A Multiple-Dose Study to Evaluate MK-1075 in Hepatitis C Virus (HCV) Infected Participants (MK-1075-004)
13. april 2018 oppdatert av: Merck Sharp & Dohme LLC
A Multiple-Dose Study to Evaluate the Safety, Pharmacodynamics and Pharmacokinetics of MK-1075 in GT3 and GT1 HCV Infected Patients
This study will evaluate safety, pharmacokinetics (PK), and the ability of MK-1075 to suppress viral load (VL) in HCV-infected participants during 7 days of once daily dose administration.
The primary hypothesis is at a once-daily dose that is sufficiently safe and well tolerated in HCV-infected participants, the mean maximum HCV RNA (log10 IU/mL) reduction is at least 3 log10 IU/mL as compared to baseline following multiple dose oral administration of MK-1075 in HCV genotype 1 (GT1) and genotype 3 (GT3) infected participants.
Studieoversikt
Status
Fullført
Forhold
Intervensjon / Behandling
Studietype
Intervensjonell
Registrering (Faktiske)
12
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:
- Female of non-childbearing potential
- Have a body mass index (BMI) >=18 to =< 37 kg/m^2
- Excepting HCV infection, be in good health
- Have a clinical diagnosis of chronic HCV infection, exclusively GT1 or exclusively GT3
- Agree to follow smoking restrictions
Exclusion Criteria:
- Has a history of clinically significant, not stably controlled endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological abnormalities or diseases.
- Have been treated with amiodarone within the prior year, or is currently on beta-blockers or verapamil
- Has a history of cancer (malignancy)
- Has a history of significant multiple and/or severe allergies (e.g., food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food
- Is positive for hepatitis B surface antigen or human immunodeficiency virus (HIV)
- Has had major surgery, donated or lost approximately 500 mL blood within 4 weeks prior to screening visit
- Has participated in another drug trial within 4 weeks prior to screening visit
- Is taking a non-permitted medication to treat a co-morbid condition
- Consumes greater than 2 glasses of alcoholic beverages
- Is a regular user of cannabis, any illicit drugs or has a history of drug (including alcohol) abuse within approximately 12 months
- Has evidence or history of chronic hepatitis not caused by HCV, including but not limited to non-HCV viral hepatitis, non-alcoholic steatohepatitis (NASH), drug-induced hepatitis, or autoimmune hepatitis
- Has been treated with other HCV inhibitors, such as sofosbuvir or VX-135
- Has evidence of advanced or decompensated liver disease, bridging fibrosis or higher grade fibrosis from a prior liver biopsy
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: Parallell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: GT1: 200 mg MK-1075
Fasted GT1 participants are administered 200 mg MK-1075 in tablet form, orally, once daily for 7 consecutive days
|
Two 100 mg tablets of MK-1075 administered orally, once daily for 7 consecutive days
|
|
Eksperimentell: GT1: 400 mg MK-1075
Fasted GT1 participants are administered 400 mg MK-1075 in tablet form, orally, once daily for 7 consecutive days
|
Four 100 mg tablets of MK-1075 administered orally, once daily for 7 consecutive days
|
|
Eksperimentell: GT1: 800 mg MK-1075
Fasted GT1 participants are administered 800 mg MK-1075 in tablet form, orally, once daily for 7 consecutive days
|
Eight 100 mg tablets of MK-1075 administered orally, once daily for 7 consecutive days
|
|
Eksperimentell: GT3: 200 mg MK-1075
Fasted GT3 participants are administered 200 mg MK-1075 in tablet form, orally, once daily for 7 consecutive days
|
Two 100 mg tablets of MK-1075 administered orally, once daily for 7 consecutive days
|
|
Eksperimentell: GT3: 400 mg MK-1075
Fasted GT3 participants are administered 400 mg MK-1075 in tablet form, orally, once daily for 7 consecutive days
|
Four 100 mg tablets of MK-1075 administered orally, once daily for 7 consecutive days
|
|
Eksperimentell: GT3: 800 mg MK-1075
Fasted GT3 participants are administered 800 mg MK-1075 in tablet form, orally, once daily for 7 consecutive days
|
Eight 100 mg tablets of MK-1075 administered orally, once daily for 7 consecutive days
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Number of Participants Who Experienced an Adverse Event (AE)
Tidsramme: Up to Day 42
|
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product which does not necessarily have to have a causal relationship with this treatment.
An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure.
Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
|
Up to Day 42
|
|
Number of Participants Who Discontinued Treatment Due to an AE
Tidsramme: Up to Day 7
|
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product which does not necessarily have to have a causal relationship with this treatment.
An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure.
Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
|
Up to Day 7
|
|
Change From Baseline in Maximum log10 HCV RNA Following Multiple Dose Oral Administration of MK-1075
Tidsramme: Day 1 (pre-dose, 2, 4, 8, 12, and 24 hours postdose); Days 3, 4, 5, 6 (pre-dose); Day 7 (predose, 4, 12, 24, 48, 72, 96, 120, and 192 hours postdose); Days 21, 28 and 42
|
Blood was collected on Days 1, 3, 4, 5, 6, 7, 21, 28 and 42, where baseline measurement was defined as the measurement obtained pre-dose on the first day of dosing.
Change from baseline in log10 HCV RNA levels, was determined, and the maximum reduction in HCV RNA was analyzed by an ANOVA model with a fixed effect for treatment.
The primary hypothesis is, with a posterior probability larger than 70%, there is at least a 3 log10 reduction from baseline in HCV RNA.
|
Day 1 (pre-dose, 2, 4, 8, 12, and 24 hours postdose); Days 3, 4, 5, 6 (pre-dose); Day 7 (predose, 4, 12, 24, 48, 72, 96, 120, and 192 hours postdose); Days 21, 28 and 42
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Area Under the Plasma Concentration Time Curve From Time 0 to 24 Hrs (AUC 0-24hr) of MK-1075 Following Multiple Dose Oral Administration of MK-1075
Tidsramme: Day 7 at the following time points: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose
|
Blood was collected from pre-dose up to 24 hours post-dose in order to determine the plasma AUC 0-24hr of MK-1075 for pooled GT1 and GT3 genotypes.
A non-compartmental analysis on MK-1075 plasma concentrations was performed where actual sampling times, converted to elapsed time relative to dosing times, by using the software Phoenix WinNonlin® Professional (Version 6.3).
AUC was calculated using the linear-up/log-down trapezoidal method.
|
Day 7 at the following time points: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose
|
|
AUC 0-24hr of Metabolite M1 Following Multiple Dose Oral Administration of MK-1075
Tidsramme: Day 7 at the following time points: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose
|
Blood was collected from pre-dose up to 24 hours post-dose in order to determine the plasma AUC 0-24hr of the MK-1075 metabolite M1 for pooled GT1 and GT3 genotypes.
A non-compartmental analysis on M1 plasma concentrations was performed where actual sampling times, converted to elapsed time relative to dosing times, by using the software Phoenix WinNonlin® Professional (Version 6.3).
AUC was calculated using the linear-up/log-down trapezoidal method.
|
Day 7 at the following time points: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose
|
|
Area Under the Plasma Concentration Time Curve From Time 0 to Last (AUC 0-last) of MK-1075 Following Multiple Dose Oral Administration of MK-1075
Tidsramme: Day 7 at the following time points: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours postdose
|
Blood was collected from pre-dose up to 120 hours post-dose in order to determine the plasma AUC 0-last of MK-1075 for pooled GT1 and GT3 genotypes.
A non-compartmental analysis on MK-1075 plasma concentrations was performed where actual sampling times, converted to elapsed time relative to dosing times, by using the software Phoenix WinNonlin® Professional (Version 6.3).
AUC was calculated using the linear-up/log-down trapezoidal method.
|
Day 7 at the following time points: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours postdose
|
|
AUC 0-last of Metabolite M1 Following Multiple Dose Oral Administration of MK-1075
Tidsramme: Day 7 at the following time points: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours postdose
|
Blood was collected from pre-dose up to 120 hours post-dose in order to determine the plasma AUC 0-last of M1 for pooled GT1 and GT3 genotypes.
A non-compartmental analysis on M1 plasma concentrations was performed where actual sampling times, converted to elapsed time relative to dosing times, by using the software Phoenix WinNonlin® Professional (Version 6.3).
AUC was calculated using the linear-up/log-down trapezoidal method.
|
Day 7 at the following time points: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours postdose
|
|
Plasma Concentration at 24 Hours Post-dose (C24hr) of MK-1075 Following Multiple Dose Oral Administration of MK-1075
Tidsramme: Day 7 at 24 hours postdose
|
Blood was collected at 24 hours post-dose in order to determine the plasma C24hr of MK- 1075 for pooled GT1 and GT3 genotypes.
A non-compartmental analysis on MK-1075 plasma concentrations was performed where actual sampling times, converted to elapsed time relative to dosing times, by using the software Phoenix WinNonlin® Professional (Version 6.3).
|
Day 7 at 24 hours postdose
|
|
C24hr of Metabolite M1 Following Multiple Dose Oral Administration of MK-1075
Tidsramme: Day 7 at 24 hours postdose
|
Blood was collected at 24 hours post-dose in order to determine the plasma C24hr of MK-1075 metabolite M1 for pooled GT1 and GT3 genotypes.
A non-compartmental analysis on M1 plasma concentrations was performed where actual sampling times, converted to elapsed time relative to dosing times, by using the software Phoenix WinNonlin® Professional (Version 6.3).
|
Day 7 at 24 hours postdose
|
Samarbeidspartnere og etterforskere
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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 (Faktiske)
23. juni 2015
Primær fullføring (Faktiske)
23. desember 2015
Studiet fullført (Faktiske)
23. desember 2015
Datoer for studieregistrering
Først innsendt
1. juni 2015
Først innsendt som oppfylte QC-kriteriene
1. juni 2015
Først lagt ut (Anslag)
3. juni 2015
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
13. november 2018
Siste oppdatering sendt inn som oppfylte QC-kriteriene
13. april 2018
Sist bekreftet
1. april 2018
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- 1075-004
- 2015-001687-18 (EudraCT-nummer)
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