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
調査の概要
詳細な説明
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.
研究の種類
入学 (実際)
段階
- フェーズ 1
連絡先と場所
研究場所
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London、イギリス、HA1 3UJ
- PAREXEL Early Phase Clinical Unit
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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.
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 主な目的:処理
- 割り当て:ランダム化
- 介入モデル:順次割り当て
- マスキング:ダブル
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的:2mg 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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実験的:7.5mg 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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実験的:15mg 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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実験的:30mg 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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実験的:60mg 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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実験的: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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プラセボコンパレーター:Placebo - Part A
0.9% saline
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Identical volume to that of Y242
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実験的:60mg Y242 (Part B1)
Y242 single subcutaneous dose, administered once a week for 5 weeks
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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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実験的: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)
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プラセボコンパレーター:Placebo - Part B
0.9% saline
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Identical volume to that of Y242
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この研究は何を測定していますか?
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs)
時間枠: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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Body Weight
時間枠: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
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協力者と研究者
スポンサー
捜査官
- スタディチェア:Stephen Bloom DSc, MD FRCP、Imperial College London
- 主任研究者:John Lambert, MBBS PhD、Parexel
- スタディディレクター:Tricia Tan BSc MRCP, MB ChB、Imperial College London
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
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