Trial Outcomes & Findings for ch14.18 Pharmacokinetic Study in High-risk Neuroblastoma (NCT NCT01592045)

NCT ID: NCT01592045

Last Updated: 2015-09-23

Results Overview

Twenty-two PK samples will be obtained at the following timepoints: Courses 1 and 3: Day: 0 Days: 3, 4, 5 and 6: post ch14.18 Days 7:10 to 14 hours post ch14.18 Days 9 to 11: Single sample Days 14 to 17: Single sample Courses 2 and 4: Day 0: Pre-IL-2 Day 7: Pre-ch14.18 Day 10 (Course 4 only): Post ch14.18 End of Treatment: Within 2 weeks post isotretinoin

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

28 participants

Primary outcome timeframe

PK samples obtained during Courses 1 and 3: Days 0, 3, 4, 5, 6, 7, 9, 10, 11, 14, 15, 16, 17; PK samples obtained during Courses 2 and 4: Days 0, 7, 10; End of Treatment

Results posted on

2015-09-23

Participant Flow

Participant milestones

Participant milestones
Measure	Sequence 1 UTC ch14.18 for two courses followed by NCI ch14.18 for three courses ch14.18 -NCI: 25 mg/m\^2/day IV for four consecutive days ch14.18-UTC: 17.5 mg/m\^2/day IV for four consecutive days Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF): GM-CSF will be administered SC at a dose of 250 mcg/m\^2/day for 14 days during Courses 1, 3, and 5. Aldesleukin (IL-2): Aldesleukin (IL-2) will be administered IV at a dose of 3 MIU/m\^2/day for the first week and at a dose of 4.5 MIU/m\^2/day for the second week during Courses 2 and 4. Isotretinoin: Isotretinoin (13-cis-retinoic acid; ISOT) will be administered by mouth over six courses as follows: If weight \> 12 kg: 80 mg/m\^2/dose twice daily (total daily dose is 160 mg/m\^2/day, divided twice daily). If weight ≤ 12 kg: 2.67 mg/kg/dose twice daily (total daily dose is 5.33 mg/kg/day, divided twice daily).	Sequence 2 NCI ch14.18 for two courses followed by UTC ch14.18 for three courses ch14.18 -NCI: 25 mg/m\^2/day IV for four consecutive days ch14.18-UTC: 17.5 mg/m\^2/day IV for four consecutive days Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF): GM-CSF will be administered SC at a dose of 250 mcg/m\^2/day for 14 days during Courses 1, 3, and 5. Aldesleukin (IL-2): Aldesleukin (IL-2) will be administered IV at a dose of 3 MIU/m\^2/day for the first week and at a dose of 4.5 MIU/m\^2/day for the second week during Courses 2 and 4. Isotretinoin: Isotretinoin (13-cis-retinoic acid; ISOT) will be administered by mouth over six courses as follows: If weight \> 12 kg: 80 mg/m\^2/dose twice daily (total daily dose is 160 mg/m\^2/day, divided twice daily). If weight ≤ 12 kg: 2.67 mg/kg/dose twice daily (total daily dose is 5.33 mg/kg/day, divided twice daily).
Overall Study STARTED	14	14
Overall Study Completed Course 1	13	14
Overall Study Completed Course 2	13	13
Overall Study Completed Course 3	11	13
Overall Study Completed Course 4	11	12
Overall Study Completed Course 5	9	12
Overall Study COMPLETED	9	12
Overall Study NOT COMPLETED	5	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Sequence 1 UTC ch14.18 for two courses followed by NCI ch14.18 for three courses ch14.18 -NCI: 25 mg/m\^2/day IV for four consecutive days ch14.18-UTC: 17.5 mg/m\^2/day IV for four consecutive days Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF): GM-CSF will be administered SC at a dose of 250 mcg/m\^2/day for 14 days during Courses 1, 3, and 5. Aldesleukin (IL-2): Aldesleukin (IL-2) will be administered IV at a dose of 3 MIU/m\^2/day for the first week and at a dose of 4.5 MIU/m\^2/day for the second week during Courses 2 and 4. Isotretinoin: Isotretinoin (13-cis-retinoic acid; ISOT) will be administered by mouth over six courses as follows: If weight \> 12 kg: 80 mg/m\^2/dose twice daily (total daily dose is 160 mg/m\^2/day, divided twice daily). If weight ≤ 12 kg: 2.67 mg/kg/dose twice daily (total daily dose is 5.33 mg/kg/day, divided twice daily).	Sequence 2 NCI ch14.18 for two courses followed by UTC ch14.18 for three courses ch14.18 -NCI: 25 mg/m\^2/day IV for four consecutive days ch14.18-UTC: 17.5 mg/m\^2/day IV for four consecutive days Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF): GM-CSF will be administered SC at a dose of 250 mcg/m\^2/day for 14 days during Courses 1, 3, and 5. Aldesleukin (IL-2): Aldesleukin (IL-2) will be administered IV at a dose of 3 MIU/m\^2/day for the first week and at a dose of 4.5 MIU/m\^2/day for the second week during Courses 2 and 4. Isotretinoin: Isotretinoin (13-cis-retinoic acid; ISOT) will be administered by mouth over six courses as follows: If weight \> 12 kg: 80 mg/m\^2/dose twice daily (total daily dose is 160 mg/m\^2/day, divided twice daily). If weight ≤ 12 kg: 2.67 mg/kg/dose twice daily (total daily dose is 5.33 mg/kg/day, divided twice daily).
Overall Study Disease Progression	1	1
Overall Study Adverse Event	1	1
Overall Study Withdrawal by Subject	1	0
Overall Study Moved out of country	2	0

Baseline Characteristics

ch14.18 Pharmacokinetic Study in High-risk Neuroblastoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sequence 1 n=14 Participants UTC ch14.18 for two courses followed by NCI ch14.18 for three courses ch14.18 -NCI: 25 mg/m\^2/day IV for four consecutive days ch14.18-UTC: 17.5 mg/m\^2/day IV for four consecutive days Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF): GM-CSF will be administered SC at a dose of 250 mcg/m\^2/day for 14 days during Courses 1, 3, and 5. Aldesleukin (IL-2): Aldesleukin (IL-2) will be administered IV at a dose of 3 MIU/m\^2/day for the first week and at a dose of 4.5 MIU/m\^2/day for the second week during Courses 2 and 4. Isotretinoin: Isotretinoin (13-cis-retinoic acid; ISOT) will be administered by mouth over six courses as follows: If weight \> 12 kg: 80 mg/m\^2/dose twice daily (total daily dose is 160 mg/m\^2/day, divided twice daily). If weight ≤ 12 kg: 2.67 mg/kg/dose twice daily (total daily dose is 5.33 mg/kg/day, divided twice daily).	Sequence 2 n=14 Participants NCI ch14.18 for two courses followed by UTC ch14.18 for three courses ch14.18 -NCI: 25 mg/m\^2/day IV for four consecutive days ch14.18-UTC: 17.5 mg/m\^2/day IV for four consecutive days Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF): GM-CSF will be administered SC at a dose of 250 mcg/m\^2/day for 14 days during Courses 1, 3, and 5. Aldesleukin (IL-2): Aldesleukin (IL-2) will be administered IV at a dose of 3 MIU/m\^2/day for the first week and at a dose of 4.5 MIU/m\^2/day for the second week during Courses 2 and 4. Isotretinoin: Isotretinoin (13-cis-retinoic acid; ISOT) will be administered by mouth over six courses as follows: If weight \> 12 kg: 80 mg/m\^2/dose twice daily (total daily dose is 160 mg/m\^2/day, divided twice daily). If weight ≤ 12 kg: 2.67 mg/kg/dose twice daily (total daily dose is 5.33 mg/kg/day, divided twice daily).	Total n=28 Participants Total of all reporting groups
Age, Continuous	4 years n=5 Participants	4 years n=7 Participants	4 years n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	8 Participants n=7 Participants	16 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=5 Participants	12 Participants n=7 Participants	22 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) White	12 Participants n=5 Participants	11 Participants n=7 Participants	23 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	14 participants n=5 Participants	14 participants n=7 Participants	28 participants n=5 Participants
Pre-ASCT Response Complete Response (CR)	5 participants n=5 Participants	3 participants n=7 Participants	8 participants n=5 Participants
Pre-ASCT Response Very Good Partial Response (VGPR)	5 participants n=5 Participants	4 participants n=7 Participants	9 participants n=5 Participants
Pre-ASCT Response Partial Response (PR)	4 participants n=5 Participants	7 participants n=7 Participants	11 participants n=5 Participants

PRIMARY outcome

Timeframe: PK samples obtained during Courses 1 and 3: Days 0, 3, 4, 5, 6, 7, 9, 10, 11, 14, 15, 16, 17; PK samples obtained during Courses 2 and 4: Days 0, 7, 10; End of Treatment

Outcome measures

Outcome measures
Measure	UTC ch14.18 n=27 Participants United Therapeutics Manufactured ch14.18	NCI ch14.18 n=27 Participants NCI Manufactured ch14.18
Area Under the Plasma Concentration Curve (AUC)	518 mcg*hr/mL Standard Deviation 418	470 mcg*hr/mL Standard Deviation 376

PRIMARY outcome

Timeframe: PK samples obtained during Courses 1 and 3: Days 0, 3, 4, 5, 6, 7, 9, 10, 11, 14, 15, 16, 17; PK samples obtained during Courses 2 and 4: Days 0, 7, 10; End of Treatment

Outcome measures

Outcome measures
Measure	UTC ch14.18 n=27 Participants United Therapeutics Manufactured ch14.18	NCI ch14.18 n=27 Participants NCI Manufactured ch14.18
Peak Plasma Concentration (Cmax)	6468 ng/mL Standard Deviation 719	6689 ng/mL Standard Deviation 853

Adverse Events

UTC ch14.18

Serious events: 17 serious events

Other events: 27 other events

Deaths: 0 deaths

NCI ch14.18

Serious events: 12 serious events

Other events: 27 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Allison Lim

United Therapeutics Corporation

Phone: 919-425-8799

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Institution and/or Principal Investigator agree not to publish or publicly present any interim results of the Study without the prior written consent of Sponsor, not to be unreasonably withheld or delayed, except as provided below. Institution and/or Principal Investigator further agree to provide Sponsor with drafts of any such publication or presentation for review and approval no less than 30 days prior to submission for publication or the date of public presentation.
Publication restrictions are in place

Restriction type: OTHER

Measure	UTC ch14.18 n=27 participants at risk United Therapeutics Manufactured ch14.18	NCI ch14.18 n=27 participants at risk NCI Manufactured ch14.18
Infections and infestations Device Related Infection	11.1% 3/27 • Number of events 3 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.	3.7% 1/27 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.
Infections and infestations Gastroenteritis Viral	7.4% 2/27 • Number of events 2 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.	3.7% 1/27 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.
Infections and infestations Sepsis	3.7% 1/27 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.	3.7% 1/27 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.
Infections and infestations Alpha Hemolytic Stretococcal Infection	3.7% 1/27 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.	0.00% 0/27 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.
Infections and infestations Bacteremia	3.7% 1/27 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.	3.7% 1/27 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.
Infections and infestations Bacterial Infection	0.00% 0/27 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.	3.7% 1/27 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.
Infections and infestations Enterobacter Sepsis	3.7% 1/27 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.	0.00% 0/27 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.
Infections and infestations Influenza	0.00% 0/27 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.	3.7% 1/27 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.
Infections and infestations Pneumonia	0.00% 0/27 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.	3.7% 1/27 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.
Infections and infestations Pneumonia Bacterial	0.00% 0/27 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.	3.7% 1/27 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.
Infections and infestations Streptococcal Bacteremia	3.7% 1/27 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.	0.00% 0/27 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.
General disorders Pyrexia	18.5% 5/27 • Number of events 7 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.	11.1% 3/27 • Number of events 7 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.
General disorders Disease Progression	3.7% 1/27 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.	0.00% 0/27 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.
General disorders Fatigue	3.7% 1/27 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.	0.00% 0/27 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.
General disorders Malaise	3.7% 1/27 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.	0.00% 0/27 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.
Metabolism and nutrition disorders Hypokalemia	11.1% 3/27 • Number of events 3 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.	0.00% 0/27 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.
Metabolism and nutrition disorders Dehydration	0.00% 0/27 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.	3.7% 1/27 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.
Metabolism and nutrition disorders Hypercalcemia	0.00% 0/27 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.	3.7% 1/27 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.
Metabolism and nutrition disorders Hypoalbuminemia	3.7% 1/27 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.	0.00% 0/27 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.
Metabolism and nutrition disorders Hyponatremia	3.7% 1/27 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.	0.00% 0/27 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.
Metabolism and nutrition disorders Hypophosphatemia	3.7% 1/27 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.	0.00% 0/27 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.
Gastrointestinal disorders Diarrhea	3.7% 1/27 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.	3.7% 1/27 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.
Gastrointestinal disorders Abdominal Pain	3.7% 1/27 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.	0.00% 0/27 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.
Gastrointestinal disorders Constipation	3.7% 1/27 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.	0.00% 0/27 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.
Gastrointestinal disorders Ileus	3.7% 1/27 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.	0.00% 0/27 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.
Gastrointestinal disorders Nausea	0.00% 0/27 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.	3.7% 1/27 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.
Gastrointestinal disorders Vomiting	0.00% 0/27 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.	3.7% 1/27 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.
Blood and lymphatic system disorders Anemia	0.00% 0/27 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.	7.4% 2/27 • Number of events 2 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.
Immune system disorders Anaphylactic Reaction	0.00% 0/27 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.	3.7% 1/27 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.
Immune system disorders Serum Sickness	0.00% 0/27 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.	3.7% 1/27 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.
Cardiac disorders Palpitations	0.00% 0/27 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.	3.7% 1/27 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.
Eye disorders Mydriasis	3.7% 1/27 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.	0.00% 0/27 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.
Hepatobiliary disorders Hyperbilirubinemia	3.7% 1/27 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.	0.00% 0/27 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.
Investigations Blood Creatinine Increased	3.7% 1/27 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.	0.00% 0/27 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.
Nervous system disorders Convulsion	3.7% 1/27 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.	0.00% 0/27 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.
Psychiatric disorders Agitation	3.7% 1/27 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.	0.00% 0/27 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.
Renal and urinary disorders Renal Failure Acute	3.7% 1/27 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.	0.00% 0/27 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.
Skin and subcutaneous tissue disorders Herpes Simplex	0.00% 0/27 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.	3.7% 1/27 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.
Vascular disorders Capillary Leak Syndrome	3.7% 1/27 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.	0.00% 0/27 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.
Vascular disorders Hypertension	0.00% 0/27 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.	3.7% 1/27 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were reported at the time of informed consent through 30 days after the last dose of study therapy.