- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT01515319
Safety and Pharmacokinetic Study of Y242 in Adult Subjects (Y242-01)
A Randomised, Placebo Controlled Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Y242 in Adult Subjects
Studieoversigt
Detaljeret beskrivelse
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.
The 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.
Undersøgelsestype
Tilmelding (Faktiske)
Fase
- Fase 1
Kontakter og lokationer
Studiesteder
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-
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London, Det Forenede Kongerige, HA1 3UJ
- PAREXEL Early Phase Clinical Unit
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Inclusion Criteria:
- Adult males aged 18 to 50 years inclusive with BMI between 23.0 and 30.0 kg/m^2 inclusive;
- Subjects who are healthy as determined by pre study medical history, physical examination and 12 lead ECG;
- Subjects 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;
- Subjects who are negative for hepatitis B surface antigen (HBsAg), hepatitis C antibody and human immunodeficiency virus (HIV) I and II tests at screening;
- Subjects who are negative for drugs of abuse and alcohol tests at screening and admissions;
- Subjects who are non-smokers for at least 3 months preceding screening;
- Subjects who agree to use medically acceptable methods of contraception for at least 3 months after study drug administration;
- Subjects who are able and willing to give written informed consent.
Exclusion Criteria:
- Subjects who do not conform to the above inclusion criteria;
- Subjects 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;
- Subjects who have a clinically relevant surgical history;
- Subjects who have a clinically relevant family history;
- Subjects who have a history of relevant atopy;
- Subjects who have a history of relevant drug hypersensitivity;
- Subjects who have a history of alcoholism;
- Subjects who have a history of drug abuse;
- Subjects who have a history of migraine;
- Subjects 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);
- Subjects who have a significant infection or known inflammatory process on screening;
- Subjects who have acute gastrointestinal symptoms at the time of screening or admission (e.g. nausea, vomiting, diarrhoea, heartburn);
- Subjects who have an acute infection such as influenza at the time of screening or admission;
- Subjects who have used prescription drugs within 4 weeks of first dosing;
- Subjects 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;
- Subjects who have donated blood or blood products within 3 months of Day -2 (admission);
- Subjects who have used any investigational drug in any clinical trial within 3 months of Day -2 (admission);
- Subjects who have received the last dose of investigational drug greater than 3 months ago but who are on extended follow-up;
- Subjects who have previously received Y242;
- Subjects who are vegans or have any dietary restrictions;
- Subjects who cannot communicate reliably with the Investigator;
- Subjects who are unlikely to co-operate with the requirements of the study;
- History or evidence of abnormal eating behaviour, as observed through the Dutch Eating Behaviour (DEBQ) and SCOFF questionnaires at screening.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Sekventiel tildeling
- Maskning: Dobbelt
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
|
Eksperimentel: 2mg Y242 (Part A)
Y242 single dose, subcutaneous
|
Single ascending dose: subcutaneous injection of 2, 7.5, 15, 30, 60 and 90 mg Y242 (Part A); Multiple ascending dose: Y242 single subcutaneous dose, administered once a week for 5 weeks (Part B)
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|
Eksperimentel: 7.5mg Y242 (Part A)
Y242 single dose, subcutaneous
|
Single ascending dose: subcutaneous injection of 2, 7.5, 15, 30, 60 and 90 mg Y242 (Part A); Multiple ascending dose: Y242 single subcutaneous dose, administered once a week for 5 weeks (Part B)
|
|
Eksperimentel: 15mg Y242 (Part A)
Y242 single dose, subcutaneous
|
Single ascending dose: subcutaneous injection of 2, 7.5, 15, 30, 60 and 90 mg Y242 (Part A); Multiple ascending dose: Y242 single subcutaneous dose, administered once a week for 5 weeks (Part B)
|
|
Eksperimentel: 30mg Y242 (Part A)
Y242 single dose, subcutaneous
|
Single ascending dose: subcutaneous injection of 2, 7.5, 15, 30, 60 and 90 mg Y242 (Part A); Multiple ascending dose: Y242 single subcutaneous dose, administered once a week for 5 weeks (Part B)
|
|
Eksperimentel: 60mg Y242 (Part A)
Y242 single dose, subcutaneous
|
Single ascending dose: subcutaneous injection of 2, 7.5, 15, 30, 60 and 90 mg Y242 (Part A); Multiple ascending dose: Y242 single subcutaneous dose, administered once a week for 5 weeks (Part B)
|
|
Eksperimentel: 90mg Y242 (Part A)
Y242 single dose, subcutaneous
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Single ascending dose: subcutaneous injection of 2, 7.5, 15, 30, 60 and 90 mg Y242 (Part A); Multiple ascending dose: Y242 single subcutaneous dose, administered once a week for 5 weeks (Part B)
|
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Placebo komparator: Placebo - Part A
0.9% saline
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Identical volume to that of Y242
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Eksperimentel: 60mg Y242 (Part B1)
Y242 single subcutaneous dose, administered once a week for 5 weeks
|
Single ascending dose: subcutaneous injection of 2, 7.5, 15, 30, 60 and 90 mg Y242 (Part A); Multiple ascending dose: Y242 single subcutaneous dose, administered once a week for 5 weeks (Part B)
|
|
Eksperimentel: 90mg Y242 (Part B2-B4)
Y242 single subcutaneous dose, administered once a week for 5 weeks
|
Single ascending dose: subcutaneous injection of 2, 7.5, 15, 30, 60 and 90 mg Y242 (Part A); Multiple ascending dose: Y242 single subcutaneous dose, administered once a week for 5 weeks (Part B)
|
|
Placebo komparator: Placebo - Part B
0.9% saline
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Identical volume to that of Y242
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs)
Tidsramme: Up to 73 days
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A treatment-emergent AE (TEAE) as defined as an AE that started after administration of IMP; in Part B this was an AE that started after the first dose of IMP.
Adverse events with onset prior to dosing were considered as pre-treatment AEs.
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Up to 73 days
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Body Weight
Tidsramme: up to 32 day
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Summary of Time-Matched % Change from Baseline in Body Weight (Baseline = Day -1) following multiple dose of Y242 (Part B)
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up to 32 day
|
Samarbejdspartnere og efterforskere
Sponsor
Samarbejdspartnere
Efterforskere
- Studiestol: Stephen Bloom DSc, MD FRCP, Imperial College London
- Ledende efterforsker: John Lambert, MBBS PhD, Parexel
- Studieleder: Tricia Tan BSc MRCP, MB ChB, Imperial College London
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Faktiske)
Studieafslutning (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- QLON/2011/Y242-01
- 2011-003549-17 (EudraCT nummer)
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
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