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- Sperimentazione clinica NCT00840320
Repeat Dose Safety Study for Compound to Treat Anemia
21 giugno 2017 aggiornato da: GlaxoSmithKline
A Phase I, Randomized, Single-Blind, Placebo-Controlled, Dose-Escalation Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Repeat Oral Doses of 1278863A in Healthy Subjects
The purpose of this study is to characterize the safety and tolerability of repeat doses of compound 1278863A in healthy subjects.
Panoramica dello studio
Descrizione dettagliata
Compound 1278863A is a novel small molecule agent, which stimulates erythropoiesis through inhibition of hypoxia-inducible factor (HIF)-prolyl hydroxylases (EGLNs).
This compound is being developed for the treatment of anemia.
Compound 111427 was the first administration of compound 1278863A to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single oral doses up to 300 mg in healthy adult subjects.
This study, PHI112842, will be the first administration of compound 1278863A to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of repeat oral doses up to 300 mg for 14 days in healthy adult subjects.
At least 6 subjects will complete each cohort.
Multiple blood samples for pharmacokinetic analyses will be obtained post-dose in each cohort.
Safety will be assessed by measurement of vital signs, cardiac monitoring, collection of adverse event assessments and laboratory safety tests.
Blood samples will be collected for pharmacodynamic analyses.
Tipo di studio
Interventistico
Iscrizione (Effettivo)
24
Fase
- Fase 1
Contatti e Sedi
Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.
Luoghi di studio
-
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Victoria
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Melbourne, Victoria, Australia, 3004
- GSK Investigational Site
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-
Criteri di partecipazione
I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.
Criteri di ammissibilità
Età idonea allo studio
Da 18 anni a 55 anni (Adulto)
Accetta volontari sani
No
Sessi ammissibili allo studio
Tutto
Descrizione
Inclusion Criteria:
- Healthy as determined by a responsible physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
- Male or female between 18 and 55 years of age, inclusive.
- A female subject must be of non-childbearing potential.
- Male subjects must agree to use one of the acceptable contraception methods listed in the protocol
- Body weight greater than or equal to 50 kg and BMI within the range 19 - 31 kg/m2 (inclusive).
- Capable of giving written informed consent
- QTcB or QTcF < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block.
Exclusion Criteria:
- The subject has a positive pre-study drug screen.
A hemoglobin value at screening is:
- Male subjects or post-menopausal females: > 15.5 g/dL
- Female subjects: > 14.5 g/dL
The values of hematological parameters at screening are:
MCV: outside the reference range and clinically significant deemed by the investigator and GSK Medical Monitor
The values of the following tests at screening are:
- TIBC: outside the reference range
- Serum iron: outside the reference range
- Serum ferritin: outside the reference range
- A value at screening is greater than the upper limit of reference range for the following clinical laboratory parameters: AST, ALT, direct bilirubin.
- Clinically significant abnormal CPK determined by the investigator and GSK Medical Monitor.
- Calculated creatinine clearance: < 60mL/min
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
- A positive test for HIV antibody.
- History of drug abuse or dependence within 6 months of the study.
- History of regular alcohol consumption within 6 months of the study
- Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
- 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 drug
- History of sensitivity to any of the study drugs, 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.
- History of sensitivity to heparin or heparin-induced thrombocytopenia. (if the clinical research unit uses heparin to maintain intravenous cannula patency)
- Subjects with a pre-existing condition interfering with normal gastrointestinal anatomy or motility, and/or hepatic function that could interfere with the absorption, metabolism, and/or excretion of the study drugs.
- History of peptic ulcer disease.
- History of malignancy tumor. Non-melanoma skin cancer that has been definitely removed is allowed.
- Pregnant females as determined by positive serum or urine hCG test at screening or prior to dosing.
- Lactating females.
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
- Unwillingness or inability to follow the procedures, or lifestyle and/or dietary restrictions outlined in the protocol.
- Consumption of red wine, seville oranges, grapefruit or grapefruit juice, exotic citrus fruits, grapefruit hybrids or fruit juices of the prohibited fruits from 7 days prior to the first dose of study medication
- 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.
- Subject is mentally or legally incapacitated.
Piano di studio
Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Scienza basilare
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Separare
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
---|---|
Sperimentale: 1
Repeat doses of active at escalating doses
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15mg, 25mg, 50mg, 150mg
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Comparatore placebo: 2
Repeat doses of placebo
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placebo corrispondente
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Lasso di tempo |
---|---|
adverse events reporting
Lasso di tempo: throughout study
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throughout study
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Safety Labs (hematology)
Lasso di tempo: Screening, Days -1, 1-3, 5, 7, 9, 11, 14-18, 21, 25, 28
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Screening, Days -1, 1-3, 5, 7, 9, 11, 14-18, 21, 25, 28
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vital signs (blood pressure and heart rate)
Lasso di tempo: Days 1-15, 28
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Days 1-15, 28
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12-lead ECG
Lasso di tempo: Screening, Days 1-2, 4, 6, 8, 10, 12, 14, 28
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Screening, Days 1-2, 4, 6, 8, 10, 12, 14, 28
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dual-lead cardiac monitoring (telemetry monitoring)
Lasso di tempo: Days -1 to 3, 14
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Days -1 to 3, 14
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clinical monitoring/observation
Lasso di tempo: throughout
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throughout
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Safety Labs (Chemistry)
Lasso di tempo: Screening, Days -1, 1-3, 7, 10, 14-15, 17, 21, 28
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Screening, Days -1, 1-3, 7, 10, 14-15, 17, 21, 28
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Safety Labs (Urinalysis)
Lasso di tempo: Screening, Days -1, 1-3, 7, 10, 14-15, 17, 21, 28
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Screening, Days -1, 1-3, 7, 10, 14-15, 17, 21, 28
|
Misure di risultato secondarie
Misura del risultato |
Lasso di tempo |
---|---|
AUC(0-∞) on Day 1, AUC(0-τ), Cmax, tmax and t1/2, on Days 1 and 14
Lasso di tempo: Days 1-2, 4, 6, 8, 10, 12, 14-18
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Days 1-2, 4, 6, 8, 10, 12, 14-18
|
Trough plasma concentrations at the end of the dosing interval
Lasso di tempo: Days 2, 4, 6, 8, 10 and 12
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Days 2, 4, 6, 8, 10 and 12
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Hemoglobin actual values, rate of rise, maximum change from baseline, and rate of decline following stopping of dosing
Lasso di tempo: Days 1, 7, 14, 21, 28
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Days 1, 7, 14, 21, 28
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Fetal hemoglobin actual values, change from baseline, and percent of total hemoglobin
Lasso di tempo: Days 1, 7, 14, 21, 28
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Days 1, 7, 14, 21, 28
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Actual values and change from baseline in erythropoietin
Lasso di tempo: Days 1-4, 7, 14-15, 18, 21
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Days 1-4, 7, 14-15, 18, 21
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Actual values and change from baseline in absolute VEGF
Lasso di tempo: Days 1-2, 14-15, 18, 21
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Days 1-2, 14-15, 18, 21
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Actual values and change from baseline in hepcidin
Lasso di tempo: Days 1-2, 7, 14-15, 18, 21
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Days 1-2, 7, 14-15, 18, 21
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Actual values and change from baseline in total iron binding capacity (TIBC)
Lasso di tempo: Screening, Days 1, 7, 14, 18, 21
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Screening, Days 1, 7, 14, 18, 21
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Actual values and change from baseline in transferring saturation (%)
Lasso di tempo: Days 1, 7, 14, 18, 21
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Days 1, 7, 14, 18, 21
|
Collaboratori e investigatori
Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.
Sponsor
Studiare le date dei record
Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.
Studia le date principali
Inizio studio (Effettivo)
13 marzo 2009
Completamento primario (Effettivo)
2 settembre 2009
Completamento dello studio (Effettivo)
2 settembre 2009
Date di iscrizione allo studio
Primo inviato
9 febbraio 2009
Primo inviato che soddisfa i criteri di controllo qualità
9 febbraio 2009
Primo Inserito (Stima)
10 febbraio 2009
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
22 giugno 2017
Ultimo aggiornamento inviato che soddisfa i criteri QC
21 giugno 2017
Ultimo verificato
1 giugno 2017
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
- 112842
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .