Last updated: 11/07/2018 09:28:56
A phase 2 clinical study to investigate effects of darapladib in subjects with diabetic macular edema
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
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
Observational study model:
Not applicable
Primary completion date:
2013-21-02
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
GSK Investigational Site
Nedlands, Western Australia, Australia, 6009
Status
Study Complete
Location
GSK Investigational Site
Freiburg, Baden-Wuerttemberg, Germany, 79106
Status
Study Complete
Location
GSK Investigational Site
Muenster, Nordrhein-Westfalen, Germany, 48145
Status
Study Complete
Location
GSK Investigational Site
Ulm, Baden-Wuerttemberg, Germany, 89075
Status
Study Complete
Location
GSK Investigational Site
Sydney, New South Wales, Australia, 2000
Status
Study Complete
Location
GSK Investigational Site
Parramatta, New South Wales, Australia, 2150
Status
Study Complete
Location
GSK Investigational Site
Koeln, Nordrhein-Westfalen, Germany, 51109
Status
Study Complete
Location
GSK Investigational Site
East Melbourne, Victoria, Australia, 3002
Status
Study Complete
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
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.
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