Hepatitis C
Conditions
Brief summary
The purpose of this study is to evaluate the safety and pharmacokinetics of MK-1075, and to determine the ability of MK-1075 to reduce HCV viral load, following administration of a single dose in HCV-infected participants.
Detailed description
Per protocol, panels may be omitted if the objectives of the study are met in preceding panels.
Interventions
DRUGMK-1075
MK-1075 supplied as 10 mg or 100 mg tablets for oral administration.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
In each panel (A, B, C, and D), participants will receive a single dose of MK-1075 (100, 200, 400, and 800 mg, respectively) in a fasted state. Safety and viral load (VL) data from the previous panel will be assessed before dosing the subsequent panel.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male or female of non-child bearing potential * In good health other than HCV genotype (GT) 1 infection
Exclusion criteria
* Is mentally incapacitated or legally institutionalized * Has a history of clinically significant and not stably controlled endocrine, gastrointestinal, cardiovascular, hematological, hepatic (excepting HCV infection), immunological, renal, respiratory, genitourinary or major neurological (including stroke and chronic seizures) abnormalities or diseases * Has a history of cancer * Is positive for hepatitis B surface antigen (HBsAg) or human immunodeficiency virus (HIV) * Has participated in another investigational trial within 4 weeks (or 5 half-lives) prior to Screening * Consumes \>2 alcoholic beverages a day or uses illegal drugs * 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 clinical or laboratory evidence of advanced or decompensated liver disease, evidence of bridging fibrosis or higher grade fibrosis (Metavir score ≥3) from prior liver biopsy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Experiencing an Adverse Event (AE) | Up to Study Day 14 | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), 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 pre-existing condition that was temporally associated with the use of the Sponsor's product, was also an AE. The percentage of participants that experienced an AE was reported for each treatment panel. |
| Percentage of Participants Who Discontinued Study Due to an AE | Up to Study Day 14 | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), 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 pre-existing condition that was temporally associated with the use of the Sponsor's product, was also an AE. The percentage of participants that discontinued the study due to an AE was reported for each treatment panel. |
| Maximum HCV Viral Load (VL) Change From Baseline Over Time Following Single-Dose MK-1075 | Pre-dose (baseline), 2, 4, 8, 12, 16, 24, 32, 48, 72, and 120 hours post-dose | For assessment of antiviral activity of MK-1075 at each study dose, baseline and post-dose HCV ribonucleic acid (RNA) (log10) were measured at pre-dose and 2, 4, 8, 12, 16, 24, 32, 48, 72, and 120 hours post-dose. For each participant, baseline measurement was defined as the measurement obtained pre-dose on the first day of dosing. The estimated change from baseline in HCV RNA VL (log10) was calculated for each participant by time point after each single dose, and the maximum change (reduction) in HCV RNA was determined and reported for each treatment arm using an Analysis of Variance (ANOVA) model. |
Participant flow
Pre-assignment details
Nine participants were enrolled and allocated to single doses of either 100, 200, or 400 mg of MK-1075. As per the protocol, planned Panel D (800 mg MK-1075) was not enrolled since the study objective was achieved in Panel C.
Participants by arm
| Arm | Count |
|---|---|
| MK-1075 100 mg (Panel A) HCV-infected participants receive a single 100 mg dose of MK-1075. | 3 |
| MK-1075 200 mg (Panel B) HCV-infected participants receive a single 200 mg dose of MK-1075. | 3 |
| MK-1075 400 mg (Panel C) HCV-infected participants receive a single 400 mg dose of MK-1075. | 3 |
| Total | 9 |
Baseline characteristics
| Characteristic | MK-1075 100 mg (Panel A) | MK-1075 200 mg (Panel B) | MK-1075 400 mg (Panel C) | Total |
|---|---|---|---|---|
| Age, Continuous | 48.7 years STANDARD_DEVIATION 15.7 | 44.0 years STANDARD_DEVIATION 8 | 49.7 years STANDARD_DEVIATION 2.5 | 47.4 years STANDARD_DEVIATION 9.3 |
| Sex: Female, Male Female | 2 Participants | 0 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 2 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 3 |
| other Total, other adverse events | 2 / 3 | 2 / 3 | 1 / 3 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 0 / 3 |
Outcome results
Primary
Maximum HCV Viral Load (VL) Change From Baseline Over Time Following Single-Dose MK-1075
For assessment of antiviral activity of MK-1075 at each study dose, baseline and post-dose HCV ribonucleic acid (RNA) (log10) were measured at pre-dose and 2, 4, 8, 12, 16, 24, 32, 48, 72, and 120 hours post-dose. For each participant, baseline measurement was defined as the measurement obtained pre-dose on the first day of dosing. The estimated change from baseline in HCV RNA VL (log10) was calculated for each participant by time point after each single dose, and the maximum change (reduction) in HCV RNA was determined and reported for each treatment arm using an Analysis of Variance (ANOVA) model.
Time frame: Pre-dose (baseline), 2, 4, 8, 12, 16, 24, 32, 48, 72, and 120 hours post-dose
Population: Per Protocol (PP) Population: all participants who received at least 1 dose of study drug and who complied with the protocol
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MK-1075 100 mg (Panel A) | Maximum HCV Viral Load (VL) Change From Baseline Over Time Following Single-Dose MK-1075 | Baseline HCV RNA | 5.72 log(IU/ml) | Standard Error 0.016 |
| MK-1075 100 mg (Panel A) | Maximum HCV Viral Load (VL) Change From Baseline Over Time Following Single-Dose MK-1075 | Maximum HCV RNA Change | 0.673 log(IU/ml) | Standard Error 0.078 |
| MK-1075 200 mg (Panel B) | Maximum HCV Viral Load (VL) Change From Baseline Over Time Following Single-Dose MK-1075 | Baseline HCV RNA | 6.837 log(IU/ml) | Standard Error 0.145 |
| MK-1075 200 mg (Panel B) | Maximum HCV Viral Load (VL) Change From Baseline Over Time Following Single-Dose MK-1075 | Maximum HCV RNA Change | 1.15 log(IU/ml) | Standard Error 0.315 |
| MK-1075 400 mg (Panel C) | Maximum HCV Viral Load (VL) Change From Baseline Over Time Following Single-Dose MK-1075 | Baseline HCV RNA | 6.31 log(IU/ml) | Standard Error 0.336 |
| MK-1075 400 mg (Panel C) | Maximum HCV Viral Load (VL) Change From Baseline Over Time Following Single-Dose MK-1075 | Maximum HCV RNA Change | 1.593 log(IU/ml) | Standard Error 0.134 |
Primary
Percentage of Participants Experiencing an Adverse Event (AE)
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), 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 pre-existing condition that was temporally associated with the use of the Sponsor's product, was also an AE. The percentage of participants that experienced an AE was reported for each treatment panel.
Time frame: Up to Study Day 14
Population: All Participants as Treated (APaT): all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-1075 100 mg (Panel A) | Percentage of Participants Experiencing an Adverse Event (AE) | 66.7 Percentage of Participants |
| MK-1075 200 mg (Panel B) | Percentage of Participants Experiencing an Adverse Event (AE) | 66.7 Percentage of Participants |
| MK-1075 400 mg (Panel C) | Percentage of Participants Experiencing an Adverse Event (AE) | 33.3 Percentage of Participants |
Primary
Percentage of Participants Who Discontinued Study Due to an AE
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), 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 pre-existing condition that was temporally associated with the use of the Sponsor's product, was also an AE. The percentage of participants that discontinued the study due to an AE was reported for each treatment panel.
Time frame: Up to Study Day 14
Population: APaT: all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-1075 100 mg (Panel A) | Percentage of Participants Who Discontinued Study Due to an AE | 0 Percentage of Participants |
| MK-1075 200 mg (Panel B) | Percentage of Participants Who Discontinued Study Due to an AE | 0 Percentage of Participants |
| MK-1075 400 mg (Panel C) | Percentage of Participants Who Discontinued Study Due to an AE | 0 Percentage of Participants |