Trial Outcomes & Findings for Bridging the Docosahexaenoic Acid (DHA) Gap: The Effects of Omega-3 Fatty Acid Supplementation in Premature Infants (NCT NCT01908907)

NCT ID: NCT01908907

Last Updated: 2019-03-21

Results Overview

This study was designed to determine feasibility and tolerability of enteral DHA supplementation, but was not intended to determine the effects of DHA on health related outcomes. Tolerability was measured by days to reach full enteral feedings, days on study oil, GA at completion of the study and postnatal growth. The days to reach full enteral feedings was defined as enteral intake of 100kcal/kg/d. Safety and tolerability was closely monitored under the oversight of an independent DSMB.

Recruitment status

COMPLETED

Study phase

Target enrollment

60 participants

Primary outcome timeframe

From enrollment until the infant reaches full feed or is discharged from the NICU, whichever comes first, assessed up to 50 days.

Results posted on

2019-03-21

Participant Flow

Ninety infants, less than or equal to one week of age, were recruited from the Sanford Health Boekelheide Neonatal Intensive Care Unit (NICU) between October 2012 and March 2014.

Preterm infants were between 24 and 33 6/7 weeks gestational age (GA) at birth. Adaptive enrollment was used to assure that infants \<28 weeks GA were enrolled over the same time period as more commonly admitted preterm infants \>28 weeks GA.

Participant milestones

Participant milestones
Measure	DHA Oil DHA oil administered 50 mg/d (0.18ml)as an oil emulsion enterally with feedings or by gavage tube if the infant has one. DHA oil administered at 50 mg/d (0.18ml) Or MCT oil administered at 0.18 ml	Medium Chain Triglyceride (MCT) Control Oil MCT oil administered 0.18ml as an oil emulsion enterally with feedings or by gavage tube if the infant has one. Placebo Group:MCT oil administered at 0.18 ml as an oil emulsion
Overall Study STARTED	31	29
Overall Study COMPLETED	29	29
Overall Study NOT COMPLETED	2	0

Reasons for withdrawal

Reasons for withdrawal
Measure	DHA Oil DHA oil administered 50 mg/d (0.18ml)as an oil emulsion enterally with feedings or by gavage tube if the infant has one. DHA oil administered at 50 mg/d (0.18ml) Or MCT oil administered at 0.18 ml	Medium Chain Triglyceride (MCT) Control Oil MCT oil administered 0.18ml as an oil emulsion enterally with feedings or by gavage tube if the infant has one. Placebo Group:MCT oil administered at 0.18 ml as an oil emulsion
Overall Study Physician Decision	1	0
Overall Study Protocol Violation	1	0

Baseline Characteristics

Bridging the Docosahexaenoic Acid (DHA) Gap: The Effects of Omega-3 Fatty Acid Supplementation in Premature Infants

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	DHA Supplemented n=31 Participants Preterm infants (31) randomized to receive 50mg/d of enteral DHA supplementation	Placebo Supplemented n=29 Participants Preterm infants (29) randomized to receive placebo study oil	Total n=60 Participants Total of all reporting groups
Age, Continuous	30.69 weeks of GA STANDARD_DEVIATION 2.42 • n=5 Participants	30.35 weeks of GA STANDARD_DEVIATION 2.46 • n=7 Participants	30.52 weeks of GA STANDARD_DEVIATION 2.43 • n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants	15 Participants n=7 Participants	30 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	14 Participants n=7 Participants	30 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Non-Hispanic	28 Participants n=5 Participants	25 Participants n=7 Participants	53 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Region of Enrollment United States	31 Participants n=5 Participants	29 Participants n=7 Participants	60 Participants n=5 Participants

PRIMARY outcome

Timeframe: From enrollment until the infant reaches full feed or is discharged from the NICU, whichever comes first, assessed up to 50 days.

Population: Comparison between preterm groups that received either DHA oil or MCT (placebo control) oil were made.

Outcome measures

Outcome measures
Measure	DHA Oil n=31 Participants DHA oil administered 50 mg/d (0.18ml)as an oil emulsion enterally with feedings or by gavage tube if the infant has one. DHA oil administered at 50 mg/d (0.18ml) Or MCT oil administered at 0.18 ml	(MCT) Control Oil n=29 Participants MCT oil administered 0.18ml as an oil emulsion enterally with feedings or by gavage tube if the infant has one. Placebo Group:MCT oil administered at 0.18 ml as an oil emulsion
Days to Reach Full Enteral Feedings and Days on Study Oil. Days to reach full enteral feedings	20.00 days Standard Deviation 8.32	16.21 days Standard Deviation 7.41
Days to Reach Full Enteral Feedings and Days on Study Oil. Days on Study oil	34.00 days Standard Deviation 19.2	33.71 days Standard Deviation 16.32

PRIMARY outcome

Timeframe: 30 days from birth

Population: Comparison between preterm groups that received either DHA oil or MCT (placebo control) oil were made. They had DHA levels measured to be used as a reference population in our NICU.

A linear mixed model was used to explore weight over time.

Outcome measures

Outcome measures
Measure	DHA Oil n=31 Participants DHA oil administered 50 mg/d (0.18ml)as an oil emulsion enterally with feedings or by gavage tube if the infant has one. DHA oil administered at 50 mg/d (0.18ml) Or MCT oil administered at 0.18 ml	(MCT) Control Oil n=29 Participants MCT oil administered 0.18ml as an oil emulsion enterally with feedings or by gavage tube if the infant has one. Placebo Group:MCT oil administered at 0.18 ml as an oil emulsion
Feasibility and Tolerability of Daily Enteral DHA Oil - Weight Change	18.4 Grams per day Standard Error 0.57	18.4 Grams per day Standard Error 0.57

PRIMARY outcome

Timeframe: At baseline (enrollment, < 1 week of age), full feedings, discharge

Linear mixed models were also used to examine the association between each FA of interest and treatment group over time. Since only three time points were available for FA measurement, only a random intercept was included in the models. For these models, the random effect for multiples was again found to be not needed and removed. Primary outcome variables for this analysis included LNA, ALA, ARA and DHA. Only early/late preterm status was included in the model as a covariate since this was a stratification variable. Continuous dependent variables were transformed using the natural logarithm as needed to meet the assumptions of the regression model (this included LNA and ALA).

Outcome measures

Outcome measures
Measure	DHA Oil n=31 Participants DHA oil administered 50 mg/d (0.18ml)as an oil emulsion enterally with feedings or by gavage tube if the infant has one. DHA oil administered at 50 mg/d (0.18ml) Or MCT oil administered at 0.18 ml	(MCT) Control Oil n=29 Participants MCT oil administered 0.18ml as an oil emulsion enterally with feedings or by gavage tube if the infant has one. Placebo Group:MCT oil administered at 0.18 ml as an oil emulsion
Long Chain Polyunsaturated Fatty Acid (LCPUFA) Levels - Docosahexaenoic Acid (DHA) Levels in Whole Blood Baseline Comparisons	2.91 mol% (composition) of fat Standard Deviation 0.45	2.88 mol% (composition) of fat Standard Deviation 0.68
Long Chain Polyunsaturated Fatty Acid (LCPUFA) Levels - Docosahexaenoic Acid (DHA) Levels in Whole Blood Discharge	2.87 mol% (composition) of fat Standard Deviation 0.50	3.55 mol% (composition) of fat Standard Deviation 0.44
Long Chain Polyunsaturated Fatty Acid (LCPUFA) Levels - Docosahexaenoic Acid (DHA) Levels in Whole Blood Full Enteral Feedings	2.83 mol% (composition) of fat Standard Deviation 0.50	3.03 mol% (composition) of fat Standard Deviation 0.54

PRIMARY outcome

Timeframe: 30 days from birth

Population: Comparison between preterm groups that received either DHA oil or MCT (placebo control) oil were made. They had DHA levels measured to be used as a reference population in our NICU.

A linear mixed model was used to explore length over time.

Outcome measures

Outcome measures
Measure	DHA Oil n=31 Participants DHA oil administered 50 mg/d (0.18ml)as an oil emulsion enterally with feedings or by gavage tube if the infant has one. DHA oil administered at 50 mg/d (0.18ml) Or MCT oil administered at 0.18 ml	(MCT) Control Oil n=29 Participants MCT oil administered 0.18ml as an oil emulsion enterally with feedings or by gavage tube if the infant has one. Placebo Group:MCT oil administered at 0.18 ml as an oil emulsion
Feasibility and Tolerability of Daily Enteral DHA Oil - Length Change	0.13 Centimeters per day Standard Error 0.006	0.12 Centimeters per day Standard Error 0.004

PRIMARY outcome

Timeframe: 30 days from birth

Population: Comparison between preterm groups that received either DHA oil or MCT (placebo control) oil were made. They had DHA levels measured to be used as a reference population in our NICU.

A linear mixed model was used to explore head circumference over time.

Outcome measures

Outcome measures
Measure	DHA Oil n=31 Participants DHA oil administered 50 mg/d (0.18ml)as an oil emulsion enterally with feedings or by gavage tube if the infant has one. DHA oil administered at 50 mg/d (0.18ml) Or MCT oil administered at 0.18 ml	(MCT) Control Oil n=29 Participants MCT oil administered 0.18ml as an oil emulsion enterally with feedings or by gavage tube if the infant has one. Placebo Group:MCT oil administered at 0.18 ml as an oil emulsion
Feasibility and Tolerability of Daily Enteral DHA Oil - Head Circumference	0.10 Centimeters per day Standard Error 0.004	0.10 Centimeters per day Standard Error 0.004

SECONDARY outcome

Timeframe: At baseline (enrollment, <1 week of age), full feedings and discharge

Outcome measures

Outcome measures
Measure	DHA Oil n=31 Participants DHA oil administered 50 mg/d (0.18ml)as an oil emulsion enterally with feedings or by gavage tube if the infant has one. DHA oil administered at 50 mg/d (0.18ml) Or MCT oil administered at 0.18 ml	(MCT) Control Oil n=29 Participants MCT oil administered 0.18ml as an oil emulsion enterally with feedings or by gavage tube if the infant has one. Placebo Group:MCT oil administered at 0.18 ml as an oil emulsion
LCPUFA Levels - Arachidonic Acid (ARA) in Whole Blood Baseline	13.21 wt:wt% of total fat in sample Standard Deviation 2.22	14.89 wt:wt% of total fat in sample Standard Deviation 1.89
LCPUFA Levels - Arachidonic Acid (ARA) in Whole Blood Full Enteral Feedings	14.35 wt:wt% of total fat in sample Standard Deviation 1.51	14.87 wt:wt% of total fat in sample Standard Deviation 1.50
LCPUFA Levels - Arachidonic Acid (ARA) in Whole Blood Discharge	14.31 wt:wt% of total fat in sample Standard Deviation 1.26	13.94 wt:wt% of total fat in sample Standard Deviation 1.67

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (<1 week of age), full enteral feedings and discharge

Outcome measures

Outcome measures
Measure	DHA Oil n=31 Participants DHA oil administered 50 mg/d (0.18ml)as an oil emulsion enterally with feedings or by gavage tube if the infant has one. DHA oil administered at 50 mg/d (0.18ml) Or MCT oil administered at 0.18 ml	(MCT) Control Oil n=29 Participants MCT oil administered 0.18ml as an oil emulsion enterally with feedings or by gavage tube if the infant has one. Placebo Group:MCT oil administered at 0.18 ml as an oil emulsion
LCPUFA Levels - Alpha-linolenic Acid (ALA) in Whole Blood Baseline	0.74 wt:wt% (composition) of total fat Standard Deviation 0.50	0.55 wt:wt% (composition) of total fat Standard Deviation 0.33
LCPUFA Levels - Alpha-linolenic Acid (ALA) in Whole Blood Full enteral feedings	0.21 wt:wt% (composition) of total fat Standard Deviation 0.13	0.20 wt:wt% (composition) of total fat Standard Deviation 0.11
LCPUFA Levels - Alpha-linolenic Acid (ALA) in Whole Blood Discharge	0.24 wt:wt% (composition) of total fat Standard Deviation 0.13	0.26 wt:wt% (composition) of total fat Standard Deviation 0.13

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, full feedings and discharge

Outcome measures

Outcome measures
Measure	DHA Oil n=31 Participants DHA oil administered 50 mg/d (0.18ml)as an oil emulsion enterally with feedings or by gavage tube if the infant has one. DHA oil administered at 50 mg/d (0.18ml) Or MCT oil administered at 0.18 ml	(MCT) Control Oil n=29 Participants MCT oil administered 0.18ml as an oil emulsion enterally with feedings or by gavage tube if the infant has one. Placebo Group:MCT oil administered at 0.18 ml as an oil emulsion
LCPUFA Levels - Linoleic Acid (LNA) Full feedings	14.72 wt:wt% (composition) of fat in sample Standard Deviation 2.05	14.95 wt:wt% (composition) of fat in sample Standard Deviation 2.04
LCPUFA Levels - Linoleic Acid (LNA) Discharge	15.37 wt:wt% (composition) of fat in sample Standard Deviation 2.39	16.64 wt:wt% (composition) of fat in sample Standard Deviation 3.18
LCPUFA Levels - Linoleic Acid (LNA) Baseline	18.45 wt:wt% (composition) of fat in sample Standard Deviation 4.51	16.45 wt:wt% (composition) of fat in sample Standard Deviation 3.39

Adverse Events

DHA Oil

Serious events: 1 serious events

Other events: 31 other events

Deaths: 0 deaths

(MCT) Control Oil

Serious events: 0 serious events

Other events: 29 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	DHA Oil n=31 participants at risk DHA oil administered 50 mg/d (0.18ml)as an oil emulsion enterally with feedings or by gavage tube if the infant has one. DHA oil administered at 50 mg/d (0.18ml) Or MCT oil administered at 0.18 ml	(MCT) Control Oil n=29 participants at risk MCT oil administered 0.18ml as an oil emulsion enterally with feedings or by gavage tube if the infant has one. Placebo Group:MCT oil administered at 0.18 ml as an oil emulsion
Infections and infestations Sepsis	3.2% 1/31 • Number of events 1 • Monitored for 30 days after last dose of study medication.	0.00% 0/29 • Monitored for 30 days after last dose of study medication.
General disorders Death	3.2% 1/31 • Number of events 1 • Monitored for 30 days after last dose of study medication.	0.00% 0/29 • Monitored for 30 days after last dose of study medication.

Other adverse events

Additional Information

Lora Black, Senior Director of Clinical Research

Sanford Health

Phone: 605-328-1368

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	DHA Oil n=31 participants at risk DHA oil administered 50 mg/d (0.18ml)as an oil emulsion enterally with feedings or by gavage tube if the infant has one. DHA oil administered at 50 mg/d (0.18ml) Or MCT oil administered at 0.18 ml	(MCT) Control Oil n=29 participants at risk MCT oil administered 0.18ml as an oil emulsion enterally with feedings or by gavage tube if the infant has one. Placebo Group:MCT oil administered at 0.18 ml as an oil emulsion
Respiratory, thoracic and mediastinal disorders Bronchopulmonary Dysplasia	6.5% 2/31 • Number of events 2 • Monitored for 30 days after last dose of study medication.	10.3% 3/29 • Number of events 3 • Monitored for 30 days after last dose of study medication.
Infections and infestations Sepsis (Grade 4)	9.7% 3/31 • Number of events 3 • Monitored for 30 days after last dose of study medication.	10.3% 3/29 • Number of events 3 • Monitored for 30 days after last dose of study medication.
Eye disorders Retinopathy of Prematurity	22.6% 7/31 • Number of events 7 • Monitored for 30 days after last dose of study medication.	17.2% 5/29 • Number of events 5 • Monitored for 30 days after last dose of study medication.
Gastrointestinal disorders Gastro-esophageal Reflux Disease	19.4% 6/31 • Number of events 6 • Monitored for 30 days after last dose of study medication.	13.8% 4/29 • Number of events 4 • Monitored for 30 days after last dose of study medication.
Metabolism and nutrition disorders Milk Soy Protein Intolerance	12.9% 4/31 • Number of events 5 • Monitored for 30 days after last dose of study medication.	13.8% 4/29 • Number of events 4 • Monitored for 30 days after last dose of study medication.
Nervous system disorders Intraventricular Hemorrhage	0.00% 0/31 • Monitored for 30 days after last dose of study medication.	3.4% 1/29 • Number of events 1 • Monitored for 30 days after last dose of study medication.
Cardiac disorders Periventricular Leukomalacia	0.00% 0/31 • Monitored for 30 days after last dose of study medication.	3.4% 1/29 • Number of events 1 • Monitored for 30 days after last dose of study medication.
Blood and lymphatic system disorders Thrombocytopenia	3.2% 1/31 • Number of events 1 • Monitored for 30 days after last dose of study medication.	0.00% 0/29 • Monitored for 30 days after last dose of study medication.
Endocrine disorders Adrenal insufficiency	3.2% 1/31 • Number of events 1 • Monitored for 30 days after last dose of study medication.	0.00% 0/29 • Monitored for 30 days after last dose of study medication.
Blood and lymphatic system disorders Anemia	64.5% 20/31 • Number of events 20 • Monitored for 30 days after last dose of study medication.	48.3% 14/29 • Number of events 14 • Monitored for 30 days after last dose of study medication.
Respiratory, thoracic and mediastinal disorders Apnea	19.4% 6/31 • Number of events 6 • Monitored for 30 days after last dose of study medication.	31.0% 9/29 • Number of events 9 • Monitored for 30 days after last dose of study medication.
Blood and lymphatic system disorders Other Blood and lymphatic disorders	0.00% 0/31 • Monitored for 30 days after last dose of study medication.	13.8% 4/29 • Number of events 5 • Monitored for 30 days after last dose of study medication.
Investigations Blood bilirubin increased	6.5% 2/31 • Number of events 2 • Monitored for 30 days after last dose of study medication.	3.4% 1/29 • Number of events 1 • Monitored for 30 days after last dose of study medication.
Cardiac disorders Other Cardiac Disorders	3.2% 1/31 • Number of events 1 • Monitored for 30 days after last dose of study medication.	3.4% 1/29 • Number of events 1 • Monitored for 30 days after last dose of study medication.
Hepatobiliary disorders Cholecystitis	3.2% 1/31 • Number of events 1 • Monitored for 30 days after last dose of study medication.	3.4% 1/29 • Number of events 2 • Monitored for 30 days after last dose of study medication.
Cardiac disorders Congenital heart defect	0.00% 0/31 • Monitored for 30 days after last dose of study medication.	3.4% 1/29 • Number of events 1 • Monitored for 30 days after last dose of study medication.
Infections and infestations Conjunctivitis	3.2% 1/31 • Number of events 1 • Monitored for 30 days after last dose of study medication.	6.9% 2/29 • Number of events 2 • Monitored for 30 days after last dose of study medication.
Gastrointestinal disorders Constipation	0.00% 0/31 • Monitored for 30 days after last dose of study medication.	6.9% 2/29 • Number of events 2 • Monitored for 30 days after last dose of study medication.
Gastrointestinal disorders Dysfunctional bottling/swallowing	22.6% 7/31 • Number of events 7 • Monitored for 30 days after last dose of study medication.	3.4% 1/29 • Number of events 1 • Monitored for 30 days after last dose of study medication.
Endocrine disorders Other Endocrine Disorders	3.2% 1/31 • Number of events 1 • Monitored for 30 days after last dose of study medication.	0.00% 0/29 • Monitored for 30 days after last dose of study medication.
Gastrointestinal disorders Gastritis	0.00% 0/31 • Monitored for 30 days after last dose of study medication.	3.4% 1/29 • Number of events 1 • Monitored for 30 days after last dose of study medication.
Gastrointestinal disorders Gastrointestinal Disorder NOS	0.00% 0/31 • Monitored for 30 days after last dose of study medication.	3.4% 1/29 • Number of events 1 • Monitored for 30 days after last dose of study medication.
General disorders Other General Disorder	6.5% 2/31 • Number of events 2 • Monitored for 30 days after last dose of study medication.	6.9% 2/29 • Number of events 2 • Monitored for 30 days after last dose of study medication.
Metabolism and nutrition disorders Hypercalcemia	3.2% 1/31 • Number of events 1 • Monitored for 30 days after last dose of study medication.	0.00% 0/29 • Monitored for 30 days after last dose of study medication.
Endocrine disorders Hypothyroidism	0.00% 0/31 • Monitored for 30 days after last dose of study medication.	3.4% 1/29 • Number of events 1 • Monitored for 30 days after last dose of study medication.
Respiratory, thoracic and mediastinal disorders Hypoxia	3.2% 1/31 • Number of events 1 • Monitored for 30 days after last dose of study medication.	0.00% 0/29 • Monitored for 30 days after last dose of study medication.
Infections and infestations Other Infections and Infestations	0.00% 0/31 • Monitored for 30 days after last dose of study medication.	3.4% 1/29 • Number of events 1 • Monitored for 30 days after last dose of study medication.
Psychiatric disorders Irritability	6.5% 2/31 • Number of events 2 • Monitored for 30 days after last dose of study medication.	0.00% 0/29 • Monitored for 30 days after last dose of study medication.
Infections and infestations Meningitis	0.00% 0/31 • Monitored for 30 days after last dose of study medication.	3.4% 1/29 • Number of events 1 • Monitored for 30 days after last dose of study medication.
Metabolism and nutrition disorders Other Metabolism and Nutrition Disorders	3.2% 1/31 • Number of events 1 • Monitored for 30 days after last dose of study medication.	0.00% 0/29 • Monitored for 30 days after last dose of study medication.
Musculoskeletal and connective tissue disorders Other Musculoskeletal Disorders	0.00% 0/31 • Monitored for 30 days after last dose of study medication.	3.4% 1/29 • Number of events 3 • Monitored for 30 days after last dose of study medication.
Musculoskeletal and connective tissue disorders Osteoporosis	3.2% 1/31 • Number of events 1 • Monitored for 30 days after last dose of study medication.	0.00% 0/29 • Monitored for 30 days after last dose of study medication.
General disorders Pain	0.00% 0/31 • Monitored for 30 days after last dose of study medication.	3.4% 1/29 • Number of events 1 • Monitored for 30 days after last dose of study medication.
Cardiac disorders Patent Ductus Arteriosus	9.7% 3/31 • Number of events 3 • Monitored for 30 days after last dose of study medication.	10.3% 3/29 • Number of events 3 • Monitored for 30 days after last dose of study medication.
Respiratory, thoracic and mediastinal disorders Periodic Breathing	6.5% 2/31 • Number of events 2 • Monitored for 30 days after last dose of study medication.	17.2% 5/29 • Number of events 5 • Monitored for 30 days after last dose of study medication.
Cardiac disorders Physiologic murmur	41.9% 13/31 • Number of events 15 • Monitored for 30 days after last dose of study medication.	20.7% 6/29 • Number of events 7 • Monitored for 30 days after last dose of study medication.
Infections and infestations Pneumonia	6.5% 2/31 • Number of events 2 • Monitored for 30 days after last dose of study medication.	0.00% 0/29 • Monitored for 30 days after last dose of study medication.
Respiratory, thoracic and mediastinal disorders Pneumothorax	3.2% 1/31 • Number of events 1 • Monitored for 30 days after last dose of study medication.	0.00% 0/29 • Monitored for 30 days after last dose of study medication.
Skin and subcutaneous tissue disorders Rash	16.1% 5/31 • Number of events 5 • Monitored for 30 days after last dose of study medication.	13.8% 4/29 • Number of events 4 • Monitored for 30 days after last dose of study medication.
Renal and urinary disorders Other Renal and Urinary Disorders	3.2% 1/31 • Number of events 1 • Monitored for 30 days after last dose of study medication.	6.9% 2/29 • Number of events 2 • Monitored for 30 days after last dose of study medication.
Respiratory, thoracic and mediastinal disorders Respiratory Failure	3.2% 1/31 • Number of events 1 • Monitored for 30 days after last dose of study medication.	0.00% 0/29 • Monitored for 30 days after last dose of study medication.
Respiratory, thoracic and mediastinal disorders Other Respiratory Disorder	16.1% 5/31 • Number of events 5 • Monitored for 30 days after last dose of study medication.	10.3% 3/29 • Number of events 3 • Monitored for 30 days after last dose of study medication.
Musculoskeletal and connective tissue disorders Scoliosis	0.00% 0/31 • Monitored for 30 days after last dose of study medication.	3.4% 1/29 • Number of events 1 • Monitored for 30 days after last dose of study medication.
Skin and subcutaneous tissue disorders Other Skin Disorders	6.5% 2/31 • Number of events 2 • Monitored for 30 days after last dose of study medication.	0.00% 0/29 • Monitored for 30 days after last dose of study medication.
Vascular disorders Thromboembolic Event	3.2% 1/31 • Number of events 1 • Monitored for 30 days after last dose of study medication.	0.00% 0/29 • Monitored for 30 days after last dose of study medication.
Infections and infestations Tracheitis	0.00% 0/31 • Monitored for 30 days after last dose of study medication.	6.9% 2/29 • Number of events 2 • Monitored for 30 days after last dose of study medication.
Infections and infestations Urinary Tract Infection	3.2% 1/31 • Number of events 1 • Monitored for 30 days after last dose of study medication.	3.4% 1/29 • Number of events 1 • Monitored for 30 days after last dose of study medication.
Renal and urinary disorders Urinary Tract Obstruction	0.00% 0/31 • Monitored for 30 days after last dose of study medication.	3.4% 1/29 • Number of events 1 • Monitored for 30 days after last dose of study medication.
Vascular disorders Other Vascular Disorders	3.2% 1/31 • Number of events 1 • Monitored for 30 days after last dose of study medication.	0.00% 0/29 • Monitored for 30 days after last dose of study medication.