Safety, Pharmacokinetics, and Pharmacodynamics of MK-8876 in Participants With Hepatitis C Infection (MK-8876-003)
Primary Purpose
Hepatitis C
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
MK-8876
Sponsored by
About this trial
This is an interventional treatment trial for Hepatitis C
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Panel A: HCV GT3 MK-8876 150 mg
Panel B: HCV GT3 MK-8876 800 mg
Panel E: HCV GT1a MK-8876 800 mg
Arm Description
Participants infected with HCV GT3 received 150 mg MK-8876 once daily (q.d.) by mouth for 7 days.
Participants infected with HCV GT3 received 800 mg MK-8876 q.d. by mouth for 7 days.
Participants infected with HCV GT1a received 800 mg MK-8876 q.d. by mouth for 7 days.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (hr) Post-dose (AUC0-24 hr) of MK-8876
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
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
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
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
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.
Full Information
NCT ID
NCT01930058
First Posted
August 23, 2013
Last Updated
September 27, 2018
Sponsor
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT01930058
Brief Title
Safety, Pharmacokinetics, and Pharmacodynamics of MK-8876 in Participants With Hepatitis C Infection (MK-8876-003)
Official Title
A Multiple Dose Study to Evaluate Safety, Pharmacokinetics and Pharmacodynamics of MK-8876 in Hepatitis C Patients
Study Type
Interventional
2. Study Status
Record Verification Date
September 2018
Overall Recruitment Status
Completed
Study Start Date
October 2, 2013 (Actual)
Primary Completion Date
May 5, 2014 (Actual)
Study Completion Date
May 5, 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
9 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Panel A: HCV GT3 MK-8876 150 mg
Arm Type
Experimental
Arm Description
Participants infected with HCV GT3 received 150 mg MK-8876 once daily (q.d.) by mouth for 7 days.
Arm Title
Panel B: HCV GT3 MK-8876 800 mg
Arm Type
Experimental
Arm Description
Participants infected with HCV GT3 received 800 mg MK-8876 q.d. by mouth for 7 days.
Arm Title
Panel E: HCV GT1a MK-8876 800 mg
Arm Type
Experimental
Arm Description
Participants infected with HCV GT1a received 800 mg MK-8876 q.d. by mouth for 7 days.
Intervention Type
Drug
Intervention Name(s)
MK-8876
Intervention Description
MK-8876 10 mg or 100 mg tablets taken q.d. by mouth.
Primary Outcome Measure Information:
Title
Mean Change From Baseline in HCV Viral Load
Description
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
Secondary Outcome Measure Information:
Title
Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (hr) Post-dose (AUC0-24 hr) of MK-8876
Description
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.
Time Frame
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7
Title
Maximum Plasma Concentration (Cmax) of MK-8876
Description
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.
Time Frame
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7
Title
Trough Plasma Concentration (C24hr) of MK-8876
Description
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 Frame
24 hours post-dose on Days 1 and 7
Title
Time to Maximum Plasma Concentration (Tmax) of MK-8876
Description
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.
Time Frame
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7
Title
Apparent Terminal Plasma Half-life (t½) of MK-8876
Description
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.
Time Frame
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Day 7
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Available IPD and Supporting Information:
Available IPD/Information Type
CSR Synopsis
Available IPD/Information URL
http://www.merck.com/clinical-trials/study.html?id=8876-003&kw=8876-003
Learn more about this trial
Safety, Pharmacokinetics, and Pharmacodynamics of MK-8876 in Participants With Hepatitis C Infection (MK-8876-003)
We'll reach out to this number within 24 hrs