A Phase I, 2-part (Part 1 Being a Single Dose Escalation and Part 2, a Parallel Group) Study of Toll-like Receptor (TLR4) Agonist (GSK1795091) in Healthy Subjects
13. November 2020 aktualisiert von: GlaxoSmithKline
A 2-part Randomized, Double-blind (Sponsor-unblinded), Placebo-controlled, Ascending Dose and Parallel Group Study of TLR4 Agonist (GSK1795091) Administered to Healthy Subjects
This study is an ascending dose first-time-in-human study to determine the safety, tolerability, pharmacodynamic (PD), and pharmacokinetics (PK) profile of GSK1795091 in healthy subjects. The results will support the design of future clinical trials of GSK1795091 administered to subjects with advanced malignancies in combination with immune system modulators.
Part 1 will be a randomized, double-blind (sponsor-unblinded), placebo-controlled, single center, single dose escalation, sequential group evaluation of intravenously administered GSK1795091 to evaluate the safety and tolerability in healthy subjects. Part 2 will be an open-label, parallel group evaluation of 2 doses of GSK1795091 administered, either 1 week apart (Part 2, Cohort 1) or 2 weeks apart (Part 2, Cohort 2). In Part 2, on Day 1, subjects will receive intravenous GSK1795091 at a dose determined by results from Part 1. The total duration of this study is approximately 10 weeks from screening to the last study visit.
Studienübersicht
Status
Abgeschlossen
Bedingungen
Intervention / Behandlung
Studientyp
Interventionell
Einschreibung (Tatsächlich)
42
Phase
- Phase 1
Kontakte und Standorte
Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.
Studienorte
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Berlin, Deutschland, 14050
- GSK Investigational Site
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Teilnahmekriterien
Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.
Zulassungskriterien
Studienberechtigtes Alter
18 Jahre bis 50 Jahre (Erwachsene)
Akzeptiert gesunde Freiwillige
Ja
Studienberechtigte Geschlechter
Alle
Beschreibung
Inclusion Criteria:
- Between 18 and 50 years of age inclusive, at the time of signing the informed consent.
- Healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests, vital signs and 12-lead ECG. (A subject with a clinically insignificant abnormality or laboratory parameter(s) may be included only if the Investigator documents that the finding is unlikely to represent a safety risk and will not interfere with the study procedures.)
- Body weight 55-95 kilogram (kg) and body mass index within the range 19-30 kg/meter (m)^2 (inclusive).
- Male or Female of non-childbearing potential:
Males: Male subjects with female partners of child bearing potential must comply with the pre specified contraception requirements.
Females: A female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum or urine human chorionic gonadotropin test), not lactating, and is either of non-reproductive potential or reproductive potential. If of reproductive potential, then the subject should agree to follow one of the options listed per GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential from 30 days prior to the first dose and until 30 days after the last dose of study medication The Investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception
- Capable of giving signed informed consent
Exclusion Criteria:
- History of any significant medical condition (e.g. cardiac, pulmonary, metabolic, renal, gastrointestinal, rheumatological, etc.)
- History of frequent (>1 per week) headache or myalgia, asthma, syncope.
- History of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome).
- Alanine aminotransferase (ALT) and bilirubin >1.1×upper limit of normal (ULN; isolated bilirubin >1.5×ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- Vital signs:
Systolic blood pressure (SBP) <90 and >140 milliliter of mercury (mmHg); diastolic BP <50 and >90 mmHg; heart rate (HR) <50 and >90 beats per minute (bpm); temperature >37.5 degree Celsius
- Clinically significant ECG abnormality and/or HR < 50 and >90 bpm; PR interval >220 milliseconds (msec); QRS duration >120 msec; and QTcF > 450 msec
- Anticipated requirement for any prescription medication during the study
- History of regular alcohol consumption within 6 months of the study averaging a weekly intake of >14 drinks for males or >7 drinks for females or inability to abstain from alcohol from 1 day prior to the inpatient period of the study until discharge (one drink is equivalent to 8 grams of alcohol: 200 milliliter [mL] of beer, 100 mL of wine or 1 measure (25 mL) of spirits)
- Urinary cotinine levels indicative of smoking or history or regular use of tobacco or nicotine-containing products within 2 months prior to screening or inability to abstain from smoking during the study
- 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 Medical Monitor, contraindicates their participation
- Presence of hepatitis B surface antigen, positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment. Subjects with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C ribonucleic acid polymerase chain reaction test is obtained.
- A positive pre-study drug/alcohol screen.
- A positive test for human immunodeficiency antivirus antibody.
- Donation of blood or blood products in excess of 500 mL within a 56-day period.
- The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first visit (Day -2) 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 visit (Day -2).
- Exposure to GSK1795091 in a previous cohort of this study.
- Subject is unable to refrain from taking non-prescription drugs (including vitamins and dietary or herbal supplements), within 7 days prior to the first dose of study medication until completion of the follow-up visit, unless in the opinion of the investigator and sponsor, the medication will not interfere with the study.
- Subject is able to understand and communicate in German/or native language of the site. Subject, or close relative of the subject, is the investigator or a sub-investigator, research assistant, pharmacist, study coordinator, or other staff directly involved with the conduct of the study at that site
- Vulnerable subjects (eg subjects kept in detention)
Studienplan
Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Zufällig
- Interventionsmodell: Parallele Zuordnung
- Maskierung: Doppelt
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
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Experimental: Part 1: GSK1795091 or Placebo
In Part 1, subjects in sequential cohorts will receive single ascending doses of intravenous (IV) injection of GSK1795091 or matching placebo, with a starting dose of 7 nanogram (ng), on Day 1 until the highest dose is evaluated.
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GSK1795091 will be supplied as solution for injection vial.
Each 5 mL vial contains 0.001 milligram/mL (mg/mL; 1000 ng/mL) or 0.0001 mg/mL (100 ng/mL)of GSK1795091 and will be administered as IV bolus over 2-5 minutes (min) followed by a IV bolus of 10 mL normal saline.
Matching placebo will be supplied as a solution for injection vial and will be administered as IV bolus over 2-5 min followed by a IV bolus of 10 mL normal saline
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Experimental: Part 2 Cohort 1: GSK1795091
In Part 2 Cohort 1, subjects will receive IV injection of GSK1795091 on Day 1, at dose determined in part 1, and second dose on Day 8 (one week apart)
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GSK1795091 will be supplied as solution for injection vial.
Each 5 mL vial contains 0.001 milligram/mL (mg/mL; 1000 ng/mL) or 0.0001 mg/mL (100 ng/mL)of GSK1795091 and will be administered as IV bolus over 2-5 minutes (min) followed by a IV bolus of 10 mL normal saline.
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Experimental: Part 2 Cohort 2: GSK1795091
In Part 2 Cohort 2, subjects will receive IV injection of GSK1795091 on Day 1, at dose determined in part 1, and a second dose on Day 15 (two weeks apart)
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GSK1795091 will be supplied as solution for injection vial.
Each 5 mL vial contains 0.001 milligram/mL (mg/mL; 1000 ng/mL) or 0.0001 mg/mL (100 ng/mL)of GSK1795091 and will be administered as IV bolus over 2-5 minutes (min) followed by a IV bolus of 10 mL normal saline.
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Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
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Number of Participants With Non-serious Adverse Events (AE) and Serious Adverse Events (SAE)
Zeitfenster: Up to Day 32
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An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or events associated with liver injury and impaired liver function were categorized as SAE.
All participants enrolled into the study who have received a dose of study medication (GSK1795091 or placebo) were included in the All Subjects Population.
Participants with non-serious AEs (5 percentage threshold) and SAEs has been reported.
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Up to Day 32
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Change From Baseline in Body Temperature Part 1
Zeitfenster: Baseline, Day 1 (1, 2, 4, 6, 8, 12, 16 hours), Day 2, Day 3, Day 4, Day 5, and Day 7.
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Body temperature was measured in semi-supine position after 5 minutes rest.
Baseline values are the last non-missing pre-dose assessments.
Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value.
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Baseline, Day 1 (1, 2, 4, 6, 8, 12, 16 hours), Day 2, Day 3, Day 4, Day 5, and Day 7.
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Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) Part 1
Zeitfenster: Baseline, Day 1 (1, 2, 4, 6, 8, 12, 16 hours), Day 2, Day 3, Day 4, Day 5, and Day 7.
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Systolic and diastolic BP was measured in semi-supine position after 5 minutes rest.
Baseline values are the last non-missing pre-dose assessments.
Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value.
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Baseline, Day 1 (1, 2, 4, 6, 8, 12, 16 hours), Day 2, Day 3, Day 4, Day 5, and Day 7.
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Change From Baseline in Pulse Rate Part 1
Zeitfenster: Baseline, Day 1 (1, 2, 4, 6, 8, 12, 16 hours), Day 2, Day 3, Day 4, Day 5, and Day 7.
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Pulse rate was measured in semi-supine position after 5 minutes rest.
Baseline values are the last non-missing pre-dose assessments.
Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value.
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Baseline, Day 1 (1, 2, 4, 6, 8, 12, 16 hours), Day 2, Day 3, Day 4, Day 5, and Day 7.
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Change From Baseline in Respiratory Rate Part 1
Zeitfenster: Baseline, Day 1 (1, 2, 4, 6, 8, 12, 16 hours), Day 2, Day 3, Day 4, Day 5, and Day 7.
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Respiratory rate was measured in semi-supine position after 5 minutes rest.
Baseline values are the last non-missing pre-dose assessments.
Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value.
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Baseline, Day 1 (1, 2, 4, 6, 8, 12, 16 hours), Day 2, Day 3, Day 4, Day 5, and Day 7.
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Number of Participants With Hematology Parameters Outside Reference Range Part 1
Zeitfenster: Up to Day 7
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Hematology parameters included hemoglobin (HGB), hematocrit (HCT), Red Blood Cell (RBC) count, White Blood Cell (WBC) count with differential (neutrophils, lymphocytes, monocytes, eosinophils, basophils), platelet count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC).
Reference range for basophil was 0.01 - 0.07*10^9/Liters (L), eosinophils 0.03 - 0.5*10^9/L, HCT 0.38 - 0.48 proportion of RBC in blood, HGB 126 - 165*gram (g)/L, lymphocytes 1.08 - 3*10^9/L, MCH 26.3 - 32.8*picogram (pg), MCHC 324 - 359*g/L, MCV 77 - 94.9*femtoliter (fL), monocytes 0.3 - 0.92*10^9/L, neutrophils 1.46 - 5.85*10^9/L, platelets 155 - 342*10^9/L, erythrocytes 4.12 - 5.74*10^12/L, leukocytes 3.19 - 8.71*10^9/L.
Values below these ranges were considered as low and above these ranges were considered as high (H).
Data for participants from any visit post-screening with values > reference range high and < reference range low are report.
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Up to Day 7
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Number of Participants With Clinical Chemistry Parameters Outside Reference Range
Zeitfenster: Up to Day 7
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Clinical chemistry parameters with reference range were albumin 35-52*g/L, Alkaline phosphatase (ALP) 30-120*International units/L (IU/L), Alanine aminotransferase (ALT) 0-50 * IU/L, Aspartate aminotransferase (AST) 0-50*IU/L, direct bilirubin 0-3.4* micromoles/L (µmol/L), bilirubin 5-21*µmol/L, calcium 2.2-2.65*
millimoles/L (mmol/L), cholesterol 0-5.19* mmol/L, creatinine 59-104* µmol/L, C-reactive protein (CRP) 0-5*milligram (mg)/L,Gamma Glutamyl Transferase (GGT) 4.1-5.9*mmol/L,
high density lipoproteins (HDL) cholesterol 0.99-2.32*mmol/L,
potassium 3.5-5.1*mmol/L,
low density lipoproteins (LDL) cholesterol 0-3.3*mmol/L, protein 66-83*g/L, sodium 136-146 * mmol/L, triglycerides 0-2.25 * mmol/L, glucose 4.1-5.9*mmol/L,
and urea 2.8-7.2*mmol/L.
Values below these ranges were considered as low and above these ranges were considered as high.
Data for participants from any visit post-screening with values > reference range high and < reference range low are reported.
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Up to Day 7
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Casts, Round Epithelial Cells (REC), Squamous Epithelial Cells (SEC), Urine Erythrocytes and Urine Leukocytes at Indicated Time Points
Zeitfenster: Pre-dose Day -1 and Day 1, Day 2, Day 4 and Day 7
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Urinalysis included microscopic examination parameters like Casts, REC, SEC, Urine erythrocytes and Urine leukocytes.
Data at indicated time points were reported.
Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles).
NA indicates standard deviation could not be calculated as only 1 participant was analyzed at the given time point.
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Pre-dose Day -1 and Day 1, Day 2, Day 4 and Day 7
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Ketones and Urine Glucose at Indicated Time Points
Zeitfenster: Pre-dose Day -1 and Day 1, Day 2, Day 4 and Day 7
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Urinalysis included parameters like ketones and urine glucose.
Data at indicated time points were reported.
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Pre-dose Day -1 and Day 1, Day 2, Day 4 and Day 7
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Occult Blood at Indicated Time Points
Zeitfenster: Pre-dose Day -1 and Day 1, Day 2, Day 4 and Day 7
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Urinalysis included parameter like Occult blood.
Data at indicated time points were reported.
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Pre-dose Day -1 and Day 1, Day 2, Day 4 and Day 7
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Urine Protein at Indicated Time Points
Zeitfenster: Pre-dose Day -1 and Day 1, Day 2, Day 4 and Day 7
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Urinalysis included parameter like Urine protein.
Data at indicated time points were reported.
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Pre-dose Day -1 and Day 1, Day 2, Day 4 and Day 7
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Specific Gravity at Indicated Time Points
Zeitfenster: Pre-dose Day -1 and Day 1, Day 2, Day 4 and Day 7
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Urinalysis included parameter like specific gravity.
Urinary specific gravity is a measure of the concentration of solutes in the urine.
It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine.
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Pre-dose Day -1 and Day 1, Day 2, Day 4 and Day 7
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Urine Potential of Hydrogen (pH) at Indicated Time Points
Zeitfenster: Pre-dose Day -1 and Day 1, Day 2, Day 4 and Day 7
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Urinalysis parameters included urine pH.
pH is calculated on a scale of 0 to 14, values on the scale refer to the degree of alkalinity or acidity.
A pH of 7 is neutral.
A pH less than 7 is acidic, and a pH greater than 7 is basic.
Normal urine has a slightly acid pH (5.0 - 6.0).
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Pre-dose Day -1 and Day 1, Day 2, Day 4 and Day 7
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Number of Participants With Abnormal Electrocardiograms (ECG) Findings Worst Case Post-Baseline
Zeitfenster: Up to Day 32
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Single measurements of 12-lead ECGs were obtained after 10 minutes of rest in a semi-supine position for the participant.
Participants with abnormal ECG findings that are clinically not significant (NCS) and clinically significant (CS) data has been presented here.
The data of worst case post-Baseline is presented here.
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Up to Day 32
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Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
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Maximum Observed Drug Concentration (Cmax) of GSK1795091 for Part 1
Zeitfenster: Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
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Blood samples were collected at indicated time points.
The Pharmacokinetic (PK) parameters were calculated for each participant using a non-compartmental method.
All participants for whom, at least, one valid and evaluable pharmacokinetic parameter (AUC or Cmax) was derived were included in PK Parameter Population.
Only those participants with data available at the specified data points were analyzed.
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Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
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Time of Occurrence of Cmax (Tmax) and Terminal Half Life (t1/2) of GSK1795091 for Part 1
Zeitfenster: Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
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Blood samples were collected at indicated time points.
The PK parameters were calculated for each participant using a non-compartmental method.
Only those participants with data available at the specified data points were analyzed.
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Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
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Partial Area Under the Concentration-time Curve to Time t (AUC[0-t]), Area Under the Concentration-time Curve (AUC) From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of GSK1795091 for Part 1
Zeitfenster: Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
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Blood samples were collected at indicated time points.
The PK parameters were calculated for each participant using a non-compartmental method.
AUC (0-t) was used interchangeably with AUC to last time of quantifiable concentration (AUC[0-last]) .Only those participants with data available at the specified data points were analyzed.
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Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
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Clearance (CL) of GSK1795091 for Part 1
Zeitfenster: Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
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Blood samples were collected at indicated time points.
The PK parameters were calculated for each participant using a non-compartmental method.
Only those participants with data available at the specified data points were analyzed.
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Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
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Volume of Distribution of GSK1795091 for Part 1
Zeitfenster: Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
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Blood samples were collected at indicated time points.
The PK parameters were calculated for each participant using a non-compartmental method.
Only those participants with data available at the specified data points were analyzed.
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Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
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Percentage Fold Change of Concentration of Interleukin 6 (IL-6) From Baseline for Part 1
Zeitfenster: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
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Blood samples were collected at indicated time points for the assessment of IL-6.
Baseline (Day 1) was taken as the mean of the planned pre-dose measurements.
Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value.
Percentage fold change equals to 100*change from Baseline divided by Baseline.
All participants in the "All Subjects Population" for whom valid and evaluable pharmacodynamic parameters were derived are included in Pharmacodynamic (PD) Population.
Data from multiplex immunoassay has been reported.
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Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
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Percentage Fold Change of Concentration of Tumor Necrosis Factor (TNF)-Alpha From Baseline for Part 1
Zeitfenster: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
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Blood samples were collected at indicated time points for the assessment of TNF-alpha.
Baseline (Day 1) was taken as the mean of the planned pre-dose measurements.
Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value.
Percentage fold change equals to 100*change from Baseline divided by Baseline.
Data from multiplex immunoassay has been reported.
Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles).
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Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
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Percentage Fold Change of Concentration of Interferon (IFN)-Gamma From Baseline for Part 1
Zeitfenster: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
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Blood samples were collected at indicated time points for the assessment of IFN-gamma.
Baseline (Day 1) was taken as the mean of the planned pre-dose measurements.
Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value.
Percentage fold change equals to 100*change from Baseline divided by Baseline.
Data from multiplex immunoassay has been reported.
Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles).
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Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
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Percentage Fold Change of Concentration of Inducible Protein (IP)-10 From Baseline for Part 1
Zeitfenster: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
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Blood samples were collected at indicated time points for the assessment of IP-10.
Baseline (Day 1) was taken as the mean of the planned pre-dose measurements.
Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value.
Percentage fold change equals to 100*change from Baseline divided by Baseline.
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Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
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Percentage Fold Change of Concentration of Monocyte Chemotactic Protein 1 (MCP-1) From Baseline for Part 1
Zeitfenster: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
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Blood samples were collected at indicated time points for the assessment of MCP-1.
Baseline (Day 1) was taken as the mean of the planned pre-dose measurements.
Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value.
Percentage fold change equals to 100*change from Baseline divided by Baseline.
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Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
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Percentage Fold Change of Colony Stimulating Factor 2 (GCSF) From Baseline for Part 1
Zeitfenster: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
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Blood samples were collected at indicated time points for the assessment of GCSF.
Baseline was taken as the mean of the planned pre-dose measurements.
Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value.
Percentage fold change equals to 100*change from Baseline divided by Baseline.
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Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
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Percentage Fold Change of Interleukin 1 Receptor Antagonist (IL-1Ra) From Baseline for Part 1
Zeitfenster: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
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Blood samples were collected at indicated time points for the assessment of IL-1Ra.
Baseline was taken as the mean of the planned pre-dose measurements.
Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value.
Percentage fold change equals to 100*change from Baseline divided by Baseline.
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Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
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Percentage Fold Change of Interleukin 10 (IL-10) From Baseline for Part 1
Zeitfenster: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
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Blood samples were collected at indicated time points for the assessment of IL-10.
Baseline was taken as the mean of the planned pre-dose measurements.
Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value.
Percentage fold change equals to 100*change from Baseline divided by Baseline.
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Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
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Change From Baseline in WBC Differential for Part 1
Zeitfenster: Baseline, 4, 24 and 144 hours
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WBC differential included Lymphocytes Count, Monocytes Count, Granulocytes Count including neutrophils and eosinophil.
Baseline (Day 1) was taken as the mean of the planned pre-dose measurements.
Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value.
Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles).
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Baseline, 4, 24 and 144 hours
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Change From Baseline in CRP for Part 1
Zeitfenster: Baseline, Days 2, 4 and 7
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Blood samples were collected at indicated time points for the assessment of CRP.
Baseline was taken as the mean of the planned pre-dose measurements.
Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value.
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Baseline, Days 2, 4 and 7
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Maximum Observed Drug Concentration (Cmax) of GSK1795091 for Part 2
Zeitfenster: Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
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Cmax assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose.
The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of Adverse events (AEs) of unknown etiology.
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Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
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Time of Occurrence of Cmax (Tmax) and Terminal Half Life (t1/2) of GSK1795091 for Part 2
Zeitfenster: Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
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Tmax and t1/2 assessments were planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose.
The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
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Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
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Partial Area Under the Concentration-time Curve to Time = t (AUC[0-t]), Area Under the Concentration-time Curve (AUC) From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of GSK1795091 for Part 2
Zeitfenster: Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
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AUC (0-t) and AUC (0-inf) assessments were planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose.
The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
|
Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
|
|
Area Under the Concentration-time Curve (AUC) Time Curve for a Dosing Interval (AUC[0-tau]), AUC (0-last) of GSK1795091 for Part 2
Zeitfenster: Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
|
AUC (0-tau) and AUC (0-last) assessments were planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose.
The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
|
Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
|
|
Clearance (CL) of GSK1795091 for Part 2
Zeitfenster: Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
|
CL assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose.
The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
|
Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
|
|
Volume of Distribution of GSK1795091 for Part 2
Zeitfenster: Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
|
Volume of distribution assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose.
The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
|
Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
|
|
Accumulation Ratio of GSK1795091 for Part 2
Zeitfenster: Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
|
Accumulation ratio assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose.
The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
|
Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
|
|
Time Invariance of GSK1795091 for Part 2
Zeitfenster: Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
|
Time invariance assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose.
The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
|
Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose
|
|
Percentage Fold Change of Concentration of Interleukin 6 (IL-6) From Baseline for Part 2
Zeitfenster: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
|
IL-6 assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose.
The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
|
Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
|
|
Percentage Fold Change of Concentration of TNF-alpha From Baseline for Part 2
Zeitfenster: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
|
TNF-alpha assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose.
The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
|
Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
|
|
Percentage Fold Change of Concentration of IFN-gamma From Baseline for Part 2
Zeitfenster: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
|
IFN-gamma assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose.
The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
|
Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
|
|
Percentage Fold Change of Concentration of IP-10 From Baseline for Part 2
Zeitfenster: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
|
IP-10 assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose.
The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
|
Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
|
|
Percentage Fold Change of Concentration of MCP-1 From Baseline for Part 2
Zeitfenster: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
|
MCP-1 assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose.
The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
|
Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
|
|
Percentage Fold Change of Concentration of GCSF From Baseline for Part 2
Zeitfenster: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
|
GCSF assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose.
The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
|
Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
|
|
Percentage Fold Change of Concentration of IL-1Ra From Baseline for Part 2
Zeitfenster: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
|
IL-1Ra assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose.
The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
|
Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
|
|
Percentage Fold Change of Concentration of IL-10 From Baseline for Part 2
Zeitfenster: Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
|
IL-10 assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose.
The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
|
Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours
|
|
Change From Baseline in WBC Differential for Part 2
Zeitfenster: Baseline, 2, 24 and 144 hours
|
WBC differential assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose.
The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
|
Baseline, 2, 24 and 144 hours
|
|
Number of Participants With Urinalysis Parameters Outside Reference Range for Part 2
Zeitfenster: Up to Day 7
|
Urinalysis as part of safety assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose.
The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
|
Up to Day 7
|
|
Number of Participants With Hematology Parameters Outside Reference Range in Part 2
Zeitfenster: Up to Day 7
|
Hematology as part of safety assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose.
The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
|
Up to Day 7
|
|
Number of Participants With Clinical Chemistry Parameters Outside Reference Range in Part 2
Zeitfenster: Up to Day 7
|
Clinical chemistry as part of safety assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose.
The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
|
Up to Day 7
|
|
Change From Baseline in CRP for Part 2
Zeitfenster: Baseline and Pre-dose, 1, 2, 4, 8, 12, 16, 24, and 48 hours post dose
|
CRP assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose.
The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
|
Baseline and Pre-dose, 1, 2, 4, 8, 12, 16, 24, and 48 hours post dose
|
|
Change From Baseline in Body Temperature for Part 2
Zeitfenster: Baseline and up to Day 7
|
Body temperature was planned to be measured in Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose.
The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
|
Baseline and up to Day 7
|
|
Change From Baseline in SBP and DBP for Part 2
Zeitfenster: Baseline and up to Day 7
|
SBP and DBP was planned to be measured in Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose.
The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
|
Baseline and up to Day 7
|
|
Change From Baseline in Respiratory Rate for Part 2
Zeitfenster: Baseline and up to Day 7
|
Respiratory rate was planned to be measured in Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose.
The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
|
Baseline and up to Day 7
|
|
Change From Baseline in Pulse Rate for Part 2
Zeitfenster: Baseline and up to Day 7
|
Pulse rate was planned to be measured in Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose.
Baseline (Day 1) was taken as the mean of the planned pre-dose measurements.
Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value.
The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
|
Baseline and up to Day 7
|
Mitarbeiter und Ermittler
Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.
Sponsor
Publikationen und hilfreiche Links
Die Bereitstellung dieser Publikationen erfolgt freiwillig durch die für die Eingabe von Informationen über die Studie verantwortliche Person. Diese können sich auf alles beziehen, was mit dem Studium zu tun hat.
Studienaufzeichnungsdaten
Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.
Haupttermine studieren
Studienbeginn (Tatsächlich)
10. Januar 2017
Primärer Abschluss (Tatsächlich)
13. Oktober 2017
Studienabschluss (Tatsächlich)
13. Oktober 2017
Studienanmeldedaten
Zuerst eingereicht
9. Juni 2016
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
9. Juni 2016
Zuerst gepostet (Schätzen)
14. Juni 2016
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
27. November 2020
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
13. November 2020
Zuletzt verifiziert
1. November 2020
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Andere Studien-ID-Nummern
- 204685
- 2016-000759-28 (EudraCT-Nummer)
Plan für individuelle Teilnehmerdaten (IPD)
Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?
JA
Beschreibung des IPD-Plans
IPD for this study is available via the Clinical Study Data Request site.
IPD-Sharing-Zeitrahmen
IPD is available via the Clinical Study Data Request site (copy the URL below to your browser)
IPD-Sharing-Zugriffskriterien
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place.
Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
Art der unterstützenden IPD-Freigabeinformationen
- STUDIENPROTOKOLL
- SAFT
- ICF
- CSR
Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .
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