Compare Safety/Efficacy of Labeled vs Wait-Extend Regimen... | NCT02262260

NCT02262260

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Ranibizumab labeled regime arm	Experimental	Ranibizumab (Anti VEGF) 0.5mg treatment will be given monthly and will be continued until maximum visual acuity is achieved (the patient's visual acuity is stable for three consecutive monthly assessments performed while on ranibizumab treatment). Thereafter patients should be monitored monthly for visual acuity. Treatment will be resumed when monitoring indicates loss of visual acuity due to DME. Monthly injections should then be administered until stable visual acuity is reached again for three consecutive monthly assessments (implying a minimum of two injections). The interval between two doses should not be shorter than 1 month	Drug: Labeled regime arm
Ranibizumab wait and Extend regime arm	Experimental	Ranibizumab (Anti VEGF) 0.5 mg will be injected subsequently at baseline, month 1 and 2. After the three initial loading doses, patients will be called for the control visits 1 month later. If the visual acuity has reached a stable level and there is no sign of edema on OCT, patients will not receive intravitreal injection and will be called to come back 6 weeks later. The interval is increased by 2 weeks until a maximum of 8 weeks as long as the patient presents as stable regarding visual acuity, central retinal thickness and clinical findings. If there is a negative change, the interval is shortened back to 4 weeks.	Drug: Wait and Extend regime arm

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Labeled regime arm	Drug	Treatment will be given monthly and will be continued until maximum visual acuity is achieved (the patient's visual acuity is stable for three consecutive monthly assessments performed while on ranibizumab treatment). Thereafter patients should be monitored monthly for visual acuity. Treatment will be resumed when monitoring indicates loss of visual acuity due to DME. Monthly injections should then be administered until stable visual acuity is reached again for three consecutive monthly assessments (implying a minimum of two injections). The interval between two doses should not be shorter than 1 month.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Mean Change in "Best-corrected Visual Acuity" at Month 12	Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (ETDRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of ETDRS is 0 to 100 letters. A positive average change from baseline of BCVA indicates improvement	12 months

Secondary Outcomes

Measure	Description	Time Frame
Mean Change in Central Retinal Thickness (CRT)	CRT was assessed by Optical Coherence Tomography (OCT).	12 months
Mean Number of Injections	Mean number of injections over a 12-month treatment period

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Written informed consent must be obtained before any assessment is performed.
M or F patients >18 years of age who have signed an informed consent
Patients with Type 1 or Type 2 DM (according to ADA or WHO guidelines) with HbA1c not more than 12.0% at screening (Visit 1). Patients should be on diet, exercise, and/or pharmacological treatment for diabetes.
Patients with visual impairment due to focal or diffuse macular edema with center involvement in at least one eye, as demonstrated with color fundus photography, fluorescein angiography and OCT within 28 days of the baseline treatment. If both eyes are eligible, the one with the worse visual acuity, as assessed at Visit 1, will be selected for study treatment unless, based on medical reasons, the investigator deems the other eye the more appropriate candidate for study treatment. The study eye must fulfill the following criteria at Visit 1:
BCVA score between 78 and 39 letters, inclusively, using ETDRS-like visual acuity testing charts at a testing distance of 4 meters (approximate Snellen equivalent of 20/32 to 20/160)
Decrease in vision is due to DME and not due to other causes, in the opinion of the investigator

Exclusion Criteria

Concomitant conditions in the study eye according to defined criteria such as infection, inflammation, uncontrolled glaucoma
Active PDR in the study eye or evidence of vitreomacular traction in either eye
Patients who are monocular or have a BCVA score in the non-study eye (fellow eye) £ 24 letters at Visit 1
Concomitant systemic condition according to defined criteria, eg. history of stroke, uncontrolled diabetes, renal failure, unsatisfactory controlled hypertension
Use of other investigational drugs within 5 half-lives of enrollment, or within 30 days until the expected PD effect has returned to baseline, whichever is longer.
History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes.
History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment.

Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.

Contacts/Locations Module

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Novartis Investigative Site		Istanbul	TUR	34098	Turkey (Türkiye)
Novartis Investigative Site

References Module

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No data is available for this block.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Labeled Regime Arm	Treatment will be given monthly and will be continued until maximum visual acuity is achieved (the patient's visual acuity is stable for three consecutive monthly assessments performed while on ranibizumab treatment). Thereafter patients should be monitored monthly for visual acuity. Treatment will be resumed when monitoring indicates loss of visual acuity due to DME. Monthly injections should then be administered until stable visual acuity is reached again for three consecutive monthly assessments (implying a minimum of two injections). The interval between two doses should not be shorter than 1 month

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
SAP	No	Yes	No	Statistical Analysis Plan	Feb 12, 2018	Aug 30, 2018

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

No data available

No data is available for this block.

Intervention Browse Module

Masking Info

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Labeled Regime Arm	Treatment will be given monthly and will be continued until maximum visual acuity is achieved (the patient's visual acuity is stable for three consecutive monthly assessments performed while on ranibizumab treatment). Thereafter patients should be monitored monthly for visual acuity. Treatment will be resumed when monitoring indicates loss of visual acuity due to DME. Monthly injections should then be administered until stable visual acuity is reached again for three consecutive monthly assessments (implying a minimum of two injections). The interval between two doses should not be shorter than 1 month
BG001	Wait and Extend Regime Arm	Lucentis (ranibizumab) 0.5 mg will be injected subsequently at baseline, month 1 and 2. After the three initial loading doses, patients will be called for the control visits 1 month later. If the visual acuity has reached a stable level and there is no sign of edema on OCT, patients will not receive intravitreal injection and will be called to come back 6 weeks later. The interval is increased by 2 weeks until a maximum of 8 weeks as long as the patient presents as stable regarding visual acuity, central retinal thickness and clinical findings. If there is a negative change, the interval is shortened back to 4 weeks.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00045 BG00142 BG00287

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	OG00076.44± 1.78 OG00173.09± 1.68

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Wilcoxon (Mann-Whitney)		0.5														Non-Inferiority	In order to demonstrate that the "wait and extend" regimen of ranibizumab is non-inferior to the posology described in the prescribing information, mean change in BCVA at month 12 from the baseline visit were determined for both treatment groups, and a comparison was made between the two groups using the Independent Samples t-test.

Secondary

Mean Change in Central Retinal Thickness (CRT)

CRT was assessed by Optical Coherence Tomography (OCT).

Study completers- The patients who have completed 12 months of treatment and follow-up are defined as Study Completers.

Posted

Mean

Standard Error

Micrometers

12 months

ID	Title	Description
OG000	Labeled Regime Arm	Treatment will be given monthly and will be continued until maximum visual acuity is achieved (the patient's visual acuity is stable for three consecutive monthly assessments performed while on ranibizumab treatment). Thereafter patients should be monitored monthly for visual acuity. Treatment will be resumed when monitoring indicates loss of visual acuity due to DME. Monthly injections should then be administered until stable visual acuity is reached again for three consecutive monthly assessments (implying a minimum of two injections). The interval between two doses should not be shorter than 1 month
OG001	Wait and Extend Regime Arm	Lucentis (ranibizumab) 0.5 mg will be injected subsequently at baseline, month 1 and 2. After the three initial loading doses, patients will be called for the control visits 1 month later. If the visual acuity has reached a stable level and there is no sign of edema on OCT, patients will not receive intravitreal injection and will be called to come back 6 weeks later. The interval is increased by 2 weeks until a maximum of 8 weeks as long as the patient presents as stable regarding visual acuity, central retinal thickness and clinical findings. If there is a negative change, the interval is shortened back to 4 weeks.

Secondary

Mean Number of Injections

Mean number of injections over a 12-month treatment period

Study completers- The patients who have completed 12 months of treatment and follow-up are defined as Study Completers. Statistical analysis not performed for the injection numbers

Posted

Mean

Standard Error

Injections

12 months

ID	Title	Description
OG000	Labeled Regime Arm	Treatment will be given monthly and will be continued until maximum visual acuity is achieved (the patient's visual acuity is stable for three consecutive monthly assessments performed while on ranibizumab treatment). Thereafter patients should be monitored monthly for visual acuity. Treatment will be resumed when monitoring indicates loss of visual acuity due to DME. Monthly injections should then be administered until stable visual acuity is reached again for three consecutive monthly assessments (implying a minimum of two injections). The interval between two doses should not be shorter than 1 month
OG001	Wait and Extend Regime Arm	Lucentis (ranibizumab) 0.5 mg will be injected subsequently at baseline, month 1 and 2. After the three initial loading doses, patients will be called for the control visits 1 month later. If the visual acuity has reached a stable level and there is no sign of edema on OCT, patients will not receive intravitreal injection and will be called to come back 6 weeks later. The interval is increased by 2 weeks until a maximum of 8 weeks as long as the patient presents as stable regarding visual acuity, central retinal thickness and clinical findings. If there is a negative change, the interval is shortened back to 4 weeks.

Secondary

Mean Number of Visits

Mean number of visits over a 12-month treatment period

Study completers- The patients who have completed 12 months of treatment and follow-up are defined as Study Completers. Statistical analysis not performed to compare visits

Posted

Mean

Standard Error

Number of visits

12 months

ID	Title	Description
OG000	Labeled Regime Arm	Treatment will be given monthly and will be continued until maximum visual acuity is achieved (the patient's visual acuity is stable for three consecutive monthly assessments performed while on ranibizumab treatment). Thereafter patients should be monitored monthly for visual acuity. Treatment will be resumed when monitoring indicates loss of visual acuity due to DME. Monthly injections should then be administered until stable visual acuity is reached again for three consecutive monthly assessments (implying a minimum of two injections). The interval between two doses should not be shorter than 1 month
OG001	Wait and Extend Regime Arm	Lucentis (ranibizumab) 0.5 mg will be injected subsequently at baseline, month 1 and 2. After the three initial loading doses, patients will be called for the control visits 1 month later. If the visual acuity has reached a stable level and there is no sign of edema on OCT, patients will not receive intravitreal injection and will be called to come back 6 weeks later. The interval is increased by 2 weeks until a maximum of 8 weeks as long as the patient presents as stable regarding visual acuity, central retinal thickness and clinical findings. If there is a negative change, the interval is shortened back to 4 weeks.

Secondary

Proportion of Patients Who Gained ≥5 Letters

BCVA score was based on the number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart assessed at a starting distance of 4 meters. An increased score indicates improvement in acuity. This outcome assessed the number of participants who had improvement of ≥5 letters of visual acuity at month 12 as compared with baseline

Study completers- The patients who have completed 12 months of treatment and follow-up are defined as Study Completers

Posted

Number

Participants

12 months

ID	Title	Description
OG000	Labeled Regime Arm	Treatment will be given monthly and will be continued until maximum visual acuity is achieved (the patient's visual acuity is stable for three consecutive monthly assessments performed while on ranibizumab treatment). Thereafter patients should be monitored monthly for visual acuity. Treatment will be resumed when monitoring indicates loss of visual acuity due to DME. Monthly injections should then be administered until stable visual acuity is reached again for three consecutive monthly assessments (implying a minimum of two injections). The interval between two doses should not be shorter than 1 month
OG001	Wait and Extend Regime Arm	Lucentis (ranibizumab) 0.5 mg will be injected subsequently at baseline, month 1 and 2. After the three initial loading doses, patients will be called for the control visits 1 month later. If the visual acuity has reached a stable level and there is no sign of edema on OCT, patients will not receive intravitreal injection and will be called to come back 6 weeks later. The interval is increased by 2 weeks until a maximum of 8 weeks as long as the patient presents as stable regarding visual acuity, central retinal thickness and clinical findings. If there is a negative change, the interval is shortened back to 4 weeks.

Secondary

Proportion of Patients Who Gained ≥10 Letters

BCVA score was based on the number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart assessed at a starting distance of 4 meters. An increased score indicates improvement in acuity. This outcome assessed the number of participants who had improvement of ≥10 letters of visual acuity at month 12 as compared with baseline

Study completers- The patients who have completed 12 months of treatment and follow-up are defined as Study Completers

Posted

Number

Participants

12 months

ID	Title	Description
OG000	Labeled Regime Arm	Treatment will be given monthly and will be continued until maximum visual acuity is achieved (the patient's visual acuity is stable for three consecutive monthly assessments performed while on ranibizumab treatment). Thereafter patients should be monitored monthly for visual acuity. Treatment will be resumed when monitoring indicates loss of visual acuity due to DME. Monthly injections should then be administered until stable visual acuity is reached again for three consecutive monthly assessments (implying a minimum of two injections). The interval between two doses should not be shorter than 1 month
OG001	Wait and Extend Regime Arm	Lucentis (ranibizumab) 0.5 mg will be injected subsequently at baseline, month 1 and 2. After the three initial loading doses, patients will be called for the control visits 1 month later. If the visual acuity has reached a stable level and there is no sign of edema on OCT, patients will not receive intravitreal injection and will be called to come back 6 weeks later. The interval is increased by 2 weeks until a maximum of 8 weeks as long as the patient presents as stable regarding visual acuity, central retinal thickness and clinical findings. If there is a negative change, the interval is shortened back to 4 weeks.

Secondary

Proportion of Patients Who Gained ≥15 Letters

BCVA score was based on the number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart assessed at a starting distance of 4 meters. An increased score indicates improvement in acuity. This outcome assessed the number of participants who had improvement of ≥15 letters of visual acuity at month 12 as compared with baseline

Study completers- The patients who have completed 12 months of treatment and follow-up are defined as Study Completers

Posted

Number

Participants

12 months

ID	Title	Description
OG000	Labeled Regime Arm	Treatment will be given monthly and will be continued until maximum visual acuity is achieved (the patient's visual acuity is stable for three consecutive monthly assessments performed while on ranibizumab treatment). Thereafter patients should be monitored monthly for visual acuity. Treatment will be resumed when monitoring indicates loss of visual acuity due to DME. Monthly injections should then be administered until stable visual acuity is reached again for three consecutive monthly assessments (implying a minimum of two injections). The interval between two doses should not be shorter than 1 month
OG001	Wait and Extend Regime Arm	Lucentis (ranibizumab) 0.5 mg will be injected subsequently at baseline, month 1 and 2. After the three initial loading doses, patients will be called for the control visits 1 month later. If the visual acuity has reached a stable level and there is no sign of edema on OCT, patients will not receive intravitreal injection and will be called to come back 6 weeks later. The interval is increased by 2 weeks until a maximum of 8 weeks as long as the patient presents as stable regarding visual acuity, central retinal thickness and clinical findings. If there is a negative change, the interval is shortened back to 4 weeks.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Labeled Treatment Arm	Treatment will be given monthly and will be continued until maximum visual acuity is achieved (the patient's visual acuity is stable for three consecutive monthly assessments performed while on ranibizumab treatment). Thereafter patients should be monitored monthly for visual acuity. Treatment will be resumed when monitoring indicates loss of visual acuity due to DME. Monthly injections should then be administered until stable visual acuity is reached again for three consecutive monthly assessments (implying a minimum of two injections). The interval between two doses should not be shorter than 1 month	1	45	10	45	12	45
EG001	Wait and Extend Regimen Arm	Lucentis (ranibizumab) 0.5 mg will be injected subsequently at baseline, month 1 and 2. After the three initial loading doses, patients will be called for the control visits 1 month later. If the visual acuity has reached a stable level and there is no sign of edema on OCT, patients will not receive intravitreal injection and will be called to come back 6 weeks later. The interval is increased by 2 weeks until a maximum of 8 weeks as long as the patient presents as stable regarding visual acuity, central retinal thickness and clinical findings. If there is a negative change, the interval is shortened back to 4 weeks.	0	42	7	42	9	42

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Angina pectoris	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected45 at risk EG0010 affected42 at risk
Coronary artery disease	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected45 at risk EG0011 affected42 at risk
Myocardial infarction	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0002 affected45 at risk EG0011 affected42 at risk
Vitreous hemorrhage	Eye disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected45 at risk EG0011 affected42 at risk
Fatigue	General disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected45 at risk EG0010 affected42 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected45 at risk EG0010 affected42 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected45 at risk EG0011 affected42 at risk
Pneumonia	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0000 affected45 at risk EG0011 affected42 at risk
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA (21.0)	Systematic Assessment	EG0000 affected45 at risk EG0011 affected42 at risk
Diabetes mellitus inadequate control	Metabolism and nutrition disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected45 at risk EG0010 affected42 at risk
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.0)	Systematic Assessment	EG0001 affected45 at risk EG0010 affected42 at risk
Gallbladder neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.0)	Systematic Assessment	EG0001 affected45 at risk EG0010 affected42 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected45 at risk EG0011 affected42 at risk
Proteinuria	Renal and urinary disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected45 at risk EG0011 affected42 at risk
Renal failure	Renal and urinary disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected45 at risk EG0010 affected42 at risk
Diabetic foot	Skin and subcutaneous tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0002 affected45 at risk EG0010 affected42 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected45 at risk EG0011 affected42 at risk
Iron deficiency anaemia	Blood and lymphatic system disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected45 at risk EG0010 affected42 at risk
Angina pectoris	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected45 at risk EG0010 affected42 at risk
Vertigo	Ear and labyrinth disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected45 at risk EG0011 affected42 at risk
Dry eye	Eye disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected45 at risk EG0010 affected42 at risk
Eye haemorrhage	Eye disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected45 at risk EG0011 affected42 at risk
Itchy eyes	Eye disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected45 at risk EG0010 affected42 at risk
Ocular hyperemia	Eye disorders	MedDRA (21.0)	Systematic Assessment	EG0002 affected45 at risk EG0011 affected42 at risk
Vitreoretinal traction syndrome	Eye disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected45 at risk EG0011 affected42 at risk
Vitreous hemorrhage	Eye disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected45 at risk EG0011 affected42 at risk
Vitreous opacity	Eye disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected45 at risk EG0010 affected42 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected45 at risk EG0012 affected42 at risk
Constipation	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected45 at risk EG0011 affected42 at risk
Diarrhea	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected45 at risk EG0012 affected42 at risk
Gastric spasm	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected45 at risk EG0010 affected42 at risk
Gastritis	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected45 at risk EG0011 affected42 at risk
Nausea	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected45 at risk EG0010 affected42 at risk
Ocular hyperemia	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected45 at risk EG0010 affected42 at risk
Gall bladder stone	Hepatobiliary disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected45 at risk EG0011 affected42 at risk
Gallbladder inflammation	Hepatobiliary disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected45 at risk EG0010 affected42 at risk
Hepatic steatosis	Hepatobiliary disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected45 at risk EG0011 affected42 at risk
Adenovirus infection	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 affected45 at risk EG0010 affected42 at risk
Eye infection	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0000 affected45 at risk EG0011 affected42 at risk
Foot infection	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0000 affected45 at risk EG0011 affected42 at risk
Influenza	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 affected45 at risk EG0010 affected42 at risk
Pneumonia	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0000 affected45 at risk EG0011 affected42 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 affected45 at risk EG0010 affected42 at risk
Urinary tract infection	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 affected45 at risk EG0010 affected42 at risk
Increased intraocular pressure	Investigations	MedDRA (21.0)	Systematic Assessment	EG0001 affected45 at risk EG0010 affected42 at risk
Hyponatremia	Metabolism and nutrition disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected45 at risk EG0011 affected42 at risk
Vitamin D deficiency	Metabolism and nutrition disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected45 at risk EG0011 affected42 at risk
Gallbladder papillary adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.0)	Systematic Assessment	EG0001 affected45 at risk EG0010 affected42 at risk
Tinnitus	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected45 at risk EG0010 affected42 at risk
Impaired renal function	Renal and urinary disorders	MedDRA (21.0)	Systematic Assessment	EG0001 affected45 at risk EG0010 affected42 at risk
Renal cyst	Renal and urinary disorders	MedDRA (21.0)	Systematic Assessment	EG0000 affected45 at risk EG0011 affected42 at risk

ID	Term
C000608097	DMAC2L protein, human