Safety and Effect on Central Retinal Thickness of BI 1026... | NCT02732951

ID	Type	Description	Link
2015-003529-33	EudraCT Number

Status Module

Label	Type	Description	Intervention Names
BI 1026706	Experimental		Drug: BI 1026706
Placebo	Active Comparator		Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
BI 1026706	Drug		BI 1026706
Placebo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in Central Subfield Foveal Thickness (CSFT) at Week 12	The change from baseline in CSFT at Week 12 and the BI 1026706 effect was compared between the BI 1026706 treatment group and the placebo group as measured by Spectral-domain Optical Coherence Tomography (SD-OCT). Baseline was defined as the CSFT value measured at the visit when patients were randomised. Mean presented here is an adjusted mean.	Baseline and Week 12

Secondary Outcomes

Measure	Description	Time Frame
Number of Subjects With Serious Adverse Events (SAEs), Investigator Defined Drug-related Adverse Events (AEs) and Adverse Events of Special Interest (AESIs)	Number of subjects with serious adverse events (SAEs), Investigator defined drug-related Adverse events (AEs) and adverse events of special interest (AESIs) comparing the BI 1026706 treatment group with the placebo group is presented.	From first drug administration until 4 days after last drug administration, up to 89 days.

Eligibility Module

Eligibility Criteria

Inclusion criteria:

Patients 18 years of age and older
Male patients or female patients of non-childbearing potential
Diagnosis of Diabetes mellitus type 1 or type 2
Retinal thickening due to Diabetic macular edema (DME) involving the center of the macula in the study eye as confirmed by the Investigator on clinical exam
Center-involved DME confirmed on Spectral-Domain Optical Coherence Tomography (SD-OCT) with central subfield thickness (CSFT) of at least 300 µm in the study eye at screening, confirmed by Central Reading Centre
Best corrected visual acuity ETDRS (Early Treatment Diabetic Retinopathy Study) letter score in the study eye of 84 or below, but at least 70 at screening
Further inclusion criteria apply

Exclusion criteria:

Macular edema considered to be due to other causes than DME in the study eye
Additional eye disease in the study eye that, in the opinion of the Investigator, might affect macular edema or could compromise or alter visual acuity during the course of the trial
Anterior segment and vitreous abnormalities in the study eye that would compromise the adequate assessment of the best corrected visual acuity or an adequate examination of the posterior pole
Intraocular surgery in the study eye within 4 months prior to randomization or planned intraocular surgery, including cataract, during the study period
Proliferative diabetic retinopathy or iris neovascularisation in the study eye
Aphakia in the study eye
Any indication that requires immediate treatment or for which treatment is expected in the study eye with anti-Vascular Endothelial Growth Factor (VEGF) or with laser photocoagulation during the period, as per Investigator's judgment
History of prior laser photocoagulation or other surgical, intravitreal or peribulbar treatment in the study eye within 4 months prior to randomization, either for DME or an ocular condition other than DME
History of fluocinolone acetonide intravitreal implant in the study eye
Application of intraocular corticosteroids in the study eye within 2 years prior to randomization in phakic eyes or 9 months in pseudophakic eyes
History of topical steroid or nonsteroidal anti-inflammatory drugs (NSAID) treatment in the study eye within 30 days prior to randomization
Systemic anti-VEGF or pro-VEGF treatment within 4 months prior to randomization
Initiation of intensive insulin treatment (multiple daily injections or a pump) within 3 months prior to randomization or plans to do so in the next 4 months
Change in oral antidiabetic medication within 3 months prior to randomization
Patients with a clinically relevant abnormal screening haematology, blood chemistry, or urinalysis
Renal impairment with estimated creatinine clearance < 30 mL/min (as calculated by Cockcroft-Gault equation)
Myocardial infarction or unstable angina pectoris within 3 months before randomization
Uncontrolled arterial hypertension defined as a single measurement of systolic >180 mmHg, two consecutive measurements of systolic >160 mmHg, or diastolic >100mmHg on optimal medical regimen
Further exclusion criteria apply

Name	Affiliation	Role
Boehringer Ingelheim	Boehringer Ingelheim	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Brussels-UNIV Brugmann -Horta		Brussels		1020	Belgium
Leuven - UNIV UZ Leuven (Sint-Rafaël)

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo Matching to BI 1026706	Patients were administered film-coated tablet of placebo to match 100 mg BI 1026706 twice daily orally for 12 weeks.
FG001	BI 1026706	Patients were administered film-coated tablet of 100 mg BI 1026706 twice daily orally for 12 weeks.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
SAP	No	Yes	No	Statistical Analysis Plan	Jul 26, 2017	Sep 27, 2018

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
	BG00062.2± 9.7 BG00163.9± 8.7 BG00263.0± 9.2

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00014 BG00114 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0004 BG0014 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in Central Subfield Foveal Thickness (CSFT) at Week 12

The change from baseline in CSFT at Week 12 and the BI 1026706 effect was compared between the BI 1026706 treatment group and the placebo group as measured by Spectral-domain Optical Coherence Tomography (SD-OCT). Baseline was defined as the CSFT value measured at the visit when patients were randomised. Mean presented here is an adjusted mean.

Full analysis set (FAS): FAS includes all patients who were randomised, treated with at least 1 dose of BI 1026706 or placebo, and with a baseline and at least one post randomisation central subfield foveal thickness (CSFT) measurement.

Posted

Mean

Standard Deviation

Micrometre [μm]

Baseline and Week 12

ID	Title	Description
OG000	Placebo Matching to BI 1026706	Patients were administered film-coated tablet of placebo to match 100 mg BI 1026706 twice daily orally for 12 weeks.
OG001	BI 1026706	Patients were administered film-coated tablet of 100 mg BI 1026706 twice daily orally for 12 weeks.

Units	Counts
Participants	OG00047 OG00147

Title

Denominators

Categories

Title	Measurements
	OG000-6.19± 11.61 OG00110.26± 11.64

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	Null hypothesis = The CSFT change from baseline at Week 12 is equal in both groups	Mixed model for repeated measurements	Kenward-Roger approximation was used for denominator degrees of freedom.	0.3199		Adjusted Mean	16.45	Standard Error of the Mean	16.45	2-Sided	95	-16.23	49.13			Fixed effects of treatment, prior anti-diabetic macular oedema treatment status, visit, treatment by visit interaction, baseline, baseline by visit interaction; patient as a random effect; unstructured covariance matrix for within patient errors.

Secondary

Number of Subjects With Serious Adverse Events (SAEs), Investigator Defined Drug-related Adverse Events (AEs) and Adverse Events of Special Interest (AESIs)

Number of subjects with serious adverse events (SAEs), Investigator defined drug-related Adverse events (AEs) and adverse events of special interest (AESIs) comparing the BI 1026706 treatment group with the placebo group is presented.

Treated set (TS): TS includes all patients who were treated with at least 1 dose of trial drug, either BI 1026706 or placebo.

Posted

Number

Count of participants

From first drug administration until 4 days after last drug administration, up to 89 days.

ID	Title	Description
OG000	Placebo Matching to BI 1026706	Patients were administered film-coated tablet of placebo to match 100 mg BI 1026706 twice daily orally for 12 weeks.
OG001	BI 1026706	Patients were administered film-coated tablet of 100 mg BI 1026706 twice daily orally for 12 weeks.

Units	Counts
Participants

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Myocardial infarction	Cardiac disorders	20.1	Systematic Assessment	EG0000 affected53 at risk EG0011 affected52 at risk
Inguinal hernia	Gastrointestinal disorders	20.1	Systematic Assessment	EG0000 affected53 at risk EG0011 affected52 at risk
Localised infection	Infections and infestations	20.1	Systematic Assessment	EG0001 affected53 at risk EG0010 affected52 at risk
Pneumonia	Infections and infestations	20.1	Systematic Assessment	EG0000 affected53 at risk EG0011 affected52 at risk
Alanine aminotransferase increased	Investigations	20.1	Systematic Assessment	EG0000 affected53 at risk EG0011 affected52 at risk
Aspartate aminotransferase increased	Investigations	20.1	Systematic Assessment	EG0000 affected53 at risk EG0011 affected52 at risk
Haemoglobin decreased	Investigations	20.1	Systematic Assessment	EG0000 affected53 at risk EG0011 affected52 at risk
Red blood cell count decreased	Investigations	20.1	Systematic Assessment	EG0000 affected53 at risk EG0011 affected52 at risk
Generalised tonic-clonic seizure	Nervous system disorders	20.1	Systematic Assessment	EG0001 affected53 at risk EG0010 affected52 at risk
Glycosuria	Renal and urinary disorders	20.1	Systematic Assessment	EG0000 affected53 at risk EG0011 affected52 at risk
Reactive perforating collagenosis	Skin and subcutaneous tissue disorders	20.1	Systematic Assessment	EG0000 affected53 at risk EG0011 affected52 at risk

ID	Term
D008268	Macular Degeneration
D012162	Retinal Degeneration
D012164	Retinal Diseases
D005128	Eye Diseases

ID	Title	Description
BG000	Placebo Matching to BI 1026706	Patients were administered film-coated tablet of placebo to match 100 mg BI 1026706 twice daily orally for 12 weeks.
BG001	BI 1026706	Patients were administered film-coated tablet of 100 mg BI 1026706 twice daily orally for 12 weeks.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo Matching to BI 1026706	Patients were administered film-coated tablet of placebo to match 100 mg BI 1026706 twice daily orally for 12 weeks.	0	53	2	53	12	53
EG001	BI 1026706	Patients were administered film-coated tablet of 100 mg BI 1026706 twice daily orally for 12 weeks.	0	52	7	52	14	52

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Visual acuity reduced	Eye disorders	20.1	Systematic Assessment	EG0002 affected53 at risk EG0013 affected52 at risk
Nasopharyngitis	Infections and infestations	20.1	Systematic Assessment	EG0004 affected53 at risk EG0016 affected52 at risk
Gamma-glutamyltransferase increased	Investigations	20.1	Systematic Assessment	EG0003 affected53 at risk EG0010 affected52 at risk
Headache	Nervous system disorders	20.1	Systematic Assessment	EG0001 affected53 at risk EG0014 affected52 at risk
Somnolence	Nervous system disorders	20.1	Systematic Assessment	EG0003 affected53 at risk EG0011 affected52 at risk