Safety and Pharmacokinetic Study of Y242 in Adult Subjects (Y242-01)

This study has been completed.
Sponsor:
Collaborator:
Medical Research Council
Information provided by (Responsible Party):
Imperial College London
ClinicalTrials.gov Identifier:
NCT01515319
First received: December 22, 2011
Last updated: March 27, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Obesity
Drug: Y242
Drug: 0.9% saline
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomised, Placebo Controlled Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Y242 in Adult Subjects

Resource links provided by NLM:


Further study details as provided by Imperial College London:

Primary Outcome Measures:
  • Safety measures [ Time Frame: up to 50 days ] [ Designated as safety issue: Yes ]
    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).


Secondary Outcome Measures:
  • Area under the plasma concentration versus time curve of Y242 [ Time Frame: Predose, 0.5h, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h, 192h postdose. ] [ Designated as safety issue: No ]
    area under the plasma concentration-time curves (AUC0-∞, AUC0-t, AUC0-τ)

  • Energy intake at mealtimes [ Time Frame: up to 50 days ] [ Designated as safety issue: No ]
    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.

  • Maximum observed plasma concentration (Cmax) [ Time Frame: Predose, 0.5h, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h, 192h postdose. ] [ Designated as safety issue: No ]
  • Apparent terminal rate constant (λz) and the apparent terminal half-life (t½) [ Time Frame: Predose, 0.5h, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h, 192h postdose. ] [ Designated as safety issue: No ]
  • Extent of accumulation in plasma (RO) [ Time Frame: Predose, 0.5h, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h, 192h postdose. ] [ Designated as safety issue: No ]
  • Body weight [ Time Frame: up to 50 days ] [ Designated as safety issue: No ]
    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.

  • Visual analogue scales measuring nausea and satiety [ Time Frame: up to 50 days ] [ Designated as safety issue: No ]
    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.

  • Fluid intake and output [ Time Frame: up to 50 days ] [ Designated as safety issue: No ]
    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.


Enrollment: 68
Study Start Date: April 2012
Study Completion Date: February 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Y242
Single ascending dose study in Part A Multiple ascending dose study in Part B
Drug: Y242
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)
Placebo Comparator: Placebo (0.9% saline)
0.9% saline placebo
Drug: 0.9% saline
Identical volume to that of Y242

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Adult males aged 18 to 50 years inclusive with BMI between 23.0 and 30.0 kg/m2 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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01515319

Locations
United Kingdom
PAREXEL Early Phase Clinical Unit
London, United Kingdom, HA1 3UJ
Sponsors and Collaborators
Imperial College London
Medical Research Council
Investigators
Study Chair: Stephen Bloom, MD FRCP DSc Imperial College London
Principal Investigator: John Lambert, MBBS PhD PAREXEL Early Phase Clinical Unit
Study Director: Tricia Tan, MB ChB BSc MRCP Imperial College London
  More Information

No publications provided

Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT01515319     History of Changes
Other Study ID Numbers: QLON/2011/Y242-01, 2011-003549-17
Study First Received: December 22, 2011
Last Updated: March 27, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Imperial College London:
Obesity
Peptide YY
Food intake
Safety
Pharmacokinetics

Additional relevant MeSH terms:
Obesity
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms

ClinicalTrials.gov processed this record on September 22, 2014