Trial Outcomes & Findings for BIBF 1120 for Recurrent High-Grade Gliomas (NCT NCT01380782)

Last Updated: 2014-08-18

Results Overview

To determine the efficacy of BIBF 1120 in bevacizumab-naive participants with recurrent glioblastoma (GBM) as measured by 6-month progression-free survival (PFS6).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

37 participants

Primary outcome timeframe

Six months

Results posted on

2014-08-18

Participant Flow

Study activated at Dana-Farber Cancer Institute in May 2012 and was eventually activated at Massachusetts General Hospital, Cleveland Clinic, and University of Virginia. The bevacizumab-treated arm closed to accrual in December 2012 and the bevacizumab-naive arm closed in March 2013, both due to futility.

Participant milestones

Participant milestones
Measure	Arm A (Bevacizumab-naive) - GBM Participants who had not been treated with bevacizumab prior to entering the study, and whose current histology was glioblastoma (GBM).	Arm A (Bevacizumab-naive) - AG Participants who had not been treated with bevacizumab prior to entering the study, and whose current histology was anaplastic glioma (AG).	Arm B (Bevacizumab Treated) - GBM Participants who had been previously treated with bevacizumab prior to entering the study, and whose currently histology was glioblastoma (GBM).	Arm B (Bevacizumab Treated) - AG Participants who had been previously treated with bevacizumab prior to entering the study, and whose currently histology was anaplastic glioma (AG).
Overall Study STARTED	12	10	11	4
Overall Study COMPLETED	0	0	0	0
Overall Study NOT COMPLETED	12	10	11	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A (Bevacizumab-naive) - GBM Participants who had not been treated with bevacizumab prior to entering the study, and whose current histology was glioblastoma (GBM).	Arm A (Bevacizumab-naive) - AG Participants who had not been treated with bevacizumab prior to entering the study, and whose current histology was anaplastic glioma (AG).	Arm B (Bevacizumab Treated) - GBM Participants who had been previously treated with bevacizumab prior to entering the study, and whose currently histology was glioblastoma (GBM).	Arm B (Bevacizumab Treated) - AG Participants who had been previously treated with bevacizumab prior to entering the study, and whose currently histology was anaplastic glioma (AG).
Overall Study Adverse Event	0	1	0	0
Overall Study Death	1	0	0	0
Overall Study Lack of Efficacy	10	9	10	3
Overall Study Physician Decision	1	0	0	0
Overall Study Withdrawal by Subject	0	0	1	1

Baseline Characteristics

BIBF 1120 for Recurrent High-Grade Gliomas

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A Bevacizumab-naive n=22 Participants Bevacizumab-naive participants	Arm B Bevacizumab-treated n=14 Participants Bevacizumab-treated participants	Total n=36 Participants Total of all reporting groups
Age, Continuous	54 years n=5 Participants	52 years n=7 Participants	52 years n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants	3 Participants n=7 Participants	18 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	11 Participants n=7 Participants	18 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	1 Participants n=5 Participants	0 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	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	19 Participants n=5 Participants	11 Participants n=7 Participants	30 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	21 Participants n=5 Participants	12 Participants n=7 Participants	33 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Karnofsky Performance Status	90 Units on a scale n=5 Participants	90 Units on a scale n=7 Participants	90 Units on a scale n=5 Participants

PRIMARY outcome

Timeframe: Six months

To determine the efficacy of BIBF 1120 in bevacizumab-naive participants with recurrent glioblastoma (GBM) as measured by 6-month progression-free survival (PFS6).

Outcome measures

Outcome measures
Measure	Arm A (Bevacizumab-naive) - GBM n=12 Participants Participants who had not been treated with bevacizumab prior to entering the study, and whose current histology was glioblastoma (GBM).	Arm A (Bevacizumab-naive) - AG Participants who had not been treated with bevacizumab prior to entering the study, and whose current histology was anaplastic glioma (AG).	Arm B (Bevacizumab Treated) - GBM Participants who had been previously treated with bevacizumab prior to entering the study, and whose currently histology was glioblastoma (GBM).	Arm B (Bevacizumab Treated) - AG Participants who had been previously treated with bevacizumab prior to entering the study, and whose currently histology was anaplastic glioma (AG).
6-Month Progression Free Survival	0 percentage of participants	—	—	—

PRIMARY outcome

Timeframe: 3 months

To determine the efficacy of BIBF 1120 in bevacizumab-treated participants with recurrent GBM as measured by 3-month progression free survival (PFS3).

Outcome measures

Outcome measures
Measure	Arm A (Bevacizumab-naive) - GBM n=10 Participants Participants who had not been treated with bevacizumab prior to entering the study, and whose current histology was glioblastoma (GBM).	Arm A (Bevacizumab-naive) - AG Participants who had not been treated with bevacizumab prior to entering the study, and whose current histology was anaplastic glioma (AG).	Arm B (Bevacizumab Treated) - GBM Participants who had been previously treated with bevacizumab prior to entering the study, and whose currently histology was glioblastoma (GBM).	Arm B (Bevacizumab Treated) - AG Participants who had been previously treated with bevacizumab prior to entering the study, and whose currently histology was anaplastic glioma (AG).
3-Month Progression Free Survival	0 percentage of participants	—	—	—

SECONDARY outcome

Timeframe: 2 years

Best radiographic response in both populations. There were no participants with partial or complete responses, so the results are being reported in the proportion of participants who experienced stable disease (SD) as their best response (as opposed to progressive disease).

Outcome measures

Outcome measures
Measure	Arm A (Bevacizumab-naive) - GBM n=12 Participants Participants who had not been treated with bevacizumab prior to entering the study, and whose current histology was glioblastoma (GBM).	Arm A (Bevacizumab-naive) - AG n=10 Participants Participants who had not been treated with bevacizumab prior to entering the study, and whose current histology was anaplastic glioma (AG).	Arm B (Bevacizumab Treated) - GBM n=10 Participants Participants who had been previously treated with bevacizumab prior to entering the study, and whose currently histology was glioblastoma (GBM).	Arm B (Bevacizumab Treated) - AG n=4 Participants Participants who had been previously treated with bevacizumab prior to entering the study, and whose currently histology was anaplastic glioma (AG).
Proportion of Participants Experiencing Stable Disease (SD) as Their Best Radiographic Response	33 % of patients with best response SD	40 % of patients with best response SD	10 % of patients with best response SD	25 % of patients with best response SD

SECONDARY outcome

Timeframe: 2 years

Overall survival in both populations

Outcome measures

Outcome measures
Measure	Arm A (Bevacizumab-naive) - GBM n=12 Participants Participants who had not been treated with bevacizumab prior to entering the study, and whose current histology was glioblastoma (GBM).	Arm A (Bevacizumab-naive) - AG n=10 Participants Participants who had not been treated with bevacizumab prior to entering the study, and whose current histology was anaplastic glioma (AG).	Arm B (Bevacizumab Treated) - GBM n=10 Participants Participants who had been previously treated with bevacizumab prior to entering the study, and whose currently histology was glioblastoma (GBM).	Arm B (Bevacizumab Treated) - AG n=4 Participants Participants who had been previously treated with bevacizumab prior to entering the study, and whose currently histology was anaplastic glioma (AG).
Overall Survival	6.9 months Interval 3.7 to 8.1	11.3 months Interval 2.7 to 14.6	2.6 months Interval 1.0 to 6.9	7.3 months Interval 1.4 to 18.1

SECONDARY outcome

Timeframe: 2 years

Time-to-tumor progression in both populations.

Outcome measures

Outcome measures
Measure	Arm A (Bevacizumab-naive) - GBM n=12 Participants Participants who had not been treated with bevacizumab prior to entering the study, and whose current histology was glioblastoma (GBM).	Arm A (Bevacizumab-naive) - AG n=10 Participants Participants who had not been treated with bevacizumab prior to entering the study, and whose current histology was anaplastic glioma (AG).	Arm B (Bevacizumab Treated) - GBM n=10 Participants Participants who had been previously treated with bevacizumab prior to entering the study, and whose currently histology was glioblastoma (GBM).	Arm B (Bevacizumab Treated) - AG n=4 Participants Participants who had been previously treated with bevacizumab prior to entering the study, and whose currently histology was anaplastic glioma (AG).
Time-to-tumor Progression	28 days Interval 27.0 to 83.0	28 days Interval 27.0 to 138.0	28 days Interval 22.0 to 28.0	36 days Interval 27.0 to 55.0

SECONDARY outcome

Timeframe: 2 years

Safety profile in both populations - as adverse events are posted separately in detail, these results will demonstrate serious adverse events (defined as grades 3-5) that were judged at least possibly related to Nintedanib (BIBF 1120).

Outcome measures

Outcome measures
Measure	Arm A (Bevacizumab-naive) - GBM n=37 Participants Participants who had not been treated with bevacizumab prior to entering the study, and whose current histology was glioblastoma (GBM).	Arm A (Bevacizumab-naive) - AG Participants who had not been treated with bevacizumab prior to entering the study, and whose current histology was anaplastic glioma (AG).	Arm B (Bevacizumab Treated) - GBM Participants who had been previously treated with bevacizumab prior to entering the study, and whose currently histology was glioblastoma (GBM).	Arm B (Bevacizumab Treated) - AG Participants who had been previously treated with bevacizumab prior to entering the study, and whose currently histology was anaplastic glioma (AG).
Safety Profile as Summarized With Descriptive Statistics (Using Toxicity Data Gathered on Trial) Abdominal pain	1 number of incidents	—	—	—
Safety Profile as Summarized With Descriptive Statistics (Using Toxicity Data Gathered on Trial) Reversible transaminase elevation	8 number of incidents	—	—	—
Safety Profile as Summarized With Descriptive Statistics (Using Toxicity Data Gathered on Trial) Hypertension	1 number of incidents	—	—	—
Safety Profile as Summarized With Descriptive Statistics (Using Toxicity Data Gathered on Trial) Hypophosphatemia	3 number of incidents	—	—	—
Safety Profile as Summarized With Descriptive Statistics (Using Toxicity Data Gathered on Trial) Intracranial hemorrhage	1 number of incidents	—	—	—
Safety Profile as Summarized With Descriptive Statistics (Using Toxicity Data Gathered on Trial) Colonic perforation	2 number of incidents	—	—	—
Safety Profile as Summarized With Descriptive Statistics (Using Toxicity Data Gathered on Trial) Pulmonary embolism	1 number of incidents	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Arm A - 6 months; Arm B - 3 months

To explore the efficacy of BIBF 1120 in bevacizumab-naïve and bevacizumab-treated participants with recurrent anaplastic gliomas (AG) survival was assessed at 6 months for Arm A and 3 months for Arm B.

Outcome measures

Outcome measures
Measure	Arm A (Bevacizumab-naive) - GBM n=10 Participants Participants who had not been treated with bevacizumab prior to entering the study, and whose current histology was glioblastoma (GBM).	Arm A (Bevacizumab-naive) - AG n=4 Participants Participants who had not been treated with bevacizumab prior to entering the study, and whose current histology was anaplastic glioma (AG).	Arm B (Bevacizumab Treated) - GBM Participants who had been previously treated with bevacizumab prior to entering the study, and whose currently histology was glioblastoma (GBM).	Arm B (Bevacizumab Treated) - AG Participants who had been previously treated with bevacizumab prior to entering the study, and whose currently histology was anaplastic glioma (AG).
Exploratory Objective #1: Progression-free Survival at 3- and 6-months for Participants With Recurrent Anaplastic Gliomas (AG)	0 percentage of participants	0 percentage of participants	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 2 years

To explore the extent to which the tumor's genotype and expression profile correlate with outcome.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 2 years

To explore the correlation between serum angiogenic peptides, circulating endothelial cells, and circulating progenitor cells with response to therapy.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 2 years

To explore the correlation between perfusion MRI, diffusion MRI and response to therapy.

Outcome measures

Outcome data not reported

Adverse Events

Arm A

Serious events: 8 serious events

Other events: 22 other events

Deaths: 0 deaths

Arm B

Serious events: 5 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Patrick Y. Wen, MD

Dana-Farber Cancer Institute

Phone: 6176322166

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Arm A n=22 participants at risk Bevacizumab-naive participants	Arm B n=14 participants at risk Bevacizumab-treated participants
Gastrointestinal disorders Abdominal pain	0.00% 0/22 • Adverse events were collected on each participant from the time the informed consent document was signed up until 30 days after the last dose of study drug. Abnormal laboratory values or diagnostic tests results constitute AEs only if they induce clinical signs or symptoms or require treatment or further diagnostic tests.	7.1% 1/14 • Number of events 1 • Adverse events were collected on each participant from the time the informed consent document was signed up until 30 days after the last dose of study drug. Abnormal laboratory values or diagnostic tests results constitute AEs only if they induce clinical signs or symptoms or require treatment or further diagnostic tests.
Psychiatric disorders Agitation	4.5% 1/22 • Number of events 1 • Adverse events were collected on each participant from the time the informed consent document was signed up until 30 days after the last dose of study drug. Abnormal laboratory values or diagnostic tests results constitute AEs only if they induce clinical signs or symptoms or require treatment or further diagnostic tests.	0.00% 0/14 • Adverse events were collected on each participant from the time the informed consent document was signed up until 30 days after the last dose of study drug. Abnormal laboratory values or diagnostic tests results constitute AEs only if they induce clinical signs or symptoms or require treatment or further diagnostic tests.
Investigations Alanine aminotransferase increased	0.00% 0/22 • Adverse events were collected on each participant from the time the informed consent document was signed up until 30 days after the last dose of study drug. Abnormal laboratory values or diagnostic tests results constitute AEs only if they induce clinical signs or symptoms or require treatment or further diagnostic tests.	7.1% 1/14 • Number of events 1 • Adverse events were collected on each participant from the time the informed consent document was signed up until 30 days after the last dose of study drug. Abnormal laboratory values or diagnostic tests results constitute AEs only if they induce clinical signs or symptoms or require treatment or further diagnostic tests.
Investigations Aspartate aminotransferase increased	0.00% 0/22 • Adverse events were collected on each participant from the time the informed consent document was signed up until 30 days after the last dose of study drug. Abnormal laboratory values or diagnostic tests results constitute AEs only if they induce clinical signs or symptoms or require treatment or further diagnostic tests.	7.1% 1/14 • Number of events 1 • Adverse events were collected on each participant from the time the informed consent document was signed up until 30 days after the last dose of study drug. Abnormal laboratory values or diagnostic tests results constitute AEs only if they induce clinical signs or symptoms or require treatment or further diagnostic tests.
Gastrointestinal disorders Colonic perforation	4.5% 1/22 • Number of events 2 • Adverse events were collected on each participant from the time the informed consent document was signed up until 30 days after the last dose of study drug. Abnormal laboratory values or diagnostic tests results constitute AEs only if they induce clinical signs or symptoms or require treatment or further diagnostic tests.	0.00% 0/14 • Adverse events were collected on each participant from the time the informed consent document was signed up until 30 days after the last dose of study drug. Abnormal laboratory values or diagnostic tests results constitute AEs only if they induce clinical signs or symptoms or require treatment or further diagnostic tests.
General disorders Death NOS	4.5% 1/22 • Number of events 1 • Adverse events were collected on each participant from the time the informed consent document was signed up until 30 days after the last dose of study drug. Abnormal laboratory values or diagnostic tests results constitute AEs only if they induce clinical signs or symptoms or require treatment or further diagnostic tests.	14.3% 2/14 • Number of events 2 • Adverse events were collected on each participant from the time the informed consent document was signed up until 30 days after the last dose of study drug. Abnormal laboratory values or diagnostic tests results constitute AEs only if they induce clinical signs or symptoms or require treatment or further diagnostic tests.
Psychiatric disorders Delirium	4.5% 1/22 • Number of events 1 • Adverse events were collected on each participant from the time the informed consent document was signed up until 30 days after the last dose of study drug. Abnormal laboratory values or diagnostic tests results constitute AEs only if they induce clinical signs or symptoms or require treatment or further diagnostic tests.	0.00% 0/14 • Adverse events were collected on each participant from the time the informed consent document was signed up until 30 days after the last dose of study drug. Abnormal laboratory values or diagnostic tests results constitute AEs only if they induce clinical signs or symptoms or require treatment or further diagnostic tests.
Psychiatric disorders Depression	4.5% 1/22 • Number of events 1 • Adverse events were collected on each participant from the time the informed consent document was signed up until 30 days after the last dose of study drug. Abnormal laboratory values or diagnostic tests results constitute AEs only if they induce clinical signs or symptoms or require treatment or further diagnostic tests.	0.00% 0/14 • Adverse events were collected on each participant from the time the informed consent document was signed up until 30 days after the last dose of study drug. Abnormal laboratory values or diagnostic tests results constitute AEs only if they induce clinical signs or symptoms or require treatment or further diagnostic tests.
Nervous system disorders Dysphasia	4.5% 1/22 • Number of events 1 • Adverse events were collected on each participant from the time the informed consent document was signed up until 30 days after the last dose of study drug. Abnormal laboratory values or diagnostic tests results constitute AEs only if they induce clinical signs or symptoms or require treatment or further diagnostic tests.	0.00% 0/14 • Adverse events were collected on each participant from the time the informed consent document was signed up until 30 days after the last dose of study drug. Abnormal laboratory values or diagnostic tests results constitute AEs only if they induce clinical signs or symptoms or require treatment or further diagnostic tests.
Nervous system disorders Edema cerebral	4.5% 1/22 • Number of events 1 • Adverse events were collected on each participant from the time the informed consent document was signed up until 30 days after the last dose of study drug. Abnormal laboratory values or diagnostic tests results constitute AEs only if they induce clinical signs or symptoms or require treatment or further diagnostic tests.	7.1% 1/14 • Number of events 1 • Adverse events were collected on each participant from the time the informed consent document was signed up until 30 days after the last dose of study drug. Abnormal laboratory values or diagnostic tests results constitute AEs only if they induce clinical signs or symptoms or require treatment or further diagnostic tests.
Gastrointestinal disorders Enterocolitis	0.00% 0/22 • Adverse events were collected on each participant from the time the informed consent document was signed up until 30 days after the last dose of study drug. Abnormal laboratory values or diagnostic tests results constitute AEs only if they induce clinical signs or symptoms or require treatment or further diagnostic tests.	7.1% 1/14 • Number of events 2 • Adverse events were collected on each participant from the time the informed consent document was signed up until 30 days after the last dose of study drug. Abnormal laboratory values or diagnostic tests results constitute AEs only if they induce clinical signs or symptoms or require treatment or further diagnostic tests.
Nervous system disorders Hydrocephalus	0.00% 0/22 • Adverse events were collected on each participant from the time the informed consent document was signed up until 30 days after the last dose of study drug. Abnormal laboratory values or diagnostic tests results constitute AEs only if they induce clinical signs or symptoms or require treatment or further diagnostic tests.	7.1% 1/14 • Number of events 1 • Adverse events were collected on each participant from the time the informed consent document was signed up until 30 days after the last dose of study drug. Abnormal laboratory values or diagnostic tests results constitute AEs only if they induce clinical signs or symptoms or require treatment or further diagnostic tests.
Nervous system disorders Intracranial hemorrhage	4.5% 1/22 • Number of events 2 • Adverse events were collected on each participant from the time the informed consent document was signed up until 30 days after the last dose of study drug. Abnormal laboratory values or diagnostic tests results constitute AEs only if they induce clinical signs or symptoms or require treatment or further diagnostic tests.	0.00% 0/14 • Adverse events were collected on each participant from the time the informed consent document was signed up until 30 days after the last dose of study drug. Abnormal laboratory values or diagnostic tests results constitute AEs only if they induce clinical signs or symptoms or require treatment or further diagnostic tests.
Musculoskeletal and connective tissue disorders Muscle weakness left-sided	0.00% 0/22 • Adverse events were collected on each participant from the time the informed consent document was signed up until 30 days after the last dose of study drug. Abnormal laboratory values or diagnostic tests results constitute AEs only if they induce clinical signs or symptoms or require treatment or further diagnostic tests.	7.1% 1/14 • Number of events 1 • Adverse events were collected on each participant from the time the informed consent document was signed up until 30 days after the last dose of study drug. Abnormal laboratory values or diagnostic tests results constitute AEs only if they induce clinical signs or symptoms or require treatment or further diagnostic tests.
Musculoskeletal and connective tissue disorders Muscle weakness right-sided	4.5% 1/22 • Number of events 1 • Adverse events were collected on each participant from the time the informed consent document was signed up until 30 days after the last dose of study drug. Abnormal laboratory values or diagnostic tests results constitute AEs only if they induce clinical signs or symptoms or require treatment or further diagnostic tests.	0.00% 0/14 • Adverse events were collected on each participant from the time the informed consent document was signed up until 30 days after the last dose of study drug. Abnormal laboratory values or diagnostic tests results constitute AEs only if they induce clinical signs or symptoms or require treatment or further diagnostic tests.
Psychiatric disorders Suicidal ideation	4.5% 1/22 • Number of events 2 • Adverse events were collected on each participant from the time the informed consent document was signed up until 30 days after the last dose of study drug. Abnormal laboratory values or diagnostic tests results constitute AEs only if they induce clinical signs or symptoms or require treatment or further diagnostic tests.	0.00% 0/14 • Adverse events were collected on each participant from the time the informed consent document was signed up until 30 days after the last dose of study drug. Abnormal laboratory values or diagnostic tests results constitute AEs only if they induce clinical signs or symptoms or require treatment or further diagnostic tests.
Psychiatric disorders Suicidal attempt	4.5% 1/22 • Number of events 1 • Adverse events were collected on each participant from the time the informed consent document was signed up until 30 days after the last dose of study drug. Abnormal laboratory values or diagnostic tests results constitute AEs only if they induce clinical signs or symptoms or require treatment or further diagnostic tests.	0.00% 0/14 • Adverse events were collected on each participant from the time the informed consent document was signed up until 30 days after the last dose of study drug. Abnormal laboratory values or diagnostic tests results constitute AEs only if they induce clinical signs or symptoms or require treatment or further diagnostic tests.
Vascular disorders Thromboembolic event	4.5% 1/22 • Number of events 1 • Adverse events were collected on each participant from the time the informed consent document was signed up until 30 days after the last dose of study drug. Abnormal laboratory values or diagnostic tests results constitute AEs only if they induce clinical signs or symptoms or require treatment or further diagnostic tests.	7.1% 1/14 • Number of events 1 • Adverse events were collected on each participant from the time the informed consent document was signed up until 30 days after the last dose of study drug. Abnormal laboratory values or diagnostic tests results constitute AEs only if they induce clinical signs or symptoms or require treatment or further diagnostic tests.
Vascular disorders Vascular disorders - Other	0.00% 0/22 • Adverse events were collected on each participant from the time the informed consent document was signed up until 30 days after the last dose of study drug. Abnormal laboratory values or diagnostic tests results constitute AEs only if they induce clinical signs or symptoms or require treatment or further diagnostic tests.	7.1% 1/14 • Number of events 2 • Adverse events were collected on each participant from the time the informed consent document was signed up until 30 days after the last dose of study drug. Abnormal laboratory values or diagnostic tests results constitute AEs only if they induce clinical signs or symptoms or require treatment or further diagnostic tests.