ObesityPhase 1/2PP14201b1cNCT02221765
Safety, Tolerability and Efficacy Study of PP1420 in HV
A Phase 1/2 study testing PP1420 in people with Obesity, run by Imperial College London at 1 site in United Kingdom.
Trial 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. 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?
- PP1420
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 49 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Aug 2014to May 2016
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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 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.
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 23Show 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.
- 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.
- Unwilling or unable 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
NIHR/ Wellcome Trust Imperial Clinical Research Facility
London, W120HS
About this study
Official title: A Double-Blind, Randomised, Placebo-Controlled Dose Escalation Study to Assess the Safety, Tolerability and Efficacy of Single and Multiple Doses of PP 1420 in Healthy Subjects.
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.
Read more
We now plan to study the safety and PK of PP1420 up to 64mg. We will also assess:
- Its efficacy in reducing food intake after a single dose in a Phase 1B study in healthy volunteers.
- Its efficacy in reducing food intake and weight after multiple dosing in a Phase 1C study in healthy volunteers.
Read the detailed description
More than 25% 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 is only one medications licensed 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 can be risky and 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.
PP1420 has previously been give to healthy volunteers in single doses up to 8mg without any serious problems. All doses were well tolerated.
This study will examine the safety and tolerability of PP 1420 when given at single doses of higher doses, up to 64 mg, and the safety, tolerability and efficacy of PP 1420 when given in multiple doses for up to 28 days.
- Conditions
- Obesity
- Being tested
- PP1420, Placebo
- Keywords
- Obesity, Overnutrition, Nutrition Disorders, Overweight, Body Weight, Signs and Symptoms
- Medical subject headings
- Obesity, Overnutrition, Nutrition Disorders, Overweight, Body Weight, Signs and Symptoms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PP1420Drug
Also called Pancreatic Polypeptide 1420
Single dose of PP 1420, administered subcutaneously. Dose levels: 8, 16, 32, 64 mg.
PlaceboDrug
0.9% (w/v) saline single-dose, administered subcutaneously
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: PP1420; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Within 7-10 days
Secondary outcomes (1)
Pharmacokinetic parameters
Pharmacokinetic parameters: AUC0-∞, AUC0-t, maximum observed plasma drug concentration (Cmax), time of maximum observed concentration (tmax), terminal elimination half-life (t½) and clearance.
Measured: Within 7-10 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2014 (estimated)
- Study startAug 2014
- Primary completionMay 2016
- Study completionMay 2016
Why it stopped: Expected PK\&no safety issues in 1B.1Cwon't proceed due to lack of 1Befficacy
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 49 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, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02221765
- Sponsor's protocol ID
- ICIM1420/14/01
- Other IDs
- 2014-001908-22, 2014
- Acronym
- PP14201b1c
- Status last verified
- Sep 2021
- First submitted
- 19 Aug 2014
- Last updated
- 22 Sep 2021
- Results posted
- No
- Data monitoring committee
- Yes
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 22 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-Blind, Randomised, Placebo-Controlled Dose Escalation Study to Assess the Safety, Tolerability and Efficacy of Single and Multiple Doses of PP 1420 in Healthy Subjects.
- ClinicalTrials.gov ID
- NCT02221765
- Acronym / sponsor ID
- PP14201b1c / ICIM1420/14/01
- Conditions
- Obesity
- Keywords
- Obesity, Overnutrition, Nutrition Disorders, Overweight, Body Weight, Signs and Symptoms
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Expected PK\&no safety issues in 1B.1Cwon't proceed due to lack of 1Befficacy
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- Wellcome Trust, Imperial College Healthcare NHS Trust
- Study start
- Aug 2014
- Primary completion
- May 2016 (actual)
- Study completion
- May 2016 (actual)
- First posted
- 20 Aug 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Its efficacy in reducing food intake after a single dose in a Phase 1B study in healthy volunteers.
- Its efficacy in reducing food intake and weight after multiple dosing in a Phase 1C study in healthy volunteers.
Detailed description
More than 25% 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 is only one medications licensed 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 can be risky and 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.
PP1420 has previously been give to healthy volunteers in single doses up to 8mg without any serious problems. All doses were well tolerated.
This study will examine the safety and tolerability of PP 1420 when given at single doses of higher doses, up to 64 mg, and the safety, tolerability and efficacy of PP 1420 when given in multiple doses for up to 28 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: PP1420, Drug: PlaceboVisit 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. |
| Arm 2 | Experimental | Drug: PP1420, Drug: PlaceboVisit 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. |
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 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.
Key exclusion criteria (23 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 |
|---|---|---|
| PP1420Also: Pancreatic Polypeptide 1420Single dose of PP 1420, administered subcutaneously. Dose levels: 8, 16, 32, 64 mg. | Drug | Arm 1, Arm 2 |
| Placebo0.9% (w/v) saline single-dose, administered subcutaneously | Drug | Arm 1, Arm 2 |
Primary outcome
Safety and tolerability:
Time frame: Within 7-10 days
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.
1 secondary outcome
Pharmacokinetic parameters
Time frame: Within 7-10 days
Results and safety
The study was stopped early (reason given: Expected PK\&no safety issues in 1B.1Cwon't proceed due to lack of 1Befficacy). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2021.
- 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.
- Background: 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.
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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 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 1/2 study testing PP1420 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 23 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: stopped early, as of the sponsor's last update on 22 Sep 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Expected PK\&no safety issues in 1B.1Cwon't proceed due to lack of 1Befficacy). Results are not available in the source record.
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?
Safety and tolerability: (time frame: Within 7-10 days). 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 NCT02221765, 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 22 Sep 2021.