ObesityPhase 1FTIHNCT00857883
A First-Time-In-Human Study in Healthy Subjects
A Phase 1 study of Obesity, run by GlaxoSmithKline at 1 site in United Kingdom.
Trial summary
This is a first-time-in-human study. The overall purpose of the study is to assess whether the drug is safe and well tolerated after single, increasing doses. The blood levels of the drug after different doses will be measured and the effect of the drug on pleasurable eating behaviour will be assessed. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Obesity
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 56 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 17 Nov 2008to 1 Aug 2009
- Phase
- Phase 1
- 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
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Part A and Part B: Healthy male or female subject as determined by a responsible physician, based on a medical evaluation including history, physical examination, vital signs, laboratory tests and cardiac monitoring. Male subjects must agree to use one of the contraception methods listed in Section 8 from dosing until 84 days after the last dosing session.
- Female subjects must be of non-childbearing potential including pre-menopausal women with documented (medical report verification) hysterectomy, tubal ligation, or postmenopausal defined as 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy.
- Part C: Only healthy male subjects will be enrolled (females not included due to the potential influence of the menstrual cycle on eating behaviour). Male subjects must agree to use one of the contraception methods listed in Section 8 from dosing until 84 days after the last dosing session.
- Between 18 and 50 years of age, inclusive, at the time of signing and dating the informed consent form.
- Body weight > 45 kg and BMI within the range 20 - 30 kg/m2 (inclusive) for Part A and B and a BMI within the range 25 - 35 kg/m2 (inclusive) for Part C.
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
Who cannot join
- As a result of the medical interview, physical examination, or screening investigations, the Investigator considers the subject unfit 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 HIV antibody.
- A history of uncorrected thyroid dysfunction or an abnormal thyroid function test assessed by TSH at screening
- History of regular 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 (males), or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females). One unit is equivalent to 8g of alcohol, a half-pint (~240 mL) of beer or 1 (25 ml) measure of spirits or 1 glass (125 ml) of wine.
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- Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
- Has a history of any gastrointestinal or hepatic conditions that could affect absorption of the investigational product.
- Has QTc at screening > 450 msec. Note that if the initial QTc value is prolonged, the ECG should be repeated two more times (with 5 minutes between ECG readings) and the average of the 3 QTc values used to determine eligibility.
- Has clinically significant rhythm abnormalities identified during 24-hour screening Holter assessment.
- Systolic BP outside the range 85 to 160 mmHg, diastolic BP outside the range 45 to 100 mmHg, and/or heart rate outside the range 40 to 110 bpm.
- Self-administered Beck Depression Inventory II scale total score greater than nine. Suicide question score greater than zero.
- 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, 5 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 (including St John's Wort) within 14 days or 5 half-lives (whichever is longer) prior to the dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not 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 or GSK Medical Monitor, contraindicates their participation.
- Where participation in the study would result in donation of blood or blood products 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
- Consumption of red wine, seville oranges, grapefruit or grapefruit juice from 7 days prior to the dose of study medication until collection of the final pharmacokinetic blood sample.
- Vegans and milk intolerance as reported by the subject (Part C only)
- Unwillingness or inability to follow the procedures outlined in the protocol
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
GSK Investigational Site
Cambridge, Cambridgeshire, CB2 0QQ
About this study
Official title: A First-Time-In-Human, Three-Part, Placebo-Controlled, Dose Escalation Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GSK1521498 in Healthy Subjects
This is a first-time-in-human study. The overall purpose of the study is to assess whether the drug is safe and well tolerated after single, increasing doses. The blood levels of the drug after different doses will be measured and the effect of the drug on pleasurable eating behaviour will be assessed.
Read the detailed description
The human body naturally produces substances known as opioids and the pleasurable (or hedonic) response to eating highly sugary or fatty foods is increased by opioids. The drug to be tested in this study attaches to specific binding sites in the brain, known as mu-opioid receptors. This may stop the natural effect of opioids and therefore reduce the pleasurable response to food. We predict that this in turn may help patients with obesity to lose weight more effectively. The study is divided into three parts:
Part A: This part of the study will start with a very low dose of study drug, which will then be gradually increased in subesquent doses. This is known as dose-rising and is the way to assess safety and tolerability (any side effects that make taking the drug unpleasant). Effects will be compared to those seen when a placebo (a "dummy" drug) is taken. Up to 4 groups of 6-9 healthy male or female volunteers will be enrolled in this part of the study.
Part B: A dose selected from Part A that was well tolerated will be used to check if there is a difference in the blood levels of the study drug when taken without food in liquid form, without food as a capsule, or with a high fat meal as a capsule. One group of 12 healthy male or female volunteers will be enrolled in this part of the study.
Part C: A well tolerated dose selected from Parts A \& B will be used to test whether the drug has an effect on preferences for sugary and high fat food, when compared to placebo. Up to 32 healthy overweight male volunteers will be enrolled in this part of the study.
- Conditions
- Obesity
- Being tested
- GSK1521498 or placebo
- Keywords
- Obesity, Food Effect, Pharmacokinetics, First-Time-In-Humans, Pharmacodynamics, Healthy Volunteers
- Medical subject headings
- Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK1521498 or placeboDrug
GSK1521498 is a mu-opioid receptor inverse agonist
| Study group | Role | What they receive |
|---|---|---|
| Part A | Placebo comparator | Part A: This part of the study will start with a very low dose of study drug, which will then be gradually increased in subsequent doses. This is known as dose-rising and is the way to assess safety and tolerability (i.e. possible presence of any side effects that make taking the drug unpleasant) of increasing doses of the study drug. Effects will be compared to those seen when a placebo is taken. Up to 4 groups of 6-9 healthy male or female volunteers will be enrolled. Receives: Drug: GSK1521498 or placebo |
| Part B | Active comparator | Part B: A dose selected from Part A that was well tolerated will be used to check if there is a difference in the pharmacokinetics (blood levels) of the study drug when taken without food in liquid form, or as a capsule, or as a capsule together with a high fat meal to assess the effect of food. One group of 12 healthy male or female volunteers will be enrolled. Receives: Drug: GSK1521498 or placebo |
| Part C | Placebo comparator | Part C: A well tolerated dose selected from Parts A \& B will be used to test whether the drug has an effect on individual preferences for sugary and high fat food, when compared to placebo. Up to 32 healthy overweight male volunteers will be enrolled. Receives: Drug: GSK1521498 or placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety: adverse events, changes in clinical chemistry, haematology, urine parameters, blood pressure, heart rate, ECG, Bond & Lader visual Analog Scale, Profile of Mood States
Measured: 19 weeks
Tolerability: adverse events, changes in clinical chemistry, haematology, urine parameters, blood pressure, heart rate, ECG, Bond & Lader visual Analog Scale, Profile of Mood States
Measured: 19 weeks
Pharmacokinetic parameters
Measured: Predose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48 and 72 hours post dose administrations
Secondary outcomes (2)
Bioavailability of liquid form of drug and capsule and effect of food on the capsule
Measured: Approx 4 weeks
Pharmacodynamics - response to sweet and high fat foods before and after drug administration
Measured: Approx 10 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2009 (estimated)
- Study start17 Nov 2008
- Primary completion1 Aug 2009
- Study completion1 Aug 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ObesityStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe 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
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00857883
- Sponsor's protocol ID
- 111314
- Acronym
- FTIH
- Status last verified
- Jun 2017
- First submitted
- 24 Feb 2009
- Last updated
- 26 Jun 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A First-Time-In-Human, Three-Part, Placebo-Controlled, Dose Escalation Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GSK1521498 in Healthy Subjects
- ClinicalTrials.gov ID
- NCT00857883
- Acronym / sponsor ID
- FTIH / 111314
- Conditions
- Obesity
- Keywords
- Obesity, Food Effect, Pharmacokinetics, First-Time-In-Humans, Pharmacodynamics, Healthy Volunteers
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 17 Nov 2008 (actual)
- Primary completion
- 1 Aug 2009 (actual)
- Study completion
- 1 Aug 2009 (actual)
- First posted
- 9 Mar 2009 (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.
This is a first-time-in-human study. The overall purpose of the study is to assess whether the drug is safe and well tolerated after single, increasing doses. The blood levels of the drug after different doses will be measured and the effect of the drug on pleasurable eating behaviour will be assessed.
Detailed description
The human body naturally produces substances known as opioids and the pleasurable (or hedonic) response to eating highly sugary or fatty foods is increased by opioids. The drug to be tested in this study attaches to specific binding sites in the brain, known as mu-opioid receptors. This may stop the natural effect of opioids and therefore reduce the pleasurable response to food. We predict that this in turn may help patients with obesity to lose weight more effectively. The study is divided into three parts:
Part A: This part of the study will start with a very low dose of study drug, which will then be gradually increased in subesquent doses. This is known as dose-rising and is the way to assess safety and tolerability (any side effects that make taking the drug unpleasant). Effects will be compared to those seen when a placebo (a "dummy" drug) is taken. Up to 4 groups of 6-9 healthy male or female volunteers will be enrolled in this part of the study.
Part B: A dose selected from Part A that was well tolerated will be used to check if there is a difference in the blood levels of the study drug when taken without food in liquid form, without food as a capsule, or with a high fat meal as a capsule. One group of 12 healthy male or female volunteers will be enrolled in this part of the study.
Part C: A well tolerated dose selected from Parts A \& B will be used to test whether the drug has an effect on preferences for sugary and high fat food, when compared to placebo. Up to 32 healthy overweight male volunteers will be enrolled in this part of the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Part A | Placebo comparator | Drug: GSK1521498 or placeboPart A: This part of the study will start with a very low dose of study drug, which will then be gradually increased in subsequent doses. This is known as dose-rising and is the way to assess safety and tolerability (i.e. possible presence of any side effects that make taking the drug unpleasant) of increasing doses of the study drug. Effects will be compared to those seen when a placebo is taken. Up to 4 groups of 6-9 healthy male or female volunteers will be enrolled. |
| Part B | Active comparator | Drug: GSK1521498 or placeboPart B: A dose selected from Part A that was well tolerated will be used to check if there is a difference in the pharmacokinetics (blood levels) of the study drug when taken without food in liquid form, or as a capsule, or as a capsule together with a high fat meal to assess the effect of food. One group of 12 healthy male or female volunteers will be enrolled. |
| Part C | Placebo comparator | Drug: GSK1521498 or placeboPart C: A well tolerated dose selected from Parts A \& B will be used to test whether the drug has an effect on individual preferences for sugary and high fat food, when compared to placebo. Up to 32 healthy overweight male volunteers will be enrolled. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Part A and Part B: Healthy male or female subject as determined by a responsible physician, based on a medical evaluation including history, physical examination, vital signs, laboratory tests and cardiac monitoring. Male subjects must agree to use one of the contraception methods listed in Section 8 from dosing until 84 days after the last dosing session.
- Female subjects must be of non-childbearing potential including pre-menopausal women with documented (medical report verification) hysterectomy, tubal ligation, or postmenopausal defined as 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy.
- Part C: Only healthy male subjects will be enrolled (females not included due to the potential influence of the menstrual cycle on eating behaviour). Male subjects must agree to use one of the contraception methods listed in Section 8 from dosing until 84 days after the last dosing session.
- Between 18 and 50 years of age, inclusive, at the time of signing and dating the informed consent form.
- Body weight > 45 kg and BMI within the range 20 - 30 kg/m2 (inclusive) for Part A and B and a BMI within the range 25 - 35 kg/m2 (inclusive) for Part C.
Key exclusion criteria (24 listed)
- As a result of the medical interview, physical examination, or screening investigations, the Investigator considers the subject unfit 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 HIV antibody.
- A history of uncorrected thyroid dysfunction or an abnormal thyroid function test assessed by TSH at screening
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 |
|---|---|---|
| GSK1521498 or placeboGSK1521498 is a mu-opioid receptor inverse agonist | Drug | Part A, Part B, Part C |
Primary outcome
Safety: adverse events, changes in clinical chemistry, haematology, urine parameters, blood pressure, heart rate, ECG, Bond & Lader visual Analog Scale, Profile of Mood States
Time frame: 19 weeks
Tolerability: adverse events, changes in clinical chemistry, haematology, urine parameters, blood pressure, heart rate, ECG, Bond & Lader visual Analog Scale, Profile of Mood States
Time frame: 19 weeks
Pharmacokinetic parameters
Time frame: Predose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48 and 72 hours post dose administrations
2 secondary outcomes
Bioavailability of liquid form of drug and capsule and effect of food on the capsule
Time frame: Approx 4 weeks
Pharmacodynamics - response to sweet and high fat foods before and after drug administration
Time frame: Approx 10 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2017.
- Results for study 111314 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
- Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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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.
GSK Clinical Trials study director
GlaxoSmithKline
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 of Obesity, run by GlaxoSmithKline 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 6 inclusion and 24 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 26 Jun 2017. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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: adverse events, changes in clinical chemistry, haematology, urine parameters, blood pressure, heart rate, ECG, Bond & Lader visual Analog Scale, Profile of Mood States (time frame: 19 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 26 Jun 2017.