Last updated: 11/07/2018 09:28:56

A phase 2 clinical study to investigate effects of darapladib in subjects with diabetic macular edema

Request patient level data
GSK study ID
115403
See study documents
Clinicaltrials.gov ID
NCT01506895
See results summary
EudraCT ID
2011-002944-28
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

Official title: A phase 2, multi-national, multi-centre, double masked, randomised, placebo controlled, parallel-group study to investigate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of darapladib administered for 3 months to adult subjects with diabetic macular edema with centre involvement
Trial description: The purpose of this study is to characterize the systemic and ocular safety and tolerability, pharmacokinetics, exploratory efficacy and pharmacodynamics of 3 months of repeat administration of oral darapladib in diabetic macular edema patients with centre involvement.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Allocation:
Randomized
Primary outcomes:

Mean change from Baseline in Early treatment diabetic retinopathy study (ETDRS) Best Corrected Visual Acuity (BCVA) on Day 90

Timeframe: Baseline (Day -3 to -1) and Day 90

Mean change from Baseline in Spectral Domain Optical Coherance Tomography (SD-OCT) central subfield retinal thickness in the study eye on Day 90

Timeframe: Baseline (Day -3 to -1) and Day 90

Secondary outcomes:

Change from Baseline in vital signs- Diastolic blood pressure (DBP) and systolic blood pressure (SBP)

Timeframe: Baseline (Day -3 to -1) to Follow-up/Day 125

Change from Baseline in vital signs- Heart rate

Timeframe: Baseline (Day -3 to -1) to Follow-up/Day 125

Change from Baseline in hematology parameters- basophils, eosinophils, lymphocytes, monocytes, total neutrophils, platelet count and white blood cell (WBC) count

Timeframe: Baseline (Day -3 to -1) to Follow-up/Day 125

Change from Baseline in hematology parameters- Glycosylated hemoglobin A1c

Timeframe: Baseline (Day -3 to -1) and Day 90

Change from Baseline in hematology parameters- Hemoglobin and mean corpuscle hemoglobin concentration (MCHC)

Timeframe: Baseline (Day -3 to -1) to Follow-up/Day 125

Change from Baseline in hematology parameters- Hematocrit

Timeframe: Baseline (Day -3 to -1) to Follow-up/Day 125

Change from Baseline in hematology parameters- Mean Corpuscle Hemoglobin (MCH)

Timeframe: Baseline (Day -3 to -1) to Follow-up/Day 125

Change from Baseline in hematology parameters- Mean Corpuscle Volume (MCV)

Timeframe: Baseline (Day -3 to -1) to Follow-up/Day 125

Change from Baseline in hematology parameters- red blood cells (RBC) and reticulocytes

Timeframe: Baseline (Day -3 to -1) to Follow-up/Day 125

Change from Baseline in clinical chemistry parameters- Albumin and total protein

Timeframe: Baseline (Day -3 to -1) to Follow-up/Day 125

Change from Baseline in clinical chemistry parameters- alkaline phosphatase (ALP), alanine amino transferase (ALT), aspartate amino transferase (AST) and gamma glutamyl transferase (GGT)

Timeframe: Baseline (Day -3 to -1) to Follow-up/Day 125

Change from Baseline in clinical chemistry parameters- Direct bilirubin, total bilirubin, creatinine and uric acid

Timeframe: Baseline (Day -3 to -1) to Follow-up/Day 125

Change from Baseline in clinical chemistry parameters- Calcium, cholesterol, chloride, carbon dioxide (CO2)/bicarbonate content, glucose (plasma efficiency)

Timeframe: Baseline (Day -3 to -1) to Follow-up/Day 125

Change from Baseline in clinical chemistry parameters- High density lipoprotein (HDL) cholesterol, direct, potassium, low density lipoprotein (LDL) cholesterol, direct, sodium, triglycerides and urea/blood urea nitrogen (BUN)

Timeframe: Baseline (Day -3 to -1) to Follow-up/Day 125

Number of participants with abnormal urinalysis parameters- Urine occult blood (dipstick)

Timeframe: Up to Follow-up/Day 125

Number of participants with abnormal urinalysis parameters- Urine glucose (dipstick)

Timeframe: Up to Follow-up/Day 125

Number of participants with abnormal urinalysis parameters- Urine ketones (dipstick)

Timeframe: Up to Follow-up/Day 125

Number of participants with abnormal urinalysis parameters- Urine protein (dipstick)

Timeframe: Up to Follow-up/Day 125

Summary of urinalysis parameter- Urine pH

Timeframe: Up to Follow-up/Day 125

Summary of urinalysis parameter- Urine specific gravity

Timeframe: Up to Follow-up/Day 125

Number of participants with adverse events (AE) and serious AE

Timeframe: Up to Follow-up/Day 125

Plasma pharmacokinetic (PK) parameters- Maximum plasma concentration (Cmax) of darapladib

Timeframe: Pre-dose (within 30 minutes prior to darapladib administration), 1, 2, 3, 4 hours (± 15 minutes) after the morning dose and 6 and 8 hours (± 30 minutes) after the morning dose on Day 30 and Day 60

Pharmacodynamic parameters- Lipoprotein associated phospholipase A2 (Lp-PLA2) peak % inhibition and trough % inhibition of darapladib

Timeframe: Day 30 (Pre-dose (within 30 minutes prior to darapladib administration), 1, 2, 3, 4 hours (± 15 minutes) after the morning dose and 6 and 8 hours (± 30 minutes) after the morning dose)

Interventions:
  • Drug: darapladib
  • Drug: placebo
    • Enrollment:
    54
    Primary completion date:
    2013-21-02
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    Giovanni Staurenghi, Li Ye, Mindy H. Magee, Ronald P. Danis, John Wurzelmann, Peter Adamson, Megan M. McLaughlin . Darapladib, a Lipoprotein-Associated Phospholipase A2 Inhibitor, in Diabetic Macular Edema : A 3-Month Placebo-Controlled Study. Ophthalmology. 2015;122(5):990-996.
    Medical condition
    Retinopathy, Diabetic
    Product
    darapladib
    Collaborators
    Not applicable
    Study date(s)
    February 2012 to February 2013
    Type
    Interventional
    Phase
    2

    Participation criteria

    Sex
    Female & Male
    Age
    18+ years
    Accepts healthy volunteers
    No
    • A female subject is eligible to participate if she is of: Non-childbearing potential or child-bearing potential and agrees to contraception for an appropriate period of time
    • Diagnosis of diabetes mellitus (type 1 or type 2)
    • Additional eye disease in the study eye that could compromise study assessments
    • Intraocular surgery, or laser photocoagulation in the study eye within 3 months of dosing
    Inclusion and exclusion criteria
    Inclusion criteria:
    • A female subject is eligible to participate if she is of: Non-childbearing potential or child-bearing potential and agrees to contraception for an appropriate period of time
    • Diagnosis of diabetes mellitus (type 1 or type 2)
    • Confirmation of DME in the study eye by angiography
    • Confirmation of retinal thickening in the study eye by study doctor
    • Best corrected visual acuity score of 78-24 letters in the study eye
    Exclusion criteria:
    • Additional eye disease in the study eye that could compromise study assessments
    • Intraocular surgery, or laser photocoagulation in the study eye within 3 months of dosing
    • Uncontrolled intraocular pressure in the study eye despite treatment with glaucoma medication
    • Uncontrolled diabetes
    • Certain types of liver disease
    • Severe reduction in kidney function OR removal of a kidney OR kidney transplant
    • Blood pressure higher than normal despite lifestyle changes and treatment with medications
    • Certain medications that may interfere with the study medication or eye assessments (these will be identified by the study doctor)
    • Current severe heart failure
    • Severe asthma that is poorly controlled with medication
    • Previous severe allergic reaction to food, medications, drink, insect stings, etc
    • If both birth parents are at least 50% Japanese, Chinese, or Korean ancestry, must have a blood sample collected for Lp-PLA2 activity. Those with Lp-PLA2 activity less than or equal to 20.0 nmol/min/mL are excluded
    • Recent participation in a study of an investigational medication
    • Any other reason the investigator deems the subject should not participate in the study
    • Other protocol-defined inclusion/exclusion criteria may apply

    Trial location(s)

    Location
    Status
    Contact us
    Contact us
    Location
    GSK Investigational Site
    Nedlands, Western Australia, Australia, 6009
    Status
    Study Complete
    Contact us
    Location
    GSK Investigational Site
    Glostrup, Denmark
    Status
    Study Complete
    Contact us
    Location
    GSK Investigational Site
    Freiburg, Baden-Wuerttemberg, Germany, 79106
    Status
    Study Complete
    Contact us
    Location
    GSK Investigational Site
    AMSTERDAM, Netherlands, 1105 AZ
    Status
    Terminated/Withdrawn
    Contact us
    Location
    GSK Investigational Site
    Padova, Veneto, Italy, 35128
    Status
    Study Complete
    Contact us
    Location
    GSK Investigational Site
    ROTTERDAM, Netherlands, 3011 BH
    Status
    Study Complete
    Contact us
    Showing 1 - 6 of 16 Results

    Study documents

    Clinical study report
    Available language(s): English
    Download document(s)
    Scientific result summary
    Available language(s): English
    Download document(s)

    If you wish to request for full study report, please contact - [email protected]

    Results overview

    Results posted on ClinicalTrials.gov

    Recruitment status
    Study complete
    Actual primary completion date
    2013-21-02
    Actual study completion date
    2013-21-02

    Plain language summaries

    Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

    Additional information about the trial

    Participate in clinical trial
    Additional information
    Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
    Click here
    Access to clinical trial data by researchers
    Visit website