A First-Time-in-Human Study to Assess the Safety and Tolerability of PP 1420 in Healthy Subjects

NCT01052493 | Completed Phase 1 Results DMC

• 2 other identifiers: ICIM1420/09/012009-017522-39
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

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 "Pancreatic Polypeptide" (PP). We have previously shown that injections of human PP reduces appetite and food intake. We have now developed a very similar chemical, PP 1420, as a treatment for obesity. PP 1420 has been tested in animals and has been shown to be safe, and to reduce their appetite. This study will test PP 1420 for its safety and tolerability in humans.

Conditions

Obesity

Keywords

obesity; pancreatic polypeptide; gut hormones

Outcome Measures

Primary Outcomes (1)

• Number of Subjects With Adverse Events (AEs)

  Number of subjects with adverse events recorded through the trial period

  7-12 weeks

Secondary Outcomes (5)

• AUC0-t(Last)

  24 hours

• AUC0-∞

  24 hours

• Maximum Observed Plasma Drug Concentration (Cmax)

  Within 24 hours

• Time of Maximum Observed Concentration (Tmax)

  Within 24 hours

• Terminal Elimination Half-life (t½)

  Within 24 hours

Study Arms (4)

2mg PP 1420

EXPERIMENTAL

PP 1420 single dose, subcutaneous

Drug: PP 1420

4mg PP 420

EXPERIMENTAL

PP 1420 single dose, subcutaneous

Drug: PP 1420

8mg PP 1420

EXPERIMENTAL

PP 1420 single dose, subcutaneous

Drug: PP 1420

Placebo

PLACEBO COMPARATOR

0.9% saline

Drug: Placebo

Interventions

PP 1420 DRUG

Single dose of PP 1420, administered subcutaneously at either 2mg, 4mg or 8mg.

Also known as: PP 1420 pancreatic polypeptide analog

2mg PP 1420; 4mg PP 420; 8mg PP 1420

Placebo DRUG

0.9% saline

Also known as: Saline

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Gender Eligibility Details: Healthy 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 18 - 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)

Sir John McMichael Centre for Clinical Studies, Imperial College Healthcare NHS Trust

London, W12 0NN, 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 RESULT

MeSH Terms

Conditions

Obesity

Interventions

PP 1420; Sodium Chloride

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Dr Tricia Tan
• Organization: Imperial College London

t.tan@imperial.ac.uk

020 83838038

Study Officials

• Stephen Bloom FRCP DSc, MB BChir

  Imperial College London

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This was a double-blind study
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: There were three dosing periods. Each subject (n=12) was randomised to receive up to two doses of placebo and/or up to three ascending doses of PP 1420 dosed as s.c. injection. During each dosing period eight subjects received active drug and four received placebo. Subjects could also be randomised to receive one further dose of PP 1420 or placebo, if needed, to explore an intermediate dose based upon a review of safety, tolerability, and PK data from the previous cohorts.

Study Record Dates

• First Submitted: January 19, 2010
• First Posted: January 20, 2010
• Study Start: April 1, 2010
• Primary Completion: October 18, 2010
• Study Completion: October 18, 2010
• Last Updated: February 12, 2021
• Results First Posted: February 12, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)