Safety, Tolerability and Efficacy Study of PP1420 in HV

• Status: Terminated
• Trial end date: 2016-05-01
• Target enrollment: 0
• Participant gender: Male

Summary

Obesity is a growing pandemic which affects 1 in 4 adults in the UK, and shortens life by increasing cardiovascular disease, diabetes and cancer. Current treatments for obesity have either poor efficacy or significant side effects. Pancreatic polypeptide (PP) is a promising new drug target as it produces powerful appetite suppression which, following a 90-minute infusion continues to act for 24 h in man. We have developed a new long lasting high potency analogue of PP, PP1420. This is delivered as a once-a-day subcutaneous injection via a painless fine-gauge needle.

In a first-time-in-man Phase 1a trial, that PP 1420 proved safe, well tolerated, and had extended pharmacokinetics compared to PP itself.

We now plan to study the safety and PK of PP1420 up to 64mg. We will also assess:

1. Its efficacy in reducing food intake after a single dose in a Phase 1B study in healthy volunteers.

2. Its efficacy in reducing food intake and weight after multiple dosing in a Phase 1C study in healthy volunteers.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Imperial College London
• Collaborators: Imperial College Healthcare NHS Trust; Wellcome Trust
• Treatments: Pancreatic Polypeptide

Criteria

Inclusion Criteria:

1. Healthy male as determined by a responsible physician, based on a medical evaluation including history, physical examination, vital signs, laboratory tests and 12-lead ECG.

2. Between 18 and 50 years of age, inclusive, at the time of signing and dating the informed consent form.

3. Body weight 70 kg and body mass index (BMI) within the range 25 - 35 kg/m2 (inclusive).

4. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

5. Willing and able to comply with the protocol for the duration of the study.

Exclusion Criteria:

1. As a result of the medical interview, physical examination, or screening investigations, the Investigator considers the subject unsuitable for the study.

2. The subject has a positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.

3. A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.

4. A positive test for human immunodeficiency virus (HIV) antibody.

5. History of migraine.

6. History or evidence of abnormal eating behaviour, as observed through the Dutch Eating Behaviour (DEBQ) and SCOFF questionnaires.

7. History of excessive alcohol consumption within 6 months of the study defined as an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units. One unit is equivalent to 8 g of alcohol, a half-pint (approximately 240 mL) of beer or 1 measure (25 mL) of spirits or 1 glass (125 mL) of wine.

8. Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.

9. Has QTc at screening >450 msec.

10. Systolic blood pressure outside the range 85 - 160 mmHg, diastolic blood pressure outside the range 45 - 100 mmHg, and/or heart rate outside the range 40 - 110 bpm.

11. The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the dosing day in the current study: 90 days, five half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).

12. Exposure to more than four new chemical entities within 12 months prior to the first dosing day.

13. Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements within 14 days or five half-lives (whichever is longer) prior to the dose of study medication, which, in the opinion of the Investigator, may interfere with the study procedures or compromise subject safety.

14. History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the Investigator, contraindicates their participation.

15. Where participation in the study would result in donation of blood in excess of 500 mL within 3 months before or after the study.

16. Unwilling to abstain from:

• Consumption of caffeine- or xanthine- containing products for 24 hours prior to dosing until the post-dose assessment at each treatment level.

• Use of illicit drugs.

• Alcohol for 48 hours prior to dosing until final post-dose assessment at each treatment level.

• Smoking or otherwise consuming tobacco for 24 hours prior to dosing until the post-dose assessment at each treatment level.

17. Unwilling or unable to use a condom during sexual activity from first dose until the end of the study.

18. Vegans and subjects with milk or wheat intolerance or allergy as reported by the subject.

19. Unwillingness or inability to follow the procedures outlined in the protocol.