Safety, Pharmacokinetics, and Pharmacodynamics of MK-8876 in Participants With Hepatitis C Infection (MK-8876-003)

A Multiple Dose Study to Evaluate Safety, Pharmacokinetics and Pharmacodynamics of MK-8876 in Hepatitis C Patients

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01930058

Enrollment

Registered

2013-08-28

Start date

2013-10-02

Completion date

2014-05-05

Last updated

2018-10-25

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Hepatitis C

Brief summary

This adaptive design study will evaluate the safety, pharmacokinetics, and effect on hepatitis C virus (HCV) RNA levels of multiple doses of MK-8876 in participants with HCV infection. The study will consist of 4 parts evaluating participants infected with specific hepatitis C virus genotypes and up to 10 panels allowing for additional participants to enroll in each panel as specified in the study analysis. The hypothesis evaluated in the study is that a ≥2.5 log IU/mL reduction in HCV RNA from Baseline will accompany multiple dose administration of MK-8876 in participants with HCV infection.

Interventions

DRUGMK-8876

MK-8876 10 mg or 100 mg tablets taken q.d. by mouth.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Inclusion criteria

* is male, or female of non-childbearing potential (non-childbearing potential is defined as postmenopausal without menses for ≥1 year or after medically documented hysterectomy, oophorectomy, or tubal ligation) * agrees to use a medically acceptable method of contraception through 90 days after the last dose of study drug if participant has a female partner of childbearing potential must (males should use a condom and their partner of childbearing potential must use hormonal contraception, intrauterine device, diaphragm, cervical cap, or female condom) * has a body mass index (BMI) between 18 and 37 kg/m\^2 * has a clinical diagnosis of chronic HCV infection defined by positive serology for HCV for ≥6 months * agrees to follow the smoking and other trial restrictions

Exclusion criteria

* is mentally or legally institutionalized or incapacitated, has significant emotional problems at study start or has clinically significant psychiatric disorder of the last 5 years * has a history of clinically significant endocrine, gastrointestinal (except HCV infection), cardiovascular, hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases * has a history of stroke, chronic seizures, or major neurological disorder * has a history of cancer (except adequately treated non-melanomatous skin carcinoma, carcinoma in situ of the cervix, or other malignancies which have been successfully treated for ≥10 years * has a history of significant multiple and/or severe allergies or has had an anaphylactic reaction or significant intolerability to drugs or food * has a history of clinically significant hepatic disease, Gilbert's disease, biliary tract disease, or human immunodeficiency virus * has had major surgery or donated or lost \>1 unit of blood within 4 weeks before the study * has participated in another investigational trial within 4 weeks before the study * Is unable to refrain from or anticipates the use of any medication from 2 weeks before the study and throughout the study * consumes \>2 glasses of alcoholic beverages per day * consumes \>6 servings (1 serving is \ 120 mg caffeine) of coffee, tea, cola, energy drinks, or other caffeinated beverages per day * is a regular user of any illicit drugs or history of drug abuse within 12 months of the study * has evidence or history of chronic hepatitis not caused by HCV (except acute non-HCV-related hepatitis that resolved \>6 months before the study) * has previously received treatment with another HCV non-nucleoside inhibitor (previous use of other HCV investigational therapies or marketed compounds is permitted if treatment ended ≥3 months before the study) * has clinical or laboratory evidence of advanced or decompensated liver disease

Design outcomes

Primary

Measure	Time frame	Description
Mean Change From Baseline in HCV Viral Load	Baseline and Day 7	The mean change (log10) in HCV ribonucleic acid (RNA) from baseline to Day 7 was determined for each panel of participants.

Secondary

Measure	Time frame	Description
Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (hr) Post-dose (AUC0-24 hr) of MK-8876	Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7	AUC0-24hr is a measure of the mean concentration of drug in plasma after dosing to 24 hr post-dose. Plasma AUC0-24hr was calculated on Day 1 and Day 7 of MK-8876 dosing.
Maximum Plasma Concentration (Cmax) of MK-8876	Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7	Cmax is a measure of the maximum plasma concentration of drug post-dose. Plasma Cmax was determined on Day 1 and Day 7 of MK-8876 dosing.
Trough Plasma Concentration (C24hr) of MK-8876	24 hours post-dose on Days 1 and 7	C24hr is a measure of the plasma drug concentration 24 hours post-dose (i.e., trough concentration). Plasma C24hr was determined on Day 1 and Day 7 of MK-8876 dosing.
Time to Maximum Plasma Concentration (Tmax) of MK-8876	Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7	Tmax is a measure of time required to reach the maximum plasma drug concentration post-dose. Plasma Tmax was calculated on Day 1 and Day 7 of MK-8876 dosing.
Apparent Terminal Plasma Half-life (t½) of MK-8876	Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Day 7	t½ is the time required for the maximum plasma drug concentration to reduce by 50% post-dose. Plasma t½ was determined on Day 7 of MK-8876 dosing.

Participant flow

Participants by arm

Arm	Count
Panel A: HCV GT3 MK-8876 150 mg Participants infected with HCV GT3 received 150 mg MK-8876 q.d. by mouth for 7 days.	3
Panel B: HCV GT3 MK-8876 800 mg Participants infected with HCV GT3 received 800 mg MK-8876 q.d. by mouth for 7 days.	3
Panel E: HCV GT1a MK-8876 800 mg Participants infected with HCV GT1a received 800 mg MK-8876 q.d. by mouth for 7 days.	3
Total	9

Baseline characteristics

Characteristic	Panel A: HCV GT3 MK-8876 150 mg	Panel B: HCV GT3 MK-8876 800 mg	Panel E: HCV GT1a MK-8876 800 mg	Total
Age, Continuous	32 Years STANDARD_DEVIATION 2.6	45 Years STANDARD_DEVIATION 12.5	49.7 Years STANDARD_DEVIATION 7.4	42.2 Years STANDARD_DEVIATION 10.8
Sex: Female, Male Female	0 Participants	0 Participants	0 Participants	0 Participants
Sex: Female, Male Male	3 Participants	3 Participants	3 Participants	9 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	1 / 3	2 / 6
serious Total, serious adverse events	0 / 3	0 / 6

Outcome results

Primary

Mean Change From Baseline in HCV Viral Load

The mean change (log10) in HCV ribonucleic acid (RNA) from baseline to Day 7 was determined for each panel of participants.

Time frame: Baseline and Day 7