A Multiple-Dose Study to Evaluate MK-1075 in Hepatitis C Virus (HCV) Infected Participants (MK-1075-004)
13 april 2018 bijgewerkt door: 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.
Studie Overzicht
Toestand
Voltooid
Conditie
Interventie / Behandeling
Studietype
Ingrijpend
Inschrijving (Werkelijk)
12
Fase
- Fase 1
Deelname Criteria
Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
18 jaar tot 65 jaar (Volwassen, Oudere volwassene)
Accepteert gezonde vrijwilligers
Nee
Geslachten die in aanmerking komen voor studie
Allemaal
Beschrijving
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
Studie plan
Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
|
Experimenteel: 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
|
|
Experimenteel: 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
|
|
Experimenteel: 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
|
|
Experimenteel: 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
|
|
Experimenteel: 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
|
|
Experimenteel: 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
|
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Number of Participants Who Experienced an Adverse Event (AE)
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
|
Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
|
Medewerkers en onderzoekers
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Sponsor
Studie record data
Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.
Bestudeer belangrijke data
Studie start (Werkelijk)
23 juni 2015
Primaire voltooiing (Werkelijk)
23 december 2015
Studie voltooiing (Werkelijk)
23 december 2015
Studieregistratiedata
Eerst ingediend
1 juni 2015
Eerst ingediend dat voldeed aan de QC-criteria
1 juni 2015
Eerst geplaatst (Schatting)
3 juni 2015
Updates van studierecords
Laatste update geplaatst (Werkelijk)
13 november 2018
Laatste update ingediend die voldeed aan QC-criteria
13 april 2018
Laatst geverifieerd
1 april 2018
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
Andere studie-ID-nummers
- 1075-004
- 2015-001687-18 (EudraCT-nummer)
Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .