Safety, Pharmacokinetics, and Pharmacodynamics of Ruzasvi... | NCT02076100

NCT02076100

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
2013-005094-41	EudraCT Number
MK-8408-003	Other Identifier	Merck Protocol Number

Status Module

Oversight Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Part I GT3 Participants	Experimental	Participants receive Ruzasvir capsules, orally, starting at a dose of 60 mg once per day (QD) x 5 days with doses increasing or decreasing as clinically indicated.	Drug: Ruzasvir
Part II GT1a Participants	Experimental	Participants receive Ruzasvir capsules, orally, starting at a dose of 60 mg once per day (QD) x 5 days with doses increasing or decreasing as clinically indicated.	Drug: Ruzasvir
Part III GT2b Participants	Experimental	Participants receive Ruzasvir capsules, orally, starting at a dose of 60 mg once per day (QD) x 5 days with doses increasing or decreasing as clinically indicated.	Drug: Ruzasvir

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Ruzasvir	Drug	Ruzasvir capsules, orally, starting at a dose of 60 mg once per day (QD) x 5 days with doses increasing or decreasing as clinically indicated.	Part I GT3 Participants

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Maximum log10 HCV Ribonucleic Acid (RNA) Change From Baseline	Blood was collected at baseline and on Days 1, 2, 3, 4 and 5 to determine HCV RNA levels. Least squares means (LSM) and confidence intervals (CI) were obtained from an analysis of variance (ANOVA) model with maximum log10 HCV RNA change from baseline as response and a fixed effect for treatment. The primary hypothesis was that the mean change from baseline would be a reduction of ≥3 log10. A positive change from baseline indicates a reduction from baseline in log10 HCV RNA.	Baseline and up to Day 5
Number of Participants Who Experienced One or More Adverse Events (AEs)	An adverse event (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 61 days
Number of Participants Who Discontinued Study Drug Due To An AE	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 5 days

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Body mass index (BMI) >=18 to<=37 kg/m^2
In general good health, except for HCV infection
Clinical diagnosis of chronic HCV infection exclusively GT3 (Panels A-D) or exclusively GT1a (Panels E-F), or exclusively GT2b (Panels G-H).
Must agree to follow the smoking restrictions defined by the CRU
Must agree to use an acceptable method of contraception during the study and for 90 days after the last dose of ruzasvir

Exclusion Criteria:

Clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological abnormalities or diseases
History of clinically significant hepatic disease, Gilbert's disease or biliary tract disease
History of cancer (malignancy) with the exception of adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix, or successfully-treated malignancies ≥10 years prior to screening
History of significant multiple and/or severe allergies or has had an anaphylactic reaction or significant intolerability to prescription or nonprescription drugs or food
Positive for hepatitis B or human immunodeficiency virus (HIV)
Major surgery or donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to screening
Participated in another investigational trial within 4 weeks prior to the screening visit
QTc interval >=470 msec (for males) or >= 480 msec (for females)
Unable to refrain from or anticipates use of any medication (prescription and/or non-prescription) or herbal remedies beginning approximately 2 weeks prior to first study drug dose, throughout the trial until the post-trial visit
Consumes >2 glasses of alcoholic beverages per day
Regular user (including "recreational use") of any illicit drugs or history of drug (including alcohol) abuse within approximately 12 months
Evidence or history of chronic hepatitis not caused by HCV
Previous treatment with other HCV NS5A inhibitors such as MK-8742, daclatasvir, or MK-8325
Treatment with other HCV therapies such as the HCV protease
Evidence of advanced or decompensated liver disease; evidence of bridging fibrosis or higher grade fibrosis (Metavir score >=3)

Name	Affiliation	Role
Medical Director	Merck Sharp & Dohme LLC	Study Director

Arm/Group Information

ID	Title	Description
FG000	Ruzasvir 10 mg - GT3	GT3 participants were administered 10 mg Ruzasvir in capsule form, orally, once per day for 5 days.
FG001	Ruzasvir 30 mg - GT3	GT3 participants were administered 30 mg Ruzasvir in capsule form, orally, once per day for 5 days.
FG002	Ruzasvir 60 mg - GT3	GT3 participants were administered 60 mg Ruzasvir in capsule form, orally, once per day for 5 days.
FG003	Ruzasvir 120 mg - GT3	GT3 participants were administered 120 mg Ruzasvir in capsule form, orally, once per day for 5 days.
FG004	Ruzasvir 10 mg - GT2b	GT2b participants were administered 10 mg Ruzasvir in capsule form, orally, once per day for 5 days.
FG005	Ruzasvir 60 mg - GT2b	GT2b participants were administered 60 mg Ruzasvir in capsule form, orally, once per day for 5 days.
FG006	Ruzasvir 60 mg - GT1a	GT1a participants were administered 60 mg Ruzasvir in capsule form, orally, once per day for 5 days. One participant was later determined to be GT1b.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Ruzasvir 10 mg - GT3	GT3 participants were administered 10 mg Ruzasvir in capsule form, orally, once per day for 5 days.
BG001	Ruzasvir 30 mg - GT3	GT3 participants were administered 30 mg Ruzasvir in capsule form, orally, once per day for 5 days.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Maximum log10 HCV Ribonucleic Acid (RNA) Change From Baseline

Blood was collected at baseline and on Days 1, 2, 3, 4 and 5 to determine HCV RNA levels. Least squares means (LSM) and confidence intervals (CI) were obtained from an analysis of variance (ANOVA) model with maximum log10 HCV RNA change from baseline as response and a fixed effect for treatment. The primary hypothesis was that the mean change from baseline would be a reduction of ≥3 log10. A positive change from baseline indicates a reduction from baseline in log10 HCV RNA.

Participants who complied with the protocol sufficiently to ensure that generated data would exhibit the effects of treatment, according to the underlying scientific model. Compliance covers considerations such as exposure to treatment, availability of measurements and absence of major protocol violations.

Posted

Least Squares Mean

90% Confidence Interval

log10 IU/mL

Baseline and up to Day 5

ID	Title	Description
OG000	Ruzasvir 10 mg - GT3

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Ruzasvir 10 mg - GT3	GT3 participants were administered 10 mg Ruzasvir in capsule form, orally, once per day for 5 days.

ID	Term
D000086982	Blood-Borne Infections
D003141	Communicable Diseases
D007239	Infections
D006525	Hepatitis, Viral, Human