Prader-Willi Syndrome
Conditions
Brief summary
This is a multicenter, open label, multi cohort study to evaluate the efficacy and safety of somatropin in a cohort of Japanese participants with PWS.
Interventions
BIOLOGICALsomatropin - GH naïve pediatric cohort
somatropin 0.245 mg/kg/week
BIOLOGICALsomatropin - GH treated cohort
somatropin 0.084 mg/kg/week
BIOLOGICALsomatropin - adult cohort
somatropin 0.084 mg/kg/week
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
0 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female participants with documentation of genetically confirmed diagnosis of PWS. 2. No plan to initiate a new treatment that may affect the body composition, such as gonadal hormone replacement therapy. 3. Currently on appropriate diet and exercise programs and willing to continue throughout the study period at the discretion of the investigator. 4. Participants, and if required by local/site regulations their parent(s)/legal guardian(s) must be willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures. 5. Evidence of a personally signed and dated ICD (and written assent where applicable based on age and country regulation) indicating that the participant or a legally acceptable representative/parent(s)/legal guardian has been informed of all pertinent aspects of the study. Refer to Appendix 1 for the detailed process of obtaining consent. For inclusion of GH naïve pediatric cohort, participants must meet criteria 6 to 8: 6. 18 years or younger. 7. Naïve to GH treatment. 8. Tanner stage 1 (for testes in males, for breasts in females). For inclusion of GH treated pediatric cohort, participants must meet criteria 9 and 10: 9. Continued GH treatment for at least 2 years with stable dose for the last 6 months and being on GH at time of inclusion. The recent dose should be higher than 0.084 mg/kg/week. 10. Participants who are about to complete GH treatment for his/her short stature (eg, due to meeting the treatment stopping criteria defined as a height SDS more than -2.5 for Japanese adult standards). For inclusion of adult cohort, participants must meet criteria 11 to 13: 11. 18 years of chronological age or older at Day 1 visit. 12. Off from GH treatment for at least 1 year. 13. Serum IGF-I level within +2 SDS, adjusted for age and sex.
Exclusion criteria
1. Participants with uncontrolled diabetes at the discretion of the investigator. 2. Participants with malignant tumors. 3. Participants with severe obesity or serious respiratory impairment. 4. Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study. 5. Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half- lives preceding the first dose of study intervention used in this study (whichever is longer). 6. Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Month 12 in Lean Body Mass Measured by Dual-Energy X-ray Absorptiometry (DEXA): Adult Cohort | Baseline, Month 12 | Lean body mass, a measurement of body composition, was assessed by DEXA scan, and calculated as lean body mass (%) = lean body mass kilogram (kg) / (lean body mass \[kg\] + fat mass \[kg\]) \*100. |
| Change From Baseline to Month 12 in Lean Body Mass Measured by DEXA: GH Naive Pediatric and GH Treated Pediatric Cohort | Baseline, Month 12 | Lean body mass, a measurement of body composition, was assessed by DEXA scan, and calculated as lean body mass (%) = lean body mass (kg) / (lean body mass \[kg\] + fat mass \[kg\])\*100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Month 12 in Body Fat (Percentage) Measured by DEXA: Adult Cohort | Baseline, Month 12 | Body fat was assessed by DEXA scan. and calculated as body fat (%) = body fat (kg) / \[lean body mass (kg) + body fat (kg)\]\*100. |
| Change From Baseline to Month 12 in Body Fat (Percentage) Measured by DEXA: GH Naive Pediatric and GH Treated Pediatric Cohort | Baseline, Month 12 | Body fat was assessed by DEXA scan. and calculated as body fat (%) = body fat (kg) / \[lean body mass (kg) + body fat (kg)\]\*100. |
| Change From Baseline to Month 12 in Adipose Tissue Distribution Measured by Abdominal Computed Tomography (CT) | Baseline, Month 12 | Adipose tissue distribution was measured by abdominal CT. Areas of subcutaneous adipose tissue (SAT) (centimeter square \[cm\^2\]), visceral adipose tissue (VAT) (cm\^2) were measured at the level of the umbilicus by abdominal CT. |
| Change From Baseline to Month 12 in Lean Body Mass Measured by Bioelectrical Impedance Analysis (BIA)-Adult Cohort | Baseline, Month 12 | Lean body mass, a measurement of body composition, was assessed by DEXA scan, and calculated as lean body mass (%) = lean body mass (kg) / (lean body mass \[kg\] + fat mass \[kg\])\*100. |
| Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events | From day 1 up to 28 days after end of study treatment (maximum duration up to 38 months) | An adverse event was any untoward medical occurrence in administered medicinal product, event need not necessarily have a causal relationship with product treatment or usage. A serious adverse event was any untoward medical occurrence in a participant administered a medicinal or nutritional product (including pediatric formulas) at any dose that: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); resulted in congenital anomaly/birth defect. Treatment emergent AEs were events emerged during treatment period and were absent before treatment or that worsened relative to pretreatment state. TEAEs consist of SAEs and non-SAEs |
| Number of Participants With Laboratory Test Abnormalities | From Day 1 up to 28 days after end of study treatment (maximum duration up to 38 months) | Criteria for abnormal laboratory values for chemistry parameters: alanine aminotransferase, alkaline phosphatase greater than (\>) 3.0\*upper limit of normal (ULN), albumin \> 1.2\*ULN, urea nitrogen millimoles per liter (mmol/L) \> 1.3\*ULN, HDL cholesterol mmol/L less than (\<) 0.8\* lower limit of normal (LLN), LDL cholesterol mmol/L \>1.2\*ULN, triglycerides mmol/L \> 1.3\*ULN, thyrotropin milliunits per liter (mU/L) \<0.8\*LLN and \>1.2\*ULN, glucose (mmol/L) \>1.5\*ULN, hemoglobin A1C liter of cells per liter of blood (L/L) \>1.3\*ULN. |
| Bone Maturation | 12 months | Bone maturation is the process whereby the tissue undergoes changes from the embryonic rudiment of bone to the adult form. Bone maturation was calculated as bone age divided by chronological age. Participants with bone maturation value greater than 1 is presented in this outcome measure. |
| Change From Baseline to Month 6 in Lean Body Mass Measured by DEXA: Adult Cohort Only | Baseline, Month 6 | Lean body mass, a measurement of body composition, was assessed by DEXA scan, and calculated as lean body mass (%) = lean body mass (kg) / (lean body mass \[kg\] + fat mass \[kg\])\*100. |
| Change From Baseline to Month 12 in Lean Body Mass Measured by BIA-GH Naive Pediatric and GH Treated Pediatric Cohort | Baseline, Month 12 | Lean body mass, a measurement of body composition, was assessed by DEXA scan, and calculated as lean body mass (%) = lean body mass (kg) / (lean body mass \[kg\] + fat mass \[kg\])\*100. |
Countries
Japan
Participant flow
Recruitment details
Participants diagnosed with Prader-Willi syndrome (PWS ) received somatropin, a recombinant human growth hormone (r-hGH) in this study.
Pre-assignment details
This study had 3 cohorts (GH naive pediatric cohort, GH treated pediatric cohort and adult cohort).
Participants by arm
| Arm | Count |
|---|---|
| GH Naive Pediatric Cohort Participants 18 years or younger, naive to GH treatment, received somatropin 0.245 mg/kg/week subcutaneously. Treatment period was of 12 months and extension period was of 36 months. Participants were followed up to 28 days. | 6 |
| GH Treated Pediatric Cohort Participants 18 years or younger, who continued GH treatment for at least 2 years with stable dose for the last 6 months and were on GH at time of inclusion, received somatropin 0.084 mg/kg/week subcutaneously. The dosage was adjusted according to participants symptoms and IGF-1 levels with maximum dose up to 1.6 mg/day. Treatment period was of 12 months and extension period was of 36 months. Participants were followed up to 28 days. | 7 |
| Adult Cohort Adult participants who were off from GH treatment for at least 1 year, initially received somatropin 0.042 mg/kg/week subcutaneously. Dose was titrated up to 0.084 mg/kg/week from Month 1 visit. The dosage was adjusted according to participants symptoms and serum IGF-1 levels with maximum dose up to 1.6 mg/day. Treatment period was of 12 months and extension period was of 36 months. Participants were followed up to 28 days. | 20 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Extension Period | Adverse Event | 0 | 0 | 3 |
| Extension Period | Other | 0 | 0 | 1 |
| Extension Period | Physician Decision | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | Total | Adult Cohort | GH Treated Pediatric Cohort | GH Naive Pediatric Cohort |
|---|---|---|---|---|
| Age, Customized 13-17 years | 5 Participants | 0 Participants | 5 Participants | 0 Participants |
| Age, Customized 18-44 years | 21 Participants | 20 Participants | 1 Participants | 0 Participants |
| Age, Customized 6-12 years | 4 Participants | 0 Participants | 1 Participants | 3 Participants |
| Age, Customized Less than (<6) years | 3 Participants | 0 Participants | 0 Participants | 3 Participants |
| Age, Customized More than equal to (>=) 45 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 33 Participants | 20 Participants | 7 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 33 Participants | 20 Participants | 7 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 18 Participants | 13 Participants | 3 Participants | 2 Participants |
| Sex: Female, Male Male | 15 Participants | 7 Participants | 4 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 7 | 0 / 20 |
| other Total, other adverse events | 5 / 6 | 7 / 7 | 19 / 20 |
| serious Total, serious adverse events | 0 / 6 | 1 / 7 | 3 / 20 |
Outcome results
Primary
Change From Baseline to Month 12 in Lean Body Mass Measured by DEXA: GH Naive Pediatric and GH Treated Pediatric Cohort
Lean body mass, a measurement of body composition, was assessed by DEXA scan, and calculated as lean body mass (%) = lean body mass (kg) / (lean body mass \[kg\] + fat mass \[kg\])\*100.
Time frame: Baseline, Month 12
Population: Efficacy evaluable set included all participants assigned to study intervention and who took at least one dose of study intervention and had at least one efficacy evaluation. Here Number of Participants Analyzed signifies participants evaluable for this outcome measure and this time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adult Cohort | Change From Baseline to Month 12 in Lean Body Mass Measured by DEXA: GH Naive Pediatric and GH Treated Pediatric Cohort | 4.59 Percentage of body mass | Standard Deviation 4.49 |
| GH Treated Pediatric Cohort | Change From Baseline to Month 12 in Lean Body Mass Measured by DEXA: GH Naive Pediatric and GH Treated Pediatric Cohort | -1.34 Percentage of body mass | Standard Deviation 3.238 |
Primary
Change From Baseline to Month 12 in Lean Body Mass Measured by Dual-Energy X-ray Absorptiometry (DEXA): Adult Cohort
Lean body mass, a measurement of body composition, was assessed by DEXA scan, and calculated as lean body mass (%) = lean body mass kilogram (kg) / (lean body mass \[kg\] + fat mass \[kg\]) \*100.
Time frame: Baseline, Month 12
Population: Efficacy evaluable set included all participants assigned to study intervention and who took at least one dose of study intervention and had at least one efficacy evaluation. Here Number of Participants Analyzed signifies participants evaluable for this outcome measure and this time point.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Adult Cohort | Change From Baseline to Month 12 in Lean Body Mass Measured by Dual-Energy X-ray Absorptiometry (DEXA): Adult Cohort | 3.09 Percentage of body mass |
Secondary
Bone Maturation
Bone maturation is the process whereby the tissue undergoes changes from the embryonic rudiment of bone to the adult form. Bone maturation was calculated as bone age divided by chronological age. Participants with bone maturation value greater than 1 is presented in this outcome measure.
Time frame: 12 months
Population: FAS included all participants assigned to study intervention and who took at least one dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adult Cohort | Bone Maturation | 4 Participants |
| GH Treated Pediatric Cohort | Bone Maturation | 0 Participants |
Secondary
Change From Baseline to Month 12 in Adipose Tissue Distribution Measured by Abdominal Computed Tomography (CT)
Adipose tissue distribution was measured by abdominal CT. Areas of subcutaneous adipose tissue (SAT) (centimeter square \[cm\^2\]), visceral adipose tissue (VAT) (cm\^2) were measured at the level of the umbilicus by abdominal CT.
Time frame: Baseline, Month 12
Population: Efficacy evaluable set included all participants assigned to study intervention and who took at least one dose of study intervention and had at least one efficacy evaluation. Here Number of Participants Analyzed signifies participants evaluable for this outcome measure and this time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Adult Cohort | Change From Baseline to Month 12 in Adipose Tissue Distribution Measured by Abdominal Computed Tomography (CT) | Change at Month 12, SAT | 60.423 Centimeter square (cm^2) | Standard Deviation 138.2001 |
| Adult Cohort | Change From Baseline to Month 12 in Adipose Tissue Distribution Measured by Abdominal Computed Tomography (CT) | Change at Month 12, VAT | 4.825 Centimeter square (cm^2) | Standard Deviation 13.5401 |
| GH Treated Pediatric Cohort | Change From Baseline to Month 12 in Adipose Tissue Distribution Measured by Abdominal Computed Tomography (CT) | Change at Month 12, VAT | -13.403 Centimeter square (cm^2) | Standard Deviation 28.549 |
| GH Treated Pediatric Cohort | Change From Baseline to Month 12 in Adipose Tissue Distribution Measured by Abdominal Computed Tomography (CT) | Change at Month 12, SAT | 102.222 Centimeter square (cm^2) | Standard Deviation 211.9111 |
| Adult Cohort | Change From Baseline to Month 12 in Adipose Tissue Distribution Measured by Abdominal Computed Tomography (CT) | Change at Month 12, SAT | -13.764 Centimeter square (cm^2) | Standard Deviation 31.0212 |
| Adult Cohort | Change From Baseline to Month 12 in Adipose Tissue Distribution Measured by Abdominal Computed Tomography (CT) | Change at Month 12, VAT | -4.040 Centimeter square (cm^2) | Standard Deviation 16.8243 |
Secondary
Change From Baseline to Month 12 in Body Fat (Percentage) Measured by DEXA: Adult Cohort
Body fat was assessed by DEXA scan. and calculated as body fat (%) = body fat (kg) / \[lean body mass (kg) + body fat (kg)\]\*100.
Time frame: Baseline, Month 12
Population: Efficacy evaluable set included all participants assigned to study intervention and who took at least one dose of study intervention and had at least one efficacy evaluation. Here Number of Participants Analyzed signifies participants evaluable for this outcome measure and this time point.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Adult Cohort | Change From Baseline to Month 12 in Body Fat (Percentage) Measured by DEXA: Adult Cohort | -3.09 Percentage of body fat |
Secondary
Change From Baseline to Month 12 in Body Fat (Percentage) Measured by DEXA: GH Naive Pediatric and GH Treated Pediatric Cohort
Body fat was assessed by DEXA scan. and calculated as body fat (%) = body fat (kg) / \[lean body mass (kg) + body fat (kg)\]\*100.
Time frame: Baseline, Month 12
Population: Efficacy evaluable set included all participants assigned to study intervention and who took at least one dose of study intervention and had at least one efficacy evaluation. Here Number of Participants Analyzed signifies participants evaluable for this outcome measure and this time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adult Cohort | Change From Baseline to Month 12 in Body Fat (Percentage) Measured by DEXA: GH Naive Pediatric and GH Treated Pediatric Cohort | -4.59 Percentage of body fat | Standard Deviation 4.49 |
| GH Treated Pediatric Cohort | Change From Baseline to Month 12 in Body Fat (Percentage) Measured by DEXA: GH Naive Pediatric and GH Treated Pediatric Cohort | 1.34 Percentage of body fat | Standard Deviation 3.238 |
Secondary
Change From Baseline to Month 12 in Lean Body Mass Measured by BIA-GH Naive Pediatric and GH Treated Pediatric Cohort
Lean body mass, a measurement of body composition, was assessed by DEXA scan, and calculated as lean body mass (%) = lean body mass (kg) / (lean body mass \[kg\] + fat mass \[kg\])\*100.
Time frame: Baseline, Month 12
Population: Efficacy evaluable set included all participants assigned to study intervention and who took at least one dose of study intervention and had at least one efficacy evaluation. Here Number of Participants Analyzed signifies participants evaluable for this outcome measure and this time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adult Cohort | Change From Baseline to Month 12 in Lean Body Mass Measured by BIA-GH Naive Pediatric and GH Treated Pediatric Cohort | 3.32 Percentage of body mass | Standard Deviation 3.867 |
| GH Treated Pediatric Cohort | Change From Baseline to Month 12 in Lean Body Mass Measured by BIA-GH Naive Pediatric and GH Treated Pediatric Cohort | 0.58 Percentage of body mass | Standard Deviation 4.711 |
Secondary
Change From Baseline to Month 12 in Lean Body Mass Measured by Bioelectrical Impedance Analysis (BIA)-Adult Cohort
Lean body mass, a measurement of body composition, was assessed by DEXA scan, and calculated as lean body mass (%) = lean body mass (kg) / (lean body mass \[kg\] + fat mass \[kg\])\*100.
Time frame: Baseline, Month 12
Population: Efficacy evaluable set included all participants assigned to study intervention and who took at least one dose of study intervention and had at least one efficacy evaluation. Here Number of Participants Analyzed signifies participants evaluable for this outcome measure and this time point.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Adult Cohort | Change From Baseline to Month 12 in Lean Body Mass Measured by Bioelectrical Impedance Analysis (BIA)-Adult Cohort | 2.03 Percentage of body mass |
Secondary
Change From Baseline to Month 6 in Lean Body Mass Measured by DEXA: Adult Cohort Only
Lean body mass, a measurement of body composition, was assessed by DEXA scan, and calculated as lean body mass (%) = lean body mass (kg) / (lean body mass \[kg\] + fat mass \[kg\])\*100.
Time frame: Baseline, Month 6
Population: Efficacy evaluable set included all participants assigned to study intervention and who took at least one dose of study intervention and had at least one efficacy evaluation.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Adult Cohort | Change From Baseline to Month 6 in Lean Body Mass Measured by DEXA: Adult Cohort Only | 2.38 Percentage of body mass |
Secondary
Number of Participants With Laboratory Test Abnormalities
Criteria for abnormal laboratory values for chemistry parameters: alanine aminotransferase, alkaline phosphatase greater than (\>) 3.0\*upper limit of normal (ULN), albumin \> 1.2\*ULN, urea nitrogen millimoles per liter (mmol/L) \> 1.3\*ULN, HDL cholesterol mmol/L less than (\<) 0.8\* lower limit of normal (LLN), LDL cholesterol mmol/L \>1.2\*ULN, triglycerides mmol/L \> 1.3\*ULN, thyrotropin milliunits per liter (mU/L) \<0.8\*LLN and \>1.2\*ULN, glucose (mmol/L) \>1.5\*ULN, hemoglobin A1C liter of cells per liter of blood (L/L) \>1.3\*ULN.
Time frame: From Day 1 up to 28 days after end of study treatment (maximum duration up to 38 months)
Population: FAS included all participants assigned to study intervention and who took at least one dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Adult Cohort | Number of Participants With Laboratory Test Abnormalities | 5 Participants |
| GH Treated Pediatric Cohort | Number of Participants With Laboratory Test Abnormalities | 3 Participants |
| Adult Cohort | Number of Participants With Laboratory Test Abnormalities | 16 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events
An adverse event was any untoward medical occurrence in administered medicinal product, event need not necessarily have a causal relationship with product treatment or usage. A serious adverse event was any untoward medical occurrence in a participant administered a medicinal or nutritional product (including pediatric formulas) at any dose that: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); resulted in congenital anomaly/birth defect. Treatment emergent AEs were events emerged during treatment period and were absent before treatment or that worsened relative to pretreatment state. TEAEs consist of SAEs and non-SAEs
Time frame: From day 1 up to 28 days after end of study treatment (maximum duration up to 38 months)
Population: Full analysis set (FAS) included all participants assigned to study intervention and who took at least one dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Adult Cohort | Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events | Treatment Emergent SAEs | 0 Participants |
| Adult Cohort | Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events | TEAEs | 5 Participants |
| GH Treated Pediatric Cohort | Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events | Treatment Emergent SAEs | 1 Participants |
| GH Treated Pediatric Cohort | Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events | TEAEs | 7 Participants |
| Adult Cohort | Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events | Treatment Emergent SAEs | 3 Participants |
| Adult Cohort | Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events | TEAEs | 19 Participants |