{ "FullStudy":{ "Rank":217904, "Study":{ "ProtocolSection":{ "IdentificationModule":{ "NCTId":"NCT01515319", "OrgStudyIdInfo":{ "OrgStudyId":"QLON/2011/Y242-01" }, "SecondaryIdInfoList":{ "SecondaryIdInfo":[ { "SecondaryId":"2011-003549-17", "SecondaryIdType":"EudraCT Number" } ] }, "Organization":{ "OrgFullName":"Imperial College London", "OrgClass":"OTHER" }, "BriefTitle":"Safety and Pharmacokinetic Study of Y242 in Adult Subjects", "OfficialTitle":"A Randomised, Placebo Controlled Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Y242 in Adult Subjects", "Acronym":"Y242-01" }, "StatusModule":{ "StatusVerifiedDate":"March 2013", "OverallStatus":"Completed", "ExpandedAccessInfo":{ "HasExpandedAccess":"No" }, "StartDateStruct":{ "StartDate":"April 2012" }, "PrimaryCompletionDateStruct":{ "PrimaryCompletionDate":"February 2013", "PrimaryCompletionDateType":"Actual" }, "CompletionDateStruct":{ "CompletionDate":"February 2013", "CompletionDateType":"Actual" }, "StudyFirstSubmitDate":"December 22, 2011", "StudyFirstSubmitQCDate":"January 18, 2012", "StudyFirstPostDateStruct":{ "StudyFirstPostDate":"January 24, 2012", "StudyFirstPostDateType":"Estimate" }, "LastUpdateSubmitDate":"March 27, 2013", "LastUpdatePostDateStruct":{ "LastUpdatePostDate":"March 29, 2013", "LastUpdatePostDateType":"Estimate" } }, "SponsorCollaboratorsModule":{ "ResponsibleParty":{ "ResponsiblePartyType":"Sponsor" }, "LeadSponsor":{ "LeadSponsorName":"Imperial College London", "LeadSponsorClass":"OTHER" }, "CollaboratorList":{ "Collaborator":[ { "CollaboratorName":"Medical Research Council", "CollaboratorClass":"OTHER_GOV" } ] } }, "OversightModule":{ "OversightHasDMC":"Yes" }, "DescriptionModule":{ "BriefSummary":"Obesity causes 600 premature deaths per week in the UK and existing treatments are not effective. When humans eat, the bowels naturally secrete chemicals into the bloodstream which make people feel full and which stop eating. One of these chemicals is known as Peptide YY (PYY). The investigators have previously shown that injections of PYY reduce appetite and food intake in human volunteers. The investigators have now developed a very similar chemical, Y242, as a treatment for obesity. Y242 has been tested in animals and has been shown to be safe, to reduce their appetite, and to last for much longer than PYY itself. This study will test Y242 to ensure that it is well tolerated in humans, and to see how long it lasts in the blood stream after being injected under the skin. It will also look for any effects on appetite.", "DetailedDescription":"Obesity causes 600 premature deaths per week in the UK and existing treatments are less than ideal. Intravenous infusion of a hormone called PYY reduces food intake but its effects only last for a few hours and it can cause nausea. Y242 is a longacting analogue of PYY. Given subcutaneously in rodents, it has a profile of action of at least 72 hours and strongly inhibits food intake. It causes weight loss without behavioural effects. With MRC funding, Y242 has passed Good Laboratory Practice toxicology testing and the present proposal is a first in human study to investigate its safety, tolerability and pharmacokinetics in overweight but otherwise healthy men.\n\nThe study is a combined single ascending dose (part A) and multiple ascending dose (part B) Phase 1 investigation. The primary objective is to investigate safety and tolerability. The secondary objective is to assess Y242's pharmacokinetic (PK) profile. Possible effects on food consumption will be explored. For part A up to 48 subjects are planned, with up to 40 subjects for part B. In each part subjects are divided into groups, each of which is dosed with the same level, starting with a single dose (part A) much lower than is expected to cause an effect. Subjects are admitted to a Unit so they can be closely observed for adverse effects and safety tests, blood concentrations of the drug and food and liquid intake and output will be monitored. Subjects are allocated at random (like tossing a coin) to receive Y242 or placebo (dummy). Safety, tolerability and pharmacokinetic data will be summarised and available results considered in deciding dose escalation, with stopping rules designed to enable us to explore the relationship between dose and adverse effect (eg nausea) without causing unacceptable nausea or other symptoms in the volunteers." }, "ConditionsModule":{ "ConditionList":{ "Condition":[ "Obesity" ] }, "KeywordList":{ "Keyword":[ "Obesity", "Peptide YY", "Food intake", "Safety", "Pharmacokinetics" ] } }, "DesignModule":{ "StudyType":"Interventional", "PhaseList":{ "Phase":[ "Phase 1" ] }, "DesignInfo":{ "DesignAllocation":"Randomized", "DesignInterventionModel":"Parallel Assignment", "DesignPrimaryPurpose":"Treatment", "DesignMaskingInfo":{ "DesignMasking":"Double", "DesignWhoMaskedList":{ "DesignWhoMasked":[ "Participant", "Investigator" ] } } }, "EnrollmentInfo":{ "EnrollmentCount":"68", "EnrollmentType":"Actual" } }, "ArmsInterventionsModule":{ "ArmGroupList":{ "ArmGroup":[ { "ArmGroupLabel":"Y242", "ArmGroupType":"Experimental", "ArmGroupDescription":"Single ascending dose study in Part A Multiple ascending dose study in Part B", "ArmGroupInterventionList":{ "ArmGroupInterventionName":[ "Drug: Y242" ] } },{ "ArmGroupLabel":"Placebo (0.9% saline)", "ArmGroupType":"Placebo Comparator", "ArmGroupDescription":"0.9% saline placebo", "ArmGroupInterventionList":{ "ArmGroupInterventionName":[ "Drug: 0.9% saline" ] } } ] }, "InterventionList":{ "Intervention":[ { "InterventionType":"Drug", "InterventionName":"Y242", "InterventionDescription":"Single ascending dose: subcutaneous injection of 2, 7.5, 15, 30, 60 and 120 mg Y242 (Part A) Multiple ascending doses at weekly intervals, doses to be determined (Part B)", "InterventionArmGroupLabelList":{ "InterventionArmGroupLabel":[ "Y242" ] } },{ "InterventionType":"Drug", "InterventionName":"0.9% saline", "InterventionDescription":"Identical volume to that of Y242", "InterventionArmGroupLabelList":{ "InterventionArmGroupLabel":[ "Placebo (0.9% saline)" ] } } ] } }, "OutcomesModule":{ "PrimaryOutcomeList":{ "PrimaryOutcome":[ { "PrimaryOutcomeMeasure":"Safety measures", "PrimaryOutcomeDescription":"Safety monitoring will include assessment of adverse events (AEs), physical examination, 12-lead electrocardiograms (ECGs), lead II ECG monitoring, vital signs (blood pressure pulse rate and body temperature) and clinical laboratory safety tests (serum biochemistry, haematology, coagulation, TSH and urinalysis).", "PrimaryOutcomeTimeFrame":"up to 50 days" } ] }, "SecondaryOutcomeList":{ "SecondaryOutcome":[ { "SecondaryOutcomeMeasure":"Area under the plasma concentration versus time curve of Y242", "SecondaryOutcomeDescription":"area under the plasma concentration-time curves (AUC0-∞, AUC0-t, AUC0-τ)", "SecondaryOutcomeTimeFrame":"Predose, 0.5h, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h, 192h postdose." },{ "SecondaryOutcomeMeasure":"Energy intake at mealtimes", "SecondaryOutcomeDescription":"Exploratory PD evaluation will include evaluation of the following: energy intake at mealtimes, body weight, visual analogue scales (VAS) of nausea and satiety and fluid intake and output.", "SecondaryOutcomeTimeFrame":"up to 50 days" },{ "SecondaryOutcomeMeasure":"Maximum observed plasma concentration (Cmax)", "SecondaryOutcomeTimeFrame":"Predose, 0.5h, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h, 192h postdose." },{ "SecondaryOutcomeMeasure":"Apparent terminal rate constant (λz) and the apparent terminal half-life (t½)", "SecondaryOutcomeTimeFrame":"Predose, 0.5h, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h, 192h postdose." },{ "SecondaryOutcomeMeasure":"Extent of accumulation in plasma (RO)", "SecondaryOutcomeTimeFrame":"Predose, 0.5h, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h, 192h postdose." },{ "SecondaryOutcomeMeasure":"Body weight", "SecondaryOutcomeDescription":"Exploratory PD evaluation will include evaluation of the following: energy intake at mealtimes, body weight, visual analogue scales (VAS) of nausea and satiety and fluid intake and output.", "SecondaryOutcomeTimeFrame":"up to 50 days" },{ "SecondaryOutcomeMeasure":"Visual analogue scales measuring nausea and satiety", "SecondaryOutcomeDescription":"Exploratory PD evaluation will include evaluation of the following: energy intake at mealtimes, body weight, visual analogue scales (VAS) of nausea and satiety and fluid intake and output.", "SecondaryOutcomeTimeFrame":"up to 50 days" },{ "SecondaryOutcomeMeasure":"Fluid intake and output", "SecondaryOutcomeDescription":"Exploratory PD evaluation will include evaluation of the following: energy intake at mealtimes, body weight, visual analogue scales (VAS) of nausea and satiety and fluid intake and output.", "SecondaryOutcomeTimeFrame":"up to 50 days" } ] } }, "EligibilityModule":{ "EligibilityCriteria":"Inclusion Criteria:\n\nAdult males aged 18 to 50 years inclusive with BMI between 23.0 and 30.0 kg/m2 inclusive;\nSubjects who are healthy as determined by pre study medical history, physical examination and 12 lead ECG;\nSubjects whose clinical laboratory test results are either within the normal range or if outside this range the abnormalities are judged to be not clinically relevant and are acceptable to the Investigator;\nSubjects who are negative for hepatitis B surface antigen (HBsAg), hepatitis C antibody and human immunodeficiency virus (HIV) I and II tests at screening;\nSubjects who are negative for drugs of abuse and alcohol tests at screening and admissions;\nSubjects who are non-smokers for at least 3 months preceding screening;\nSubjects who agree to use medically acceptable methods of contraception for at least 3 months after study drug administration;\nSubjects who are able and willing to give written informed consent.\n\nExclusion Criteria:\n\nSubjects who do not conform to the above inclusion criteria;\nSubjects who have a clinically relevant history or presence of gastrointestinal (especially associated with vomiting), respiratory, renal, hepatic, haematological, lymphatic, neurological (especially if associated with balance disorders or vomiting e.g. migraine or labyrinthitis), cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, connective tissue diseases or disorders;\nSubjects who have a clinically relevant surgical history;\nSubjects who have a clinically relevant family history;\nSubjects who have a history of relevant atopy;\nSubjects who have a history of relevant drug hypersensitivity;\nSubjects who have a history of alcoholism;\nSubjects who have a history of drug abuse;\nSubjects who have a history of migraine;\nSubjects who consume more than 21 units of alcohol a week (unit = 1 glass of wine (125 mL) = 1 measure of spirits = ½ pint of beer);\nSubjects who have a significant infection or known inflammatory process on screening;\nSubjects who have acute gastrointestinal symptoms at the time of screening or admission (e.g. nausea, vomiting, diarrhoea, heartburn);\nSubjects who have an acute infection such as influenza at the time of screening or admission;\nSubjects who have used prescription drugs within 4 weeks of first dosing;\nSubjects who have used over the counter medication excluding routine vitamins and paracetamol but including megadose (intake of 20 to 600 times the recommended daily dose) vitamin therapy within 7 days of first dosing, unless agreed as not clinically relevant by the Principal Investigator and Sponsor;\nSubjects who have donated blood or blood products within 3 months of Day -2 (admission);\nSubjects who have used any investigational drug in any clinical trial within 3 months of Day -2 (admission);\nSubjects who have received the last dose of investigational drug greater than 3 months ago but who are on extended follow-up;\nSubjects who have previously received Y242;\nSubjects who are vegans or have any dietary restrictions;\nSubjects who cannot communicate reliably with the Investigator;\nSubjects who are unlikely to co-operate with the requirements of the study;\nHistory or evidence of abnormal eating behaviour, as observed through the Dutch Eating Behaviour (DEBQ) and SCOFF questionnaires at screening.", "HealthyVolunteers":"Accepts Healthy Volunteers", "Gender":"Male", "MinimumAge":"18 Years", "MaximumAge":"50 Years", "StdAgeList":{ "StdAge":[ "Adult" ] } }, "ContactsLocationsModule":{ "OverallOfficialList":{ "OverallOfficial":[ { "OverallOfficialName":"Stephen Bloom, MD FRCP DSc", "OverallOfficialAffiliation":"Imperial College London", "OverallOfficialRole":"Study Chair" },{ "OverallOfficialName":"John Lambert, MBBS PhD", "OverallOfficialAffiliation":"Parexel", "OverallOfficialRole":"Principal Investigator" },{ "OverallOfficialName":"Tricia Tan, MB ChB BSc MRCP", "OverallOfficialAffiliation":"Imperial College London", "OverallOfficialRole":"Study Director" } ] }, "LocationList":{ "Location":[ { "LocationFacility":"PAREXEL Early Phase Clinical Unit", "LocationCity":"London", "LocationZip":"HA1 3UJ", "LocationCountry":"United Kingdom" } ] } } }, "AnnotationSection":{ "AnnotationModule":{ "UnpostedAnnotation":{ "UnpostedResponsibleParty":"Imperial College London", "UnpostedEventList":{ "UnpostedEvent":[ { "UnpostedEventType":"Release", "UnpostedEventDate":"August 15, 2019" },{ "UnpostedEventType":"Reset", "UnpostedEventDate":"September 18, 2019" } ] } } } }, "DerivedSection":{ "MiscInfoModule":{ "VersionHolder":"April 22, 2020" }, "ConditionBrowseModule":{ "ConditionMeshList":{ "ConditionMesh":[ { "ConditionMeshId":"D000009765", "ConditionMeshTerm":"Obesity" } ] }, "ConditionAncestorList":{ "ConditionAncestor":[ { "ConditionAncestorId":"D000044343", "ConditionAncestorTerm":"Overnutrition" },{ "ConditionAncestorId":"D000009748", "ConditionAncestorTerm":"Nutrition Disorders" },{ "ConditionAncestorId":"D000050177", "ConditionAncestorTerm":"Overweight" },{ "ConditionAncestorId":"D000001835", "ConditionAncestorTerm":"Body Weight" },{ "ConditionAncestorId":"D000012816", "ConditionAncestorTerm":"Signs and Symptoms" } ] }, "ConditionBrowseLeafList":{ "ConditionBrowseLeaf":[ { "ConditionBrowseLeafId":"M11284", "ConditionBrowseLeafName":"Obesity", "ConditionBrowseLeafAsFound":"Obesity", "ConditionBrowseLeafRelevance":"high" },{ "ConditionBrowseLeafId":"M23894", "ConditionBrowseLeafName":"Overnutrition", "ConditionBrowseLeafRelevance":"low" },{ "ConditionBrowseLeafId":"M11267", "ConditionBrowseLeafName":"Nutrition Disorders", "ConditionBrowseLeafRelevance":"low" },{ "ConditionBrowseLeafId":"M24773", "ConditionBrowseLeafName":"Overweight", "ConditionBrowseLeafRelevance":"low" },{ "ConditionBrowseLeafId":"M3696", "ConditionBrowseLeafName":"Body Weight", "ConditionBrowseLeafRelevance":"low" } ] }, "ConditionBrowseBranchList":{ "ConditionBrowseBranch":[ { "ConditionBrowseBranchAbbrev":"BC18", "ConditionBrowseBranchName":"Nutritional and Metabolic Diseases" },{ "ConditionBrowseBranchAbbrev":"BC23", "ConditionBrowseBranchName":"Symptoms and General Pathology" },{ "ConditionBrowseBranchAbbrev":"All", "ConditionBrowseBranchName":"All Conditions" } ] } } } } } }