to Day 3 | An adverse event (AE) was any untoward medical occurrence in a participant or clinical investigation participant administered with a pharmaceutical product that does not necessarily have a causal relationship with this treatment. A TEAE was defined as an AE with onset after the start of investigational product, or any worsening of a preexisting medical condition/AE with onset after the start of investigational product and throughout the study. Percentages are rounded off to the nearest single decimal. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Nonadherence With the Safe-Use Conditions for Administration of ZULRESSO® | Up to Day 3 | Nonadherence was defined by failure of any of following: * Home infusion provider to train all pharmacy and home healthcare providers (HHPs) in dispensing/administration of ZULRESSO® on risk of excessive sedation/loss of consciousness * HHPs to counsel participants on risk of excessive sedation/loss of consciousness * Deliver ZULRESSO® per protocol * Provide preprogrammed peristaltic pump * HHP:assess excessive sedation every 2 hours in planned nonsleep periods, change infusion bag per protocol, at least one HHP available in participant's home for the duration of infusion * Fall protocol in place * Monitor participants with pulse oximeter * Stop infusion when participant is primary caregiver of dependents and/or identification of excessive sedation/loss of consciousness/hypoxic episode * Caution participants post-infusion against engaging in hazardous activities requiring mental alertness * Complete AE of special interest/Serious AE form * Infusion resumed after hypoxia episode |
| Number of Use-Related Issues Related to the Home Administration of ZULRESSO® | Up to Day 3 | Home healthcare provider (HHP) staff completed checklists at end of each day and/or shift to document any use-related issues throughout duration of infusion. Any use-related issues determined to be critical in nature were followed up immediately and were reported adequately. Use-related issues were categorized as Critical Use Error (UE): HHP failed to complete a task or made uncorrected use error during task that could have resulted in harm, compromised medical care, incidence of nonadherence with safe use conditions for administration of ZULRESSO, or incidence of use-related issues related to home administration of ZULRESSO; Use Difficulty (UD): HHP successfully completed a task but did so while experiencing issues/operational difficulties; Close Call (CC): HHP committed error that could have led to a task failure, but self-corrected and completed task successfully. Multiple occurrences of issue throughout a single infusion was included only once in total. |
| Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | Up to Day 3 | An AE was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. TEAE was defined as an AE with onset after the start of investigational product, or any worsening of a preexisting medical condition/AE with onset after the start of investigational product and throughout the study. Percentages are rounded off to nearest single decimal. |
| Percentage of Participants With Medication Error | At screening and during the study (Up to Day 3) | Medication error was any preventable event that may cause or lead to inappropriate medication use or participant harm while the medication was in the control of the healthcare professional, participant, or consumer. Percentages are rounded off to the nearest single decimal. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at 5 active clinical sites in the United States from 08 October 2021 to 14 July 2022.
Pre-assignment details
A total of 80 participants were screened, of which 52 were enrolled and 42 were treated.
Participants by arm
| Arm | Count |
|---|---|
| ZULRESSO® Participants received a 60-hour single continuous IV infusion of ZULRESSO®, at 30 mcg/kg/hour (0 to 4 hours), at 60 mcg/kg/hour (4 to 24 hours), at 90 mcg/kg/hour (24 to 52 hours), followed by a dose taper to 60 mcg/kg/hour (52 to 56 hours), and 30 mcg/kg/hour (56 to 60 hours) during the study. | 42 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Enrolled but not Treated | 10 |
Baseline characteristics
| Characteristic | ZULRESSO® |
|---|---|
| Age, Continuous | 31.9 years STANDARD_DEVIATION 5.76 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 18 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 6 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized Not Specified | 1 Participants |
| Race/Ethnicity, Customized Other | 1 Participants |
| Race/Ethnicity, Customized White | 33 Participants |
| Sex: Female, Male Female | 42 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 42 |
| other Total, other adverse events | 15 / 42 |
| serious Total, serious adverse events | 0 / 42 |
Outcome results
Primary
Percentage of Participants With At Least One Treatment-Emergent Adverse Event (TEAE) Leading to Dose Interruption/Discontinuation
An adverse event (AE) was any untoward medical occurrence in a participant or clinical investigation participant administered with a pharmaceutical product that does not necessarily have a causal relationship with this treatment. A TEAE was defined as an AE with onset after the start of investigational product, or any worsening of a preexisting medical condition/AE with onset after the start of investigational product and throughout the study. Percentages are rounded off to the nearest single decimal.
Time frame: Up to Day 3
Population: Safety Set included all participants who were administered ZULRESSO®.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ZULRESSO® | Percentage of Participants With At Least One Treatment-Emergent Adverse Event (TEAE) Leading to Dose Interruption/Discontinuation | 7.1 percentage of participants |
Secondary
Number of Use-Related Issues Related to the Home Administration of ZULRESSO®
Home healthcare provider (HHP) staff completed checklists at end of each day and/or shift to document any use-related issues throughout duration of infusion. Any use-related issues determined to be critical in nature were followed up immediately and were reported adequately. Use-related issues were categorized as Critical Use Error (UE): HHP failed to complete a task or made uncorrected use error during task that could have resulted in harm, compromised medical care, incidence of nonadherence with safe use conditions for administration of ZULRESSO, or incidence of use-related issues related to home administration of ZULRESSO; Use Difficulty (UD): HHP successfully completed a task but did so while experiencing issues/operational difficulties; Close Call (CC): HHP committed error that could have led to a task failure, but self-corrected and completed task successfully. Multiple occurrences of issue throughout a single infusion was included only once in total.
Time frame: Up to Day 3
Population: Safety Set included all participants who were administered ZULRESSO®. Overall number of units analyzed signifies total number of use related issues.
| Arm | Measure | Group | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| ZULRESSO® | Number of Use-Related Issues Related to the Home Administration of ZULRESSO® | Critical Use Errors (UE) | 13 Issues |
| ZULRESSO® | Number of Use-Related Issues Related to the Home Administration of ZULRESSO® | Use Difficulties (UD) | 62 Issues |
| ZULRESSO® | Number of Use-Related Issues Related to the Home Administration of ZULRESSO® | Close Calls (CC) | 0 Issues |
Secondary
Percentage of Participants With Medication Error
Medication error was any preventable event that may cause or lead to inappropriate medication use or participant harm while the medication was in the control of the healthcare professional, participant, or consumer. Percentages are rounded off to the nearest single decimal.
Time frame: At screening and during the study (Up to Day 3)
Population: Safety Set included all participants who were administered ZULRESSO®.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ZULRESSO® | Percentage of Participants With Medication Error | At Screening | 28.6 percentage of participants |
| ZULRESSO® | Percentage of Participants With Medication Error | During the Study (Up to Day 3) | 54.8 percentage of participants |
Secondary
Percentage of Participants With Nonadherence With the Safe-Use Conditions for Administration of ZULRESSO®
Nonadherence was defined by failure of any of following: * Home infusion provider to train all pharmacy and home healthcare providers (HHPs) in dispensing/administration of ZULRESSO® on risk of excessive sedation/loss of consciousness * HHPs to counsel participants on risk of excessive sedation/loss of consciousness * Deliver ZULRESSO® per protocol * Provide preprogrammed peristaltic pump * HHP:assess excessive sedation every 2 hours in planned nonsleep periods, change infusion bag per protocol, at least one HHP available in participant's home for the duration of infusion * Fall protocol in place * Monitor participants with pulse oximeter * Stop infusion when participant is primary caregiver of dependents and/or identification of excessive sedation/loss of consciousness/hypoxic episode * Caution participants post-infusion against engaging in hazardous activities requiring mental alertness * Complete AE of special interest/Serious AE form * Infusion resumed after hypoxia episode
Time frame: Up to Day 3
Population: Safety Set included all participants who were administered ZULRESSO®.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ZULRESSO® | Percentage of Participants With Nonadherence With the Safe-Use Conditions for Administration of ZULRESSO® | 76.19 percentage of participants |
Secondary
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
An AE was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. TEAE was defined as an AE with onset after the start of investigational product, or any worsening of a preexisting medical condition/AE with onset after the start of investigational product and throughout the study. Percentages are rounded off to nearest single decimal.
Time frame: Up to Day 3
Population: Safety Set included all participants who were administered ZULRESSO®.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ZULRESSO® | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | 42.9 percentage of participants |