Last updated: 11/07/2018 08:22:48
A study to assess the relative bioavailability of different formulations of GSK2018682, a sphingosine-1-phosphate receptor subtype 1 agonist, in healthy volunteers.P1A114919
Clinicaltrials.gov ID
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: An open-label, randomised, crossover study to assess the relative bioavailability of different 2mg formulations of GSK2018682(S1P1 agonist) in healthy volunteers
Trial description: GSK2018682 is a potent and selective agonist for the sphingosine-1-phosphate receptor subtype 1 (S1P1) with the potential to be an effective treatment formultiple sclerosis (MS). The immunomodulatory properties of GSK2018682 are relatedto functional antagonism of S1P1 on lymphocytes, resulting in sequestration oflymphocytes within the lymphoid organs, rendering them incapable of migrating to sitesof inflammation and leading to lymphopenia. Orally administered GSK2018682 is veryeffective in murine experimental autoimmune encephalomyelitis (EAE), an animal modelof human MS.This study will assess the relative bioavailability of different oral formulations ofGSK2018682 in healthy volunteers. A tablet formulation is desired for progression intofuture clinical safety and efficacy studies as the current capsule formulation is not suitedto large scale manufacture. The information obtained in this study will help to establishthe optimal dosing form for future studies, and also determine the effect of food on thepharmacokinetics of GSK2018682.
Primary purpose:
Treatment
Trial design:
Crossover Assignment
Masking:
None (Open Label)
Allocation:
Randomized
Primary outcomes:
To assess the pharmacokinetics of different oral formulations of GSK2018682 in healthy volunteers
Timeframe: 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:
To investigate the effect of food on the pharmacokinetic parameters of the CD3 tablet formulation of GSK2018682
Timeframe: 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
Timeframe: 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)
Timeframe: 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.
Interventions:
Enrollment:
16
Primary completion date:
Not applicable
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Bronnum-Hansen H, Stenager E, Hansen T, and N Koch-Henriksen. Survival and mortality rates among Danes with MS, Int MS J 2006; 13: 66-71.
Chun J, Goetzl EJ, Hla T, Igarashi Y, Lynch KR, Moolenaar W et al, International union of pharmacology. XXXIV. Lysophospholipid receptor nomenclature. Pharmacol Rev 2002; 54 : 265-269.
Compston A and Coles A, Multiple Sclerosis. Lancet 2008; 372: 1502-17.
Confavreuax C, Vukusic S, Moreau T and P Adeleine. Relapses and progression of disability in MS N Engl J Med 2000; 343:1430-8.
GlaxoSmithKline Document Number JH2009/00002/01. GSK2018682 Investigator's Brochure.
Xu J, Gray F, Henderson A, Hicks K, Yang J, Thompson P, Oliver J .Safety, pharmacokinetics, pharmacodynamics and bioavailability of GSK2018682, a sphingosine-1-phosphate receptor modulator, in healthy volunteers.Clin Pharmacol Drug Devel.2014;3(3):170-178
Medical condition
Multiple Sclerosis, Relapsing-Remitting
Product
GSK2018682
Collaborators
Not applicable
Study date(s)
December 2010 to February 2011
Type
Interventional
Phase
1
Participation criteria
Sex
Female & Male
Age
18 - 55 years
Accepts healthy volunteers
Yes
- 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.
- 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).
Inclusion and exclusion criteria
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.
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
Trial location(s)
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
Study complete
Actual primary completion date
Not applicable
Actual study completion date
2011-15-02
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
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