Safety, Pharmacokinetics, and Pharmacodynamics of MK-2248 in Participants With Hepatitis C (MK-2248-002)
5. juni 2015 oppdatert av: Merck Sharp & Dohme LLC
A Multiple Dose Study to Evaluate Safety, Pharmacokinetics, and Pharmacodynamics of MK-2248 in Subjects With Hepatitis C Infection
The objective of this study is to identify a safe dose of MK-2248 in participants with Hepatitis C Virus (HCV) that mediates at least a 3 log10 reduction in viral load (VL) from baseline.
It is anticipated that once-daily administration of a safe and well tolerated dose of MK-2248 will reduce VL by at least 3 log10 IU/mL.
Studieoversikt
Detaljert beskrivelse
In this Phase 1b study, the pharmacokinetic (PK), pharmacodynamic (PD), and safety profile of MK-2248 in HCV-infected participants will be evaluated as follows: Part I will assess sequentially ascending MK-2248 doses from 200 mg to ≤800 mg over 4 panels (A, B, C, and D).
Part II will assess sequentially ascending MK-2248 doses from 200 mg to ≤800 mg over 4 panels (E, F, G, and H).
Part III will assess sequentially ascending MK-2248 doses ranging up to ≤800 mg in 2 panels (I and J).
The potential relationship between plasma MK-2248 levels and VL reduction will be determined.
Studietype
Intervensjonell
Registrering (Faktiske)
13
Fase
- Fase 1
Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
18 år til 65 år (Voksen, Eldre voksen)
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
Alle
Beskrivelse
Inclusion Criteria:
- clinical diagnosis of chronic HCV defined by positive serology for HCV or positive HCV RNA for at least 6 months and detectable HCV RNA in peripheral blood ≥10^5 IU/mL at screening
- Body Mass Index (BMI) ≥18 to <37 kg/m^2
- in good health other than HCV infection with normal laboratory values
Exclusion Criteria:
- history of clinically significant and not stably controlled endocrine, gastrointestinal, cardiovascular, hematological, hepatic (excepting HCV infection), immunological, renal, respiratory, genitourinary, or major neurological abnormalities or disease
- history of cancer other than adequately treated non-melanomatous skin carcinoma, malignancies which have been successfully treated ≥10 years prior with no recurrence, or cancer that is unlikely to sustain a recurrence for the duration of the trial
- history of significant multiple and/or severe allergies or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food
- positive for hepatitis B surface antigen or human immunodeficiency virus
- had major surgery or lost 1 unit of blood within 4 weeks prior to screening
- QTc interval ≥470 msec (males) or ≥480 msec (females)
- received prior treatment with other HCV inhibitors
- clinical or laboratory evidence of decompensated liver disease
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: Part I: MK-2248 200 mg (Panel A)
HCV participants will take MK-2248 200 mg by mouth once daily for 7 days.
|
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days
|
|
Eksperimentell: Part I: MK-2248 ≤800 mg (Panel B)
Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days.
|
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days
|
|
Eksperimentell: Part I: MK-2248 ≤800 mg (Panel C)
Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth for 7 days.
|
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days
|
|
Eksperimentell: Part I: MK-2248 ≤800 mg (Panel D)
Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days.
|
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days
|
|
Eksperimentell: Part II: MK-2248 200 mg (Panel E)
HCV participants will take MK-2248 200 mg by mouth once daily for 7 days.
|
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days
|
|
Eksperimentell: Part II: MK-2248 ≤800 mg (Panel F)
Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days.
|
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days
|
|
Eksperimentell: Part II: MK-2248 ≤800 mg (Panel G)
Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days.
|
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days
|
|
Eksperimentell: Part II: MK-2248 ≤800 mg (Panel H)
Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days.
|
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days
|
|
Eksperimentell: Part III: MK-2248 ≤800 mg (Panel I)
Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days.
|
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days
|
|
Eksperimentell: Part III: MK-2248 ≤800 mg (Panel J)
Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days.
|
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tidsramme |
|---|---|
|
Maximum change from baseline in VL
Tidsramme: Up to Day 42
|
Up to Day 42
|
|
Number of participants experiencing an adverse event (AE)
Tidsramme: Up to Day 42
|
Up to Day 42
|
|
Number of participants who discontinue from study treatment due to an AE
Tidsramme: Up to Day 7
|
Up to Day 7
|
Sekundære resultatmål
Resultatmål |
Tidsramme |
|---|---|
|
Plasma concentration at 24 hours post-dose (C24hr) of MK-2248 and circulating metabolite(s)
Tidsramme: Up to Day 10
|
Up to Day 10
|
|
Area under the plasma-concentration curve at zero to 24 hours post-dose (AUC[0-24hr]) of MK-2248 and circulating metabolite(s)
Tidsramme: Up to Day 10
|
Up to Day 10
|
|
Maximum observed post-dose plasma concentration (Cmax) of MK-2248 and circulating metabolite(s)
Tidsramme: Up to Day 10
|
Up to Day 10
|
|
Time post-dose at which the maximum observed plasma concentraton (Tmax) of MK-2248 and circulating metabolite(s) occurs
Tidsramme: Up to Day 10
|
Up to Day 10
|
|
Time required for Cmax to decrease by half (apparent t1/2) of MK-2248 and circulating metabolite(s) in plasma
Tidsramme: Up to Day 10
|
Up to Day 10
|
|
Accumulation ratio of MK-2248 and circulating metabolite(s) in plasma
Tidsramme: Up to Day 10
|
Up to Day 10
|
|
Total clearance (amount of drug cleared relative to the total systemically available amount per unit time [CL/F]) of MK-2248 in plasma
Tidsramme: Up to Day 10
|
Up to Day 10
|
|
Apparent volume of distribution (V/F) of MK-2248 in plasma
Tidsramme: Up to Day 10
|
Up to Day 10
|
Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart
1. juli 2014
Primær fullføring (Faktiske)
1. november 2014
Studiet fullført (Faktiske)
1. april 2015
Datoer for studieregistrering
Først innsendt
10. juni 2014
Først innsendt som oppfylte QC-kriteriene
10. juni 2014
Først lagt ut (Anslag)
11. juni 2014
Oppdateringer av studieposter
Sist oppdatering lagt ut (Anslag)
8. juni 2015
Siste oppdatering sendt inn som oppfylte QC-kriteriene
5. juni 2015
Sist bekreftet
1. juni 2015
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- 2248-002
- 2014-001494-14 (EudraCT-nummer)
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