HIV-1 Infection
Conditions
Brief summary
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and anti-retroviral activity of MK-8558 monotherapy in anti-retroviral-naïve human immunodeficiency virus type 1 (HIV-1) infected participants. The primary hypothesis is that at a dose that exhibits an acceptable safety and tolerability profile, MK-8558 has superior anti-retroviral activity compared to historical placebo data.
Interventions
DRUGMK-8558
Single dose of MK-8558 administered as a tablet at a dose up to 1600 mg.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Other than having HIV infection, is in good health based on medical history, physical examination, vital sign (VS) measurements, and laboratory safety tests, at the pre-study (screening) visit and/or prior to administration of the study drug * Is documented as being HIV-1 positive * Has a screening plasma HIV-1 ribonucleic acid (RNA) ≥ 2,500 copies/mL within 30 days prior to the treatment phase of this study * Has a screening plasma cluster of differentiation 4+ (CD4+) T-cell count of \>200/mm\^3 * Is antiretroviral therapy (ART)-naïve * Is willing to receive no other ART prior to Day 11 post-dose of the trial, unless the physician/Investigator believes that there is a strong indication to start ART before Day 11 * Has a Body Mass Index (BMI) ≤35 kg/m\^2 * Males must agree to abstinence, or barrier contraception plus partner contraception, unless confirmed to be azoospermic due to vasectomy or medical cause, for at least 35 days after the last dose of MK-8558 * Females must not be pregnant or breastfeeding, and must be a woman of nonchildbearing potential, or a woman of childbearing potential using highly effective birth control with low user dependency or who is abstinent on a long-term and persistent basis during the intervention period and at least 35 days after the last dose of study medication
Exclusion criteria
* Has acute (primary) HIV-1 infection * Has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic (with the exception of Gilbert's disease), immunological (outside of HIV-1 infection), renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases * Is mentally or legally incapacitated or has a history of a clinically significant psychiatric disorder (with the exception of situational depression) of the last 5 years * Has a history of cancer unless disease is adequately treated and deemed cured * Has an estimated creatinine clearance (CrCl) ≤ 90 mL/min * Has a history of significant multiple and/or severe allergies, or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food, or has hereditary galactose intolerance, lactase deficiency, or glucose-galactose malabsorption * Is positive for hepatitis B surface antigen * Has a history of chronic hepatitis C unless there has been documented cure * Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the pre-study (screening) visit * Is unable to refrain from or anticipates the use of any medication, including prescription and nonprescription drugs or herbal remedies beginning approximately 2 weeks (or 5 half-lives) prior to administration of the initial dose of study drug, throughout the study, until the post-study visit. There may be certain medications that are permitted * Has participated in another investigational study within 4 weeks (or 5 half-lives, whichever is greater) prior to the pre-study (screening) visit. The window will be derived from the date of the last visit in the previous study * Is under the age of legal consent or not capable of giving consent * Has been committed to an institution by way of official or judicial order * Is an excessive smoker (i.e., more than 10 cigarettes/day) and is unwilling to restrict smoking to ≤10 cigarettes per day * Consumes more than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer \[354 mL/12 ounces\], wine \[118 mL/4 ounces\], or distilled spirits \[29.5 mL/1 ounce\]) per day. Participants who consume 4 glasses of alcoholic beverages per day may be enrolled at the discretion of the investigator * Consumes excessive amounts, defined as more than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, energy drinks, or other caffeinated beverages per day * Has a positive urine drug screen (except for cannabis) at screening and/or pre-dose; rechecks are allowed
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Plasma HIV-1 Ribonucleic Acid (RNA) Concentration | Baseline and 168 hours post-dose | Plasma was collected at baseline and at 168 hours post-dose to determine the change from baseline in HIV-1 ribonucleic acid (RNA) concentration. The log10 plasma HIV-RNA was measured and analyzed based on a longitudinal data analysis (LDA) model containing fixed effects for dose level and time. |
| Number of Participants Experiencing ≥1 Adverse Event (AE) | Up to 35 days post-dose | An Adverse Event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. |
| Number of Participants Who Discontinued From the Study Due to an AE | Up to 35 days post-dose | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Concentration (Cmax) for MK-8558 in Plasma | Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose | Plasma was collected from pre-dose up to 504 hours post-dose in order to determine the Cmax for MK-8558. Data were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. |
| Time to Maximum Observed Concentration (Tmax) for MK-8558 in Plasma | Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose | Plasma was collected from pre-dose up to 504 hours post-dose in order to determine the Tmax for MK-8558. Data were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. |
| Concentration at 168 Hours Post-Dose (C168hr) for MK-8558 in Plasma | 168 hours post-dose | Plasma was collected at 168 hours post-dose in order to determine the C168hr for MK-8558. Data were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. |
| Area Under the Concentration-Time Curve From 0 to 168 Hours (AUC0-168) for MK-8558 in Plasma | Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168 hours post-dose | Plasma was collected from pre-dose up to 168 hours post-dose in order to determine the AUC0-168 for MK-8558. Data were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. |
| Apparent Volume of Distribution (Vz/F) for MK-8558 | Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose | Plasma was collected from pre-dose up to 504 hours post-dose in order to determine the Vz/F for MK-8558. Data were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. |
| Terminal Half Life (t1/2) for MK-8558 | Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose | Plasma was collected from pre-dose up to 504 hours post-dose in order to determine the t1/2 for MK-8558. Data were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. |
| Apparent Clearance (CL/F) for MK-8558 | Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose | Plasma was collected from pre-dose up to 504 hours post-dose in order to determine the CL/F for MK-8558. Data were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. |
| Area Under the Concentration-Time Curve From 0 up to the Last Quantifiable Time-Point (AUC0-last) for MK-8558 in Plasma | Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose | Plasma was collected from pre-dose up to 504 hours post-dose in order to determine the AUC0-last for MK-8558. Data were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. |
| Area Under the Concentration-Time Curve From 0 to Infinity (AUC0-inf) for MK-8558 in Plasma | Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose | Plasma was collected from pre-dose up to 504 hours post-dose in order to determine the AUC0-inf for MK-8558. Data were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. |
Countries
Germany, Romania
Participant flow
Recruitment details
Participants with Human Immunodeficiency Virus Type 1 (HIV-1) infection, who were naïve to anti-retroviral therapy (ART) between 18 and 60 years old (inclusive) were enrolled in this study.
Participants by arm
| Arm | Count |
|---|---|
| MK-8558 400 mg Single oral dose of MK-8558 administered at 400 mg following a 10-hour fast. | 5 |
| MK-8558 900 mg Single oral dose of MK-8558 administered at 900 mg following a 10-hour fast. | 6 |
| MK-8558 1600 mg Single oral dose of MK-8558 administered at 1600 mg following a 10-hour fast. | 6 |
| MK-8558 900 mg Low-Fat Single oral dose of MK-8558 administered at 900 mg following a low-fat meal. | 4 |
| Total | 21 |
Baseline characteristics
| Characteristic | MK-8558 400 mg | MK-8558 900 mg | MK-8558 1600 mg | MK-8558 900 mg Low-Fat | Total |
|---|---|---|---|---|---|
| Age, Continuous | 29.2 Years STANDARD_DEVIATION 5 | 39.3 Years STANDARD_DEVIATION 12.6 | 32.5 Years STANDARD_DEVIATION 9.8 | 32.3 Years STANDARD_DEVIATION 18.6 | 33.6 Years STANDARD_DEVIATION 11.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 6 Participants | 4 Participants | 4 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 5 Participants | 5 Participants | 4 Participants | 19 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 5 Participants | 6 Participants | 6 Participants | 4 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 6 | 0 / 6 | 0 / 4 |
| other Total, other adverse events | 4 / 5 | 3 / 6 | 4 / 6 | 0 / 4 |
| serious Total, serious adverse events | 1 / 5 | 0 / 6 | 1 / 6 | 0 / 4 |
Outcome results
Primary
Change From Baseline in Plasma HIV-1 Ribonucleic Acid (RNA) Concentration
Plasma was collected at baseline and at 168 hours post-dose to determine the change from baseline in HIV-1 ribonucleic acid (RNA) concentration. The log10 plasma HIV-RNA was measured and analyzed based on a longitudinal data analysis (LDA) model containing fixed effects for dose level and time.
Time frame: Baseline and 168 hours post-dose
Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. One participant from the 900 mg treatment group was excluded from analysis due to important protocol deviation.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-8558 400 mg | Change From Baseline in Plasma HIV-1 Ribonucleic Acid (RNA) Concentration | -0.82 log10 copies/mL |
| MK-8558 900 mg | Change From Baseline in Plasma HIV-1 Ribonucleic Acid (RNA) Concentration | -1.00 log10 copies/mL |
| MK-8558 1600 mg | Change From Baseline in Plasma HIV-1 Ribonucleic Acid (RNA) Concentration | -1.61 log10 copies/mL |
| MK-8558 900 mg Low-Fat | Change From Baseline in Plasma HIV-1 Ribonucleic Acid (RNA) Concentration | -1.81 log10 copies/mL |
Comparison: It was hypothesized that the true mean difference in the plasma HIV-1 RNA reduction from baseline between MK-8558 and placebo is ≥ 1.4 log10 copies/mL.
Comparison: It was hypothesized that the true mean difference in the plasma HIV-1 RNA reduction from baseline between MK-8558 and placebo is ≥ 1.4 log10 copies/mL.
Comparison: It was hypothesized that the true mean difference in the plasma HIV-1 RNA reduction from baseline between MK-8558 and placebo is ≥ 1.4 log10 copies/mL.
Comparison: It was hypothesized that the true mean difference in the plasma HIV-1 RNA reduction from baseline between MK-8558 and placebo is ≥ 1.4 log10 copies/mL.
Primary
Number of Participants Experiencing ≥1 Adverse Event (AE)
An Adverse Event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Time frame: Up to 35 days post-dose
Population: All participants who received at least one dose of treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MK-8558 400 mg | Number of Participants Experiencing ≥1 Adverse Event (AE) | 4 Participants |
| MK-8558 900 mg | Number of Participants Experiencing ≥1 Adverse Event (AE) | 3 Participants |
| MK-8558 1600 mg | Number of Participants Experiencing ≥1 Adverse Event (AE) | 4 Participants |
| MK-8558 900 mg Low-Fat | Number of Participants Experiencing ≥1 Adverse Event (AE) | 0 Participants |
Primary
Number of Participants Who Discontinued From the Study Due to an AE
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Time frame: Up to 35 days post-dose
Population: All participants who received at least one dose of treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MK-8558 400 mg | Number of Participants Who Discontinued From the Study Due to an AE | 0 Participants |
| MK-8558 900 mg | Number of Participants Who Discontinued From the Study Due to an AE | 0 Participants |
| MK-8558 1600 mg | Number of Participants Who Discontinued From the Study Due to an AE | 0 Participants |
| MK-8558 900 mg Low-Fat | Number of Participants Who Discontinued From the Study Due to an AE | 0 Participants |
Secondary
Apparent Clearance (CL/F) for MK-8558
Plasma was collected from pre-dose up to 504 hours post-dose in order to determine the CL/F for MK-8558. Data were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level.
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose
Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. One participant from the 900 mg treatment group was excluded from analysis due to important protocol deviation.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MK-8558 400 mg | Apparent Clearance (CL/F) for MK-8558 | 0.315 L/hr | Geometric Coefficient of Variation 37.3 |
| MK-8558 900 mg | Apparent Clearance (CL/F) for MK-8558 | 0.412 L/hr | Geometric Coefficient of Variation 14.7 |
| MK-8558 1600 mg | Apparent Clearance (CL/F) for MK-8558 | 0.321 L/hr | Geometric Coefficient of Variation 48.9 |
| MK-8558 900 mg Low-Fat | Apparent Clearance (CL/F) for MK-8558 | 0.211 L/hr | Geometric Coefficient of Variation 9.8 |
Secondary
Apparent Volume of Distribution (Vz/F) for MK-8558
Plasma was collected from pre-dose up to 504 hours post-dose in order to determine the Vz/F for MK-8558. Data were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level.
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose
Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. One participant from the 900 mg treatment group was excluded from analysis due to important protocol deviation.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MK-8558 400 mg | Apparent Volume of Distribution (Vz/F) for MK-8558 | 56.6 Liters | Geometric Coefficient of Variation 21.9 |
| MK-8558 900 mg | Apparent Volume of Distribution (Vz/F) for MK-8558 | 84.4 Liters | Geometric Coefficient of Variation 27.5 |
| MK-8558 1600 mg | Apparent Volume of Distribution (Vz/F) for MK-8558 | 79.9 Liters | Geometric Coefficient of Variation 30.8 |
| MK-8558 900 mg Low-Fat | Apparent Volume of Distribution (Vz/F) for MK-8558 | 45.6 Liters | Geometric Coefficient of Variation 20.5 |
Secondary
Area Under the Concentration-Time Curve From 0 to 168 Hours (AUC0-168) for MK-8558 in Plasma
Plasma was collected from pre-dose up to 168 hours post-dose in order to determine the AUC0-168 for MK-8558. Data were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level.
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168 hours post-dose
Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. One participant from the 900 mg treatment group was excluded from analysis due to important protocol deviation.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MK-8558 400 mg | Area Under the Concentration-Time Curve From 0 to 168 Hours (AUC0-168) for MK-8558 in Plasma | 1740 hr*μM | Geometric Coefficient of Variation 24.2 |
| MK-8558 900 mg | Area Under the Concentration-Time Curve From 0 to 168 Hours (AUC0-168) for MK-8558 in Plasma | 2780 hr*μM | Geometric Coefficient of Variation 20.7 |
| MK-8558 1600 mg | Area Under the Concentration-Time Curve From 0 to 168 Hours (AUC0-168) for MK-8558 in Plasma | 5740 hr*μM | Geometric Coefficient of Variation 36.3 |
| MK-8558 900 mg Low-Fat | Area Under the Concentration-Time Curve From 0 to 168 Hours (AUC0-168) for MK-8558 in Plasma | 5340 hr*μM | Geometric Coefficient of Variation 15.6 |
Secondary
Area Under the Concentration-Time Curve From 0 to Infinity (AUC0-inf) for MK-8558 in Plasma
Plasma was collected from pre-dose up to 504 hours post-dose in order to determine the AUC0-inf for MK-8558. Data were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level.
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose
Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. One participant from the 900 mg treatment group was excluded from analysis due to important protocol deviation.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MK-8558 400 mg | Area Under the Concentration-Time Curve From 0 to Infinity (AUC0-inf) for MK-8558 in Plasma | 2840 hr*μM | Geometric Coefficient of Variation 37.3 |
| MK-8558 900 mg | Area Under the Concentration-Time Curve From 0 to Infinity (AUC0-inf) for MK-8558 in Plasma | 4870 hr*μM | Geometric Coefficient of Variation 14.7 |
| MK-8558 1600 mg | Area Under the Concentration-Time Curve From 0 to Infinity (AUC0-inf) for MK-8558 in Plasma | 11100 hr*μM | Geometric Coefficient of Variation 48.9 |
| MK-8558 900 mg Low-Fat | Area Under the Concentration-Time Curve From 0 to Infinity (AUC0-inf) for MK-8558 in Plasma | 9520 hr*μM | Geometric Coefficient of Variation 9.8 |
Secondary
Area Under the Concentration-Time Curve From 0 up to the Last Quantifiable Time-Point (AUC0-last) for MK-8558 in Plasma
Plasma was collected from pre-dose up to 504 hours post-dose in order to determine the AUC0-last for MK-8558. Data were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level.
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose
Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. One participant from the 900 mg treatment group was excluded from analysis due to important protocol deviation.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MK-8558 400 mg | Area Under the Concentration-Time Curve From 0 up to the Last Quantifiable Time-Point (AUC0-last) for MK-8558 in Plasma | 2650 hr*μM | Geometric Coefficient of Variation 32.9 |
| MK-8558 900 mg | Area Under the Concentration-Time Curve From 0 up to the Last Quantifiable Time-Point (AUC0-last) for MK-8558 in Plasma | 4450 hr*μM | Geometric Coefficient of Variation 16.2 |
| MK-8558 1600 mg | Area Under the Concentration-Time Curve From 0 up to the Last Quantifiable Time-Point (AUC0-last) for MK-8558 in Plasma | 9680 hr*μM | Geometric Coefficient of Variation 42.6 |
| MK-8558 900 mg Low-Fat | Area Under the Concentration-Time Curve From 0 up to the Last Quantifiable Time-Point (AUC0-last) for MK-8558 in Plasma | 8580 hr*μM | Geometric Coefficient of Variation 9.6 |
Secondary
Concentration at 168 Hours Post-Dose (C168hr) for MK-8558 in Plasma
Plasma was collected at 168 hours post-dose in order to determine the C168hr for MK-8558. Data were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level.
Time frame: 168 hours post-dose
Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. One participant from the 900 mg treatment group was excluded from analysis due to important protocol deviation.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MK-8558 400 mg | Concentration at 168 Hours Post-Dose (C168hr) for MK-8558 in Plasma | 5.59 μM | Geometric Coefficient of Variation 44 |
| MK-8558 900 mg | Concentration at 168 Hours Post-Dose (C168hr) for MK-8558 in Plasma | 9.55 μM | Geometric Coefficient of Variation 17.7 |
| MK-8558 1600 mg | Concentration at 168 Hours Post-Dose (C168hr) for MK-8558 in Plasma | 20.5 μM | Geometric Coefficient of Variation 43.4 |
| MK-8558 900 mg Low-Fat | Concentration at 168 Hours Post-Dose (C168hr) for MK-8558 in Plasma | 18.8 μM | Geometric Coefficient of Variation 8.1 |
Comparison: The posterior probability (PP) that the true GM C168hr is ≥ 9.0 μM was calculated using a non-informative (Jeffrey's) prior under an assumption of normality of log C168hr.
Comparison: The PP that the true GM C168hr is ≥ 9.0 μM was calculated using a non-informative (Jeffrey's) prior under an assumption of normality of log C168hr.
Comparison: The PP that the true GM C168hr is ≥ 9.0 μM was calculated using a non-informative (Jeffrey's) prior under an assumption of normality of log C168hr.
Comparison: The PP that the true GM C168hr is ≥ 9.0 μM was calculated using a non-informative (Jeffrey's) prior under an assumption of normality of log C168hr.
Secondary
Maximum Observed Concentration (Cmax) for MK-8558 in Plasma
Plasma was collected from pre-dose up to 504 hours post-dose in order to determine the Cmax for MK-8558. Data were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level.
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose
Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. One participant from the 900 mg treatment group was excluded from analysis due to important protocol deviation.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MK-8558 400 mg | Maximum Observed Concentration (Cmax) for MK-8558 in Plasma | 24.3 μM | Geometric Coefficient of Variation 21.7 |
| MK-8558 900 mg | Maximum Observed Concentration (Cmax) for MK-8558 in Plasma | 36.7 μM | Geometric Coefficient of Variation 28.9 |
| MK-8558 1600 mg | Maximum Observed Concentration (Cmax) for MK-8558 in Plasma | 77.2 μM | Geometric Coefficient of Variation 28.9 |
| MK-8558 900 mg Low-Fat | Maximum Observed Concentration (Cmax) for MK-8558 in Plasma | 72.6 μM | Geometric Coefficient of Variation 14.3 |
Secondary
Terminal Half Life (t1/2) for MK-8558
Plasma was collected from pre-dose up to 504 hours post-dose in order to determine the t1/2 for MK-8558. Data were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level.
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose
Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. One participant from the 900 mg treatment group was excluded from analysis due to important protocol deviation.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MK-8558 400 mg | Terminal Half Life (t1/2) for MK-8558 | 125 Hours | Geometric Coefficient of Variation 24.9 |
| MK-8558 900 mg | Terminal Half Life (t1/2) for MK-8558 | 142 Hours | Geometric Coefficient of Variation 20.1 |
| MK-8558 1600 mg | Terminal Half Life (t1/2) for MK-8558 | 173 Hours | Geometric Coefficient of Variation 22.7 |
| MK-8558 900 mg Low-Fat | Terminal Half Life (t1/2) for MK-8558 | 150 Hours | Geometric Coefficient of Variation 20.6 |
Secondary
Time to Maximum Observed Concentration (Tmax) for MK-8558 in Plasma
Plasma was collected from pre-dose up to 504 hours post-dose in order to determine the Tmax for MK-8558. Data were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level.
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose
Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. One participant from the 900 mg treatment group was excluded from analysis due to important protocol deviation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MK-8558 400 mg | Time to Maximum Observed Concentration (Tmax) for MK-8558 in Plasma | 4.00 Hours |
| MK-8558 900 mg | Time to Maximum Observed Concentration (Tmax) for MK-8558 in Plasma | 4.00 Hours |
| MK-8558 1600 mg | Time to Maximum Observed Concentration (Tmax) for MK-8558 in Plasma | 4.50 Hours |
| MK-8558 900 mg Low-Fat | Time to Maximum Observed Concentration (Tmax) for MK-8558 in Plasma | 4.02 Hours |