Multiple Sclerosis, Relapsing-RemittingPhase 1P1A114919NCT01466322
A Study to Assess the Relative Bioavailability of Different Formulations of GSK2018682, a Sphingosine-1-phosphate Receptor Subtype 1 Agonist, in Healthy Volunteers.
A Phase 1 study testing GSK2018682 CD2 Capsule; GSK2018682 CD3 non-micronised Tablet; GSK2018682 CD3 micronised Tablet; GSK2018682 CD3 non-micronised Tablet in fed state in people with Multiple Sclerosis, Relapsing-Remitting, run by GlaxoSmithKline at 1 site in Australia.
Trial summary
GSK2018682 is a potent and selective agonist for the sphingosine-1- phosphate receptor subtype 1 (S1P1) with the potential to be an effective treatment for multiple sclerosis (MS). Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Multiple Sclerosis, Relapsing-Remitting
- What is being tested?
- GSK2018682 CD2 Capsule; GSK2018682 CD3 non-micronised Tablet; GSK2018682 CD3 micronised Tablet; GSK2018682 CD3 non-micronised Tablet in fed state
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteAustralia
- Study dates
- 22 Dec 2010to 15 Feb 2011
- 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
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- AST, ALT, alkaline phosphatase and bilirubin less than or equal to 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters significantly outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. Subjects with lymphocyte counts outside the normal range should always be excluded from enrollment.
- Male or female between 18 and 55 years of age inclusive, at the time of signing the informed consent.
- A female subject is eligible to participate if she is of:
- Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MIU/ml and estradiol < 40 pg/ml (<140 pmol/L) is confirmatory]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.
- Male subjects must agree to use one of the protocol-approved contraception methods. This criterion must be followed from the time of the first dose of study medication until the study follow up visit.
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- BMI within the range 19 - 29 kg/m2 (inclusive).
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- QTcB or QTcF < 450 msec.
Who cannot join
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- A positive pre-study drug/alcohol screen.
- A positive test for HIV antibody.
- History of regular alcohol consumption within 6 months of the study defined as:
- An average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 285 ml glass of full strength beer or 425 schooner of light beer or 1 glass (100 ml) of wine or 1 (30 ml) measure of spirits.
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- 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: 30 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 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.
- 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 a 56 day period.
- Pregnant females as determined by positive serum or urine hCG test at screening or prior to dosing.
- Unwillingness or inability to follow the procedures outlined in the protocol.
- Subject is mentally or legally incapacitated.
- Subjects who have asthma.
- Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
- Consumption of red wine, Seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication.
- Subjects with a history of tuberculosis or positive tuberculin (PPD) skin test or a chest X-ray suspicious for tuberculosis, any systemic infection or flu-like symptoms within the last 30 days including fever, cough or other respiratory symptoms, vaccination within the last 30 days, known herpetic flares, history of opportunistic fungal infection (e.g., coccidiomycosis, histoplasmosis, mycosis fungoides, etc.).
- Subjects with a history of, or examination suspicious for, skin cancer(s) including melanoma, basal cell or squamous cell carcinoma.
- Systolic blood pressure less than 95 mmHg or greater than 140 mmHg, or diastolic blood pressure less than or equal to 50 mmHg or greater than or equal to 95 mmHg.
- Symptomatic reduction in blood pressure after orthostatic challenge.
- Subjects with resting heart rate less than 55 beats per minute or greater than 90 beats per minute
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-label, Randomised, Crossover Study to Assess the Relative Bioavailability of Different 2mg Formulations of GSK2018682(S1P1 Agonist) in Healthy Volunteers
GSK2018682 is a potent and selective agonist for the sphingosine-1- phosphate receptor subtype 1 (S1P1) with the potential to be an effective treatment for multiple sclerosis (MS). The immunomodulatory properties of GSK2018682 are related to functional antagonism of S1P1 on lymphocytes, resulting in sequestration of lymphocytes within the lymphoid organs, rendering them incapable of migrating to sites of inflammation and leading to lymphopenia. Orally administered GSK2018682 is very effective in murine experimental autoimmune encephalomyelitis (EAE), an animal model of human MS. This study will assess the relative bioavailability of different oral formulations of GSK2018682 in healthy volunteers. A tablet formulation is desired for progression into future clinical safety and efficacy studies as the current capsule formulation is not suited to large scale manufacture. The information obtained in this study will help to establish the optimal dosing form for future studies, and also determine the effect of food on the pharmacokinetics of GSK2018682.
Read the detailed description
BACKGROUND:
Multiple sclerosis (MS) is a debilitating, progressive neurological disease characterized by inflammation of the central nervous system (CNS), resulting in demyelination and axonal damage (for review see [Compston, 2008]). The clinical course for ~85% of MS patients at diagnosis is a relapsing remitting (RRMS) form, characterized by recurrent episodes of neurological dysfunction (relapses) interspersed with longer periods of gradual improvement (remissions). Typical symptoms during RRMS include limb weakness, sensory disturbance and visual impairment. Over time, disability accumulates such that after 10 years approximately half of RRMS patients do not suffer further relapses but show gradual progression of disability, termed secondary progressive (SP) MS [Confavreuax, 2000]. Excess mortality due to MS and quality of life is improving through more rapid and accurate diagnosis combined with better complication management and administration of disease modifying therapies [Bronnum, 2006]. However, more efficacious and better tolerated medicines are needed to relieve the considerable social and economic burden associated with MS.
Sphingosine 1 phosphate (S1P) is an endogenous ligand to a conserved family of five G-protein coupled receptors(S1P receptor subtype 1 -5), with effective concentrations (EC50) ranging from submicromolar to nanomolar levels [Chun, 2002]. Validation for a therapeutic approach targeting S1P receptors in autoimmune disease has been provided by the clinical development of FTY720 in MS (fingolimod; Novartis). GSK2018682 is an agonist at recombinant human S1P1 with some activity at S1P5 receptors but displays no agonist activity towards human S1P2, S1P3 or S1P4 up to a concentration of 10 µM. This selectivity is anticipated to minimise known cardiovascular effects mediated by S1P2/3 subtypes. Orally administered GSK2018682 is very effective in murine experimental autoimmune encephalomyelitis (EAE), an animal model of human MS. GSK2018682 has been reasonably tolerated following single oral doses of 0.6mg to 24mg in an ongoing study (P1A114070) in healthy volunteers
STUDY RATIONALE:
Two Phase I studies (P1A114070 \& P1A114347) have been conducted in healthy volunteers using GSK2018682 in capsule formulation. These capsules were produced from a single batch of compound (second drug substance campaign, termed CD2) with a particle size of 15 µm (D90). In order to support further clinical development of GSK2018682, a new batch (CD3) of compound has been synthesized that has a slightly larger particle size (29 µm, D90). In addition, it is intended that longer term studies (Proof of Concept and beyond) will be conducted with a tablet form of the drug. There is also a possibility that obtaining a smaller particle size through micronisation of the CD3 batch (to produce particles with diameters of approximately 3.8 µm, D90) may improve bioavailability; so a tablet made from micronized CD3 GSK2018682 is also being developed. In order to ensure appropriate dose selection for future studies, there is a need to investigate the pharmacokinetic profiles of both new tablet forms of GSK2018682 (manufactured from CD3 campaign) and compare these to the original (CD2) capsule formulation. Therefore, this study will evaluate the relative bioavailability of single doses of each of the 3 different formulations (CD2 capsule, CD3 tablet and CD3 micronized tablet) of GSK2018682 in a cross over, randomized, 4 period, open label design. The fourth treatment arm will be added to examine the effect of food on relative bioavailability of the CD3 tablet formulation. The study will also measure the effects of each dose form of GSK2018682 on total lymphocyte counts.
DOSE RATIONALE:
A 2 mg dose will be used in the study as:
- PK can be well quantified at this dose.
- Significant (in excess of 100%) changes in PK parameters will be detectable.
- PK will be below level of quantification by 7 days after dosing.
- S1P1-mediated PD effects on lymphocytes and heart rate have not been detected.
- There is at least a 2 fold cover to exposures that do have PD effects on lymphocytes and heart rate.
- It is very likely to be a dose used in a future Phase II study (given the predicted accumulation ratio and exposure at steady state).
STUDY DESIGN:
This study will investigate single doses of GSK2018682 in a cohort of 16 healthy male and female (of non-childbearing potential) subjects according to a randomized, open-label, 4 way crossover design. The effect of food on the pharmacokinetics of the CD3 tablet formulation will be explored as it is the most likely to be used in a future Phase II study.
Treatment regimens will include:
- CD2 Capsule
- CD3 non-micronised Tablet
- CD3 micronised Tablet
- CD3 non-micronised Tablet under fed conditions
- Conditions
- Multiple Sclerosis, Relapsing-Remitting
- Being tested
- GSK2018682 CD2 Capsule; GSK2018682 CD3 non-micronised Tablet; GSK2018682 CD3 micronised Tablet; GSK2018682 CD3 non-micronised Tablet in fed state
- Keywords
- Healthy volunteers, GSK2018682, Pharmacokinetics, Relapsing Remitting Multiple Sclerosis, Pharmacodynamics
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK2018682 CD2 Capsule; GSK2018682 CD3 non-micronised Tablet; GSK2018682 CD3 micronised Tablet; GSK2018682 CD3 non-micronised Tablet in fed stateDrug
Four single dosing sessions where each regimen A,B C or D will be administered orally in a randomised, cross-over manner. At each dosing session, pharmacokinetic sampling time-points will be the same.
| Study group | Role | What they receive |
|---|---|---|
| Oral formulations of GSK2018682 | Experimental | Three oral formulations of GSK2018682. A: CD2 Capsule; B: CD3 non-micronised Tablet; C: CD3 micronised Tablet; D: CD3 non-micronised Tablet in fed state Receives: Drug: GSK2018682 CD2 Capsule; GSK2018682 CD3 non-micronised Tablet; GSK2018682 CD3 micronised Tablet; GSK2018682 CD3 non-micronised Tablet in fed state |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the pharmacokinetics of different oral formulations of GSK2018682 in healthy volunteers
-Peak blood concentration (Cmax); -Time of peak blood concentration (tmax); - Area under the blood concentration-time curve up to the last quantifiable time point (AUC(0-t)) and extrapolated to infinite time (AUC (0-∞)); -Terminal half-life (T½ ); -Apparent oral clearance (CL/F)
Measured: PK sampling at dosing and at 1, 2, 3, 4, 6, 8, 10, 16, 24, 36, 48, 72, 96, 120, and 144 hr post-dose
Secondary outcomes (3)
To investigate the effect of food on the pharmacokinetic parameters of the CD3 tablet formulation of GSK2018682
-Cmax, tmax, AUC (0-∞), T½ and apparent oral clearance
Measured: High fat breakfast to be provided within 30 mins prior to dosing
Evaluate the effect of different oral formulations of GSK2018682 on lymphocytes in healthy volunteers
Reduction from baseline in lymphocyte counts
Measured: Sampling for absolute lymphocyte count at dosing and at 6 and 24 hr post-dose.
To investigate the safety and tolerability of different oral formulations of GSK2018682 in healthy volunteers (males and females of non childbearing potential)
-Adverse event monitoring; -Laboratory parameters (haematology, clinical chemistry, urinalysis); -Telemetry ECG; -Vital signs (systolic and diastolic blood pressure, heart rate, respiratory rate, body temperature)
Measured: AE review: from dosing to follow-up; safety lab parameters: at 48 hr post-dose; Telemetry ECG: dosing to 6 hr post-dose; vital signs: pre-dose,1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 hr post-dose.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2011 (estimated)
- Study start22 Dec 2010
- Primary completion15 Feb 2011
- Study completion15 Feb 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Multiple Sclerosis, Relapsing-RemittingStudies 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
- Crossover
- Masking
- None (open label)
- Enrolment
- 16 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
- NCT01466322
- Sponsor's protocol ID
- 114919
- Acronym
- P1A114919
- Status last verified
- Jul 2017
- First submitted
- 3 Nov 2011
- Last updated
- 7 Jul 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
Bronnum-Hansen H, Stenager E, Hansen T, Koch-Henriksen H. Survival and mortality rates among Danes with MS. Int MS J. 2006 May;13(2):66-71.
PubMed 16635423Chun J, Goetzl EJ, Hla T, Igarashi Y, Lynch KR, Moolenaar W, Pyne S, Tigyi G. International Union of Pharmacology. XXXIV. Lysophospholipid receptor nomenclature. Pharmacol Rev. 2002 Jun;54(2):265-9. doi: 10.1124/pr.54.2.265.
PubMed 12037142Compston A, Coles A. Multiple sclerosis. Lancet. 2008 Oct 25;372(9648):1502-17. doi: 10.1016/S0140-6736(08)61620-7.
PubMed 18970977Confavreux C, Vukusic S, Moreau T, Adeleine P. Relapses and progression of disability in multiple sclerosis. N Engl J Med. 2000 Nov 16;343(20):1430-8. doi: 10.1056/NEJM200011163432001.
PubMed 11078767GlaxoSmithKline Document Number JH2009/00002/01. GSK2018682 Investigator's Brochure.
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Randomised, Crossover Study to Assess the Relative Bioavailability of Different 2mg Formulations of GSK2018682(S1P1 Agonist) in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT01466322
- Acronym / sponsor ID
- P1A114919 / 114919
- Conditions
- Multiple Sclerosis, Relapsing-Remitting
- Keywords
- Healthy volunteers, GSK2018682, Pharmacokinetics, Relapsing Remitting Multiple Sclerosis, Pharmacodynamics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 22 Dec 2010 (actual)
- Primary completion
- 15 Feb 2011 (actual)
- Study completion
- 15 Feb 2011 (actual)
- First posted
- 7 Nov 2011 (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.
GSK2018682 is a potent and selective agonist for the sphingosine-1- phosphate receptor subtype 1 (S1P1) with the potential to be an effective treatment for multiple sclerosis (MS). The immunomodulatory properties of GSK2018682 are related to functional antagonism of S1P1 on lymphocytes, resulting in sequestration of lymphocytes within the lymphoid organs, rendering them incapable of migrating to sites of inflammation and leading to lymphopenia. Orally administered GSK2018682 is very effective in murine experimental autoimmune encephalomyelitis (EAE), an animal model of human MS. This study will assess the relative bioavailability of different oral formulations of GSK2018682 in healthy volunteers. A tablet formulation is desired for progression into future clinical safety and efficacy studies as the current capsule formulation is not suited to large scale manufacture. The information obtained in this study will help to establish the optimal dosing form for future studies, and also determine the effect of food on the pharmacokinetics of GSK2018682.
Detailed description
BACKGROUND:
Multiple sclerosis (MS) is a debilitating, progressive neurological disease characterized by inflammation of the central nervous system (CNS), resulting in demyelination and axonal damage (for review see [Compston, 2008]). The clinical course for ~85% of MS patients at diagnosis is a relapsing remitting (RRMS) form, characterized by recurrent episodes of neurological dysfunction (relapses) interspersed with longer periods of gradual improvement (remissions). Typical symptoms during RRMS include limb weakness, sensory disturbance and visual impairment. Over time, disability accumulates such that after 10 years approximately half of RRMS patients do not suffer further relapses but show gradual progression of disability, termed secondary progressive (SP) MS [Confavreuax, 2000]. Excess mortality due to MS and quality of life is improving through more rapid and accurate diagnosis combined with better complication management and administration of disease modifying therapies [Bronnum, 2006]. However, more efficacious and better tolerated medicines are needed to relieve the considerable social and economic burden associated with MS.
Sphingosine 1 phosphate (S1P) is an endogenous ligand to a conserved family of five G-protein coupled receptors(S1P receptor subtype 1 -5), with effective concentrations (EC50) ranging from submicromolar to nanomolar levels [Chun, 2002]. Validation for a therapeutic approach targeting S1P receptors in autoimmune disease has been provided by the clinical development of FTY720 in MS (fingolimod; Novartis). GSK2018682 is an agonist at recombinant human S1P1 with some activity at S1P5 receptors but displays no agonist activity towards human S1P2, S1P3 or S1P4 up to a concentration of 10 µM. This selectivity is anticipated to minimise known cardiovascular effects mediated by S1P2/3 subtypes. Orally administered GSK2018682 is very effective in murine experimental autoimmune encephalomyelitis (EAE), an animal model of human MS. GSK2018682 has been reasonably tolerated following single oral doses of 0.6mg to 24mg in an ongoing study (P1A114070) in healthy volunteers
STUDY RATIONALE:
Two Phase I studies (P1A114070 \& P1A114347) have been conducted in healthy volunteers using GSK2018682 in capsule formulation. These capsules were produced from a single batch of compound (second drug substance campaign, termed CD2) with a particle size of 15 µm (D90). In order to support further clinical development of GSK2018682, a new batch (CD3) of compound has been synthesized that has a slightly larger particle size (29 µm, D90). In addition, it is intended that longer term studies (Proof of Concept and beyond) will be conducted with a tablet form of the drug. There is also a possibility that obtaining a smaller particle size through micronisation of the CD3 batch (to produce particles with diameters of approximately 3.8 µm, D90) may improve bioavailability; so a tablet made from micronized CD3 GSK2018682 is also being developed. In order to ensure appropriate dose selection for future studies, there is a need to investigate the pharmacokinetic profiles of both new tablet forms of GSK2018682 (manufactured from CD3 campaign) and compare these to the original (CD2) capsule formulation. Therefore, this study will evaluate the relative bioavailability of single doses of each of the 3 different formulations (CD2 capsule, CD3 tablet and CD3 micronized tablet) of GSK2018682 in a cross over, randomized, 4 period, open label design. The fourth treatment arm will be added to examine the effect of food on relative bioavailability of the CD3 tablet formulation. The study will also measure the effects of each dose form of GSK2018682 on total lymphocyte counts.
DOSE RATIONALE:
A 2 mg dose will be used in the study as:
- PK can be well quantified at this dose.
- Significant (in excess of 100%) changes in PK parameters will be detectable.
- PK will be below level of quantification by 7 days after dosing.
- S1P1-mediated PD effects on lymphocytes and heart rate have not been detected.
- There is at least a 2 fold cover to exposures that do have PD effects on lymphocytes and heart rate.
- It is very likely to be a dose used in a future Phase II study (given the predicted accumulation ratio and exposure at steady state).
STUDY DESIGN:
This study will investigate single doses of GSK2018682 in a cohort of 16 healthy male and female (of non-childbearing potential) subjects according to a randomized, open-label, 4 way crossover design. The effect of food on the pharmacokinetics of the CD3 tablet formulation will be explored as it is the most likely to be used in a future Phase II study.
Treatment regimens will include:
- CD2 Capsule
- CD3 non-micronised Tablet
- CD3 micronised Tablet
- CD3 non-micronised Tablet under fed conditions
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Oral formulations of GSK2018682 | Experimental | Drug: GSK2018682 CD2 Capsule; GSK2018682 CD3 non-micronised Tablet; GSK2018682 CD3 micronised Tablet; GSK2018682 CD3 non-micronised Tablet in fed stateThree oral formulations of GSK2018682. A: CD2 Capsule; B: CD3 non-micronised Tablet; C: CD3 micronised Tablet; D: CD3 non-micronised Tablet in fed state |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- AST, ALT, alkaline phosphatase and bilirubin less than or equal to 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters significantly outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. Subjects with lymphocyte counts outside the normal range should always be excluded from enrollment.
- Male or female between 18 and 55 years of age inclusive, at the time of signing the informed consent.
- A female subject is eligible to participate if she is of:
- Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MIU/ml and estradiol < 40 pg/ml (<140 pmol/L) is confirmatory]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.
Key exclusion criteria (22 listed)
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- A positive pre-study drug/alcohol screen.
- A positive test for HIV antibody.
- History of regular alcohol consumption within 6 months of the study defined as:
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 |
|---|---|---|
| GSK2018682 CD2 Capsule; GSK2018682 CD3 non-micronised Tablet; GSK2018682 CD3 micronised Tablet; GSK2018682 CD3 non-micronised Tablet in fed stateFour single dosing sessions where each regimen A,B C or D will be administered orally in a randomised, cross-over manner. At each dosing session, pharmacokinetic sampling time-points will be the same. | Drug | Oral formulations of GSK2018682 |
Primary outcome
To assess the pharmacokinetics of different oral formulations of GSK2018682 in healthy volunteers
Time frame: PK sampling at dosing and at 1, 2, 3, 4, 6, 8, 10, 16, 24, 36, 48, 72, 96, 120, and 144 hr post-dose
-Peak blood concentration (Cmax); -Time of peak blood concentration (tmax); - Area under the blood concentration-time curve up to the last quantifiable time point (AUC(0-t)) and extrapolated to infinite time (AUC (0-∞)); -Terminal half-life (T½ ); -Apparent oral clearance (CL/F)
3 secondary outcomes
To investigate the effect of food on the pharmacokinetic parameters of the CD3 tablet formulation of GSK2018682
Time frame: High fat breakfast to be provided within 30 mins prior to dosing
Evaluate the effect of different oral formulations of GSK2018682 on lymphocytes in healthy volunteers
Time frame: Sampling for absolute lymphocyte count at dosing and at 6 and 24 hr post-dose.
To investigate the safety and tolerability of different oral formulations of GSK2018682 in healthy volunteers (males and females of non childbearing potential)
Time frame: AE review: from dosing to follow-up; safety lab parameters: at 48 hr post-dose; Telemetry ECG: dosing to 6 hr post-dose; vital signs: pre-dose,1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 hr post-dose.
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 7 Jul 2017.
- Background: PubMed 16635423Bronnum-Hansen H, Stenager E, Hansen T, Koch-Henriksen H. Survival and mortality rates among Danes with MS. Int MS J. 2006 May;13(2):66-71.
- Background: PubMed 12037142Chun J, Goetzl EJ, Hla T, Igarashi Y, Lynch KR, Moolenaar W, Pyne S, Tigyi G. International Union of Pharmacology. XXXIV. Lysophospholipid receptor nomenclature. Pharmacol Rev. 2002 Jun;54(2):265-9. doi: 10.1124/pr.54.2.265.
- Background: PubMed 18970977Compston A, Coles A. Multiple sclerosis. Lancet. 2008 Oct 25;372(9648):1502-17. doi: 10.1016/S0140-6736(08)61620-7.
- Background: PubMed 11078767Confavreux C, Vukusic S, Moreau T, Adeleine P. Relapses and progression of disability in multiple sclerosis. N Engl J Med. 2000 Nov 16;343(20):1430-8. doi: 10.1056/NEJM200011163432001.
- BackgroundGlaxoSmithKline Document Number JH2009/00002/01. GSK2018682 Investigator's Brochure.
- 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.
- Results for study 114919 can be found on the GSK Clinical Study Register.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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Multiple Sclerosis (MS) - Relapsing-remitting
Active, not recruitingPhase 4
Safety and Efficacy Study of Fingolimod in Taiwanese Adults (≥ 20years) With Relapsing Remitting Multiple Sclerosis
Multiple Sclerosis
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 testing GSK2018682 CD2 Capsule; GSK2018682 CD3 non-micronised Tablet; GSK2018682 CD3 micronised Tablet; GSK2018682 CD3 non-micronised Tablet in fed state in people with Multiple Sclerosis, Relapsing-Remitting, run by GlaxoSmithKline at 1 site in Australia.
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 9 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 7 Jul 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 Australia. 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 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?
To assess the pharmacokinetics of different oral formulations of GSK2018682 in healthy volunteers (time frame: PK sampling at dosing and at 1, 2, 3, 4, 6, 8, 10, 16, 24, 36, 48, 72, 96, 120, and 144 hr post-dose). 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 NCT01466322, which also lists 5 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 7 Jul 2017.