A Pharmacokinetics/Pharmacodynamics Study of SCH 900518 in Previously Untreated Subjects With Genotype 1 Chronic Hepatitis C (Protocol No. P05104AM2)(COMPLETED) (NEXT-1)
21 gennaio 2015 aggiornato da: Merck Sharp & Dohme LLC
A Study of SCH 900518 in Previously Untreated Subjects With Genotype 1 Chronic Hepatitis C (Protocol No. P05104)
SCH 900518 is a potent oral inhibitor of HCV NS3 protease which disrupts hepatitis C virus (HCV) polyprotein processing.
SCH 900518, when added to the current standard of care (SOC), peginterferon-alfa plus ribavirin, would likely increase the proportion of patients achieving undetectable HCV-RNA levels and sustained virologic response (SVR).
In this study, SCH 900518 would be used in combination with low doses of ritonavir to enhance the levels of SCH 900518 within the body and reduce the number of daily SCH 900518 tablets required.
The purpose of this study is to identify the optimal dose and schedule (once or twice a day) of SCH 900518 plus ritonavir in previously untreated patients with genotype 1 chronic hepatitis C when given in combination with SOC.
The study compares SOC to 6 experimental arms.
In the experimental arms, SOC plus SCH 900518 doses of 200, 400 and 600 mg once daily or 100 mg twice daily with ritonavir 100 mg once or twice daily will be explored.
The benefits of a 4 week lead-in with PegIntron and ribavirin prior to the addition of SCH 900518 will also be explored.
Panoramica dello studio
Stato
Completato
Condizioni
Intervento / Trattamento
Tipo di studio
Interventistico
Iscrizione (Effettivo)
111
Fase
- Fase 2
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:
- Adult subjects with CHC HCV genotype 1 with no previous treatment for CHC
- 18 to 55 years of age
- Weight between 40 and 125 kg
- Previously documented CHC genotype 1 infection
- Liver biopsy within 2 years of Screening with histology consistent with chronic hepatitis C and no evidence of bridging fibrosis or cirrhosis
- Subject and subject's partner(s) must each agree to use acceptable methods of contraception for at least 2 weeks prior to Day 1 and continue until at least 6 months after last dose of study drug
- Subjects must be willing to give written informed consent
Exclusion Criteria:
- Prior treatment for hepatitis C other than herbal remedies
- HIV positive or known to be co-infected with hepatitis B
- Medically significant gallbladder or hepatobiliary findings on Screening ultrasound
- Use of any known significant inducers or substrates of CYP3A4 two weeks prior to start of study medications
- Use of herbal supplements (Milk Thistle permitted)
- Diabetic and hypertensive subjects with clinically significant ocular examination findings
- Current moderate or severe depression
History of depression associated with any of the following:
- Hospitalization for depression
- Electroconvulsive therapy for depression.
- Depression that resulted in a prolonged absence from work and/or significant disruption of daily functions
- Suicidal or homicidal ideation and/or attempt
- History of severe psychiatric disorders
- Past history or current use of lithium
- Clinical diagnosis of substance abuse of alcohol, intravenous drugs, inhalational (not including marijuana), psychotropics, narcotics, cocaine use, prescription or over-the-counter drugs within 5 years of Day 1
- Past or current use of opiate agonist substitution therapy
- Any known pre-existing medical condition (CNS, cardiac, pulmonary, immune mediated) that could interfere with the subject's participation in and completion of the study
- Active clinical gout within the last year
- Hemoglobinopathy or coagulopathy
- Myelodysplastic syndromes
- Organ transplants other than cornea and hair
- Poor venous access that precludes routine peripheral blood sampling or an indwelling venous catheter
- Subjects with a history of gastric surgery (eg, stapling, banding, bypass) or subjects with a history of malabsorption disorders (eg, celiac sprue disease)
- Evidence of active or suspected malignancy, or a history of malignancy, within the last 5 years (except adequately treated basal cell carcinoma of the skin). Subjects under evaluation for malignancy are not eligible.
- Subjects who are pregnant or nursing
- Subjects who intend to become pregnant during the study period
- Male subjects with partners who are, or intend to become, pregnant during the study period
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: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
|
Comparatore attivo: Standard of Care
PegIntron 1.5 mcg/kg SC weekly plus ribavirin 600 to 1400 mg daily (weight-based) by mouth twice daily for 48 weeks.
|
1.5 mcg/kg subcutaneously weekly for up to 24 or 48 weeks
Altri nomi:
ribavirin 600 to 1400 mg daily (weight-based dosing) by mouth twice daily for up to 24 or 48 weeks
Altri nomi:
SCH 900518 100 mg tablets taken as 200 mg PO QD, 100 mg PO BID, 400 mg PO QD, or 600 mg PO QD for 12 weeks.
Ritonavir 100 mg capsules taken as 100 mg PO QD or 100 mg PO BID for 12 weeks.
Altri nomi:
|
|
Sperimentale: 2
PegIntron 1.5 mcg/kg SC weekly plus ribavirin 600 to 1400 mg daily (weight-based) by mouth twice daily plus SCH 900518 200 mg daily plus ritonavir 100 mg daily for 12 weeks.
Depending on HCV-RNA levels after 4 weeks of SCH 900518, patients will receive an additional 12 or 36 weeks of PegIntron/ribavirin.
Total treatment duration will be 24 or 48 weeks.
|
1.5 mcg/kg subcutaneously weekly for up to 24 or 48 weeks
Altri nomi:
ribavirin 600 to 1400 mg daily (weight-based dosing) by mouth twice daily for up to 24 or 48 weeks
Altri nomi:
SCH 900518 100 mg tablets taken as 200 mg PO QD, 100 mg PO BID, 400 mg PO QD, or 600 mg PO QD for 12 weeks.
Ritonavir 100 mg capsules taken as 100 mg PO QD or 100 mg PO BID for 12 weeks.
Altri nomi:
|
|
Sperimentale: 3
PegIntron 1.5 mcg/kg SC weekly plus ribavirin 600 to 1400 mg daily (weight-based) by mouth twice daily plus SCH 900518 400 mg daily plus ritonavir 100 mg daily for 12 weeks.
Depending on HCV-RNA levels after 4 weeks of SCH 900518, patients will receive an additional 12 or 36 weeks of PegIntron/ribavirin.
Total treatment duration will be 24 or 48 weeks.
|
1.5 mcg/kg subcutaneously weekly for up to 24 or 48 weeks
Altri nomi:
ribavirin 600 to 1400 mg daily (weight-based dosing) by mouth twice daily for up to 24 or 48 weeks
Altri nomi:
SCH 900518 100 mg tablets taken as 200 mg PO QD, 100 mg PO BID, 400 mg PO QD, or 600 mg PO QD for 12 weeks.
Ritonavir 100 mg capsules taken as 100 mg PO QD or 100 mg PO BID for 12 weeks.
Altri nomi:
|
|
Sperimentale: 4
4 week lead-in with PegIntron 1.5 mcg/kg SC weekly plus ribavirin 600 to 1400 mg daily (weight-based) by mouth twice daily followed by PegIntron plus ribavirin plus SCH 900518 200 mg daily plus ritonavir 100 mg daily for 12 weeks.
Depending on HCV-RNA levels after 4 weeks of SCH 900518, patients will receive an additional 8 or 32 weeks of PegIntron/ribavirin.
Total treatment duration will be 24 or 48 weeks.
|
1.5 mcg/kg subcutaneously weekly for up to 24 or 48 weeks
Altri nomi:
ribavirin 600 to 1400 mg daily (weight-based dosing) by mouth twice daily for up to 24 or 48 weeks
Altri nomi:
SCH 900518 100 mg tablets taken as 200 mg PO QD, 100 mg PO BID, 400 mg PO QD, or 600 mg PO QD for 12 weeks.
Ritonavir 100 mg capsules taken as 100 mg PO QD or 100 mg PO BID for 12 weeks.
Altri nomi:
|
|
Sperimentale: 5
4 week lead-in with PegIntron 1.5 mcg/kg SC weekly plus ribavirin 600 to 1400 mg daily (weight-based) by mouth twice daily followed by PegIntron plus ribavirin plus SCH 900518 400 mg daily plus ritonavir 100 mg daily for 12 weeks.
Depending on HCV-RNA levels after 4 weeks of SCH 900518, patients will receive an additional 8 or 32 weeks of PegIntron/ribavirin.
Total treatment duration will be 24 or 48 weeks.
|
1.5 mcg/kg subcutaneously weekly for up to 24 or 48 weeks
Altri nomi:
ribavirin 600 to 1400 mg daily (weight-based dosing) by mouth twice daily for up to 24 or 48 weeks
Altri nomi:
SCH 900518 100 mg tablets taken as 200 mg PO QD, 100 mg PO BID, 400 mg PO QD, or 600 mg PO QD for 12 weeks.
Ritonavir 100 mg capsules taken as 100 mg PO QD or 100 mg PO BID for 12 weeks.
Altri nomi:
|
|
Sperimentale: 6
PegIntron 1.5 mcg/kg SC weekly plus ribavirin 600 to 1400 mg daily (weight-based) by mouth twice daily plus SCH 900518 100 mg twice daily plus ritonavir 100 mg twice daily for 12 weeks.
Depending on HCV-RNA levels after 4 weeks of SCH 900518, patients will receive an additional 12 or 36 weeks of PegIntron/ribavirin.
Total treatment duration will be 24 or 48 weeks.
|
1.5 mcg/kg subcutaneously weekly for up to 24 or 48 weeks
Altri nomi:
ribavirin 600 to 1400 mg daily (weight-based dosing) by mouth twice daily for up to 24 or 48 weeks
Altri nomi:
SCH 900518 100 mg tablets taken as 200 mg PO QD, 100 mg PO BID, 400 mg PO QD, or 600 mg PO QD for 12 weeks.
Ritonavir 100 mg capsules taken as 100 mg PO QD or 100 mg PO BID for 12 weeks.
Altri nomi:
|
|
Sperimentale: 7
4 week lead-in with PegIntron 1.5 mcg/kg SC weekly plus ribavirin 600 to 1400 mg daily (weight-based) by mouth twice daily followed by PegIntron plus ribavirin plus SCH 900518 600 mg daily plus ritonavir 100 mg daily for 12 weeks.
Depending on HCV-RNA levels after 4 weeks of SCH 900518, patients will receive an additional 8 or 32 weeks of PegIntron/ribavirin.
Total treatment duration will be 24 or 48 weeks.
|
1.5 mcg/kg subcutaneously weekly for up to 24 or 48 weeks
Altri nomi:
ribavirin 600 to 1400 mg daily (weight-based dosing) by mouth twice daily for up to 24 or 48 weeks
Altri nomi:
SCH 900518 100 mg tablets taken as 200 mg PO QD, 100 mg PO BID, 400 mg PO QD, or 600 mg PO QD for 12 weeks.
Ritonavir 100 mg capsules taken as 100 mg PO QD or 100 mg PO BID for 12 weeks.
Altri nomi:
|
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Lasso di tempo |
|---|---|
|
The primary efficacy endpoint is the proportion of subjects with undetectable HCV-RNA after 4 weeks of treatment with SCH 900518.
Lasso di tempo: After 4 weeks of treatment with SCH 900518
|
After 4 weeks of treatment with SCH 900518
|
Misure di risultato secondarie
Misura del risultato |
Lasso di tempo |
|---|---|
|
Rate of viral decline during the first 4 weeks of dosing with SCH 900518
Lasso di tempo: After 4 and 12 weeks of treatment with SCH 900518, at EOT and FW 24
|
After 4 and 12 weeks of treatment with SCH 900518, at EOT and FW 24
|
|
Proportion of subjects with undetectable HCV-RNA at both 4 and 12 weeks of dosing with SCH 900518
Lasso di tempo: After 4 and 12 weeks of treatment with SCH 900518, at EOT and FW 24
|
After 4 and 12 weeks of treatment with SCH 900518, at EOT and FW 24
|
|
Proportion of subjects with undetectable HCV-RNA at end of treatment (EOT) and follow-up week 24 (FW24)
Lasso di tempo: After 4 and 12 weeks of treatment with SCH 900518, at EOT and FW 24
|
After 4 and 12 weeks of treatment with SCH 900518, at EOT and FW 24
|
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
1 novembre 2008
Completamento primario (Effettivo)
1 luglio 2009
Completamento dello studio (Effettivo)
1 settembre 2010
Date di iscrizione allo studio
Primo inviato
24 novembre 2008
Primo inviato che soddisfa i criteri di controllo qualità
24 novembre 2008
Primo Inserito (Stima)
25 novembre 2008
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Stima)
22 gennaio 2015
Ultimo aggiornamento inviato che soddisfa i criteri QC
21 gennaio 2015
Ultimo verificato
1 gennaio 2015
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Malattie dell'apparato digerente
- Infezioni da virus a RNA
- Malattie virali
- Infezioni
- Infezioni a trasmissione ematica
- Malattie trasmissibili
- Malattie del fegato
- Flaviviridae Infezioni
- Epatite, virale, umana
- Infezioni da enterovirus
- Infezioni da Picornaviridae
- Epatite cronica
- Epatite
- Epatite A
- Epatite C
- Epatite C, cronica
- Meccanismi molecolari dell'azione farmacologica
- Agenti antinfettivi
- Agenti antivirali
- Inibitori enzimatici
- Agenti anti-HIV
- Agenti antiretrovirali
- Antimetaboliti
- Inibitori della proteasi
- Inibitori del citocromo P-450 CYP3A
- Inibitori dell'enzima del citocromo P-450
- Inibitori della proteasi dell'HIV
- Inibitori virali della proteasi
- Ribavirina
- Ritonavir
- Peginterferone alfa-2b
Altri numeri di identificazione dello studio
- P05104
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 .