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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01466322




Registration number
NCT01466322
Ethics application status
Date submitted
3/11/2011
Date registered
6/11/2011
Date last updated
7/07/2017

Titles & IDs
Public title
A Study to Assess the Relative Bioavailability of Different Formulations of GSK2018682, a Sphingosine-1-phosphate Receptor Subtype 1 Agonist, in Healthy Volunteers.
Scientific title
An Open-label, Randomised, Crossover Study to Assess the Relative Bioavailability of Different 2mg Formulations of GSK2018682(S1P1 Agonist) in Healthy Volunteers
Secondary ID [1] 0 0
114919
Universal Trial Number (UTN)
Trial acronym
P1A114919
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Sclerosis, Relapsing-Remitting 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GSK2018682 CD2 Capsule; GSK2018682 CD3 non-micronised Tablet; GSK2018682 CD3 micronised Tablet; GSK2018682 CD3 non-micronised Tablet in fed state

Experimental: Oral formulations of GSK2018682 - 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


Treatment: Drugs: GSK2018682 CD2 Capsule; GSK2018682 CD3 non-micronised Tablet; GSK2018682 CD3 micronised Tablet; GSK2018682 CD3 non-micronised Tablet in fed state
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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
To assess the pharmacokinetics of different oral formulations of GSK2018682 in healthy volunteers
Timepoint [1] 0 0
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 outcome [1] 0 0
To investigate the effect of food on the pharmacokinetic parameters of the CD3 tablet formulation of GSK2018682
Timepoint [1] 0 0
High fat breakfast to be provided within 30 mins prior to dosing
Secondary outcome [2] 0 0
Evaluate the effect of different oral formulations of GSK2018682 on lymphocytes in healthy volunteers
Timepoint [2] 0 0
Sampling for absolute lymphocyte count at dosing and at 6 and 24 hr post-dose.
Secondary outcome [3] 0 0
To investigate the safety and tolerability of different oral formulations of GSK2018682 in healthy volunteers (males and females of non childbearing potential)
Timepoint [3] 0 0
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.

Eligibility
Key inclusion criteria
- 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.

- 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.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- 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.

- 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/12/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
15/02/2011
Sample size
Target
Accrual to date
Final
16
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
GSK Investigational Site - Herston
Recruitment postcode(s) [1] 0 0
4006 - Herston

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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).
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01466322
Trial related presentations / 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.
Chun 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.
Compston A, Coles A. Multiple sclerosis. Lancet. 2008 Oct 25;372(9648):1502-17. doi: 10.1016/S0140-6736(08)61620-7.
Confavreux 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.
GlaxoSmithKline Document Number JH2009/00002/01. GSK2018682 Investigator's Brochure.
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries