- ICH GCP
- Registr klinických studií v USA
- Klinická studie NCT00539760
A Phase I Rheumatoid Arthritis Study in Healthy Volunteers
11. srpna 2017 aktualizováno: GlaxoSmithKline
A Phase I, Randomized, Observer- and Subject-Blind, Placebo-Controlled, Single Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GSK1827771 in Healthy Volunteers
GSK182771 is a domain antibody targeting the interleukin (IL)-1 receptor which is being developed for the treatment of rheumatoid arthritis.
This study is being done in healthy volunteers to verify the safety and tolerability of GSK182771
Přehled studie
Typ studie
Intervenční
Zápis (Aktuální)
45
Fáze
- Fáze 1
Kontakty a umístění
Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.
Studijní místa
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Indiana
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Evansville, Indiana, Spojené státy, 47714
- GSK Investigational Site
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Maryland
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Baltimore, Maryland, Spojené státy, 21225
- GSK Investigational Site
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Kritéria účasti
Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.
Kritéria způsobilosti
Věk způsobilý ke studiu
18 let až 55 let (Dospělý)
Přijímá zdravé dobrovolníky
Ano
Pohlaví způsobilá ke studiu
Všechno
Popis
Inclusion Criteria:
- Healthy adult men or women as determined by a responsible physician, based on a medical evaluation including history, physical examination, laboratory tests and cardiac assessment.
- Female subjects of non-childbearing potential.
- Male subjects must agree to abstain from or agree to use adequate contraception, in addition to having their female partner use another form of contraception. This criterion must be followed from the time of the first dose of study medication until Pharmacokinetic levels are determined to be below the LLQ.
- Men or women who are between 18 and 55 years of age, inclusive.
- Body Mass Index (BMI) within the range of 18-35 kilogram per meter square (kg/m^2) inclusive.
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
Exclusion Criteria:
- The subject has a positive pre-study urine drug/urine alcohol screen. A minimum list of drugs that will be screened for includes amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
- A history of regular alcohol consumption averaging >7 drinks/week for females or >14 drinks/week for males. One drink is equivalent to (12 g alcohol) = 5 ounces [150 milliliter (mL)] of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of 80 proof distilled spirits
- The subject is unwilling to abstain from alcohol consumption from 48 hour prior to dosing until discharge from the clinic, and for 48 hour prior to all other out-patient clinic visits.
- Smoked or used tobacco or nicotine-containing products within the previous 6 months prior to the first dose of current study medication.
- The subject has participated in a clinical trial and has received a drug or a new chemical entity within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dose of current study medication.
- Previous exposure to or treatment with PEGylated molecules.
- Use of anti-Tumor Necrosis Factor (anti-TNF) drugs within 60 days prior to dosing.
- Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days , 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 (including antibiotics) which, in the opinion of the investigator and/or GSK Medical Monitor, contraindicates the subject's participation.
- Positive pregnancy test at Screening or on Day -1 (females only).
- Any clinically significant abnormality identified on the screening medical assessment or examination, or ECG.
- Any white blood cell (WBC) or neutrophil count outside the normal range at screening or on Day -1.
- History of significant cardiac, pulmonary, metabolic, renal, hepatic, or gastrointestinal conditions that in the opinion of the investigator and/or GSK Medical Monitor, places the subject at an unacceptable risk as participant in this trial.
- History of any autoimmune or current inflammatory conditions including rheumatoid arthritis or any other joint disease.
- History of malignancy, except for surgically cured basal cell carcinoma or cured cervical carcinoma (> 2 yrs prior to dosing).
- Currently has asthma or history of chronic obstructive pulmonary disease (COPD).
- Current evidence of ongoing or acute infection.
- The subject has a history of repeated, chronic or opportunistic infections which, in the opinion of the investigator and/or GSK Medical Monitor, places the subject at an unacceptable risk as a participant in this trial.
- History of Mycobacterium tuberculosis or any other previous Mycobacterium infection.
- A positive pre-study Hepatitis B surface antigen, positive Hepatitis C antibody, or human immunodeficiency virus (HIV) antibody testing result.
- History of a severe allergic reaction, angio-edema, anaphylaxis or immunodeficiency
- History of elevated blood pressure or blood pressure >140/90 millimeters of mercury (mmHg) at screening.
- Corrected QT interval (QTc) > 450 milliseconds.
- Where participation in study would result in donation of blood in excess of 500 mL within 56 days of starting the study.
- Subject whose calculated creatinine clearance is less than 80 mL/min
- Liver function tests above the upper limit of normal at screening (alkaline transaminase (ALT), aspartate transaminase (AST) or bilirubin).
- Chronic liver or biliary disease, history of Gilbert's syndrome in a previous clinical study or at screening.
Studijní plán
Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Singl
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
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Experimentální: Subjects receiving GSK 1827771 in sub-cohort Xa (Cohort 1-5)
Eligible subjects will receive GSK1827771 with the starting dose of 0.3 milligram (mg)
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GSK1827771 will be administered using injection via subcutaneous (SC) route.
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Komparátor placeba: Subjects receiving placebo in sub-cohort Xa (Cohort 1-5)
Eligible subjects will receive placebo matching to GSK1827771
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Placebo to GSK1827771 for Injection will be administered via SC route
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Experimentální: Subjects receiving GSK 1827771 in sub-cohort Xb (Cohort 1-5)
Eligible subjects will receive GSK1827771 via injection
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GSK1827771 will be administered using injection via subcutaneous (SC) route.
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Komparátor placeba: Subjects receiving placebo in sub-cohort Xb (Cohort 1-5)
Eligible subjects will receive placebo matching to GSK1827771
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Placebo to GSK1827771 for Injection will be administered via SC route
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Experimentální: Subjects receiving GSK 1827771 in sub-cohort Xc (Cohort 1-5)
Eligible subjects will receive GSK1827771 via injection
|
GSK1827771 will be administered using injection via subcutaneous (SC) route.
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Komparátor placeba: Subjects receiving placebo in sub-cohort Xc (Cohort 1-5)
Eligible subjects will receive placebo matching to GSK1827771
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Placebo to GSK1827771 for Injection will be administered via SC route
|
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
---|---|---|
Number of subjects with abnormal clinical chemistry findings
Časové okno: Up to 29 days
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Blood samples will be collected at specific time points as a measure of safety
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Up to 29 days
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Number of subjects with abnormal clinical hematology findings
Časové okno: Up to 29 days
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Blood samples will be collected at specific time points as a measure of safety
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Up to 29 days
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Number of subjects with abnormal urinalysis findings
Časové okno: Up to 29 days
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Urine samples will be collected at specific time points as a measure of safety
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Up to 29 days
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Number of subjects with abnormal blood pressure values
Časové okno: Up to 29 days
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Systolic and diastolic blood pressure will be measured in a supine position after at least 5 minutes of rest as a measure of safety.
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Up to 29 days
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Number of subjects with abnormal heart rate values
Časové okno: Up to 29 days
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Heart rate will be measured in a supine position after at least 5 minutes of rest as a measure of safety.
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Up to 29 days
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Number of subjects with abnormal respiratory rate values
Časové okno: Up to 29 days
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Respiratory rate will be measured in a supine position after at least 5 minutes of rest as a measure of safety.
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Up to 29 days
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Number of subjects with abnormal body temperature findings
Časové okno: Up to 29 days
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Body temperature will be measured in a supine position after at least 5 minutes of rest as a measure of safety.
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Up to 29 days
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Number of subjects with abnormal electrocardiogram (ECG) findings
Časové okno: Up to 29 days
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12-lead ECG measurements will be performed in a supine position after at least 5 minutes of rest as a measure of safety
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Up to 29 days
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Number of subjects with adverse events (AEs)
Časové okno: Up to 29 days
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An adverse event is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
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Up to 29 days
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
---|---|---|
Plasma concentrations of GSK1827771
Časové okno: Pre-dose, 0.25, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 1; in morning and evening on Day 2-7; in morning on Day 14, 21, 28
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Blood samples will be collected at specific time points for calculating plasma concentrations of GSK1827771
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Pre-dose, 0.25, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 1; in morning and evening on Day 2-7; in morning on Day 14, 21, 28
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Maximum plasma concentration (Cmax) of GSK1827771
Časové okno: Pre-dose, 0.25, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 1; in morning and evening on Day 2-7; in morning on Day 14, 21, 28
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Blood samples will be collected at specific time points for calculating Cmax of GSK1827771
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Pre-dose, 0.25, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 1; in morning and evening on Day 2-7; in morning on Day 14, 21, 28
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Area under the curve (AUC) of GSK1827771
Časové okno: Pre-dose, 0.25, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 1; in morning and evening on Day 2-7; in morning on Day 14, 21, 28
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Blood samples will be collected at specific time points for calculating AUC of GSK1827771
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Pre-dose, 0.25, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 1; in morning and evening on Day 2-7; in morning on Day 14, 21, 28
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Frequency of anti-GSK1827771
Časové okno: Up to 29 days
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The presence of anti-GSK1827771 binding antibodies will be assessed using an immunoelectrochemiluminescence screening assay (ECL).
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Up to 29 days
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Titer of anti-GSK1827771
Časové okno: Up to 29 days
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Blood samples for determination of anti-GSK1827771 antibodies will be taken at specific time points.
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Up to 29 days
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Frequency of anti-PEG
Časové okno: Up to 29 days
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Antibodies to PEG components of GSK1827771 will be measured.
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Up to 29 days
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Titer of anti-PEG
Časové okno: Up to 29 days
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Antibodies to PEG components of GSK1827771 will be measured.
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Up to 29 days
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Frequency of anti-dAb
Časové okno: Up to 29 days
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Antibodies to dAb components of GSK1827771 will be measured.
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Up to 29 days
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Titer of anti-dAb
Časové okno: Up to 29 days
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Antibodies to dAb components of GSK1827771 will be measured.
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Up to 29 days
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Change from Baseline response of whole blood to ex vivo stimulation with IL-1 alpha or IL-1 beta
Časové okno: Baseline and up to 29 days
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Blood samples will be collected for assessment of pharmacodynamic activity of GSK1827771 at specific time points
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Baseline and up to 29 days
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Exploratory biomarker levels in blood
Časové okno: Up to 29 days
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Blood samples will be taken for exploratory biomarker analysis
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Up to 29 days
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Spolupracovníci a vyšetřovatelé
Zde najdete lidi a organizace zapojené do této studie.
Sponzor
Termíny studijních záznamů
Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.
Hlavní termíny studia
Začátek studia (Aktuální)
5. září 2007
Primární dokončení (Aktuální)
5. dubna 2008
Dokončení studie (Aktuální)
5. dubna 2008
Termíny zápisu do studia
První předloženo
4. října 2007
První předloženo, které splnilo kritéria kontroly kvality
4. října 2007
První zveřejněno (Odhad)
5. října 2007
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
15. srpna 2017
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
11. srpna 2017
Naposledy ověřeno
1. srpna 2017
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
Další identifikační čísla studie
- 110394
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