:HDUHUV - ClinicalTrials.gov
Alcon - Business Use OnlyDocument: TDOC-0052880Status: EffectiveEffectiveProtocol - ClinicalVersion: 2.0; Most-Recent; Effective; CURRENTDate: 20-Dec-2016Page 1 of 56a Novartis companyShort TitleClear Care Plus for Presbyopic Contact Lens WearersLong TitleClinical Study of Clear Care Plus for Presbyopic Contact Lens WearersProtocol Number:LCS739-P001 / NCT02965833Study Phase:N/ASponsor Name andAddress:Alcon Research, Ltd.6201 South FreewayFort Worth, Texas 76134-2099Investigational Product:Clear Care Plus Cleaning & Disinfecting Solution (CCP)US IND# / EudraCTN/AIndication Studied:Cleaning and disinfection of soft contact lensesInvestigator Agreement:I have read the clinical study described herein, recognize itsconfidentiality, and agree to conduct the described trial incompliance with Good Clinical Practice (GCP), the ethicalprinciples contained within the Declaration of Helsinki, thisprotocol, and all applicable regulatory requirements.Additionally, I will comply with all procedures for datarecording and reporting, will permit monitoring, auditing, andinspection of my research center, and will retain all records untilnotified by the Sponsor.Principal Investigator:SignatureDateName:Address:Printed By:Print Date:
Alcon - Business Use OnlyDocument: TDOC-0052880Status: EffectiveEffectiveProtocol - ClinicalVersion: 2.0; Most-Recent; Effective; CURRENTDate: 20-Dec-2016Page 2 of 561 SYNOPSISProtocol Number: LCS739-P001Sponsor:Alcon Research, Ltd.6201 South FreewayFort Worth, Texas76134-2099InvestigationalCLEAR CARE Plus Cleaning Study Phase:& Disinfecting Solution (CCP)12Product:34N/AProtocol Title:Clinical Study of CLEAR CARE Plus for Presbyopic Contact LensWearersInvestigator(s)/ No. ofSites:Approximately 9 sitesCenter Location(s)/United StatesNo. of SubjectsDuration of Treatment:Required: 110 completed 30 3 days per period each product (up to 66 days total)Planned: approximately120 randomized(approximately 8 to20 subjects per site)Study Population: Current presbyopic soft contact lens wearers (2-week/monthly replacementmodalities only) with symptoms of contact lens induced dryness and habitually using anon-HydraGlyde containing multi-purpose solution (MPS) (target at least 50% using aBiotrue formulation habitually).Objective(s):The overall objective of this study is to demonstrate the benefit ofCCP compared to non-HYDRAGLYDE multipurpose contact lenssolutions in presbyopes currently wearing soft contact lenses andexperiencing symptoms of dryness.The primary objective is to demonstrate superiority of CCP whencompared to the subject’s habitual multipurpose solution (HMPS) inreducing symptoms of contact lens induced dryness after 30 days ofuse, based on responses to the CLDEQ-8 (abbreviated Contact LensDry Eye Questionnaire).Printed By:Print Date:
Alcon - Business Use OnlyDocument: TDOC-0052880Status: EffectiveEffectiveProtocol - ClinicalVersion: 2.0; Most-Recent; Effective; CURRENTDate: 20-Dec-2016Page 3 of 56Protocol Number: LCS739-P001Sponsor:Alcon Research, Ltd.6201 South FreewayFort Worth, Texas76134-2099Methodology:This is a prospective, randomized, crossover (2-treatment, 2-period),stratified (BIOTRUE and other HMPS), observer-masked, and quasisubject-masked study.Treatments:Investigational Product:CCPRoute of Administration:Remove and place each lens into theappropriately marked L/R domed lensholder, and thoroughly rinse with CCPfor 5 seconds. Fill the CCP lens cup tothe fill line with CCP and place the lensholder in the lens cup. Tighten the capPrinted By:Print Date:
Alcon - Business Use OnlyDocument: TDOC-0052880Status: EffectiveSponsor:EffectiveProtocol - ClinicalVersion: 2.0; Most-Recent; Effective; CURRENTAlcon Research, Ltd.6201 South FreewayFort Worth, Texas76134-2099Date: 20-Dec-2016Page 4 of 56Protocol Number: LCS739-P001(finger tight) on the CCP lens cup andstore lenses for at least 6 hours.Refer to MOP for detailed instructionsfor use in the package insert.Subject Selection:Duration of Treatment:The subject will wear their habitual lensbrand (following manufacturerrecommended replacement) on a dailywear basis for 30 3 days using CCPdaily to care for their lenses.Dosage:Up to 32 cleaning and disinfectingcycles will be used for the study.Control Article:Habitual Multi-purpose SolutionRoute of Administration:Refer to MOP for detailed instructionsfor use in the package inserts.Duration of Treatment:The subject will wear their habitual lensbrand (following manufacturerrecommended replacement) on a dailywear basis for 30 3 days using theirhabitual solution daily to care for theirlenses.Dosage:Up to 32 cleaning and disinfectioncycles will be used for the study.Inclusion Criteria:1. Age 45-65 (both inclusive) and must sign the informedconsent.2. Current adapted two-week/monthly replacement soft contactlens wearers (at least 2 months) with symptoms of contact lensinduced dryness as defined by the Symptomatology(Eligibility) Pre-screening questionnaire.Note: Subject may be wearing multifocal contact lenses orsingle vision contact lenses prescribed for monovision or fordistance only.3. Requires a near spectacle ADD of 0.50 or greater.4. Best corrected visual acuity (BCVA) to 20/30 or better in eachPrinted By:Print Date:
Alcon - Business Use OnlyDocument: TDOC-0052880Status: EffectiveSponsor:EffectiveProtocol - ClinicalVersion: 2.0; Most-Recent; Effective; CURRENTAlcon Research, Ltd.6201 South FreewayFort Worth, Texas76134-2099Date: 20-Dec-2016Page 5 of 56Protocol Number: LCS739-P001eye at distance at Visit 1.5. Willing to wear lenses for a minimum of 5 days per week6 hours per day, and attend all study visits.6. Currently (at least 2 months) using a non- HYDRAGLYDEcontaining multi-purpose solution to care for their lenses[Opti-Free Puremoist Multi-Purpose Contact Lens Solution(OFPM) contains HYDRAGLYDE and is thus not allowed].7. Uses digital devices (eg, smart phone, tablet, laptop computer,or desktop computer) for 20 consecutive minutes at least twicea week and willing to continue the same pattern for theduration of the study as assessed at Pre-screening.Exclusion Criteria:1. Extended wear (sleeps in lenses one or more nights per week).2. Any anterior segment infection, inflammation, disease, orabnormality that contraindicates contact lens wear asdetermined by the Investigator.3. Any use of systemic medications or ocular medications forwhich contact lens wear could be contraindicated, asdetermined by the Investigator, including use of any topicalocular medications that would require instillation duringcontact lens wear.4. Monocular subjects (only 1 eye with functional vision) orsubjects fit with only 1 lens.5. A known sensitivity to any ingredients in CCP.6. Biomicroscopy findings observed during the Visit 1 slit-lampexamination that are moderate (grade 3) or worse in either eye.7. Prior refractive surgery (eg, laser assisted in situ keratomileusis[LASIK] and photorefractive keratectomy [PRK]).8. History of herpetic keratitis, ocular surgery, or irregular cornea.Printed By:Print Date:
A l c o n - B usi n ess Us e O nl yEff e cti v eProtocol - ClinicalV e rsi o n: 2 . 0 ; M o s t - R e c e n t ; E f f e c t i v e ; C U R R E N TD o c u m e nt: T D O C - 0 0 5 2 8 8 0St at us: E f f e c t i v eS p o ns o r:Al c o n R es e ar c h, Lt d.6 2 0 1 S o ut h Fr e e w a yF ort W ort h, T e x as7 6 1 3 4- 2 0 9 9D at e: 2 0- D e c- 2 0 1 6P a g e 6 of 5 6P r ot o c ol N u m b e r: L C S 7 3 9 -P 0 0 19. A p at h ol o gi c al dr y e ye t h at pr e cl u d es c o nt a ct l e ns w e ar .1 0. Us e of m e c h a ni c al e y eli d t h er a p y or e yeli d s cr u bs wit hi n1 4 d a y s b ef or e Vi sit 1 a n d n ot willi n g t o dis c o nti n u e d uri n g t h est u d y.1 1. E nr oll m e nt of t h e I n v esti g at or or his/ h e r st aff, f a mil y m e m b ersof t h e I n v es ti g at or, f a mil y m e m b ers of t h e In v esti g at or's st af f,or i n di vi d u als li vi n g i n t h e h o us e h ol ds of t h es e i n di vi d u als.1 2. E nr oll m e nt of m or e t h a n 1 m e m b er of t h e s a m e h o us e h ol d i nt h e st u d y.1 3. P arti ci p ati o n i n a n y cli ni c al st u d y wit hi n 3 0 d a ys of Vi sit 1.1 4. S u bj e cts w h o ar e c urr e ntl y usi n g or h a v e n ot dis c o nti n u e dR est asis , Xii dr a or a t o pi c al st er oi d wit hi n t h e p ast 7 d a y s.Ass ess m e nts: C L -i n d u c e d dr y n ess s y m pt o ms as m e as ur e d b y C L D E Q- 8 S y m pt o m at ol o g y pr e-scr e e ni n g q u esti o n n air e St atisti c al M et h o ds: Bi o mi cr os c o p y S n ell e n vis u al a c uit y A Es a n d d e vi c e d efi ci e n ci esPl a n n e d A n al ysis :T hr e e a n al ys is s ets will b e d efi n e d: s af et y, f ull, a n d p er pr ot o c ol ( P P).T h e s af et y a n al ys is s et will i n cl u d e all s u bj e cts/ e y es e x p os e d t o a n yPri nt e d B y:Pri nt D at e:
Alcon - Business Use OnlyDocument: TDOC-0052880Status: EffectiveSponsor:EffectiveProtocol - ClinicalVersion: 2.0; Most-Recent; Effective; CURRENTAlcon Research, Ltd.6201 South FreewayFort Worth, Texas76134-2099Date: 20-Dec-2016Page 7 of 56Protocol Number: LCS739-P001study lens care products evaluated in this study. The full analysis set(FAS) is the set of all randomized subjects who are exposed to anystudy lens care products. The PP analysis set is a subset of allrandomized subjects and excludes those who meet the criticaldeviation criteria as specified in the Deviations and Evaluability Plan(DEP). The FAS will serve as the primary analysis set for all efficacyevaluations.All data from evaluable subjects will be included in the efficacyanalysis; no imputation for missing values will be performed.Efficacy:To address the primary efficacy objective, planned analyses aresummarized below.EndpointPRIMARYCLDEQ-8 (Day 30)Printed By:ComparisonStatistical MethodCCP vs HMPSSuperiorityMixed effect repeatedmeasure model.Baseline score as a covariate.Print Date:
Alcon - Business Use OnlyDocument: TDOC-0052880Status: EffectiveSponsor:EffectiveProtocol - ClinicalVersion: 2.0; Most-Recent; Effective; CURRENTDate: 20-Dec-2016Page 8 of 56Protocol Number: LCS739-P001Alcon Research, Ltd.6201 South FreewayFort Worth, Texas76134-2099Safety:Each safety variable will be summarized descriptively. AEs will beclassified as treatment-emergent, based on treatment-specificexposure, or pre-treatment. Count and percentage will be provided byrelationship to device, and separate tables will be generated for ocularand nonocular AEs. Counts and percentages in each grade categorywill be presented for each biomicroscopy parameter. Devicedeficiencies will also be tabulated. Supporting subject listingsdescribing details of each safety variable will be provided. Listingsdescribing details of AEs reported prior to usage of the study solutionswill be presented separately from the safety analysis for thetreatment-emergent AEs.Sample SizeJustification:Sample size calculations for the primary endpoint are summarizedbelow (one-sided α 0.05).EndpointPrimaryCLDEQ-8Printed By:AssumptionsPowerNSD 10(paireddifferences)80%Detectabledifference 336 per eachof the 2crossoversequencesPrint Date:
Alcon - Business Use OnlyDocument: TDOC-0052880Status: EffectiveEffectiveProtocol - ClinicalVersion: 2.0; Most-Recent; Effective; CURRENTDate: 20-Dec-2016Page 9 of 561.1 AmendmentsAmendment 1Purpose of Amendment: To implement revisions based on the change in Exclusion CriteriaRationale: To align with study specific requirementsCurrent Study Status: Study executionCase Report Form Revision Required:YesX NoInformed Consent Modifications Required:YesX NoApplicable Investigators:X AllSelected (list below)Itemized Changes:ChangeRationaleSection 8.2: Exclusion Criterianumber 14To include range of concurrent productsprohibited to use in the study.Change from:Subjects who are currently using or havenot discontinued RESTASIS within thepast 7 days.ToSubjects who are currently using or havenot discontinued RESTASIS, XIIDRA ora topical steroid within the past 7 days.Printed By:Print Date:
Alcon - Business Use OnlyDocument: TDOC-0052880Status: EffectiveEffectiveProtocol - ClinicalVersion: 2.0; Most-Recent; Effective; CURRENTDate: 20-Dec-2016Page 10 of 561.2 Glossary of Terms for SafetyAdverse Event (AE)Any untoward medical occurrence, unintended disease or injury, oruntoward clinical signs (including abnormal laboratory findings) insubjects, users or other persons, whether or not related to theinvestigational medical device (test article). Note: For subjects, thisdefinition includes events related to the test article, the controlarticle, or the procedures involved. For users or other persons, thisdefinition is restricted to events related to the test article.Adverse DeviceEffect (ADE)Adverse event related to the use of an investigational medical device(test article) or control article. Note: This definition includes adverseevents resulting from insufficient or inadequate instructions for use,deployment, implantation, installation, or operation; anymalfunction; and use error or intentional misuse of the test article orcontrol article.Device DeficiencyInadequacy of a medical device with respect to its identity, quality,durability, reliability, safety, or performance. Note: This definitionincludes malfunctions, use errors, and inadequate labeling.MalfunctionFailure of a medical device to meet its performance specifications orotherwise perform as intended. Performance specifications includeall claims made in the labeling of the device. The intendedperformance of the device refers to the intended use for which thedevice is labeled or marketed.Product ComplaintAny oral, electronic, or written communication that allegesdeficiencies related to the identity (labeling), quality, durability,reliability, safety, effectiveness, or performance of a marketedproduct, including failure of the product, labeling or packaging tomeet specifications, whether or not the product is related to orcaused the alleged deficiency. A complaint may allege that anadverse event or medical device malfunction has occurred.Non-serious AdverseEventAdverse event that does not meet the criteria for a serious adverseevent.Serious AdverseEvent (SAE)Adverse event that led to any of the following:Printed By:Death.Print Date:
Alcon - Business Use OnlyDocument: TDOC-0052880Status: EffectiveEffectiveProtocol - ClinicalVersion: 2.0; Most-Recent; Effective; CURRENTDate: 20-Dec-2016Page 11 of 56A serious deterioration in the health of the subject that either resultedin:A life-threatening illness or injury.Note: Life-threatening means that the individual was at immediaterisk of death from the event as it occurred, ie, it does not include anevent which hypothetically might have caused death had it occurredin a more severe form.Any potentially sight-threatening event or permanent impairment toa body structure or a body function.In-patient hospitalization or prolonged hospitalization.Note: Planned hospitalization for a pre-existing condition, withoutserious deterioration in health, is not considered a serious adverseevent. In general, hospitalization signifies that the individualremained at the hospital or emergency ward for observation and/ortreatment (usually involving an overnight stay) that would not havebeen appropriate in the physician's office or an out-patient setting.Complications that occur during hospitalization are adverse events.If a complication prolongs hospitalization or fulfills any otherserious criteria, the event is serious. When in doubt as to whether“hospitalization” occurred, the event should be considered serious.A medical or surgical intervention to prevent a) or b)Any indirect harm as a consequence of incorrect diagnostic testresults when used within manufacturer’s instructions for use.Fetal distress, fetal death, or a congenital abnormality or birth defect.Refer to Section 12 for additional SAEs.Serious AdverseDevice Effect(SADE)Adverse device effect that has resulted in any of the consequencescharacteristic of a serious adverse event.Serious Public HealthThreatAny event type which results in imminent risk of death, seriousdeterioration in state of health, or serious illness that requires promptremedial action. This would include: events that are of significantand unexpected nature such that they become alarming as a potentialpublic health hazard, eg, human immunodeficiency virus (HIV) orCreutzfeldt-Jacob Disease (CJD).Printed By:Print Date:
Alcon - Business Use OnlyDocument: TDOC-0052880Status: EffectiveEffectiveProtocol - ClinicalVersion: 2.0; Most-Recent; Effective; CURRENTDate: 20-Dec-2016Page 12 of 56Use ErrorAct or omission of an act that results in a different medical deviceresponse than intended by manufacturer or expected by user.Note: This definition includes slips, lapses, and mistakes. Anunexpected physiological response of the subject does not in itselfconstitute a use error.Printed By:Print Date:
Alcon - Business Use OnlyDocument: TDOC-0052880Status: EffectiveEffectiveProtocol - ClinicalVersion: 2.0; Most-Recent; Effective; CURRENTDate: 20-Dec-2016Page 13 of 562 OVERVIEW OF STUDY PLANProcedure/AssessmentPreScreening questionnaire(symptomatology,digital device use, andHMPS identification)aInformed consentCollect demographicsand activitiesMedical and lens/lenscare historyConcomitantmedications/ changes inconcomitantmedicationsSubjective mizationDispense a new pair ofhabitual lenses andassign/dispense thestudy lens care solutionper randomization.Educate on instructionsfor use.Snellen VA with lensesBiomicroscopyCLDEQ-8QuestionnairePrinted By:Visit 1Visit 2Visit 3USVScreening &BaselinePeriod 1/Day 1Period 1Day 30 3Follow-UpPeriod 2/Day1Period 2Day 30 3Follow-Up/ExitXXXXX(X)(X)(X)XXX(X)(X)(X)XXXbXb, dXd(X)XXXXXcXXUnscheduledVisitX (beforeconsent)XXXPrint Date:(X)
Alcon - Business Use OnlyDocument: TDOC-0052880Status: EffectiveProcedure/AssessmentAssess AEsAssess devicedeficienciesDocument wear timecompliance (days,hours) and lens carecomplianceaExit formaEffectiveProtocol - ClinicalVersion: 2.0; Most-Recent; Effective; CURRENTDate: 20-Dec-2016Page 14 of 56Visit 1Visit 2Visit 3Screening &BaselinePeriod 1/Day 1Period 1Day 30 3Follow-UpPeriod 2/Day1Period 2Day 30 edVisitSource onlybWith new lenses being dispensed at the visitcBased on habitual regimendWith lenses worn for the study period.eAEs are collected from the time of informed consent.(X) as needed.AEs adverse events, BCVA best corrected visual acuity, CLDEQ-8 Contact Lens Dry Eye Questionnaire-8,HMPS Habitual multi-purpose solution, IRB Institutional review board, USV unscheduled visit, VA visual acuityPrinted By:Print Date:
Alcon - Business Use OnlyDocument: TDOC-0052880Status: EffectiveEffectiveProtocol - ClinicalVersion: 2.0; Most-Recent; Effective; CURRENTDate: 20-Dec-2016Page 15 of 563 ABBREVIATIONSAbbreviationADDADEAEBCVAB&L CCCPCICJDCLCLCCLDEQ-8CSMDEPeCRFEDCEOBOEudraCT FFASFDAfl. oz.GCPGPCMSHIVHMPSIECICHIDINDIRBL/RLASIKMedDRA mLMOPMPSN/AnOFPMPPPrinted By:DefinitionAdded magnifying powerAdverse device effectAdverse eventBest corrected visual acuityBausch & LombDegrees CelsiusClear Care Plus Cleaning & Disinfecting SolutionConfidence intervalCreutzfeldt-Jacob DiseaseConfidence limit or contact lensContact lens careContact Lens Dry Eye Questionnaire-8Clinical site monitorDeviations and evaluability planElectronic case report formElectronic data captureEthylene oxide and butylene oxideEuropean Clinical Trials DatabaseDegrees FahrenheitFull analysis setUS Food and Drug AdministrationFluid ounceGood Clinical PracticeGlobal Product Complaint Management SystemHuman immunodeficiency virusHabitual multi-purpose solutionIndependent ethics committeeInternational Council for Harmonization of Technical Requirements forPharmaceuticals for Human UseIdentificationInvestigationa
2. Current adapted two-week/monthly replacement soft contact lens wearers (at least 2 months) with symptoms of contact lens induced dryness as defined by the Symptomatology (Eligibility) Pre-screening questionnaire. Note: Subject may be wearing multifocal contact lenses or single vision contact lenses prescribed for monovision or for distance .
before or during the trial Results Database – Captures summary results of a completed trial Zarin DA, Tse T. Medicine. Moving toward transparency of clinical trials. Science. 2008 Mar 7;319(5868):1340-2. 4 History of ClinicalTrials.gov FDAMA 113 (1997): Mandates Registry – IND trials for serious and life-threatening diseases or .
CTCAE Common Toxicity Criteria for Adverse Events CV Coefficient of variation CYP Cytochrome P450 D/C Discontinue eCRF Electronic case report form DLT Dose Limiting Toxicity ECG Electrocardiogram Eg Exempli gratia (for example) EORTC European Organization for Research and
project ID: 124967, NHS REC reference number:13/EE/0110, ClinicalTrials.gov Identifier: NCT01950143), a previous intervention study conducted at QIB, investigated the influence of once-a-week consumption of broccoli soup on health parameters in a prostate cancer cohort on active surveillance.
About KEYNOTE-045 KEYNOTE-045 is a randomized, pivotal, phase 3 study (ClinicalTrials.gov, NCT02256436) evaluating KEYTRUDA monotherapy compared to investigator-choice chemotherapy (paclitaxel, docetaxel, vinunine) in the treatment of patients with metastatic or locally advanced or unresectable (inoperable) urothelial cancer that has recurred or
The trial is designed to run seamlessly with the main trial but sites can opt out if they choose not to participate. See . section. 18 for more details. 2. CIAO -ISCHEMIA (Changes in Ischemia and Angina over One year among ISCHEMIA trial screen failures with no obstructive coronary .
University Medical Center, The Netherlands. The trial of-fice is responsible for overall trial management, trial registra-tion (ClinicalTrials.gov NCT01558921, EudraCT number 2010-023957-12, CKS number 2011 –4997, NL36315.042.11, NTR 3230), database management and quality assurance. A monitoring committee appointed by the trial sponsors
Histologically or cytologically confirmed, advanced, incurable non- CRC solid tumor; patients must have progressed on or be intolerant to standard therapies. c 2 prior therapies and 1 prior therapy for MSI-H CRC and non-CRC, respectively. Clinicaltrials.gov: NCT02460198 and NCT02628067 KEYNOTE-164 a /158 b (MSI-H CRC/non-CRC) Age .
be a concise, but not superficial, treatment on GUI programming. Part III contains information on the features of Python that allow you to accomplish big things with surprisingly little code. In preparing this book the Python documentation atwww.python.orgwas indispensable. This book was composed entirely in LATEX.
