Safety, Tolerability and Efficacy Study of PP1420 in HV

NCT02221765 | Terminated Phase 1 DMC

• 2 other identifiers: ICIM1420/14/012014-001908-22
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

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

Conditions

Obesity

Keywords

Obesity; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Signs and Symptoms

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability:

  Safety and tolerability: adverse events (AEs); change from baseline in clinical chemistry, haematology and urine parameters; change from baseline outside the normal range for BP, heart rate, 12-lead electrocardiogram (ECG) parameters as specified below.

  Within 7-10 days

Secondary Outcomes (1)

• Pharmacokinetic parameters

  Within 7-10 days

Study Arms (2)

Arm 1

EXPERIMENTAL

Visit 1 - sham visit: placebo 0.9% (w/v) saline single-dose, administered subcutaneously. Visit: 2 - placebo 0.9% (w/v) saline single-dose, administered subcutaneously. Visit 3 - single dose of PP 1420, administered subcutaneously. Dose levels: 8, 16, 32, 64 mg.

Drug: PP1420; Drug: Placebo

Arm 2

EXPERIMENTAL

Visit 1 - sham visit: placebo 0.9% (w/v) saline single-dose, administered subcutaneously. Visit: 2 - single dose of PP 1420, administered subcutaneously. Dose levels: 8, 16, 32, 64 mg. Visit 3 - placebo 0.9% (w/v) saline single-dose, administered subcutaneously.

Drug: PP1420; Drug: Placebo

Interventions

PP1420 DRUG

Single dose of PP 1420, administered subcutaneously. Dose levels: 8, 16, 32, 64 mg.

Also known as: Pancreatic Polypeptide 1420

Arm 1; Arm 2

Placebo DRUG

0.9% (w/v) saline single-dose, administered subcutaneously

Arm 1; Arm 2

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• Between 18 and 50 years of age, inclusive, at the time of signing and dating the informed consent form.
• Body weight 70 kg and body mass index (BMI) within the range 25 - 35 kg/m2 (inclusive).
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• Willing and able to comply with the protocol for the duration of the study.

You may not qualify if:

• As a result of the medical interview, physical examination, or screening investigations, the Investigator considers the subject unsuitable for the study.
• 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.
• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
• A positive test for human immunodeficiency virus (HIV) antibody.
• History of migraine.
• History or evidence of abnormal eating behaviour, as observed through the Dutch Eating Behaviour (DEBQ) and SCOFF questionnaires.
• 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.
• Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
• Has QTc at screening \>450 msec.
• 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.
• 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).
• Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
• 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.
• 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.
• Where participation in the study would result in donation of blood in excess of 500 mL within 3 months before or after the study.

Sponsors & Collaborators

• Imperial College London: lead
• Wellcome Trust: collaborator
• Imperial College Healthcare NHS Trust: collaborator

Study Sites (1)

NIHR/ Wellcome Trust Imperial Clinical Research Facility

London, W120HS, United Kingdom

Location

Related Publications (3)

• Batterham RL, Le Roux CW, Cohen MA, Park AJ, Ellis SM, Patterson M, Frost GS, Ghatei MA, Bloom SR. Pancreatic polypeptide reduces appetite and food intake in humans. J Clin Endocrinol Metab. 2003 Aug;88(8):3989-92. doi: 10.1210/jc.2003-030630.

  PMID: 12915697 BACKGROUND

• Jesudason DR, Monteiro MP, McGowan BM, Neary NM, Park AJ, Philippou E, Small CJ, Frost GS, Ghatei MA, Bloom SR. Low-dose pancreatic polypeptide inhibits food intake in man. Br J Nutr. 2007 Mar;97(3):426-9. doi: 10.1017/S0007114507336799.

  PMID: 17313701 BACKGROUND

• Tan TM, Field BC, Minnion JS, Cuenco-Shillito J, Chambers ES, Zac-Varghese S, Brindley CJ, Mt-Isa S, Fiorentino F, Ashby D, Ward I, Ghatei MA, Bloom SR. Pharmacokinetics, adverse effects and tolerability of a novel analogue of human pancreatic polypeptide, PP 1420. Br J Clin Pharmacol. 2012 Feb;73(2):232-9. doi: 10.1111/j.1365-2125.2011.04082.x.

  PMID: 21834938 BACKGROUND

MeSH Terms

Conditions

Obesity; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Signs and Symptoms

Condition Hierarchy (Ancestors)

Nutritional and Metabolic Diseases; Pathological Conditions, Signs and Symptoms

Study Officials

• Stephen Bloom

  Imperial College London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2014
• First Posted: August 20, 2014
• Study Start: August 1, 2014
• Primary Completion: May 1, 2016
• Study Completion: May 1, 2016
• Last Updated: September 22, 2021

Record last verified: 2021-09

Locations

GB (1)