ObesityPhase 1NCT01052493
A First-Time-in-Human Study to Assess the Safety and Tolerability of PP 1420 in Healthy Subjects
A Phase 1 study testing PP 1420 in people with Obesity, run by Imperial College London at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 50 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Obesity
- What is being tested?
- PP 1420
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 13 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Apr 2010to 18 Oct 2010
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 22Show fewer
- 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.
- 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.
- Unwilling to abstain from use of illicit drugs.
- Unwilling to abstain from alcohol for 48 hours prior to dosing until final post-dose assessment at each treatment level.
- Unwilling to abstain from smoking or otherwise consuming tobacco for 24 hours prior to dosing until the post-dose assessment at each treatment level.
- Unwilling to use a condom during sexual activity from first dose until the end of the study.
- Vegans and subjects with milk or wheat intolerance or allergy as reported by the subject.
- Unwillingness or inability to follow the procedures outlined in the protocol.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Sir John McMichael Centre for Clinical Studies, Imperial College Healthcare NHS Trust
London, W12 0NN
About this study
Official title: A First Time in Human, Double Blind, Randomised, Placebo Controlled Dose Escalation Study to Assess the Safety and Tolerability of PP 1420 in Healthy Subjects.
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.
Read the detailed description
More than 20 percent of people in the UK are obese. People with obesity have a shorter life expectancy, and have a higher risk of having heart attacks, strokes, high blood pressure, diabetes, and certain cancers.
At the moment, there is no treatment for obesity that is both effective and safe. Advising people to change their diet and to exercise more is frequently ineffective, and any loss in weight seen is usually temporary. There are a couple of licensed medications for the purpose of losing weight, but they are limited by side effects. Finally, gastric bypass and similar surgeries are effective at reducing weight permanently, but it can be risky and is restricted only to very motivated people.
"Gut hormones" are natural chemicals made by the bowels when you eat. They work to reduce appetite and hunger when you eat, so that you will eat enough for your needs. We think that one of the reasons why gastric bypass surgery is so effective is because the surgery causes an increase in gut hormone secretion into the bloodstream, which suppresses appetite. One of these hormones is pancreatic polypeptide (PP), which is released into the bloodstream by cells in the pancreas after eating. When human PP is given to healthy volunteers as an injection, we see that they have a reduced appetite and food intake with no side effects such as feeling sick or vomiting.
Human PP does not last long in the blood stream. In order to make it into a new, safe and effective drug for obesity, we have developed a new form of PP, which is very similar but not identical to human PP, that we expect will last longer in the blood. We call this PP 1420.
In testing, PP 1420 reduced food intake in animals, and was safe in them at much higher doses than those we plan to give in the current study. This study will assess the safety and tolerability of PP 1420 in humans, and is the first time humans have been given this medication.
- Conditions
- Obesity
- Being tested
- PP 1420, Placebo
- Keywords
- obesity, pancreatic polypeptide, gut hormones
- Medical subject headings
- Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PP 1420Drug
Also called PP 1420 pancreatic polypeptide analog
Single dose of PP 1420, administered subcutaneously at either 2mg, 4mg or 8mg.
PlaceboDrug
Also called Saline
0.9% saline
| Study group | Role | What they receive |
|---|---|---|
| 2mg PP 1420 | Experimental | PP 1420 single dose, subcutaneous Receives: Drug: PP 1420 |
| 4mg PP 420 | Experimental | PP 1420 single dose, subcutaneous Receives: Drug: PP 1420 |
| 8mg PP 1420 | Experimental | PP 1420 single dose, subcutaneous Receives: Drug: PP 1420 |
| Placebo | Placebo comparator | 0.9% saline Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects With Adverse Events (AEs)
Number of subjects with adverse events recorded through the trial period
Measured: 7-12 weeks
Secondary outcomes (5)
AUC0-t(Last)
The area under the concentration vs. time curve of PP 1420 from time zero to the last sampling time, calculated by the linear trapezoidal rule
Measured: 24 hours
AUC0-∞
the area under the concentration vs. time curve for PP 1420, estimated from time zero to infinity
Measured: 24 hours
Maximum Observed Plasma Drug Concentration (Cmax)
Measured: Within 24 hours
Time of Maximum Observed Concentration (Tmax)
Measured: Within 24 hours
Terminal Elimination Half-life (t½)
Calculated from log 2/λz where λz is the apparent terminal rate constant.
Measured: Within 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2010 (estimated)
- Study startApr 2010
- Primary completion18 Oct 2010
- Study completion18 Oct 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for ObesityStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- 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.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- Wellcome Trust, Imperial College Healthcare NHS Trust
- Responsible party
- Sponsor
- Investigators
- Stephen Bloom FRCP DSc, MB BChir, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01052493
- Sponsor's protocol ID
- ICIM1420/09/01
- Other IDs
- 2009-017522-39, 2009
- Status last verified
- Jan 2021
- First submitted
- 19 Jan 2010
- Last updated
- 12 Feb 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 12915697Jesudason 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.
PubMed 17313701Tan 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.
PubMed 21834938
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A First Time in Human, Double Blind, Randomised, Placebo Controlled Dose Escalation Study to Assess the Safety and Tolerability of PP 1420 in Healthy Subjects.
- ClinicalTrials.gov ID
- NCT01052493
- Acronym / sponsor ID
- ICIM1420/09/01
- Conditions
- Obesity
- Keywords
- obesity, pancreatic polypeptide, gut hormones
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- Wellcome Trust, Imperial College Healthcare NHS Trust
- Study start
- Apr 2010 (actual)
- Primary completion
- 18 Oct 2010 (actual)
- Study completion
- 18 Oct 2010 (actual)
- First posted
- 20 Jan 2010 (estimated)
- Results
- Posted 12 Feb 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
More than 20 percent of people in the UK are obese. People with obesity have a shorter life expectancy, and have a higher risk of having heart attacks, strokes, high blood pressure, diabetes, and certain cancers.
At the moment, there is no treatment for obesity that is both effective and safe. Advising people to change their diet and to exercise more is frequently ineffective, and any loss in weight seen is usually temporary. There are a couple of licensed medications for the purpose of losing weight, but they are limited by side effects. Finally, gastric bypass and similar surgeries are effective at reducing weight permanently, but it can be risky and is restricted only to very motivated people.
"Gut hormones" are natural chemicals made by the bowels when you eat. They work to reduce appetite and hunger when you eat, so that you will eat enough for your needs. We think that one of the reasons why gastric bypass surgery is so effective is because the surgery causes an increase in gut hormone secretion into the bloodstream, which suppresses appetite. One of these hormones is pancreatic polypeptide (PP), which is released into the bloodstream by cells in the pancreas after eating. When human PP is given to healthy volunteers as an injection, we see that they have a reduced appetite and food intake with no side effects such as feeling sick or vomiting.
Human PP does not last long in the blood stream. In order to make it into a new, safe and effective drug for obesity, we have developed a new form of PP, which is very similar but not identical to human PP, that we expect will last longer in the blood. We call this PP 1420.
In testing, PP 1420 reduced food intake in animals, and was safe in them at much higher doses than those we plan to give in the current study. This study will assess the safety and tolerability of PP 1420 in humans, and is the first time humans have been given this medication.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| 2mg PP 1420 | Experimental | Drug: PP 1420PP 1420 single dose, subcutaneous |
| 4mg PP 420 | Experimental | Drug: PP 1420PP 1420 single dose, subcutaneous |
| 8mg PP 1420 | Experimental | Drug: PP 1420PP 1420 single dose, subcutaneous |
| Placebo | Placebo comparator | Drug: Placebo0.9% saline |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (22 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PP 1420Also: PP 1420 pancreatic polypeptide analogSingle dose of PP 1420, administered subcutaneously at either 2mg, 4mg or 8mg. | Drug | 2mg PP 1420, 4mg PP 420, 8mg PP 1420 |
| PlaceboAlso: Saline0.9% saline | Drug | Placebo |
Primary outcome
Number of Subjects With Adverse Events (AEs)
Time frame: 7-12 weeks
Number of subjects with adverse events recorded through the trial period
5 secondary outcomes
AUC0-t(Last)
Time frame: 24 hours
AUC0-∞
Time frame: 24 hours
Maximum Observed Plasma Drug Concentration (Cmax)
Time frame: Within 24 hours
Time of Maximum Observed Concentration (Tmax)
Time frame: Within 24 hours
Terminal Elimination Half-life (t½)
Time frame: Within 24 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 12915697Batterham 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.
- Background: PubMed 17313701Jesudason 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.
- Results publication: PubMed 21834938Tan 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stephen Bloom FRCP DSc, MB BChir principal investigator
Imperial College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PP 1420 in people with Obesity, run by Imperial College London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Feb 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Subjects With Adverse Events (AEs) (time frame: 7-12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01052493, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2021.