Eosinophilic Esophagitis (EoE)
Conditions
Brief summary
This is a continuation study of Budesonide Oral Suspension (BOS) in adults and adolescents with Eosinophilic Esophagitis (EoE) who have completed participation in the SHP621-302 extension study. The purpose of this study is to see if BOS is safe and well tolerated over the long-term in adolescents and adults with EoE.
Interventions
BOS 10 mL twice daily.
Sponsors
Takeda Development Center Americas, Inc.
Shire
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
11 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Participant completed the SHP621-302 (NCT02736409) extension study and is considered by the investigator to potentially benefit from continued BOS investigational treatment. * Participant is able to provide written informed consent (participant, parent or legal guardian and, as appropriate, participant assent) to participate in the study before completing any study-related procedures. * Females of childbearing potential must agree to continue acceptable birth control measures (example (e.g.): abstinence, surgically sterile male partner, stable oral contraceptives, or double-barrier methods) throughout study participation. * Participant is willing and has an understanding and ability to fully comply with study procedures and restrictions as defined in protocol.
Exclusion criteria
* Participant has changes in medications or diet during the SHP621-302 (NCT02736409) study that could affect participation in this continuation study. * Participant anticipates using swallowed topical corticosteroid for EoE or systemic corticosteroid for any condition during the treatment period; any temporary use (less than or equal to \[≤\] 7 days) or initiation of new steroid treatment during the study should be documented and discussed with the medical monitor prospectively but should be avoided within 4 weeks of the scheduled esophagogastroduodenoscopy (EGDs). * Participant anticipates use of Cytochrome P450 3A4 inhibitors (e.g., ketoconazole, grapefruit juice) during the continuation study. * Participant has an appearance at the EGD at the final treatment evaluation visit of SHP621-302 (NCT02736409) (Visit 8) of an esophageal stricture (high grade), as defined by the presence of a lesion that does not allow passage of a diagnostic adult upper endoscope (e.g., with an insertion tube diameter of greater than (\>) 9 millimeter \[mm\]). * Participant has presence of esophageal varices at the EGD at the final treatment evaluation visit (Visit 8) of the SHP621-302 (NCT02736409) study. * Participant has any current disease of the gastrointestinal tract, aside from EoE, including eosinophilic gastritis, enteritis, colitis, or proctitis, inflammatory bowel disease, or celiac disease. * Participant has other diseases causing or associated with esophageal eosinophilia, including hypereosinophilic syndrome, collagen vascular disease, vasculitis, achalasia, or parasitic infection. * Participant has oropharyngeal or esophageal candidiasis that failed to respond to previous treatment. Diagnosis with oropharyngeal or esophageal candidiasis at or since the final treatment evaluation visit (Visit 8) of the SHP621-302 (NCT02736409) study is not an exclusion as long as the participant is expected to respond to treatment. * Participant has a potentially serious acute or chronic infection or immunodeficiency condition, including tuberculosis, fungal, bacterial, viral/parasite infection, ocular herpes simplex, or chicken pox/measles. * Participant has upper gastrointestinal bleeding identified at the EGD at the final treatment evaluation visit (Visit 8) of the SHP621-302 (NCT02736409) study. * Participant has evidence of active infection with Helicobacter pylori. * Participant has evidence of unstable asthma. * Participant is female and pregnant or nursing. * Participant has a history of intolerance, hypersensitivity, or idiosyncratic reaction to budesonide (or any other corticosteroids), or to any other ingredients of the study medication. * Participant has a history or high risk of noncompliance with treatment or regular clinic visits.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Bone Mineral Density (BMD) For Adolescents Assessed by Dual-Energy X-ray Absorptiometry (DXA) Scan at Month 12 | Baseline, Month 12 | The sites for DXA measurement were the lumbar spine at lumbar vertebrae 1 to 4 (L1-L4) and whole body. DXA scans for determination of BMD and body composition was performed in participants aged 11-17 years. Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. In this study, the BMD Z-score is considered abnormal when the z-score is less than (\<) -2, suggesting a worse outcome (i.e., osteoporosis). Change from baseline in BMD for adolescents assessed by DXA Scan at Month 12 was reported. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | From start of study drug administration up to End of study (EOS) (Up to Month 53) | An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. A Serious Adverse Event (SAE) was any untoward medical occurrence (whether considered to be related to investigational product or not) that at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital abnormality/birth defect, and is an important medical event. Both serious and Non-serious TEAEs were reported in this outcome measure. TEAEs were defined as AEs with a start date on or after the first dose of investigational product or a start date before the date of the first dose of investigational product that increased in severity or after the date of the first dose. |
| Number of Participants With Clinically Significant Physical Examination Findings | From start of study drug administration up to EOS (Up to Month 53) | Number of participants with clinically significant physical examination findings were reported. Clinical significance was determined by investigator. |
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs | From start of study drug administration up to EOS (Up to Month 53) | Participants were assessed by investigator for any clinically significant changes in vital parameters like temperature, systolic and diastolic blood pressure, pulse, respiratory rate, BMI, and weight. Vital signs were assessed after the participant had been in a supine position for at least 5 minutes immediately prior to the assessment. The criteria for clinically significant change was as per the investigators discretion. |
| Change From Baseline in BMD For Adolescents Assessed by DXA Scan at Month 24 | Baseline, Month 24 | The sites for DXA measurement were the lumbar spine at lumbar vertebrae 1 to 4 (L1-L4) and whole body. DXA scans for determination of BMD and body composition was performed in participants aged 11-17 years. Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. In this study, the BMD Z-score is considered abnormal when the z-score is \<-2, suggesting a worse outcome (i.e., osteoporosis) and vice versa. Change from baseline in BMD for adolescents assessed by DXA Scan at Month 24 was reported. |
| Change From Baseline in BMD For Adolescents Assessed by DXA Scan at Month 36 | Baseline, Month 36 | The sites for DXA measurement were the lumbar spine at lumbar vertebrae 1 to 4 (L1-L4) and whole body. DXA scans for determination of BMD and body composition was performed in participants aged 11-17 years. Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. In this study, the BMD Z-score is considered abnormal when the z-score is \< -2, suggesting a worse outcome (i.e., osteoporosis) and vice versa. Change from baseline in BMD for adolescents assessed by DXA Scan at Month 36 was reported. |
| Change From Baseline in BMD For Adolescents Assessed by DXA Scan at Month 48 | Baseline, Month 48 | The sites for DXA measurement were the lumbar spine at lumbar vertebrae 1 to 4 (L1-L4) and whole body. DXA scans for determination of BMD and body composition was performed in participants aged 11-17 years. Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. In this study, the BMD Z-score is considered abnormal when the z-score is \< -2, suggesting a worse outcome (i.e., osteoporosis) and vice versa. Change from baseline in BMD for adolescents assessed by DXA Scan at Month 48 was reported. |
| Change From Baseline in BMD For Adolescents Assessed by DXA Scan at EOS (Up to Month 53) | Baseline, EOS (Up to Month 53) | The sites for DXA measurement were the lumbar spine at lumbar vertebrae 1 to 4 (L1-L4) and whole body. DXA scans for determination of BMD and body composition was performed in participants aged 11-17 years. Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. In this study, the BMD Z-score is considered abnormal when the z-score is \< -2, suggesting a worse outcome (i.e., osteoporosis) and vice versa. Change from baseline in BMD for adolescents assessed by DXA Scan at EOS (up to Month 53) was reported. |
| Change From Baseline in Cortisol Level After Adrenocorticotropic Hormone (ACTH) Stimulation at Month 12 | Baseline, Month 12 | ACTH testing was a standard procedure to measure the levels of cortisol in the blood following the injection of a synthetic form of ACTH (250 microgram \[mcg\]). The type of synthetic and route of administration was per investigator discretion. The change from baseline in cortisol levels was calculated at Month 12 and reported in this outcome measure. |
| Change From Baseline in Cortisol Level After ACTH Stimulation at Month 24 | Baseline, Month 24 | ACTH testing was a standard procedure to measure the levels of cortisol in the blood following the injection of a synthetic form of ACTH (250 microgram \[mcg\]). The type of synthetic and route of administration was per investigator discretion. The change from baseline in cortisol levels was calculated at Month 24 and reported in this outcome measure. |
| Change From Baseline in Cortisol Level After ACTH Stimulation at Month 36 | Baseline, Month 36 | ACTH testing was a standard procedure to measure the levels of cortisol in the blood following the injection of a synthetic form of ACTH (250 microgram \[mcg\]). The type of synthetic and route of administration was per investigator discretion. The change from baseline in cortisol levels was calculated at Month 36 and reported in this outcome measure. |
| Change From Baseline in Cortisol Level After ACTH Stimulation at Month 48 | Baseline, Month 48 | ACTH testing was a standard procedure to measure the levels of cortisol in the blood following the injection of a synthetic form of ACTH (250 microgram \[mcg\]). The type of synthetic and route of administration was per investigator discretion. The change from baseline in cortisol levels was calculated at Month 48 and reported in this outcome measure. |
| Change From Baseline in Cortisol Level After ACTH Stimulation at EOS (Up to Month 53) | Baseline, EOS (Up to Month 53) | ACTH testing was a standard procedure to measure the levels of cortisol in the blood following the injection of a synthetic form of ACTH (250 microgram \[mcg\]). The type of synthetic and route of administration was per investigator discretion. The change from baseline in cortisol levels was calculated at EOS (up to Month 53) and reported in this outcome measure. |
| Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments | From start of study drug administration up to EOS (Up to Month 53) | Clinical laboratory parameters included hematology, chemistry, urinalysis; urine pregnancy test. Number of participants with potential clinically significant changes in laboratory parameters which were deemed clinically meaningful by the investigator were reported. |
Countries
United States
Participant flow
Recruitment details
This study was conducted at 44 active sites in North America from 05 October 2017 (first participant enrolled) to 26 April 2022 (last participant completed).
Pre-assignment details
A total of 174 participants completed the study SHP621-302 (NCT02736409), of which 133 consented to participate and were enrolled in this long-term safety and efficacy study (SHP621-303). A total of 131 participants were treated in this study. This study was terminated as per sponsor's decision.
Participants by arm
| Arm | Count |
|---|---|
| BOS-BOS Participants who were randomized to BOS and PBO in Study SHP621-301 (NCT02605837) and to BOS in Study SHP621-302 (NCT02736409), were enrolled in Study SHP621-303 to receive 10 mL of BOS at a concentration of 0.2 mg/mL, twice daily, for up to 4 years 5 months. | 121 |
| PBO-BOS Participants who were randomized to and fully responded to BOS treatment in Study SHP621-301 (NCT02605837), were randomized to PBO in Study SHP621-302 (NCT02736409) and enrolled in Study SHP621-303 to receive 10 mL of BOS at a concentration of 0.2 mg/mL, twice daily, for up to 4 years 5 months. | 10 |
| Total | 131 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 0 |
| Overall Study | Death | 2 | 0 |
| Overall Study | Lost to Follow-up | 12 | 2 |
| Overall Study | Non-Compliance with Study Drug | 2 | 0 |
| Overall Study | Not treated | 1 | 1 |
| Overall Study | Physician Decision | 4 | 1 |
| Overall Study | Pregnancy | 2 | 0 |
| Overall Study | Site Terminated by Sponsor | 4 | 0 |
| Overall Study | Study Terminated by Sponsor | 56 | 6 |
| Overall Study | Withdrawal by Parent/Guardian | 2 | 0 |
| Overall Study | Withdrawal by Subject | 31 | 1 |
Baseline characteristics
| Characteristic | BOS-BOS | PBO-BOS | Total |
|---|---|---|---|
| Age, Continuous | 33.9 years STANDARD_DEVIATION 12.65 | 40.2 years STANDARD_DEVIATION 9.97 | 34.4 years STANDARD_DEVIATION 12.55 |
| Age, Customized 18 or more years | 99 Participants | 10 Participants | 109 Participants |
| Age, Customized Less than 18 years | 22 Participants | 0 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 117 Participants | 10 Participants | 127 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 0 Participants | 6 Participants |
| Race (NIH/OMB) White | 109 Participants | 10 Participants | 119 Participants |
| Sex: Female, Male Female | 47 Participants | 2 Participants | 49 Participants |
| Sex: Female, Male Male | 74 Participants | 8 Participants | 82 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 121 | 0 / 10 |
| other Total, other adverse events | 90 / 121 | 7 / 10 |
| serious Total, serious adverse events | 11 / 121 | 0 / 10 |
Outcome results
Primary
Change From Baseline in BMD For Adolescents Assessed by DXA Scan at EOS (Up to Month 53)
The sites for DXA measurement were the lumbar spine at lumbar vertebrae 1 to 4 (L1-L4) and whole body. DXA scans for determination of BMD and body composition was performed in participants aged 11-17 years. Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. In this study, the BMD Z-score is considered abnormal when the z-score is \< -2, suggesting a worse outcome (i.e., osteoporosis) and vice versa. Change from baseline in BMD for adolescents assessed by DXA Scan at EOS (up to Month 53) was reported.
Time frame: Baseline, EOS (Up to Month 53)
Population: The safety set consisted of all participants who received at least 1 dose of BOS. Here, overall number of participants analyzed signified participants who were evaluable for this outcome measure and number analyzed signifies participants who were evaluable for given categories. DXA was performed for participants aged 11-17 years only and no participants of this age range were present in PBO-BOS group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BOS-BOS | Change From Baseline in BMD For Adolescents Assessed by DXA Scan at EOS (Up to Month 53) | Baseline Lumbar Spine (L1- L4) | -0.525 Z-score | Standard Deviation 1.0583 |
| BOS-BOS | Change From Baseline in BMD For Adolescents Assessed by DXA Scan at EOS (Up to Month 53) | Change at EOS (Up to Month 53) Lumbar Spine (L1- L4) | 0.482 Z-score | Standard Deviation 0.6539 |
| BOS-BOS | Change From Baseline in BMD For Adolescents Assessed by DXA Scan at EOS (Up to Month 53) | Baseline Whole Body | -0.565 Z-score | Standard Deviation 0.9464 |
| BOS-BOS | Change From Baseline in BMD For Adolescents Assessed by DXA Scan at EOS (Up to Month 53) | Change at EOS (Up to Month 53) Whole Body | 0.350 Z-score | Standard Deviation 0.7541 |
Primary
Change From Baseline in BMD For Adolescents Assessed by DXA Scan at Month 24
The sites for DXA measurement were the lumbar spine at lumbar vertebrae 1 to 4 (L1-L4) and whole body. DXA scans for determination of BMD and body composition was performed in participants aged 11-17 years. Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. In this study, the BMD Z-score is considered abnormal when the z-score is \<-2, suggesting a worse outcome (i.e., osteoporosis) and vice versa. Change from baseline in BMD for adolescents assessed by DXA Scan at Month 24 was reported.
Time frame: Baseline, Month 24
Population: The safety set consisted of all participants who received at least 1 dose of BOS. Here, overall number of participants analyzed signified participants who were evaluable for this outcome measure and number analyzed signifies participants who were evaluable for given categories. DXA was performed for participants aged 11-17 years only and no participants of this age range were present in PBO-BOS group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BOS-BOS | Change From Baseline in BMD For Adolescents Assessed by DXA Scan at Month 24 | Baseline Whole Body | -0.565 Z-score | Standard Deviation 0.9464 |
| BOS-BOS | Change From Baseline in BMD For Adolescents Assessed by DXA Scan at Month 24 | Change at Month 24 Whole Body | 0.092 Z-score | Standard Deviation 0.5326 |
| BOS-BOS | Change From Baseline in BMD For Adolescents Assessed by DXA Scan at Month 24 | Baseline Lumbar Spine (L1- L4) | -0.525 Z-score | Standard Deviation 1.0583 |
| BOS-BOS | Change From Baseline in BMD For Adolescents Assessed by DXA Scan at Month 24 | Change at Month 24 Lumbar Spine (L1- L4) | 0.445 Z-score | Standard Deviation 0.7312 |
Primary
Change From Baseline in BMD For Adolescents Assessed by DXA Scan at Month 36
The sites for DXA measurement were the lumbar spine at lumbar vertebrae 1 to 4 (L1-L4) and whole body. DXA scans for determination of BMD and body composition was performed in participants aged 11-17 years. Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. In this study, the BMD Z-score is considered abnormal when the z-score is \< -2, suggesting a worse outcome (i.e., osteoporosis) and vice versa. Change from baseline in BMD for adolescents assessed by DXA Scan at Month 36 was reported.
Time frame: Baseline, Month 36
Population: The safety set consisted of all participants who received at least 1 dose of BOS. Here, overall number of participants analyzed signified participants who were evaluable for this outcome measure and number analyzed signifies participants who were evaluable for given categories. DXA was performed for participants aged 11-17 years only and no participants of this age range were present in PBO-BOS group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BOS-BOS | Change From Baseline in BMD For Adolescents Assessed by DXA Scan at Month 36 | Change at Month 36 Lumbar Spine (L1- L4) | 0.603 Z-score | Standard Deviation 0.9089 |
| BOS-BOS | Change From Baseline in BMD For Adolescents Assessed by DXA Scan at Month 36 | Baseline Whole Body | -0.565 Z-score | Standard Deviation 0.9464 |
| BOS-BOS | Change From Baseline in BMD For Adolescents Assessed by DXA Scan at Month 36 | Change at Month 36 Whole Body | 0.870 Z-score | Standard Deviation 0.6447 |
| BOS-BOS | Change From Baseline in BMD For Adolescents Assessed by DXA Scan at Month 36 | Baseline Lumbar Spine (L1- L4) | -0.525 Z-score | Standard Deviation 1.0583 |
Primary
Change From Baseline in BMD For Adolescents Assessed by DXA Scan at Month 48
The sites for DXA measurement were the lumbar spine at lumbar vertebrae 1 to 4 (L1-L4) and whole body. DXA scans for determination of BMD and body composition was performed in participants aged 11-17 years. Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. In this study, the BMD Z-score is considered abnormal when the z-score is \< -2, suggesting a worse outcome (i.e., osteoporosis) and vice versa. Change from baseline in BMD for adolescents assessed by DXA Scan at Month 48 was reported.
Time frame: Baseline, Month 48
Population: The safety set consisted of all participants who received at least 1 dose of BOS. Here, overall number of participants analyzed signified participants who were evaluable for this outcome measure and number analyzed signifies participants who were evaluable for given categories. DXA was performed for participants aged 11-17 years only and no participants of this age range were present in PBO-BOS group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BOS-BOS | Change From Baseline in BMD For Adolescents Assessed by DXA Scan at Month 48 | Baseline Lumbar Spine (L1- L4) | -0.525 Z-score | Standard Deviation 1.0583 |
| BOS-BOS | Change From Baseline in BMD For Adolescents Assessed by DXA Scan at Month 48 | Change at Month 48 Lumbar Spine (L1- L4) | 0.657 Z-score | Standard Deviation 0.4813 |
| BOS-BOS | Change From Baseline in BMD For Adolescents Assessed by DXA Scan at Month 48 | Baseline Whole Body | -0.565 Z-score | Standard Deviation 0.9464 |
| BOS-BOS | Change From Baseline in BMD For Adolescents Assessed by DXA Scan at Month 48 | Change at Month 48 Whole Body | 0.817 Z-score | Standard Deviation 0.4521 |
Primary
Change From Baseline in Bone Mineral Density (BMD) For Adolescents Assessed by Dual-Energy X-ray Absorptiometry (DXA) Scan at Month 12
The sites for DXA measurement were the lumbar spine at lumbar vertebrae 1 to 4 (L1-L4) and whole body. DXA scans for determination of BMD and body composition was performed in participants aged 11-17 years. Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. In this study, the BMD Z-score is considered abnormal when the z-score is less than (\<) -2, suggesting a worse outcome (i.e., osteoporosis). Change from baseline in BMD for adolescents assessed by DXA Scan at Month 12 was reported.
Time frame: Baseline, Month 12
Population: The safety set consisted of all participants who received at least 1 dose of BOS. Here, overall number of participants analyzed signified participants who were evaluable for this outcome measure and number analyzed signifies participants who were evaluable for given categories. DXA was performed for participants aged 11-17 years only and no participants of this age range were present in PBO-BOS group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BOS-BOS | Change From Baseline in Bone Mineral Density (BMD) For Adolescents Assessed by Dual-Energy X-ray Absorptiometry (DXA) Scan at Month 12 | Baseline Whole Body | -0.565 Z-score | Standard Deviation 0.9464 |
| BOS-BOS | Change From Baseline in Bone Mineral Density (BMD) For Adolescents Assessed by Dual-Energy X-ray Absorptiometry (DXA) Scan at Month 12 | Baseline Lumbar Spine (L1- L4) | -0.525 Z-score | Standard Deviation 1.0583 |
| BOS-BOS | Change From Baseline in Bone Mineral Density (BMD) For Adolescents Assessed by Dual-Energy X-ray Absorptiometry (DXA) Scan at Month 12 | Change at Month 12 Lumbar Spine (L1- L4) | 0.315 Z-score | Standard Deviation 0.3618 |
| BOS-BOS | Change From Baseline in Bone Mineral Density (BMD) For Adolescents Assessed by Dual-Energy X-ray Absorptiometry (DXA) Scan at Month 12 | Change at Month 12 Whole Body | 0.250 Z-score | Standard Deviation 0.2599 |
Primary
Change From Baseline in Cortisol Level After ACTH Stimulation at EOS (Up to Month 53)
ACTH testing was a standard procedure to measure the levels of cortisol in the blood following the injection of a synthetic form of ACTH (250 microgram \[mcg\]). The type of synthetic and route of administration was per investigator discretion. The change from baseline in cortisol levels was calculated at EOS (up to Month 53) and reported in this outcome measure.
Time frame: Baseline, EOS (Up to Month 53)
Population: The safety set consisted of all participants who received at least 1 dose of BOS. Here, overall number of participants analyzed signified participants who were evaluable for this outcome measure and number analyzed signifies participants who were evaluable for given categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BOS-BOS | Change From Baseline in Cortisol Level After ACTH Stimulation at EOS (Up to Month 53) | Baseline | 10.49 mcg/dL | Standard Deviation 5.508 |
| BOS-BOS | Change From Baseline in Cortisol Level After ACTH Stimulation at EOS (Up to Month 53) | Change at EOS (Up to Month 53) | 0.96 mcg/dL | Standard Deviation 5.362 |
| PBO-BOS | Change From Baseline in Cortisol Level After ACTH Stimulation at EOS (Up to Month 53) | Baseline | 13.15 mcg/dL | Standard Deviation 7.188 |
| PBO-BOS | Change From Baseline in Cortisol Level After ACTH Stimulation at EOS (Up to Month 53) | Change at EOS (Up to Month 53) | 1.06 mcg/dL | Standard Deviation 6.138 |
Primary
Change From Baseline in Cortisol Level After ACTH Stimulation at Month 24
ACTH testing was a standard procedure to measure the levels of cortisol in the blood following the injection of a synthetic form of ACTH (250 microgram \[mcg\]). The type of synthetic and route of administration was per investigator discretion. The change from baseline in cortisol levels was calculated at Month 24 and reported in this outcome measure.
Time frame: Baseline, Month 24
Population: The safety set consisted of all participants who received at least 1 dose of BOS. Here, overall number of participants analyzed signified participants who were evaluable for this outcome measure and number analyzed signifies participants who were evaluable for given categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BOS-BOS | Change From Baseline in Cortisol Level After ACTH Stimulation at Month 24 | Baseline | 10.49 mcg/dL | Standard Deviation 5.508 |
| BOS-BOS | Change From Baseline in Cortisol Level After ACTH Stimulation at Month 24 | Change At Month 24 | 0.81 mcg/dL | Standard Deviation 6.127 |
| PBO-BOS | Change From Baseline in Cortisol Level After ACTH Stimulation at Month 24 | Baseline | 13.15 mcg/dL | Standard Deviation 7.188 |
| PBO-BOS | Change From Baseline in Cortisol Level After ACTH Stimulation at Month 24 | Change At Month 24 | -2.58 mcg/dL | Standard Deviation 3.727 |
Primary
Change From Baseline in Cortisol Level After ACTH Stimulation at Month 36
ACTH testing was a standard procedure to measure the levels of cortisol in the blood following the injection of a synthetic form of ACTH (250 microgram \[mcg\]). The type of synthetic and route of administration was per investigator discretion. The change from baseline in cortisol levels was calculated at Month 36 and reported in this outcome measure.
Time frame: Baseline, Month 36
Population: The safety set consisted of all participants who received at least 1 dose of BOS. Here, overall number of participants analyzed signified participants who were evaluable for this outcome measure and number analyzed signifies participants who were evaluable for given categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BOS-BOS | Change From Baseline in Cortisol Level After ACTH Stimulation at Month 36 | Baseline | 10.49 mcg/dL | Standard Deviation 5.508 |
| BOS-BOS | Change From Baseline in Cortisol Level After ACTH Stimulation at Month 36 | Change At Month 36 | 0.70 mcg/dL | Standard Deviation 5.773 |
| PBO-BOS | Change From Baseline in Cortisol Level After ACTH Stimulation at Month 36 | Baseline | 13.15 mcg/dL | Standard Deviation 7.188 |
| PBO-BOS | Change From Baseline in Cortisol Level After ACTH Stimulation at Month 36 | Change At Month 36 | -1.63 mcg/dL | Standard Deviation 3.845 |
Primary
Change From Baseline in Cortisol Level After ACTH Stimulation at Month 48
ACTH testing was a standard procedure to measure the levels of cortisol in the blood following the injection of a synthetic form of ACTH (250 microgram \[mcg\]). The type of synthetic and route of administration was per investigator discretion. The change from baseline in cortisol levels was calculated at Month 48 and reported in this outcome measure.
Time frame: Baseline, Month 48
Population: The safety set consisted of all participants who received at least 1 dose of BOS. Here, overall number of participants analyzed signified participants who were evaluable for this outcome measure and number analyzed signifies participants who were evaluable for given categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BOS-BOS | Change From Baseline in Cortisol Level After ACTH Stimulation at Month 48 | Baseline | 10.49 mcg/dL | Standard Deviation 5.508 |
| BOS-BOS | Change From Baseline in Cortisol Level After ACTH Stimulation at Month 48 | Change At Month 48 | 2.02 mcg/dL | Standard Deviation 4.759 |
| PBO-BOS | Change From Baseline in Cortisol Level After ACTH Stimulation at Month 48 | Baseline | 13.15 mcg/dL | Standard Deviation 7.188 |
| PBO-BOS | Change From Baseline in Cortisol Level After ACTH Stimulation at Month 48 | Change At Month 48 | 0.20 mcg/dL | Standard Deviation 5.17 |
Primary
Change From Baseline in Cortisol Level After Adrenocorticotropic Hormone (ACTH) Stimulation at Month 12
ACTH testing was a standard procedure to measure the levels of cortisol in the blood following the injection of a synthetic form of ACTH (250 microgram \[mcg\]). The type of synthetic and route of administration was per investigator discretion. The change from baseline in cortisol levels was calculated at Month 12 and reported in this outcome measure.
Time frame: Baseline, Month 12
Population: The safety set consisted of all participants who received at least 1 dose of BOS. Here, overall number of participants analyzed signified participants who were evaluable for this outcome measure and number analyzed signifies participants who were evaluable for given categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BOS-BOS | Change From Baseline in Cortisol Level After Adrenocorticotropic Hormone (ACTH) Stimulation at Month 12 | Baseline | 10.49 micrograms per deciliter (mcg/dL) | Standard Deviation 5.508 |
| BOS-BOS | Change From Baseline in Cortisol Level After Adrenocorticotropic Hormone (ACTH) Stimulation at Month 12 | Change At Month 12 | 0.06 micrograms per deciliter (mcg/dL) | Standard Deviation 6.215 |
| PBO-BOS | Change From Baseline in Cortisol Level After Adrenocorticotropic Hormone (ACTH) Stimulation at Month 12 | Baseline | 13.15 micrograms per deciliter (mcg/dL) | Standard Deviation 7.188 |
| PBO-BOS | Change From Baseline in Cortisol Level After Adrenocorticotropic Hormone (ACTH) Stimulation at Month 12 | Change At Month 12 | 6.77 micrograms per deciliter (mcg/dL) | Standard Deviation 8.835 |
Primary
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Participants were assessed by investigator for any clinically significant changes in vital parameters like temperature, systolic and diastolic blood pressure, pulse, respiratory rate, BMI, and weight. Vital signs were assessed after the participant had been in a supine position for at least 5 minutes immediately prior to the assessment. The criteria for clinically significant change was as per the investigators discretion.
Time frame: From start of study drug administration up to EOS (Up to Month 53)
Population: The safety set consisted of all participants who received at least 1 dose of BOS.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BOS-BOS | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 Participants |
| PBO-BOS | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 Participants |
Primary
Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments
Clinical laboratory parameters included hematology, chemistry, urinalysis; urine pregnancy test. Number of participants with potential clinically significant changes in laboratory parameters which were deemed clinically meaningful by the investigator were reported.
Time frame: From start of study drug administration up to EOS (Up to Month 53)
Population: The safety set consisted of all participants who received at least 1 dose of BOS.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BOS-BOS | Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments | 0 Participants |
| PBO-BOS | Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments | 0 Participants |
Primary
Number of Participants With Clinically Significant Physical Examination Findings
Number of participants with clinically significant physical examination findings were reported. Clinical significance was determined by investigator.
Time frame: From start of study drug administration up to EOS (Up to Month 53)
Population: The safety set consisted of all participants who received at least 1 dose of BOS.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BOS-BOS | Number of Participants With Clinically Significant Physical Examination Findings | Moon Face | 0 Participants |
| BOS-BOS | Number of Participants With Clinically Significant Physical Examination Findings | Hirsutism | 0 Participants |
| BOS-BOS | Number of Participants With Clinically Significant Physical Examination Findings | Insomnia | 0 Participants |
| BOS-BOS | Number of Participants With Clinically Significant Physical Examination Findings | Mood swings | 0 Participants |
| BOS-BOS | Number of Participants With Clinically Significant Physical Examination Findings | Depression | 1 Participants |
| BOS-BOS | Number of Participants With Clinically Significant Physical Examination Findings | Acne | 2 Participants |
| PBO-BOS | Number of Participants With Clinically Significant Physical Examination Findings | Depression | 0 Participants |
| PBO-BOS | Number of Participants With Clinically Significant Physical Examination Findings | Mood swings | 0 Participants |
| PBO-BOS | Number of Participants With Clinically Significant Physical Examination Findings | Moon Face | 0 Participants |
| PBO-BOS | Number of Participants With Clinically Significant Physical Examination Findings | Acne | 0 Participants |
| PBO-BOS | Number of Participants With Clinically Significant Physical Examination Findings | Insomnia | 0 Participants |
| PBO-BOS | Number of Participants With Clinically Significant Physical Examination Findings | Hirsutism | 0 Participants |
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. A Serious Adverse Event (SAE) was any untoward medical occurrence (whether considered to be related to investigational product or not) that at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital abnormality/birth defect, and is an important medical event. Both serious and Non-serious TEAEs were reported in this outcome measure. TEAEs were defined as AEs with a start date on or after the first dose of investigational product or a start date before the date of the first dose of investigational product that increased in severity or after the date of the first dose.
Time frame: From start of study drug administration up to End of study (EOS) (Up to Month 53)
Population: The safety set consisted of all participants who received at least 1 dose of BOS.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BOS-BOS | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 93 Participants |
| BOS-BOS | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 11 Participants |
| PBO-BOS | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 7 Participants |
| PBO-BOS | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 0 Participants |