A Multiple Dose Study of Grazoprevir (MK-5172) in Hepatit... | NCT01537900

NCT01537900

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

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Document Section

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No data is available for this block.

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
2011-000435-83	EudraCT Number

Status Module

Label	Type	Description	Intervention Names
Grazoprevir 100 mg	Experimental	Participants received GZR 100 mg once daily (q.d.) for 7 days. Liver FNA was performed on Day 7.	Drug: Grazoprevir

Name	Type	Description	Arm Group Labels	Other Names
Grazoprevir	Drug	GZR 100 mg tablet by mouth q.d. for 7 days.	Grazoprevir 100 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Estimated Area Under the Liver Concentration-time Curve for 24 Hours Post-dose (AUC[H]0-24hr) of Grazoprevir	Each participant was assigned to undergo Fine Needle Aspiration (FNA) to obtain liver tissue at different time points. Specifically, one participant underwent FNA at 4 hr post-dose only, another participant underwent FNA at 8 hr post-dose only, and a third participant underwent FNA at 24 hr post-dose only. (The fourth participant underwent FNA at 72 hr post-dose and therefore was not included in the calculation of AUC0-24hr.) Therefore, in calculating AUC0-24hr, there were only 3 data points: 1 data point at 4 hr post-dose, 1 data point at 8 hr post-dose, and 1 data point at 24 hr post-dose. The model assumed that drug concentration was at steady-state, and that the concentration at 24 hr post-dose was equal to the concentration at 0 hr post-dose.	4, 8, and 24 hours post-dose on Day 7
Hepatic Concentration of GZR (C[H]Xhr)	C(H)Xhr of GZR was expressed as liver concentration (μmol GZR/L liver) using the concentration of the extracted liver sample (mass of the liver biopsy/0.2 mL solvent), and assuming that liver has the specific gravity of water (1 g/mL). The arithmetic mean C(H)Xhr concentration is based on the means of 4 FNA passes per participant in all 4 participants.	4, 8, 24, and 72 hours post-dose on Day 7
Apparent Terminal Hepatic Half-life (t[H]½ ) of GZR	t(H)1/2 is a measure of the time required for the maximum post-dose liver concentration of GZR to decrease by 50%.	4, 8, 24, and 72 hours post-dose on Day 7

Secondary Outcomes

Measure	Description	Time Frame
Plasma AUC[0-24 hr] of GZR	AUC0-24hr is a measure of the mean concentration of drug in plasma after dosing to 24 hours post-dose.	Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose on Day 7
Maximum Plasma Concentration (Cmax) of GZR

Eligibility Module

Eligibility Criteria

Inclusion criteria:

has a Body Mass Index (BMI) ≥18.5 kg/m² and ≤36.0 kg/m²
has chronic compensated, genotype 1 HCV infection
has no cirrhosis of the liver as confirmed by FibroSure®/Fibro Test® and/or local country procedure (e.g. transient elastography/Fibroscan)
does not require anticoagulants, nonsteroidal anti-inflammatory agents, and aspirin for at least fourteen (14) days preceding the initial liver biopsy and continuing throughout the entire study
if is a female participant of reproductive potential, is willing to use 2 medically acceptable forms of contraception for 2 weeks prior to start of treatment through 2 weeks after last study treatment
if is a male participant with a partner(s) of reproductive potential, is willing to use 2 medically acceptable forms of contraception from first dose to 90 days after last dose

Exclusion criteria:

has a history of stroke, chronic seizures, or major neurological disorder
has received previous treatment with a direct-acting antiviral (DAA)
has evidence of high grade bridging fibrosis from prior liver biopsy within 3 years of study entry
has evidence or history of chronic hepatitis not caused by HCV infection including but not limited to non-HCV viral hepatitis, nonalcoholic steatohepatitis (NASH), drug-induced hepatitis, or autoimmune hepatitis
has clinical or laboratory evidence of cirrhosis or other advanced liver disease
has decompensated liver disease as indicated by a history of ascites, hepatic encephalopathy, or bleeding esophageal varices
has been diagnosed with, or suspected of having, hepatocellular carcinoma (HCC)
has clinically significant abnormality on an electrocardiogram (ECG)
is co-infected with human immunodeficiency virus (HIV)
is positive for Hepatitis B surface antigen (HBsAg) or other evidence of active Hepatitis B infection
has a history of gastric bypass surgery, bowel resection or other disorder that may interfere with absorption
has a history of clinically significant uncontrolled endocrine, gastrointestinal, cardiovascular, hematological, immunological, renal, respiratory, or genitourinary abnormalities or diseases
has clinically significant neoplastic disease
uses alcohol to excess, defined as greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer [354 mL], wine [118 mL], or distilled spirits [29.5 mL]) per day
is a current regular user (including use of any illicit drugs) or history of drug (including alcohol) abuse within the last 3 months
has undergone surgery, donation of 1 unit of blood (approximately 500 mL) or participation in another investigational study within a period of 4 weeks prior to the screening visit
has a history of multiple and/or severe allergies, or anaphylactic reaction or intolerability to prescription or nonprescription drugs or food
is pregnant or lactating
is expecting to donate eggs or sperm

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

ID	Title	Description
FG000	Grazoprevir 100 mg	Participants received GZR 100 mg once daily (q.d.) for 7 days. Liver FNA was performed on Day 7.

ID	Title	Description
BG000	Grazoprevir 100 mg	Participants received GZR 100 mg q.d. for 7 days. Liver FNA was performed on Day 7.

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

Estimated Area Under the Liver Concentration-time Curve for 24 Hours Post-dose (AUC[H]0-24hr) of Grazoprevir

Each participant was assigned to undergo Fine Needle Aspiration (FNA) to obtain liver tissue at different time points. Specifically, one participant underwent FNA at 4 hr post-dose only, another participant underwent FNA at 8 hr post-dose only, and a third participant underwent FNA at 24 hr post-dose only. (The fourth participant underwent FNA at 72 hr post-dose and therefore was not included in the calculation of AUC0-24hr.) Therefore, in calculating AUC0-24hr, there were only 3 data points: 1 data point at 4 hr post-dose, 1 data point at 8 hr post-dose, and 1 data point at 24 hr post-dose. The model assumed that drug concentration was at steady-state, and that the concentration at 24 hr post-dose was equal to the concentration at 0 hr post-dose.

The per protocol population (PPP) includes all participants (4, 8, and 24 hr time points) who complied with the protocol sufficiently to ensure that the data were likely to exhibit the effects of treatment. As each data point was obtained from unique participants, there is no measure of variability.

Posted

Number

µM*hr

4, 8, and 24 hours post-dose on Day 7

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	Grazoprevir 100 mg	Participants received GZR 100 mg q.d. for 7 days. Liver FNA was performed on Day 7.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA v. 17.1	Systematic Assessment

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