Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GSK2798745 in Subjects With Diabetic Macular Edema (DME)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04292912
Recruitment Status : Not yet recruiting
First Posted : March 3, 2020
Last Update Posted : July 14, 2020
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
GSK2798745 is a potent and selective oral Transient Receptor Potential Vanilloid 4 (TRPV4) channel blocker being investigated for the treatment of DME. This is a multi-center, open-label, single arm, 28-day treatment study with an opt-in period of additional 8 weeks of treatment in subjects with DME. The opt-in period will only be for subjects determined to be eligible to continue dosing. The study will be composed of 3 periods for all subjects: Screening, 28-day Treatment period, and Follow-up visit (approximately 28 days after the final dose).

Condition or disease Intervention/treatment Phase
Macular Edema Drug: GSK2798745 Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: This is a multi-center, open-label, single arm study.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Study 212669: Phase I, Open-Label, Multi-Center Study to Evaluate Safety, Pharmacokinetics and Pharmacodynamics of GSK2798745 After 28 Day (With an Optional Additional 8 Week) Repeat Oral Administration to Adults With Diabetic Macular Edema
Estimated Study Start Date : July 10, 2020
Estimated Primary Completion Date : February 8, 2021
Estimated Study Completion Date : February 8, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Edema

Arm Intervention/treatment
Experimental: GSK2798745 3.2 mg once daily
Subjects will receive a single daily 3.2 milligram (mg) oral dose of GSK2798745 for 28 days.
Drug: GSK2798745
GSK2798745 will be available as white to almost white, round, film-coated tablet. Subjects will be required to administer one tablet per day along with a glass of water.




Primary Outcome Measures :
  1. Number of subjects with abnormal ophthalmic examination findings [ Time Frame: From start of the treatment at Day 0 to end of treatment at Day 28 ]
    A complete eye examination including: eyelids and lashes (including Meibomian glands), pupil motility and confrontation visual field examination, slit lamp evaluation of anterior ocular structures (including conjunctiva, tear film, cornea and fluorescein staining, anterior chamber, iris, lens and anterior vitreous), intraocular pressure measurement, dilated fundus examination (indirect ophthalmoscopy and slit lamp bio microscopy) will be performed and number of subjects with abnormal ophthalmic examination findings will be reported.

  2. Number of subjects with abnormal refraction and visual acuity [ Time Frame: From start of the treatment at Day 0 to end of treatment at Day 28 ]
    Refraction and visual acuity will be measured using electronic early treatment diabetic retinopathy study (ETDRS) visual acuity charts (eVA) by trained examiner and number of subjects with abnormal Refraction and visual acuity will be reported.

  3. Number of subjects with abnormal physical examination findings [ Time Frame: From start of the treatment at Day 0 to end of treatment at Day 28 ]
    A complete physical examination including measuring weight, assessments of the skin, lungs, cardiovascular, respiratory, gastrointestinal, neurological systems and abdomen (liver and spleen) will be assessed and number of subjects with abnormal physical examination findings will be reported.

  4. Number of subjects with abnormal systolic blood pressure (SBP) and diastolic blood pressure (DBP) [ Time Frame: From start of the treatment at Day 0 to end of treatment at Day 28 ]
    SBP and DBP will be assessed in the semi-supine position after 5 minutes rest.

  5. Number of subjects with abnormal pulse rate [ Time Frame: From start of the treatment at Day 0 to end of treatment at Day 28 ]
    Pulse measurements will be assessed in the semi-supine position after 5 minutes rest.

  6. Number of subjects with abnormal body temperature findings [ Time Frame: From start of the treatment at Day 0 to end of treatment at Day 28 ]
    Body temperature will be assessed and abnormal findings will be reported.

  7. Number of subjects with abnormal 12-lead electrocardiogram (ECG) findings [ Time Frame: From start of the treatment at Day 0 to end of treatment at Day 28 ]
    12-lead ECG will be obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and corrected QT (QTc) intervals. Number of subjects with abnormal 12-lead ECG findings will be reported.

  8. Number of subjects with adverse events (AE) and serious adverse events (SAE) as a measure of safety and tolerability [ Time Frame: From start of the treatment at Day 0 to end of treatment at Day 28 ]
    An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/ birth defect and other situations which involve medical or scientific judgment, and is associated with liver injury and impaired liver function. The number of subject experiencing SAE and AEs during the study will be reported.

  9. Number of subjects with abnormal hematology parameters [ Time Frame: From start of the treatment at Day 0 to end of treatment at Day 28 ]
    Number of subjects with abnormal hematology parameters will be reported. The following parameters will be analyzed: platelet count, red blood cell (RBC) count, hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), reticulocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils.

  10. Number of subjects with abnormal clinical chemistry parameters [ Time Frame: From start of the treatment at Day 0 to end of treatment at Day 28 ]
    Number of subjects with abnormal clinical chemistry parameters will be reported. The following parameters will be analyzed: blood urea nitrogen (BUN), creatinine, glucose, potassium, sodium, calcium, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, total and direct bilirubin, total protein, creatinine phosphokinase (CPK).

  11. Number of subjects with abnormal urinalysis findings [ Time Frame: From start of the treatment at Day 0 to end of treatment at Day 28 ]
    Number of subjects with abnormal urinalysis parameters will be reported. The following parameters will be analyzed: specific gravity, potential of hydrogen (pH), glucose, protein, blood, ketones and microscopic examination (if blood or protein is abnormal).

  12. Mean change from Baseline in center subfield retinal thickness in the study eye as measured by Spectral-Domain Optical Coherence Tomography (SD-OCT) [ Time Frame: Baseline and up to Day 112 ]
    Changes in center subfield retinal thickness in the study eye as measured by SD-OCT from Baseline will be reported.


Secondary Outcome Measures :
  1. Plasma concentrations of GSK2798745 [ Time Frame: Day 7 and Day 28 ]
    Blood samples of approximately 2 milliliters (mL) will be collected for measurement of plasma concentrations of GSK2798745.

  2. Plasma concentrations of major metabolite GSK3526876 [ Time Frame: Day 7 and Day 28 ]
    Blood samples of approximately 2 mL will be collected for measurement of plasma concentrations of GSK2798745 and its metabolite GSK3526876.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • At least 18 years of age inclusive, at the time of signing the informed consent.
  • Diagnosis of diabetes mellitus (type 1 or type 2).
  • Confirmation of DME with center involvement in at least one eye, including those with focal or diffuse DME as determined by Investigator-determined fluorescein angiography.
  • Retinal thickening (diabetic macular edema) involving the center of the fovea in the study eye as defined by Investigator-determined SD-OCT central subfield thickness >340 microns for Heidelberg Spectralis or >320 for Zeiss Cirrus; if both eyes are eligible, the eye with the greater OCT center subfield score is selected as the study eye if all other criteria are met. SD-OCT assessments for individual patients must be taken with the same machine throughout the duration of the study.
  • ETDRS-Best Corrected Visual Acuity (BCVA) letter score of 68 letter or worse (Snellen equivalent: equivalent to 20/50) or worse in the study eye. The non-study fellow eye should be >=73 letters or better at Day 1 pre-dose.
  • Safe to withhold treatment of the study eye with laser photocoagulation, intravitreal steroid injection, or intravitreal vascular endothelial growth factor (VEGF) inhibitor for the duration of the study. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the Investigator in consultation with the Medical Monitor agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
  • Body weight >=50 kilograms (kg) and Body mass index (BMI) within the range 18 to 40kg per square meter (inclusive) at screening.
  • Male subjects will be eligible to participate if they agree to the following first dose of study treatment until the follow-up visit: Refrain from donating sperm, plus either be abstinent from heterosexual or homosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent or Must agree to use contraception/barrier as detailed below: 1. Agree to use a male condom and female partner to use an additional highly effective contraceptive method with a failure rate of <1% per year, 2. Should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak when having sexual intercourse with a woman of childbearing potential who is not currently pregnant.
  • A female subject is eligible to participate if she is not of childbearing potential.
  • Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
  • Subject is willing and able to return for all study visits and to comply with all protocol requirements and procedures.
  • Subjects capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form.

Exclusion Criteria:

  • Additional eye disease in the study eye that in the opinion of the Investigator could compromise assessment of SD-OCT, BCVA or imaging of the posterior pole by Fundus Photography (FP), fluorescein angiography, or is likely to require intervention during the study (e.g., cataract, glaucoma with documented visual field loss, ischemic optic neuropathy, retinitis pigmentosa).
  • History of choroidal neovascularization in the study eye, or current choroidal neovascularization in the fellow eye requiring treatment.
  • Active Proliferative diabetic retinopathy (PDR) in the study eye or untreated active PDR in the fellow eye.
  • Ischemic maculopathy on fluorescein angiography defined as a total area of capillary loss greater that 2-disc areas (>5millimeter square [mm^2]) within the ETDRA macular grid or a foveal avascular zone greatest linear diameter of >1000 microns.
  • Intraocular surgery or laser photocoagulation in the study eye within 90 day of dosing which might compromise assessment of SD-OCT, BCVA or imaging of the posterior pole by FP, fluorescein angiography. Allowed in fellow eye.
  • Use of intravitreal ranibizumab, bevacizumab or aflibercept in the study eye within 90 days of dosing. Allowed in fellow eye.
  • Use of intraocular steroids in the study eye within 180 days of dosing. Allowed in fellow eye.
  • Use of or expected need for intravitreal or intraocular treatment in the study eye during course of the study. Allowed in fellow eye.
  • Use of any systemically administered anti-angiogenic agent (e.g., bevacizumab, sunitinib, cetuximab, sorafenib, pazopanib), approved or investigational, within 6 months of dosing.
  • Evidence of vitreomacular traction as determined by the Investigator.
  • Uncontrolled intraocular pressure >22 millimeters of mercury in the study eye despite treatment with glaucoma medication.
  • Within 6 months prior to the Screening Visit, use of medications known to be toxic to the retina, lens or optic nerve (e.g., desferoximine, chloroquine/hydrochloroquine, chlorpromazine, phenothiazines, tamoxifen, interferons and ethambutol) or are implicated in the development of macular edema (e.g. thiazolidinesdiones, fingolimod).
  • Uncontrolled diabetes as indicated by glycated hemoglobin (HbA1c) >10% at Screening.
  • Active ulcer disease or gastrointestinal bleeding at the time of Screening (positive Fecal Occult Blood Test (FOBT) at screening).
  • Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • History of stroke or seizure disorder within 1 year of Screening.
  • Subject who, in the Investigator's opinion, poses a significant suicide risk. Evidence of serious suicide risk may include any history of suicidal behavior and/or any evidence of suicidal ideation on any questionnaires e.g., Type 4 or 5 on the Columbia Suicidality Severity Rating Scale (CSSRS) in the last 6 months (assessed at Screening).
  • History or current evidence of any serious or clinically significant cardiac, gastrointestinal, renal, endocrine, neurologic, hematologic or other condition that is uncontrolled on permitted therapies or that would, in the opinion of the Investigator or the Medical Monitor, make the subject unsuitable for inclusion in this study.
  • ALT >1.5 times upper limit of normal (ULN).
  • Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
  • Evidence of abnormal clinical laboratory finding prior to enrollment that, in the opinion of the Investigator, makes the subject unsuitable for the study.
  • QTc >450 milliseconds (msec) or QTc >480 msec in subjects with bundle branch block.
  • Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study drug, unless in the opinion of the Investigator and GlaxoSmithKline (GSK) Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
  • Use of a listed precluded medication, including strong inhibitors or inducers of cytochrome P450 (CYP) 3A or p-glycoprotein, within the restricted timeframe relative to the first dose of the study treatment.
  • Participation in the study would result in loss of blood or blood products in excess of 500 milliliter within 3 months from screening.
  • Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
  • Current enrollment, or past participation within the last 60 days, of any clinical study involving an investigational study intervention, or any other type of medical research, before signing of consent for this study.
  • Positive human immunodeficiency virus (HIV) antibody test.
  • Presence of Hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to first dose of study intervention.
  • Positive Hepatitis C antibody test result at screening or within 3 months prior to starting study intervention.
  • Positive Hepatitis C ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study intervention.
  • Cardiac troponin at screening > ULN for the assay.
  • Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator or Medical Monitor, contraindicates participation in the study.
  • Regular alcohol consumption within 6 months prior to the study defined as: An average weekly intake of > 14 units. One unit is equivalent to 8 gram of alcohol: a half-pint (equivalent to 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04292912


Contacts
Layout table for location contacts
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 89904466 GSKClinicalSupportHD@gsk.com

Sponsors and Collaborators
GlaxoSmithKline
Investigators
Layout table for investigator information
Study Director: GSK Clinical Trials GlaxoSmithKline
Layout table for additonal information
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT04292912    
Other Study ID Numbers: 212669
First Posted: March 3, 2020    Key Record Dates
Last Update Posted: July 14, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: http://clinicalstudydatarequest.com

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
diabetic macular edema, GSK2798745, refraction, visual acuity.
Additional relevant MeSH terms:
Layout table for MeSH terms
Macular Edema
Edema
Signs and Symptoms
Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases