Trial Outcomes & Findings for Hydroxychloroquine in Individuals At-risk for Type 1 Diabetes Mellitus (NCT NCT03428945)

NCT ID: NCT03428945

Last Updated: 2024-04-09

Results Overview

The primary outcome is the time in months from random treatment assignment to the development of confirmed abnormal glucose tolerance or clinical diabetes.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 273 participants
• Primary outcome timeframe: Glucose tolerance is measured every 6 months for up to 4 years
• Results posted on: 2024-04-09

Participant Flow

Participant milestones

Measure	Hydroxychloroquine Hydroxychloroquine compound for oral use Hydroxychloroquine: Hydroxychloroquine for oral administration, dosed by weight	Placebo Placebo tablet matching active drug Placebo: Placebo tablet identical to active drug
Overall Study STARTED	183	90
Overall Study COMPLETED	168	77
Overall Study NOT COMPLETED	15	13

Reasons for withdrawal

Measure	Hydroxychloroquine Hydroxychloroquine compound for oral use Hydroxychloroquine: Hydroxychloroquine for oral administration, dosed by weight	Placebo Placebo tablet matching active drug Placebo: Placebo tablet identical to active drug
Overall Study Lost to Follow-up	5	3
Overall Study Withdrawal by Subject	10	10

Baseline Characteristics

Hydroxychloroquine in Individuals At-risk for Type 1 Diabetes Mellitus

Baseline characteristics by cohort

Measure	Hydroxychloroquine n=183 Participants Hydroxychloroquine compound for oral use Hydroxychloroquine: Hydroxychloroquine for oral administration, dosed by weight	Placebo n=90 Participants Placebo tablet matching active drug Placebo: Placebo tablet identical to active drug	Total n=273 Participants Total of all reporting groups
Age, Categorical <=18 years	165 Participants n=5 Participants	77 Participants n=7 Participants	242 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	18 Participants n=5 Participants	13 Participants n=7 Participants	31 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	11.7 years n=5 Participants	10.9 years n=7 Participants	11.3 years n=5 Participants
Sex: Female, Male Female	61 Participants n=5 Participants	33 Participants n=7 Participants	94 Participants n=5 Participants
Sex: Female, Male Male	122 Participants n=5 Participants	57 Participants n=7 Participants	179 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	15 Participants n=5 Participants	4 Participants n=7 Participants	19 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	162 Participants n=5 Participants	82 Participants n=7 Participants	244 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	6 Participants n=5 Participants	4 Participants n=7 Participants	10 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	0 Participants n=7 Participants	0 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	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	171 Participants n=5 Participants	83 Participants n=7 Participants	254 Participants n=5 Participants
Race (NIH/OMB) More than one race	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	8 Participants n=5 Participants	2 Participants n=7 Participants	10 Participants n=5 Participants
Region of Enrollment Canada	9 participants n=5 Participants	7 participants n=7 Participants	16 participants n=5 Participants
Region of Enrollment Sweden	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment United States	155 participants n=5 Participants	72 participants n=7 Participants	227 participants n=5 Participants
Region of Enrollment United Kingdom	2 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants
Region of Enrollment Italy	0 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants
Region of Enrollment Australia	13 participants n=5 Participants	7 participants n=7 Participants	20 participants n=5 Participants
Region of Enrollment Finland	3 participants n=5 Participants	0 participants n=7 Participants	3 participants n=5 Participants
Relationship to person with Type 1 Diabetes More than one first degree relative	15 Participants n=5 Participants	6 Participants n=7 Participants	21 Participants n=5 Participants
Relationship to person with Type 1 Diabetes Sibling(s)	100 Participants n=5 Participants	48 Participants n=7 Participants	148 Participants n=5 Participants
Relationship to person with Type 1 Diabetes Offspring	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Relationship to person with Type 1 Diabetes Parent(s)	42 Participants n=5 Participants	22 Participants n=7 Participants	64 Participants n=5 Participants
Relationship to person with Type 1 Diabetes Second Degree Relative	9 Participants n=5 Participants	6 Participants n=7 Participants	15 Participants n=5 Participants
Relationship to person with Type 1 Diabetes Third Degree Relative	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Relationship to person with Type 1 Diabetes No Relatives	10 Participants n=5 Participants	3 Participants n=7 Participants	13 Participants n=5 Participants
Autoantibodies positive 1 positive Autoantibody	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Autoantibodies positive 2 positive Autoantibodies	35 Participants n=5 Participants	23 Participants n=7 Participants	58 Participants n=5 Participants
Autoantibodies positive 3 positive Autoantibodies	39 Participants n=5 Participants	24 Participants n=7 Participants	63 Participants n=5 Participants
Autoantibodies positive 4 positive Autoantibodies	46 Participants n=5 Participants	18 Participants n=7 Participants	64 Participants n=5 Participants
Autoantibodies positive 5 positive Autoantibodies	61 Participants n=5 Participants	24 Participants n=7 Participants	85 Participants n=5 Participants

PRIMARY outcome

Timeframe: Glucose tolerance is measured every 6 months for up to 4 years

Population: Participants included in the time-to-event analysis

The primary outcome is the time in months from random treatment assignment to the development of confirmed abnormal glucose tolerance or clinical diabetes.

Outcome measures

Measure	Hydroxychloroquine n=168 Participants Hydroxychloroquine compound for oral use Hydroxychloroquine: Hydroxychloroquine for oral administration, dosed by weight	Placebo n=83 Participants Placebo tablet matching active drug Placebo: Placebo tablet identical to active drug
Change From Treatment Assignment Glucose Tolerance to Abnormal Glucose Tolerance or Diabetes	19.7 Months Interval 10.6 to 36.2	18.8 Months Interval 9.9 to 33.1

Adverse Events

Hydroxychloroquine

Serious events: 5 serious events

Other events: 125 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 61 other events

Deaths: 0 deaths

Serious adverse events

Measure	Hydroxychloroquine n=183 participants at risk Hydroxychloroquine compound for oral use Hydroxychloroquine: Hydroxychloroquine for oral administration, dosed by weight	Placebo n=90 participants at risk Placebo tablet matching active drug Placebo: Placebo tablet identical to active drug
Immune system disorders Anaphylaxis	0.55% 1/183 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
General disorders General disorders and administration site conditions - Other, specify	0.55% 1/183 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	1.1% 1/90 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Gastrointestinal disorders Vomiting	1.1% 2/183 • Number of events 2 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Infections and infestations Appendicitis	0.55% 1/183 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Psychiatric disorders Depression	0.00% 0/183 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	1.1% 1/90 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Psychiatric disorders Suicide attempt	0.00% 0/183 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	1.1% 1/90 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Psychiatric disorders Psychosis	0.00% 0/183 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	1.1% 1/90 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)

Other adverse events

Measure	Hydroxychloroquine n=183 participants at risk Hydroxychloroquine compound for oral use Hydroxychloroquine: Hydroxychloroquine for oral administration, dosed by weight	Placebo n=90 participants at risk Placebo tablet matching active drug Placebo: Placebo tablet identical to active drug
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other, specify	2.2% 4/183 • Number of events 5 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Blood and lymphatic system disorders Lymph node pain	0.55% 1/183 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Cardiac disorders Cardiac disorders - Other, specify	0.55% 1/183 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Ear and labyrinth disorders Ear and labyrinth disorders - Other, specify	0.55% 1/183 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Ear and labyrinth disorders Ear pain	0.55% 1/183 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Ear and labyrinth disorders Hearing impaired	0.55% 1/183 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Ear and labyrinth disorders Middle ear inflammation	0.55% 1/183 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	1.1% 1/90 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Ear and labyrinth disorders Vertigo	0.55% 1/183 • Number of events 2 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Endocrine disorders Endocrine disorders - Other, specify	0.55% 1/183 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	1.1% 1/90 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Eye disorders Blurred vision	0.55% 1/183 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Eye disorders Eye disorders - Other, specify	1.1% 2/183 • Number of events 6 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	1.1% 1/90 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Eye disorders Vision decreased	0.55% 1/183 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Gastrointestinal disorders Abdominal pain	1.1% 2/183 • Number of events 2 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	2.2% 2/90 • Number of events 2 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Gastrointestinal disorders Bloating	0.55% 1/183 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Gastrointestinal disorders Constipation	0.55% 1/183 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Gastrointestinal disorders Diarrhea	2.7% 5/183 • Number of events 5 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	1.1% 1/90 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Gastrointestinal disorders Esophagitis	0.00% 0/183 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	2.2% 2/90 • Number of events 2 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Gastrointestinal disorders Flatulence	1.1% 2/183 • Number of events 2 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Gastrointestinal disorders Gastritis	0.55% 1/183 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Gastrointestinal disorders Gastroesophageal reflux disease	0.55% 1/183 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	2.2% 2/90 • Number of events 2 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	1.6% 3/183 • Number of events 3 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	4.4% 4/90 • Number of events 5 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Gastrointestinal disorders Nausea	1.6% 3/183 • Number of events 3 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Gastrointestinal disorders Toothache	0.00% 0/183 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	1.1% 1/90 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Gastrointestinal disorders Vomiting	3.3% 6/183 • Number of events 6 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
General disorders Fever	2.7% 5/183 • Number of events 7 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
General disorders Flu like symptoms	1.1% 2/183 • Number of events 2 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	1.1% 1/90 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
General disorders General disorders and administration site conditions - Other, specify	1.6% 3/183 • Number of events 3 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	4.4% 4/90 • Number of events 5 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
General disorders Pain	1.1% 2/183 • Number of events 2 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Immune system disorders Allergic reaction	1.1% 2/183 • Number of events 2 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	2.2% 2/90 • Number of events 2 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Immune system disorders Anaphylaxis	0.55% 1/183 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Immune system disorders Autoimmune disorder	0.55% 1/183 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Immune system disorders Immune system disorders - Other, specify	0.00% 0/183 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	1.1% 1/90 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Infections and infestations Appendicitis	0.55% 1/183 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Infections and infestations Bronchial infection	1.1% 2/183 • Number of events 2 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	2.2% 2/90 • Number of events 2 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Infections and infestations Enterocolitis infectious	0.00% 0/183 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	1.1% 1/90 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Infections and infestations Esophageal infection	0.55% 1/183 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Infections and infestations Eye infection	0.55% 1/183 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Infections and infestations Gum infection	0.55% 1/183 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Infections and infestations Herpes simplex reactivation	1.6% 3/183 • Number of events 4 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Infections and infestations Infections and infestations - Other, specify	15.8% 29/183 • Number of events 33 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	14.4% 13/90 • Number of events 14 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Infections and infestations Nail infection	0.55% 1/183 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Infections and infestations Otitis media	2.2% 4/183 • Number of events 4 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	5.6% 5/90 • Number of events 5 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Infections and infestations Penile infection	0.00% 0/183 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	2.2% 2/90 • Number of events 2 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Infections and infestations Pharyngitis	1.6% 3/183 • Number of events 3 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	4.4% 4/90 • Number of events 4 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Infections and infestations Sinusitis	6.0% 11/183 • Number of events 13 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	5.6% 5/90 • Number of events 5 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Infections and infestations Skin infection	1.6% 3/183 • Number of events 3 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	1.1% 1/90 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Infections and infestations Soft tissue infection	0.00% 0/183 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	1.1% 1/90 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Infections and infestations Tooth infection	0.55% 1/183 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	1.1% 1/90 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Infections and infestations Upper respiratory infection	8.7% 16/183 • Number of events 21 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	7.8% 7/90 • Number of events 10 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Infections and infestations Wound infection	0.00% 0/183 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	1.1% 1/90 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Injury, poisoning and procedural complications Ankle fracture	0.55% 1/183 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	1.1% 1/90 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Injury, poisoning and procedural complications Fall	1.6% 3/183 • Number of events 4 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Injury, poisoning and procedural complications Fracture	4.4% 8/183 • Number of events 8 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	3.3% 3/90 • Number of events 3 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Injury, poisoning and procedural complications Injury, poisoning and procedural complications - Other, specify	4.4% 8/183 • Number of events 19 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	5.6% 5/90 • Number of events 5 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Injury, poisoning and procedural complications Venous injury	0.00% 0/183 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	1.1% 1/90 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Investigations Alanine aminotransferase increased	1.1% 2/183 • Number of events 2 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Investigations Aspartate aminotransferase increased	1.6% 3/183 • Number of events 4 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Investigations Blood bilirubin increased	1.6% 3/183 • Number of events 3 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	3.3% 3/90 • Number of events 6 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Investigations Creatinine increased	2.2% 4/183 • Number of events 4 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Investigations Investigations - Other, specify	3.3% 6/183 • Number of events 6 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	3.3% 3/90 • Number of events 3 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Investigations Lymphocyte count decreased	0.55% 1/183 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Investigations Lymphocyte count increased	0.55% 1/183 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Investigations Neutrophil count decreased	17.5% 32/183 • Number of events 56 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	28.9% 26/90 • Number of events 41 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Investigations Weight gain	0.00% 0/183 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	1.1% 1/90 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Investigations Weight loss	1.6% 3/183 • Number of events 3 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	1.1% 1/90 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Investigations White blood cell decreased	2.2% 4/183 • Number of events 4 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	4.4% 4/90 • Number of events 5 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Metabolism and nutrition disorders Dehydration	0.55% 1/183 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Metabolism and nutrition disorders Hyponatremia	2.2% 4/183 • Number of events 4 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	3.3% 3/90 • Number of events 3 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Metabolism and nutrition disorders Metabolism and nutrition disorders - Other, specify	0.55% 1/183 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Musculoskeletal and connective tissue disorders Avascular necrosis	0.55% 1/183 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/183 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	2.2% 2/90 • Number of events 2 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Musculoskeletal and connective tissue disorders Bone pain	0.55% 1/183 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	1.1% 1/90 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify	3.3% 6/183 • Number of events 8 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	1.1% 1/90 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Musculoskeletal and connective tissue disorders Neck pain	0.55% 1/183 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Musculoskeletal and connective tissue disorders Pain in extremity	0.55% 1/183 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	1.1% 1/90 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	0.55% 1/183 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	1.1% 1/90 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin papilloma	0.00% 0/183 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	3.3% 3/90 • Number of events 3 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Nervous system disorders Concentration impairment	0.55% 1/183 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Nervous system disorders Headache	2.7% 5/183 • Number of events 7 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	3.3% 3/90 • Number of events 4 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Nervous system disorders Nervous system disorders - Other, specify	1.1% 2/183 • Number of events 2 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Nervous system disorders Paresthesia	0.55% 1/183 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Nervous system disorders Presyncope	1.1% 2/183 • Number of events 2 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Nervous system disorders Syncope	1.1% 2/183 • Number of events 2 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Nervous system disorders Vasovagal reaction	2.2% 4/183 • Number of events 6 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	1.1% 1/90 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Psychiatric disorders Anxiety	1.6% 3/183 • Number of events 3 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Psychiatric disorders Insomnia	0.00% 0/183 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	1.1% 1/90 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Psychiatric disorders Psychiatric disorders - Other, specify	2.2% 4/183 • Number of events 5 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	3.3% 3/90 • Number of events 4 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Renal and urinary disorders Renal and urinary disorders - Other, specify	0.00% 0/183 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	1.1% 1/90 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Renal and urinary disorders Urinary frequency	0.55% 1/183 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Reproductive system and breast disorders Dysmenorrhea	0.55% 1/183 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	1.1% 1/90 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	2.7% 5/183 • Number of events 5 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	2.2% 2/90 • Number of events 2 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Respiratory, thoracic and mediastinal disorders Bronchospasm	0.55% 1/183 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Respiratory, thoracic and mediastinal disorders Cough	3.3% 6/183 • Number of events 6 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	2.2% 2/90 • Number of events 2 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Respiratory, thoracic and mediastinal disorders Dyspnea	0.55% 1/183 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Respiratory, thoracic and mediastinal disorders Epistaxis	1.6% 3/183 • Number of events 4 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Respiratory, thoracic and mediastinal disorders Nasal congestion	1.1% 2/183 • Number of events 2 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	1.1% 1/90 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.00% 0/183 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	1.1% 1/90 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other, specify	3.3% 6/183 • Number of events 6 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	3.3% 3/90 • Number of events 6 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Respiratory, thoracic and mediastinal disorders Sinus disorder	0.55% 1/183 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Respiratory, thoracic and mediastinal disorders Sleep apnea	0.55% 1/183 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Respiratory, thoracic and mediastinal disorders Sore throat	1.1% 2/183 • Number of events 2 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	3.3% 3/90 • Number of events 4 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Respiratory, thoracic and mediastinal disorders Wheezing	1.6% 3/183 • Number of events 4 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	1.1% 1/90 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Skin and subcutaneous tissue disorders Eczema	1.6% 3/183 • Number of events 3 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	2.2% 2/90 • Number of events 2 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Skin and subcutaneous tissue disorders Rash acneiform	0.55% 1/183 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Skin and subcutaneous tissue disorders Rash maculo-papular	2.7% 5/183 • Number of events 5 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify	8.7% 16/183 • Number of events 19 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	5.6% 5/90 • Number of events 7 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Skin and subcutaneous tissue disorders Skin hyperpigmentation	0.55% 1/183 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	0.00% 0/90 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/183 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	1.1% 1/90 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Surgical and medical procedures Surgical and medical procedures - Other, specify	5.5% 10/183 • Number of events 12 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	3.3% 3/90 • Number of events 4 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Psychiatric disorders Depression	0.00% 0/183 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	1.1% 1/90 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Psychiatric disorders Psychosis	0.00% 0/183 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	1.1% 1/90 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)
Psychiatric disorders Suicide attempt	0.00% 0/183 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)	1.1% 1/90 • Number of events 1 • Duration of study from screening to last visit encompassing each participant's duration of time in the study no more than 4 years with an average duration prior to study termination of 23.9 months. Adverse Events were defined using the Common Terminology Criteria for Adverse Events (CTCAE)

Additional Information

Dr. Kevan Herold

Yale University

Phone: 203-785-6507

Email: Kevan.Herold@yale.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place