- ICH GCP
- Registro degli studi clinici negli Stati Uniti
- Sperimentazione clinica NCT04959266
A Study to Assess the Effects of Itraconazole, Rifampicin, and Omeprazole on Pharmacokinetics of Adavosertib
A Phase I, Open-label, Non-randomised Study to Assess the Effect of Itraconazole (a CYP3A4 Inhibitor), Rifampicin (a CYP3A4 Inducer), and Omeprazole (a Proton Pump Inhibitor) on the Pharmacokinetics of a Single Oral Dose of Adavosertib in Patients With Advanced Solid Tumours
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
The study will include 3 arms consisting of a screening period of up to 28 days (Day -28 to Day -1), an intervention period (12 days for arm A, 17 days for arm B, and 12 days for arm C), and a follow-up end of treatment [EOT] visit (within 3 days after a 4-day washout period relative to the last dose of adavosertib).
Arm A of this study follows a non-randomised, open-label, 2-intervention design. Patients will receive the following 2 study interventions: a single oral dose of adavosertib alone, and a single oral dose of adavosertib administered concomitantly with itraconazole.
Arm B of this study follows a non-randomised, open-label, 2-intervention design. Patients will receive the following 2 study interventions: a single oral dose of adavosertib alone, and a single oral dose of adavosertib administered concomitantly with rifampicin.
Arm C of this study follows a non-randomised, open-label, 2-intervention design. Patients will receive the following 2 study interventions: a single oral dose of adavosertib alone, and a single oral dose of adavosertib administered concomitantly with omeprazole.
Tipo di studio
Iscrizione (Effettivo)
Fase
- Fase 1
Contatti e Sedi
Luoghi di studio
-
-
-
Madrid, Spagna, 28041
- Research Site
-
Malaga, Spagna, 29010
- Research Site
-
-
-
-
Oregon
-
Portland, Oregon, Stati Uniti, 97213
- Research Site
-
-
Texas
-
Austin, Texas, Stati Uniti, 78758
- Research Site
-
Dallas, Texas, Stati Uniti, 75230
- Research Site
-
-
Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
Inclusion Criteria:
- Histologically or cytologically documented, locally advanced or metastatic solid tumour, excluding lymphoma, for which standard therapy does not exist or has proven ineffective or intolerable.
- Eastern Cooperative Oncology Group performance status score of 0 or 1.
- Predicted life expectancy ≥ 12 weeks.
- Patients must have normal organ and marrow function at baseline, within 7 days prior to study drug administration.
- Males and females of childbearing potential who agree to use contraceptive measures must be consistent with clinical study protocol.
Exclusion Criteria:
- Persistent toxicities (Common Terminology Criteria for Adverse Events [CTCAE] Grade > 2) caused by previous anticancer therapy, excluding alopecia and CTCAE Grade 2 peripheral neuropathy.
- Refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of adavosertib, itraconazole, rifampicin, and omeprazole.
- Any significant cardiac diseases currently or within the last 6 months such as: (a) unstable angina pectoris (b) acute myocardial infarction, congestive heart failure (c) conduction abnormality not controlled with pacemaker or medication (d) significant ventricular or supraventricular arrhythmias.
Any of the following:
- History or current evidence of congenital long QT syndrome;
- concomitant medications known to prolong QT interval or history of medicationrelated QT prolongation.
- Known to have tested positive for human immunodeficiency virus or active tuberculosis infection.
- Known active hepatitis infection, positive hepatitis C antibody, hepatitis B virus surface antigen or hepatitis B virus core antibody, at screening.
- Any evidence of diseases (such as severe or uncontrolled systemic diseases, including uncontrolled hypertension, renal transplant, active infections, and active bleeding diseases) which prohibit participating in the study.
- Spinal cord compression or brain metastases unless asymptomatic, stable, and not requiring steroids for at least 4 weeks prior to start of study intervention.
- Receipt of live virus and live bacterial vaccines whilst the patient is receiving the study intervention and during the 30-day follow-up period. Inactivated flu vaccines are permitted.
- Use of an anti-cancer treatment drug ≤ 21 days (≤ 6 weeks for nitroureas or mitomycin C) or use of an investigational product within 5 half-lives prior to the first dose of adavosertib.
- Patient uses drugs that are sensitive to CYP3A4 substrates or CYP3A4 substrates with a narrow therapeutic index, or are moderate to strong inhibitors/inducers of CYP3A4 which cannot be discontinued 2 weeks or 5 halflives (whichever is longer) prior to Day 1 of dosing.
- Patients with a known hypersensitivity to adavosertib, itraconazole, rifampicin, and omeprazole or any of the excipients of the product.
- Currently pregnant (confirmed with positive pregnancy test) or breast-feeding.
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Altro
- Assegnazione: Non randomizzato
- Modello interventistico: Assegnazione incrociata
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
---|---|
Sperimentale: Arm A
Patients will receive a single oral dose of adavosertib alone, and a single oral dose of adavosertib concomitantly with itraconazole.
|
Patients will receive a single dose of Adavosertib orally in arm A, B, and C.
Patients will receive Itraconazole orally once daily for 7 days in arm A.
|
Sperimentale: Arm B
Patients will receive a single oral dose of adavosertib alone, and a single oral dose of adavosertib concomitantly with rifampicin.
|
Patients will receive a single dose of Adavosertib orally in arm A, B, and C.
Patients will receive Rifampicin orally once daily for 13 days in arm B.
|
Sperimentale: Arm C
Patients will receive a single oral dose of adavosertib alone, and a single oral dose of adavosertib concomitantly with omeprazole.
|
Patients will receive a single dose of Adavosertib orally in arm A, B, and C.
Patients will receive Omeprazole orally once daily for 5 days in arm C.
|
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
---|---|---|
Ratios of geometric means of Cmax (maximum observed plasma concentration) when administered in combination with itraconazole/rifampicin/omeprazole relative to adavosertib alone
Lasso di tempo: Arm A: Days 1-4 and 9-12; Arm B: Days 1-4 and 14-17; Arm C: Days 1-4 and 9-12
|
Assessment of the effect of itraconazole (arm A)/rifampicin (arm B)/omeprazole (arm C) on the Cmax of adavosertib following oral dosing in patients with advanced solid tumours.
|
Arm A: Days 1-4 and 9-12; Arm B: Days 1-4 and 14-17; Arm C: Days 1-4 and 9-12
|
Ratios of geometric means of AUCinf (Area under plasma concentration-time curve from time zero to infinity) when administered in combination with itraconazole/rifampicin/omeprazole relative to adavosertib alone
Lasso di tempo: Arm A: Days 1-4 and 9-12; Arm B: Days 1-4 and 14-17; Arm C: Days 1-4 and 9-12
|
Assessment of the effect of itraconazole (arm A)/rifampicin (arm B)/omeprazole (arm C) on the AUCinf of adavosertib following oral dosing in patients with advanced solid tumours.
|
Arm A: Days 1-4 and 9-12; Arm B: Days 1-4 and 14-17; Arm C: Days 1-4 and 9-12
|
Ratios of geometric means of AUClast (Area under the plasma concentration-time curve from zero to time of last quantifiable concentration) when administered in combination with itraconazole/rifampicin/omeprazole relative to adavosertib alone
Lasso di tempo: Arm A: Days 1-4 and 9-12; Arm B: Days 1-4 and 14-17; Arm C: Days 1-4 and 9-12
|
Assessment of the effect of itraconazole (arm A)/rifampicin (arm B)/omeprazole (arm C) on the AUClast of adavosertib following oral dosing in patients with advanced solid tumours.
|
Arm A: Days 1-4 and 9-12; Arm B: Days 1-4 and 14-17; Arm C: Days 1-4 and 9-12
|
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
---|---|---|
Summary of Adavosertib plasma concentrations with time
Lasso di tempo: Arm A: Days 1-4 and 9-12; Arm B: Days 1-4 and 14-17; Arm C: Days 1-4 and 9-12
|
Assessment of pharmacokinetics (PK) for adavosertib when administered alone and in combination with itraconazole (arm A) /rifampicin (arm B) /omeprazole (arm C).
|
Arm A: Days 1-4 and 9-12; Arm B: Days 1-4 and 14-17; Arm C: Days 1-4 and 9-12
|
Descriptive statistics of Cmax
Lasso di tempo: Arm A: Days 1-4 and 9-12; Arm B: Days 1-4 and 14-17; Arm C: Days 1-4 and 9-12
|
Assessment of Cmax for adavosertib when administered alone and in combination with itraconazole (arm A) /rifampicin (arm B) /omeprazole (arm C).
|
Arm A: Days 1-4 and 9-12; Arm B: Days 1-4 and 14-17; Arm C: Days 1-4 and 9-12
|
Descriptive statistics of AUCinf
Lasso di tempo: Arm A: Days 1-4 and 9-12; Arm B: Days 1-4 and 14-17; Arm C: Days 1-4 and 9-12
|
Assessment of AUCinf for adavosertib when administered alone and in combination with itraconazole (arm A) /rifampicin (arm B) /omeprazole (arm C).
|
Arm A: Days 1-4 and 9-12; Arm B: Days 1-4 and 14-17; Arm C: Days 1-4 and 9-12
|
Descriptive statistics of AUClast
Lasso di tempo: Arm A: Days 1-4 and 9-12; Arm B: Days 1-4 and 14-17; Arm C: Days 1-4 and 9-12
|
Assessment of AUClast for adavosertib when administered alone and in combination with itraconazole (arm A) /rifampicin (arm B) /omeprazole (arm C).
|
Arm A: Days 1-4 and 9-12; Arm B: Days 1-4 and 14-17; Arm C: Days 1-4 and 9-12
|
Descriptive statistics of tmax (Time to reach maximum observed concentration following drug administration)
Lasso di tempo: Arm A: Days 1-4 and 9-12; Arm B: Days 1-4 and 14-17; Arm C: Days 1-4 and 9-12
|
Assessment of tmax for adavosertib when administered alone and in combination with itraconazole (arm A) /rifampicin (arm B) /omeprazole (arm C).
|
Arm A: Days 1-4 and 9-12; Arm B: Days 1-4 and 14-17; Arm C: Days 1-4 and 9-12
|
Descriptive statistics of λz (Terminal elimination rate constant)
Lasso di tempo: Arm A: Days 1-4 and 9-12; Arm B: Days 1-4 and 14-17; Arm C: Days 1-4 and 9-12
|
Assessment of λz for adavosertib when administered alone and in combination with itraconazole (arm A) /rifampicin (arm B) /omeprazole (arm C).
|
Arm A: Days 1-4 and 9-12; Arm B: Days 1-4 and 14-17; Arm C: Days 1-4 and 9-12
|
Descriptive statistics of t½λz (Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve)
Lasso di tempo: Arm A: Days 1-4 and 9-12; Arm B: Days 1-4 and 14-17; Arm C: Days 1-4 and 9-12
|
Assessment of t½λz for adavosertib when administered alone and in combination with itraconazole (arm A) /rifampicin (arm B) /omeprazole (arm C).
|
Arm A: Days 1-4 and 9-12; Arm B: Days 1-4 and 14-17; Arm C: Days 1-4 and 9-12
|
Descriptive statistics of CL/F (Apparent total body clearance of drug from plasma after extravascular administration)
Lasso di tempo: Arm A: Days 1-4 and 9-12; Arm B: Days 1-4 and 14-17; Arm C: Days 1-4 and 9-12
|
Assessment of CL/F for adavosertib when administered alone and in combination with itraconazole (arm A) /rifampicin (arm B) /omeprazole (arm C).
|
Arm A: Days 1-4 and 9-12; Arm B: Days 1-4 and 14-17; Arm C: Days 1-4 and 9-12
|
Descriptive statistics of Vss/F (Volume of distribution (apparent) at steady state following extravascular administration)
Lasso di tempo: Arm A: Days 1-4 and 9-12; Arm B: Days 1-4 and 14-17; Arm C: Days 1-4 and 9-12
|
Assessment of Vss/F for adavosertib when administered alone and in combination with itraconazole (arm A) /rifampicin (arm B) /omeprazole (arm C).
|
Arm A: Days 1-4 and 9-12; Arm B: Days 1-4 and 14-17; Arm C: Days 1-4 and 9-12
|
Descriptive statistics of Vz/F (Apparent volume of distribution during the terminal phase after extravascular administration)
Lasso di tempo: Arm A: Days 1-4 and 9-12; Arm B: Days 1-4 and 14-17; Arm C: Days 1-4 and 9-12
|
Assessment of Vz/F for adavosertib when administered alone and in combination with itraconazole (arm A) /rifampicin (arm B) /omeprazole (arm C).
|
Arm A: Days 1-4 and 9-12; Arm B: Days 1-4 and 14-17; Arm C: Days 1-4 and 9-12
|
Descriptive statistics of Ctrough (Observed lowest drug concentration reached before the next dose is administered)
Lasso di tempo: Arm A: Days 9-11; Arm B: Days 14-17; Arm C: Day 9
|
Assessment of Ctrough for itraconazole, rifampicin and omeprazole when administered in combination with adavosertib.
|
Arm A: Days 9-11; Arm B: Days 14-17; Arm C: Day 9
|
Number of patients with serious and non-serious adverse events
Lasso di tempo: From screening to end of study [within 30 (±7) days of last adavosertib dose]
|
Assessment of the safety and tolerability of adavosertib when dosed with itraconazole (arm A), rifampicin (arm B), and omeprazole (arm C).
|
From screening to end of study [within 30 (±7) days of last adavosertib dose]
|
Collaboratori e investigatori
Sponsor
Collaboratori
Studiare le date dei record
Studia le date principali
Inizio studio (Effettivo)
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Effettivo)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Effetti fisiologici delle droghe
- Meccanismi molecolari dell'azione farmacologica
- Agenti antinfettivi
- Inibitori della sintesi degli acidi nucleici
- Inibitori enzimatici
- Agenti gastrointestinali
- Ormoni, sostituti ormonali e antagonisti ormonali
- Agenti antibatterici
- Inibitori del citocromo P-450 CYP3A
- Inibitori dell'enzima del citocromo P-450
- Agenti leprostatici
- Antagonisti ormonali
- Induttori enzimatici del citocromo P-450
- Agenti antimicotici
- Inibitori della sintesi di steroidi
- Agenti anti-ulcera
- Inibitori della pompa protonica
- Induttori del citocromo P-450 CYP3A
- Agenti antitubercolari
- Inibitori della 14-alfa demetilasi
- Antibiotici, Antitubercolari
- Induttori del citocromo P-450 CYP2B6
- Induttori del citocromo P-450 CYP2C8
- Induttori del citocromo P-450 CYP2C19
- Induttori del citocromo P-450 CYP2C9
- Rifampicina
- Itraconazolo
- Omeprazolo
- Adavosertib
Altri numeri di identificazione dello studio
- D601HC00006
Piano per i dati dei singoli partecipanti (IPD)
Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?
Descrizione del piano IPD
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Periodo di condivisione IPD
Criteri di accesso alla condivisione IPD
When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the
Disclosure Statements at:
https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Informazioni su farmaci e dispositivi, documenti di studio
Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti
Studia un dispositivo regolamentato dalla FDA degli Stati Uniti
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 .
Prove cliniche su Tumori solidi avanzati
-
Rush University Medical CenterCompletatoAdvanced Cardiac Life Support, rianimazione cardiopolmonare, volume corrente, ventilazione manualeStati Uniti
-
The Leeds Teaching Hospitals NHS TrustAttivo, non reclutanteFerite e lesioni | Chirurgia | Riabilitazione | Disturbo ortopedico | Misure di esito riferite dal paziente | Valutazione della disabilità | Recupero della funzione | Trauma multiplo/lesioni | Centri traumatologici | Indici di gravità del trauma | Advanced Trauma Life Support CareRegno Unito
-
Advanced BionicsCompletatoPerdita dell'udito da grave a profonda | negli utenti adulti di Advanced Bionics HiResolution™ Bionic Ear SystemStati Uniti
-
AstraZenecaReclutamentoAdv Solid Malig - H&N SCC, ATM Pro / Def NSCLC, carcinoma gastrico, mammario e ovaricoSpagna, Stati Uniti, Belgio, Regno Unito, Francia, Ungheria, Canada, Corea, Repubblica di, Australia
Prove cliniche su Adavosertib
-
Merck Sharp & Dohme LLCTerminato
-
AstraZenecaParexelTerminatoTumori solidi avanzatiRegno Unito
-
AstraZenecaCompletatoTumori solidi avanzatiGiappone
-
Merck Sharp & Dohme LLCTerminato
-
Merck Sharp & Dohme LLCCompletato
-
AstraZenecaCompletatoCancro ovarico | Tumori solidi localmente avanzati | Tumori solidi metastaticiStati Uniti
-
AstraZenecaParexelTerminatoTumori solidi avanzatiRegno Unito, Stati Uniti
-
Samsung Medical CenterCompletatoCancro polmonare a piccole celluleCorea, Repubblica di
-
AstraZenecaParexelCompletatoCarcinoma sieroso uterinoStati Uniti, Italia, Spagna, Francia, Canada