Human Immunodeficiency Virus, AIDS Virus
Conditions
Brief summary
This study will evaluate the anti-retroviral activity of MK-8527 in HIV-1 infected, ART-naïve participants. The primary hypothesis is that MK-8527 has superior anti-retroviral activity compared to placebo, as measured by change from baseline in plasma HIV-1 ribonucleic acid (RNA) at 168 hours postdose.
Detailed description
Up to five panels (Panels A-E) of 6 participants each will be enrolled in a sequential manner. In each panel, participants will receive a single dose of MK-8527 up to 50 mg. Historical data from previous single does studies will be used for placebo (control) comparisons.
Interventions
DRUGMK-8527
Single oral capsule
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
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 HIV infection, is in good health * Is documented HIV-1 positive * Diagnosed with HIV-1 infection ≥ 3 months prior to screening or perform the French 2008 Haute Autorité de Santé (HAS) Algorithm to confirm chronic HIV. * Is ART-naïve which is defined as having never received any antiretroviral agent or the following: ≤30 consecutive days of an investigational antiretroviral agent, excluding an Nucleoside reverse transcriptase inhibitors (NRTI), or ≤60 consecutive days of combination ART not including an NRTI * Has not received an investigational agent or marketed ART within 30 days of study drug administration * Is willing to receive no other ART for the monitoring period of the study * Has a Body Mass Index (BMI) ≤35 kg/m\^2, inclusive * If the male participant has a female partner(s) of childbearing potential, he must agree to use a medically acceptable method of contraception during the study and for 120 days after the last dose of study drug. If their partner is pregnant, males must agree to use a condom and no additional method of contraception is required for the pregnant partner * If the participant is a female with reproductive potential, she must demonstrate a serum β-human chorionic gonadotropin (β-hCG) level consistent with the nongravid state at the prestudy (screening) visit and agree to use (and/or have their partner use) 2 acceptable methods of birth control beginning at the prestudy (screening) visit, throughout the study (including washout intervals between treatment periods/panels) and until 28 days after the last dose of study drug. * If the participant is a postmenopausal female: she is without menses for at least 1 year and have a documented follicle stimulating hormone (FSH) level in the postmenopausal range at prestudy (screening) * If the participant is a surgically sterile female: she is status posthysterectomy, or oophorectomy
Exclusion criteria
* Has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological (outside of HIV-1 infection), renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases. Participants with a remote history of uncomplicated medical events (eg, uncomplicated kidney stones, as defined as spontaneous passage and no recurrence in the last 5 years, or childhood asthma) may be enrolled in the study at the discretion of the investigator. * Is mentally or legally incapacitated at the time of the prestudy (screening) visit or expected during the conduct of the study or has a history of clinically significant psychiatric disorder over the last 5 years. Participants who have had situational depression may be enrolled in the study at the discretion of the investigator. * History of cancer (malignancy) * History of significant multiple and/or severe allergies or has had an anaphylactic reaction or significant intolerability (i.e. systemic allergic reaction) to prescription or non-prescription drugs or food. * Positive for hepatitis B surface antigen * History of chronic hepatitis C unless there has been documented cure and/or participant with a positive serologic test for hepatitis C virus (HCV) has a negative HCV viral load (VL) * Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks * 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 poststudy visit. * Participated in another investigational study within 4 weeks * Consumes greater 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. * Consumes excessive amounts, defined as greater than 6 servings (1 serving approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, energy drinks, or other caffeinated beverages per day * Is an excessive smoker (i.e., more than 10 cigarettes/day) and is unwilling to restrict smoking to ≤10 cigarettes per day * Has a positive urine drug screen
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Plasma HIV-1 RNA | Baseline and 168 hours postdose | Blood samples were taken to determine HIV-1 RNA levels at Predose (baseline) and 168 hours postdose. Data were fitted with a longitudinal data analysis (LDA) model containing fixed effects for treatment, time and treatment by time interaction, and a random effect for participant.The change from baseline in plasma HIV-1 RNA in participants administered MK-8527 was calculated and results were compared with historical placebo data. |
| Percentage of Participants Who Report 1 or More Adverse Events (AEs) | Up to 28 days | An AE is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not it is considered related to the medicinal product. The percentage of participants that reported at least 1 AE will be summarized. |
| Percentage of Participants Who Were Discontinued From the Study Due to an AE | Up to 28 days | An AE is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not it is considered related to the medicinal product. The percentage of participants that were discontinued from the study due to an AE will be summarized. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Concentration (Cmax) of MK-8527-TP in PBMC | Predose and 4, 12, 24, 96, 120, 144, 168, 240, 336, 504, 672 hours or 28 days postdose | Blood samples were taken at Predose, up to approximately 28 days postdose to determine the Cmax of MK-8527-TP in PBMCs. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution. |
| Time to Cmax (Tmax) of MK-8527-TP in PBMC | Predose and 4, 12, 24, 96, 120, 144, 168, 240, 336, 504, 672 hours or 28 days postdose | Blood samples were taken at Predose, up to approximately 28 days postdose to determine the Tmax of MK-8527-TP in PBMCs. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution. |
| Concentration at 168 Hours (C168) of MK-8527-TP in PBMC | 168 hours postdose for each panel | Blood samples were taken at 168 hours postdose to determine the C168 of MK-8527-TP in PBMCs. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution. |
| Apparent Terminal Half Life (t1/2) of MK-8527-TP in PBMC | Predose and 4, 12, 24, 96, 120, 144, 168, 240, 336, 504, 672 hours or 28 days postdose | Blood samples were taken at Predose, up to approximately 28 days postdose to determine the t1/2 of MK-8527-TP in PBMCs. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution. |
| Area Under the Concentration Time Curve From Hour 0 to 168 Hours (AUC0-168) of MK-8527 in Plasma | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 168 hours postdose | Blood samples were taken at Predose, up to 168 hours postdose to determine the AUC0-168 of MK-8527 in plasma. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution. |
| Area Under the Concentration Time Curve From Hour 0 to 168 Hours (AUC0-168) of MK-8527-TP in Peripheral Blood Mononuclear Cells (PBMC) | Predose and 4, 12, 24, 96, 120, 144, and 168 hours postdose | Blood samples were taken at Predose, up to 168 hours postdose to determine the AUC0-168 of MK-8527-triphosphate (MK-8527-TP) in PBMCs. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% confidence intervals (CI) for the means were constructed on the natural log scale and referenced the t-distribution. |
| Area Under the Concentration Time Curve From Hour 0 to Infinity (AUC0-inf) of MK-8527 in Plasma | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 168 hours postdose | Blood samples were taken at Predose, up to 168 hours postdose to determine the AUC0-inf of MK-8527 in plasma. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution. |
| Maximum Concentration (Cmax) of MK-8527 in Plasma | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 168 hours postdose | Blood samples were taken at Predose, up to 168 hours postdose to determine the Cmax of MK-8527 in plasma. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution. |
| Time to Cmax (Tmax) of MK-8527 in Plasma | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 168 hours postdose | Blood samples were taken at Predose, up to 168 hours postdose to determine the Tmax of MK-8527 in plasma. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution. |
| Concentration at 168 Hours (C168) of MK-8527 in Plasma | 168 hours postdose | Blood samples were taken at 168 hours postdose to determine the C168 of MK-8527 in plasma. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution. |
| Apparent Terminal Half Life (t1/2) of MK-8527 in Plasma | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 168 hours postdose | Blood samples were taken at Predose, up to 168 hours postdose to determine the t1/2 of MK-8527 in plasma. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution. |
| Area Under the Concentration Time Curve From Hour 0 to Last (AUC0-last) of MK-8527 in Plasma | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 168 hours postdose | Blood samples were taken at Predose, up to 168 hours postdose to determine the AUC0-last of MK-8527 in plasma. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution. |
| Area Under the Concentration Time Curve From Hour 0 to Last (AUC0-last) of MK-8527-TP in PBMC | Predose and 4, 12, 24, 96, 120, 144, 168, 240, 336, 504, 672 hours or 28 days postdose | Blood samples were taken at Predose, up to approximately 28 days postdose to determine the AUC0-last of MK-8527-TP in PBMCs. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution. |
| Area Under the Concentration Time Curve From Hour 0 to Infinity (AUC0-inf) of MK-8527-TP in PBMC | Predose and 4, 12, 24, 96, 120, 144, 168, 240, 336, 504, 672 hours or 28 days postdose | Blood samples were taken at Predose, up to approximately 28 days postdose to determine the AUC0-Inf of MK-8527-TP in PBMCs. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution. |
Countries
Romania
Participant flow
Recruitment details
Anti-retroviral therapy (ART)-naïve, participants with human immunodeficiency type 1 virus (HIV-1) infection were enrolled in this study.
Participants by arm
| Arm | Count |
|---|---|
| Panel A: MK-8527 10 mg Single oral dose of 10 mg MK-8527 in capsule form after an 8-hour fast | 6 |
| Panel B: MK-8527 3 mg Single oral dose of 3 mg MK-8527 in capsule form after an 8-hour fast | 6 |
| Panel C: MK-8527 1 mg Single oral dose of 1 mg MK-8527 in capsule form after an 8-hour fast | 5 |
| Panel D: ≤50 mg MK-8527 Single oral dose of ≤50 mg MK-8527 capsule after an 8-hour fast. Dose level determined by results of previous panels. | 0 |
| Panel E: ≤50 mg MK-8527 Single oral dose of ≤50 mg MK-8527 capsule after an 8-hour fast. Dose level determined by results of previous panels. | 0 |
| Total | 17 |
Baseline characteristics
| Characteristic | Panel A: MK-8527 10 mg | Panel B: MK-8527 3 mg | Panel C: MK-8527 1 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 28.8 Years STANDARD_DEVIATION 2.3 | 33.3 Years STANDARD_DEVIATION 9 | 31.2 Years STANDARD_DEVIATION 5.6 | 31.1 Years STANDARD_DEVIATION 6.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 6 Participants | 5 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 6 Participants | 5 Participants | 17 Participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Sex: Female, Male Male | 4 Participants | 5 Participants | 5 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 5 |
| other Total, other adverse events | 0 / 6 | 2 / 6 | 0 / 5 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 5 |
Outcome results
Primary
Change From Baseline in Plasma HIV-1 RNA
Blood samples were taken to determine HIV-1 RNA levels at Predose (baseline) and 168 hours postdose. Data were fitted with a longitudinal data analysis (LDA) model containing fixed effects for treatment, time and treatment by time interaction, and a random effect for participant.The change from baseline in plasma HIV-1 RNA in participants administered MK-8527 was calculated and results were compared with historical placebo data.
Time frame: Baseline and 168 hours postdose
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. Participants from Panels D and E were not analyzed because they were not enrolled in the study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Panel A: MK-8527 10 mg | Change From Baseline in Plasma HIV-1 RNA | -1.39 log10 copies/mL |
| Panel B: MK-8527 3 mg | Change From Baseline in Plasma HIV-1 RNA | -1.66 log10 copies/mL |
| Panel C: MK-8527 1 mg | Change From Baseline in Plasma HIV-1 RNA | -0.95 log10 copies/mL |
Comparison: It was hypothesized that the true mean difference in the plasma HIV-1 RNA reduction from baseline between MK- 8527 and placebo is at least 1.0 log10 copies/mL.
Comparison: It was hypothesized that the true mean difference in the plasma HIV-1 RNA reduction from baseline between MK- 8527 and placebo is at least 1.0 log10 copies/mL.
Comparison: It was hypothesized that the true mean difference in the plasma HIV-1 RNA reduction from baseline between MK- 8527 and placebo is at least 1.0 log10 copies/mL.
Primary
Percentage of Participants Who Report 1 or More Adverse Events (AEs)
An AE is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not it is considered related to the medicinal product. The percentage of participants that reported at least 1 AE will be summarized.
Time frame: Up to 28 days
Population: Participants who received at least one dose of the investigational drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panel A: MK-8527 10 mg | Percentage of Participants Who Report 1 or More Adverse Events (AEs) | 0 Percentage of participants |
| Panel B: MK-8527 3 mg | Percentage of Participants Who Report 1 or More Adverse Events (AEs) | 33.3 Percentage of participants |
| Panel C: MK-8527 1 mg | Percentage of Participants Who Report 1 or More Adverse Events (AEs) | 0 Percentage of participants |
Primary
Percentage of Participants Who Were Discontinued From the Study Due to an AE
An AE is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not it is considered related to the medicinal product. The percentage of participants that were discontinued from the study due to an AE will be summarized.
Time frame: Up to 28 days
Population: Participants who received at least one dose of the investigational drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panel A: MK-8527 10 mg | Percentage of Participants Who Were Discontinued From the Study Due to an AE | 0 Percentage of participants |
| Panel B: MK-8527 3 mg | Percentage of Participants Who Were Discontinued From the Study Due to an AE | 0 Percentage of participants |
| Panel C: MK-8527 1 mg | Percentage of Participants Who Were Discontinued From the Study Due to an AE | 0 Percentage of participants |
Secondary
Apparent Terminal Half Life (t1/2) of MK-8527 in Plasma
Blood samples were taken at Predose, up to 168 hours postdose to determine the t1/2 of MK-8527 in plasma. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 168 hours postdose
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. The 1 mg MK-8527 arm had insufficient data for four participants. Participants from Panels D and E were not analyzed because they were not enrolled in the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: MK-8527 10 mg | Apparent Terminal Half Life (t1/2) of MK-8527 in Plasma | 40.31 Hours | Geometric Coefficient of Variation 60.27 |
| Panel B: MK-8527 3 mg | Apparent Terminal Half Life (t1/2) of MK-8527 in Plasma | 12.36 Hours | Geometric Coefficient of Variation 78.23 |
| Panel C: MK-8527 1 mg | Apparent Terminal Half Life (t1/2) of MK-8527 in Plasma | NA Hours | — |
Secondary
Apparent Terminal Half Life (t1/2) of MK-8527-TP in PBMC
Blood samples were taken at Predose, up to approximately 28 days postdose to determine the t1/2 of MK-8527-TP in PBMCs. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.
Time frame: Predose and 4, 12, 24, 96, 120, 144, 168, 240, 336, 504, 672 hours or 28 days postdose
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. Participants from Panels D and E were not analyzed because they were not enrolled in the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: MK-8527 10 mg | Apparent Terminal Half Life (t1/2) of MK-8527-TP in PBMC | 117.84 Hours | Geometric Coefficient of Variation 35 |
| Panel B: MK-8527 3 mg | Apparent Terminal Half Life (t1/2) of MK-8527-TP in PBMC | 188.66 Hours | Geometric Coefficient of Variation 122.5 |
| Panel C: MK-8527 1 mg | Apparent Terminal Half Life (t1/2) of MK-8527-TP in PBMC | 210.93 Hours | Geometric Coefficient of Variation 14.62 |
Secondary
Area Under the Concentration Time Curve From Hour 0 to 168 Hours (AUC0-168) of MK-8527 in Plasma
Blood samples were taken at Predose, up to 168 hours postdose to determine the AUC0-168 of MK-8527 in plasma. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 168 hours postdose
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. The 1 mg MK-8527 arm had insufficient data for one participant. Participants from Panels D and E were not analyzed because they were not enrolled in the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Panel A: MK-8527 10 mg | Area Under the Concentration Time Curve From Hour 0 to 168 Hours (AUC0-168) of MK-8527 in Plasma | 0.926 hr*μmol/L |
| Panel B: MK-8527 3 mg | Area Under the Concentration Time Curve From Hour 0 to 168 Hours (AUC0-168) of MK-8527 in Plasma | 0.152 hr*μmol/L |
| Panel C: MK-8527 1 mg | Area Under the Concentration Time Curve From Hour 0 to 168 Hours (AUC0-168) of MK-8527 in Plasma | 0.0189 hr*μmol/L |
Secondary
Area Under the Concentration Time Curve From Hour 0 to 168 Hours (AUC0-168) of MK-8527-TP in Peripheral Blood Mononuclear Cells (PBMC)
Blood samples were taken at Predose, up to 168 hours postdose to determine the AUC0-168 of MK-8527-triphosphate (MK-8527-TP) in PBMCs. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% confidence intervals (CI) for the means were constructed on the natural log scale and referenced the t-distribution.
Time frame: Predose and 4, 12, 24, 96, 120, 144, and 168 hours postdose
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. Participants from Panels D and E were not analyzed because they were not enrolled in the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Panel A: MK-8527 10 mg | Area Under the Concentration Time Curve From Hour 0 to 168 Hours (AUC0-168) of MK-8527-TP in Peripheral Blood Mononuclear Cells (PBMC) | 178 hr*pmol/10^6 cells |
| Panel B: MK-8527 3 mg | Area Under the Concentration Time Curve From Hour 0 to 168 Hours (AUC0-168) of MK-8527-TP in Peripheral Blood Mononuclear Cells (PBMC) | 64.1 hr*pmol/10^6 cells |
| Panel C: MK-8527 1 mg | Area Under the Concentration Time Curve From Hour 0 to 168 Hours (AUC0-168) of MK-8527-TP in Peripheral Blood Mononuclear Cells (PBMC) | 29.1 hr*pmol/10^6 cells |
Secondary
Area Under the Concentration Time Curve From Hour 0 to Infinity (AUC0-inf) of MK-8527 in Plasma
Blood samples were taken at Predose, up to 168 hours postdose to determine the AUC0-inf of MK-8527 in plasma. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 168 hours postdose
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. The 1 mg MK-8527 arm had insufficient data for four participants. Participants from Panels D and E were not analyzed because they were not enrolled in the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Panel A: MK-8527 10 mg | Area Under the Concentration Time Curve From Hour 0 to Infinity (AUC0-inf) of MK-8527 in Plasma | 1.10 hr*μmol/L |
| Panel B: MK-8527 3 mg | Area Under the Concentration Time Curve From Hour 0 to Infinity (AUC0-inf) of MK-8527 in Plasma | 0.196 hr*μmol/L |
| Panel C: MK-8527 1 mg | Area Under the Concentration Time Curve From Hour 0 to Infinity (AUC0-inf) of MK-8527 in Plasma | NA hr*μmol/L |
Secondary
Area Under the Concentration Time Curve From Hour 0 to Infinity (AUC0-inf) of MK-8527-TP in PBMC
Blood samples were taken at Predose, up to approximately 28 days postdose to determine the AUC0-Inf of MK-8527-TP in PBMCs. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.
Time frame: Predose and 4, 12, 24, 96, 120, 144, 168, 240, 336, 504, 672 hours or 28 days postdose
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. Participants from Panels D and E were not analyzed because they were not enrolled in the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Panel A: MK-8527 10 mg | Area Under the Concentration Time Curve From Hour 0 to Infinity (AUC0-inf) of MK-8527-TP in PBMC | 265 hr*pmol/10^6 cells |
| Panel B: MK-8527 3 mg | Area Under the Concentration Time Curve From Hour 0 to Infinity (AUC0-inf) of MK-8527-TP in PBMC | 146 hr*pmol/10^6 cells |
| Panel C: MK-8527 1 mg | Area Under the Concentration Time Curve From Hour 0 to Infinity (AUC0-inf) of MK-8527-TP in PBMC | 55.0 hr*pmol/10^6 cells |
Secondary
Area Under the Concentration Time Curve From Hour 0 to Last (AUC0-last) of MK-8527 in Plasma
Blood samples were taken at Predose, up to 168 hours postdose to determine the AUC0-last of MK-8527 in plasma. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 168 hours postdose
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. Participants from Panels D and E were not analyzed because they were not enrolled in the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Panel A: MK-8527 10 mg | Area Under the Concentration Time Curve From Hour 0 to Last (AUC0-last) of MK-8527 in Plasma | 0.880 hr*μmol/L |
| Panel B: MK-8527 3 mg | Area Under the Concentration Time Curve From Hour 0 to Last (AUC0-last) of MK-8527 in Plasma | 0.121 hr*μmol/L |
| Panel C: MK-8527 1 mg | Area Under the Concentration Time Curve From Hour 0 to Last (AUC0-last) of MK-8527 in Plasma | 0.0151 hr*μmol/L |
Secondary
Area Under the Concentration Time Curve From Hour 0 to Last (AUC0-last) of MK-8527-TP in PBMC
Blood samples were taken at Predose, up to approximately 28 days postdose to determine the AUC0-last of MK-8527-TP in PBMCs. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.
Time frame: Predose and 4, 12, 24, 96, 120, 144, 168, 240, 336, 504, 672 hours or 28 days postdose
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. Participants from Panels D and E were not analyzed because they were not enrolled in the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Panel A: MK-8527 10 mg | Area Under the Concentration Time Curve From Hour 0 to Last (AUC0-last) of MK-8527-TP in PBMC | 235 hr*pmol/10^6 cells |
| Panel B: MK-8527 3 mg | Area Under the Concentration Time Curve From Hour 0 to Last (AUC0-last) of MK-8527-TP in PBMC | 108 hr*pmol/10^6 cells |
| Panel C: MK-8527 1 mg | Area Under the Concentration Time Curve From Hour 0 to Last (AUC0-last) of MK-8527-TP in PBMC | 49.5 hr*pmol/10^6 cells |
Secondary
Concentration at 168 Hours (C168) of MK-8527 in Plasma
Blood samples were taken at 168 hours postdose to determine the C168 of MK-8527 in plasma. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.
Time frame: 168 hours postdose
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. Participants from Panels D and E were not analyzed because they were not enrolled in the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Panel A: MK-8527 10 mg | Concentration at 168 Hours (C168) of MK-8527 in Plasma | NA μmol/L |
| Panel B: MK-8527 3 mg | Concentration at 168 Hours (C168) of MK-8527 in Plasma | NA μmol/L |
| Panel C: MK-8527 1 mg | Concentration at 168 Hours (C168) of MK-8527 in Plasma | NA μmol/L |
Secondary
Concentration at 168 Hours (C168) of MK-8527-TP in PBMC
Blood samples were taken at 168 hours postdose to determine the C168 of MK-8527-TP in PBMCs. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.
Time frame: 168 hours postdose for each panel
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. Participants from Panels D and E were not analyzed because they were not enrolled in the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Panel A: MK-8527 10 mg | Concentration at 168 Hours (C168) of MK-8527-TP in PBMC | 0.509 pmol/10^6 cells |
| Panel B: MK-8527 3 mg | Concentration at 168 Hours (C168) of MK-8527-TP in PBMC | 0.334 pmol/10^6 cells |
| Panel C: MK-8527 1 mg | Concentration at 168 Hours (C168) of MK-8527-TP in PBMC | 0.0978 pmol/10^6 cells |
Secondary
Maximum Concentration (Cmax) of MK-8527 in Plasma
Blood samples were taken at Predose, up to 168 hours postdose to determine the Cmax of MK-8527 in plasma. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 168 hours postdose
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. Participants from Panels D and E were not analyzed because they were not enrolled in the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Panel A: MK-8527 10 mg | Maximum Concentration (Cmax) of MK-8527 in Plasma | 0.177 μmol/L |
| Panel B: MK-8527 3 mg | Maximum Concentration (Cmax) of MK-8527 in Plasma | 0.0371 μmol/L |
| Panel C: MK-8527 1 mg | Maximum Concentration (Cmax) of MK-8527 in Plasma | 0.0162 μmol/L |
Secondary
Maximum Concentration (Cmax) of MK-8527-TP in PBMC
Blood samples were taken at Predose, up to approximately 28 days postdose to determine the Cmax of MK-8527-TP in PBMCs. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.
Time frame: Predose and 4, 12, 24, 96, 120, 144, 168, 240, 336, 504, 672 hours or 28 days postdose
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. Participants from Panels D and E were not analyzed because they were not enrolled in the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Panel A: MK-8527 10 mg | Maximum Concentration (Cmax) of MK-8527-TP in PBMC | 1.81 pmol/10^6 cells |
| Panel B: MK-8527 3 mg | Maximum Concentration (Cmax) of MK-8527-TP in PBMC | 0.644 pmol/10^6 cells |
| Panel C: MK-8527 1 mg | Maximum Concentration (Cmax) of MK-8527-TP in PBMC | 0.265 pmol/10^6 cells |
Secondary
Time to Cmax (Tmax) of MK-8527 in Plasma
Blood samples were taken at Predose, up to 168 hours postdose to determine the Tmax of MK-8527 in plasma. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 168 hours postdose
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. Participants from Panels D and E were not analyzed because they were not enrolled in the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panel A: MK-8527 10 mg | Time to Cmax (Tmax) of MK-8527 in Plasma | 0.50 Hours |
| Panel B: MK-8527 3 mg | Time to Cmax (Tmax) of MK-8527 in Plasma | 0.50 Hours |
| Panel C: MK-8527 1 mg | Time to Cmax (Tmax) of MK-8527 in Plasma | 0.50 Hours |
Secondary
Time to Cmax (Tmax) of MK-8527-TP in PBMC
Blood samples were taken at Predose, up to approximately 28 days postdose to determine the Tmax of MK-8527-TP in PBMCs. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.
Time frame: Predose and 4, 12, 24, 96, 120, 144, 168, 240, 336, 504, 672 hours or 28 days postdose
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. Participants from Panels D and E were not analyzed because they were not enrolled in the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panel A: MK-8527 10 mg | Time to Cmax (Tmax) of MK-8527-TP in PBMC | 18.00 Hours |
| Panel B: MK-8527 3 mg | Time to Cmax (Tmax) of MK-8527-TP in PBMC | 24.00 Hours |
| Panel C: MK-8527 1 mg | Time to Cmax (Tmax) of MK-8527-TP in PBMC | 24.00 Hours |