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Mental DisordersPhase 1MAA113746NCT01371799

A Study to Examine the Pharmacodynamic Effects of GSK1034702 on Neurophysiological Biomarkers of Cognition in Nicotine Abstained Otherwise Healthy Smokers

A Phase 1 study testing Drug in people with Mental Disorders, run by GlaxoSmithKline at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This will be a double blind, randomised, placebo controlled, cross over study in which up to 20 otherwise healthy male nicotine abstinent smokers will be tested following 3 acute treatment conditions (placebo, 4 and 8mg of GSK1034702). Read more about this study

Who is it for?
Ages 18 to 55 years, men onlyHealthy volunteers can take part
Conditions the study is for
Mental Disorders
What is being tested?
Drug
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
9 participants
Where
1 siteUnited Kingdom
Study dates
17 Dec 2009to 18 Jun 2010
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 55 years
  • Men only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

None listed.

Who cannot join

  • A subject will not be eligible for inclusion in this study if any of the following criteria apply:
  • Current or past diagnosis of psychiatric disorder, as assessed by the MINI.
  • Subjects, who in the investigator's judgement, pose a significant suicide risk. Evidence of serious suicide risk may include any history of suicidal behavior and/or any suicidal ideation of type 4 or 5 on the C-SSRS in the last 6 months.
  • Current or past diagnosis of cardiovascular disease including but not limited to hypertension, cardiac arrhythmias, personal or family history of long QT syndrome, cardiac conduction disorder and/or risk factors for coronary artery disease (i.e. family history in more than 2 first degree relatives) or other clinically significant cardiac disease
  • Current or past diagnosis of cerebrovascular disease (e.g., stroke, transient ischemic attacks, aneurysms).
  • Current or past diagnosis of autonomic dysfunction (e.g. prone to fainting, orthostatic hypotension). Current or past diagnosis of acute or chronic respiratory disease (excluding childhood asthma and allergic rhinitis) and/or abnormal spirometry for age, sex and height at screening
Show all 21Show fewer
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • Subjects with a history of gastrointestinal bleeding and/or a history of peptic ulcer disease and/or presence of active gastrointestinal disease.
  • Subjects with an unstable medical disorder or a disorder (including surgical interventions) that would likely interfere with the action, absorption, distribution, metabolism or excretion of GSK1034702, may pose a safety concern, or interfere with accurate assessment of safety.
  • History of regular alcohol consumption within 6 months of the study defined as: For males: an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units. One unit is equivalent to a half-pint (220 mL) of beer or 1 (125 mL) measure of spirits or 1 glass (125 mL) of wine.
  • 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.
  • Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort and Gingko biloba) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first 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.
  • Consumption of red wine, seville oranges, grapefruit or grapefruit juice (and exotic citrus fruits, grapefruit hybrids or fruit juices) from 7 days prior to the first dose of study medication.
  • 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.
  • History of sensitivity to heparin or heparin-induced thrombocytopenia.
  • The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first 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.
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 90 day period.
  • 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, CB2 2GG

Other trials in United Kingdom

About this study

Official title: A Double Blind, Randomized, Placebo Controlled, Cross-over Study to Examine the Pharmacodynamic Effects of GSK1034702 on Neurophysiological Biomarkers of Cognition in Nicotine Abstained Otherwise Healthy Smokers

This will be a double blind, randomised, placebo controlled, cross over study in which up to 20 otherwise healthy male nicotine abstinent smokers will be tested following 3 acute treatment conditions (placebo, 4 and 8mg of GSK1034702). Each subject will undergo screening assessments within 30 days prior to administration of the first dose of study medication. There will be 3 treatment sessions and dosing will be separated by a minimum 1 week washout period. There will be two testing days (day 1 and day 2) per treatment session. On each treatment session subjects will be admitted on day 1. On day 1, subjects will be administered placebo and approximately 3 hours later, there will be a Baseline EEG/ERP recording, neuropsychological (Cogstate battery) testing and mood/craving/dependence questionnaire assessments . Subjects will be allowed to smoke until approximately midnight on day 1. On day 2, subjects will undergo a pre-drug neuropsychological (Cogstate battery) testing and questionnaire assessments of mood/craving. This will be conducted approximately 1 hour prior to dosing. Subjects will be randomized to one of six treatment sequences. Post dose EEG/ERP recording, neuropsychological (Cogstate battery) testing and mood/craving measurements will be conducted between 3 and 6 hours post treatment to coincide with peak pharmacokinetic effects. This testing will be performed approximately at 12pm following at least 12hrs of nicotine abstinence. Blood samples will be collected at baseline (pre-drug) and following drug administration to quantify exposure levels.

Being tested
Drug
Keywords
Schizophrenia
Medical subject headings
Mental Disorders, Schizophrenia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DrugDrug

    Placebo

  • DrugDrug

    4mg and 8mg Study drug

Study groups in NCT01371799
Study groupRoleWhat they receive
Study drug at 4mgExperimentalGSK1034702 at 4mg
Receives: Drug: Drug
Study drug at 8mgExperimentalGSK1034702 at 8mg
Receives: Drug: Drug
PlaceboPlacebo comparatorPlacebo
Receives: Drug: Drug

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Measures will include changes in cognition measures of specific biomarkers

    To investigate the effects of GSK1034702 on the mismatch negativity neurophysiologic marker of cognition.

    Measured: 12 months

Secondary outcomes (6)
  1. Measures will include changes in the neurophysiologic markers of cognition

    To investigate the effects of GSK1034702 on other neurophysiologic markers of cognition including, P50 suppression, P300, PPI and synchronized oscillations.

    Measured: 12 Months

  2. Measures of changes in cognition biomarkers vs. the stduy drug

    To investigate the relationship between changes in the above neurophysiologic markers of cognitive function and drug exposure

    Measured: 12 months

  3. Measures of cogstate tests of attention in tests mentioned To investigate the effects of GSK1034702 on Cogstate neuropsychologic tests of attention, working memory, learning and executive function

    To investigate the effects of GSK1034702 on Cogstate neuropsychologic tests of attention, working memory, learning and executive function

    Measured: 12 months

  4. Measures of difference between the tests in cogstate and the drug levels at different concentrations To investigate the relationship between changes in Cogstate behavioural task performance and drug exposure

    To investigate the relationship between changes in Cogstate behavioural task performance and drug exposure

    Measured: 12 months

  5. Safety measures and PK parameters and PK parameters will be measures, Vital signs, BP. To obtain further safety and PK information following oral administration of GSK1034702 to healthy subjects

    To obtain further safety and PK information following oral administration of GSK1034702 to healthy subjects

    Measured: 12 months

  6. Measures in modd/craving To investigate changes in mood/craving in the nicotine "on" state (baseline), following nicotine abstinence and following treatment

    To investigate changes in mood/craving in the nicotine "on" state (baseline), following nicotine abstinence and following treatment

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jun 2011 (estimated)
  2. Study start17 Dec 2009
  3. Primary completion18 Jun 2010
  4. Study completion18 Jun 2010

Resources

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
Crossover
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01371799
Sponsor's protocol ID
113746
Acronym
MAA113746
Status last verified
Jun 2017
First submitted
14 Apr 2011
Last updated
14 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.

Publications

  • Nathan PJ, Watson J, Lund J, Davies CH, Peters G, Dodds CM, Swirski B, Lawrence P, Bentley GD, O'Neill BV, Robertson J, Watson S, Jones GA, Maruff P, Croft RJ, Laruelle M, Bullmore ET. The potent M1 receptor allosteric agonist GSK1034702 improves episodic memory in humans in the nicotine abstinence model of cognitive dysfunction. Int J Neuropsychopharmacol. 2013 May;16(4):721-31. doi: 10.1017/S1461145712000752. Epub 2012 Aug 29.

    PubMed 22932339
  • te Beek ET, Hay JL, Bullman JN, Burgess C, Nahon KJ, Klaassen ES, Gray FA, van Gerven JM. Pharmacokinetics and central nervous system effects of the novel dual NK1 /NK3 receptor antagonist GSK1144814 in alcohol-intoxicated volunteers. Br J Clin Pharmacol. 2013 May;75(5):1328-39. doi: 10.1111/bcp.12004.

    PubMed 23067311

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Drug in people with Mental Disorders, 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 0 inclusion and 21 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 14 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?

Measures will include changes in cognition measures of specific biomarkers (time frame: 12 months). 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 NCT01371799, which also lists 2 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 14 Jun 2017.

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