HIV-1 Infection
Conditions
Brief summary
The study will evaluate the safety, tolerability, pharmacokinetics, and anti-retroviral activity of MK-4250 monotherapy in anti-retroviral therapy (ART)-naïve, HIV-1 infected participants. The primary hypothesis of the study is that at a dose that is sufficiently safe and generally well tolerated, MK-4250 has superior antiretroviral activity compared to a historical placebo, as measured by change from baseline in plasma HIV-1 ribonucleic acid (RNA) (log10 copies/mL) at 168 hours postdose.
Detailed description
The study consists of 5 panels; Panel C (MK-4250 ≤600 mg) was removed from the study with Protocol Amendment 1.
Interventions
DRUGMK-4250
MK-4250 tablets for oral administration
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
* Male or non-pregnant and non-breast feeding female * If female with reproductive potential: must demonstrate a serum β-human chorionic gonadotropin (β -hCG) level consistent with the nongravid state and agree to use a highly effective method of birth control until 30 days after the dose of trial drug * If postmenopausal female: without menses for at least 1 year and has a documented follicle stimulating hormone (FSH) level in the postmenopausal range at pretrial (screening), AND/OR status post hysterectomy or oophorectomy * Documented HIV-1 positive as determined by a positive Enzyme-linked Immunosorbent Assay (ELISA) or Quantitative Polymerase Chain Reaction (QT-PCR) with confirmation (e.g., Western Blot). * No evidence at screening for mutations (e.g., E92Q, N55H, Q148K, Q148R and Y143R) affecting susceptibility to Integrase Strand Transfer Inhibitors (InSTIs) * Diagnosed with HIV-1 infection ≥ 3 months prior to screening or confirmed chronic HIV infection * Screening plasma Cluster of Differentiation (CD) 4+ T cell count of \>200/mm\^3 * Screening plasma HIV-1 RNA ≥5,000 copies/mL within 30 days prior to the treatment phase of this study * Anti-retroviral therapy (ART)-naïve, which is defined as having never received any antiretroviral agent OR ≤30 consecutive days of an investigational antiretroviral agent which is not an InSTI and no exposure to such an investigational antiretroviral agent within 60 days prior to screening OR ≤60 consecutive days of combination ART which does not include an InSTI and no exposure to such ART within 60 days prior to screening * Never received any InSTI * Willing to receive no other ART for the duration of the treatment phase of this study * Body Mass Index (BMI) ≤35 kg/m\^2 * Other than HIV infection, have baseline health judged to be stable
Exclusion criteria
* Mentally or legally institutionalized / incapacitated, or significant emotional problems at the time of pretrial (screening) visit or expected during the conduct of the trial or has a history of clinically significant psychiatric disorder within the last 5 years * History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological (outside of HIV-1 infection), renal, respiratory, genitourinary or major neurological abnormalities or diseases * History of cancer (malignancy). Exceptions: (1) adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix; (2) other malignancies which have been successfully treated ≥10 years prior to the pretrial (screening) visit with no evidence of recurrence; or, (3) deemed highly unlikely to sustain a recurrence for the duration of the trial * History of significant multiple and/or severe allergies (e.g., food, drug, latex allergy); anaphylactic reaction or significant intolerability (i.e., systemic allergic reaction) to prescription or non-prescription drugs or food; or hereditary galactose intolerance, lactose deficiency, or glucose-galactose malabsorption. * Positive for hepatitis B surface antigen * History of chronic hepatitis C (HCV) infection. Participants with a documented cure and/or a positive serologic test for HCV with a negative HCV viral load may be included * Major surgery or donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the pretrial (screening) visit * Participated in another investigational trial within 4 weeks prior to the Day 1 dosing visit. The 4 week window will be derived from the date of the last trial medication and / or blood collection in a previous trial and/or an adverse event related to trial drug to the Day 1 dosing visit of the current trial * Unable to refrain from or anticipates the use of any medication, including prescription and non-prescription drugs or herbal remedies beginning approximately 2 weeks prior to administration of the initial dose of trial drug, throughout the trial, until the post-trial visit * 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. Participants who consume 4 glasses of alcoholic beverages per day may be enrolled * Consumes excessive amounts, defined as greater 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 * Excessive smoker (i.e., more than 10 cigarettes/day) and is unwilling to restrict smoking to ≤10 cigarettes per day * Cardiac QTc interval ≥470 msec (for males) or ≥480 msec (for females) * Positive urine drug screen (except for cannabis) at screening and/or predose; rechecks are allowed * Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is investigational site or Sponsor staff directly involved with this trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Plasma HIV-1 RNA Copies Per mL at 168 Hours | Baseline and Day 7 | Plasma HIV-1 RNA was measured at Baseline and 168 hours after dosing. The log10 plasma HIV-RNA copies/mL measurements from participants in each panel were pooled and analyzed based on a longitudinal data analysis model. The change from Baseline in plasma HIV-1 RNA in participants administered MK-4250 was compared with historical placebo data. |
| Percentage of Participants Experiencing ≥1 Adverse Events (AE) | Up to Day 14 | The percentage of participants experiencing ≥1 AE was calculated. An AE was defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy could be determined. |
| Percentage of Participants Who Discontinued Study Due to an Adverse Event (AE) | Up to Day 14 | The percentage of participants who discontinued from the study due to an adverse event was calculated. An AE was defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy could be determined. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Concentration (Cmax) of MK-4250 Reached in Plasma | Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, 192, and 240 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time, and no 240-hour postdose time. | The maximum concentration (Cmax) of MK-4250 in plasma was observed. |
| Concentration of MK-4250 at 168 Hours (C168hr) | 168 hours after administration of MK-4250. | The concentration of MK-4250 at 168 hours postdose (C168hr) was observed. |
| Apparent Terminal Half-life (t1/2) of MK-4250 | Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, 192, and 240 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time, and no 240-hour postdose time. | The apparent terminal half-life (t1/2) of MK-4250 in plasma was calculated. |
| Area Under the Concentration-Time Curve From 0 to Last Measurable Concentration (AUC0-last) for MK-4250 | Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, 192, and 240 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time, and no 240-hour postdose time. | The area under the concentration-time curve up to the last measurable concentration (AUC0-last) of MK-4250 in plasma was calculated. |
| Apparent Volume of Distribution (Vz/F) of MK-4250 | Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, 192, and 240 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time, and no 240-hour postdose time. | The apparent volume of distribution (Vz/F) of MK-4250 in plasma was calculated. |
| Time to Maximum Concentration (Tmax) of MK-4250 Reached in Plasma | Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, 192, and 240 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time, and no 240-hour postdose time. | The time to maximum concentration (Vz/F) of MK-4250 in plasma was calculated. |
| Apparent Clearance (CL/F) of MK-4250 | Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, 192, and 240 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time, and no 240-hour postdose time. | The apparent clearance (CL/F) of MK-4250 in plasma was calculated. |
| Area Under the Concentration-Time Curve From 0 to Infinity (AUC0-inf) for MK-4250 | Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, 192, and 240 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time, and no 240-hour postdose time. | The area under the concentration-time curve extrapolated to infinity (AUC0-inf) of MK-4250 in plasma was calculated. |
| Area Under the Concentration-Time Curve From 0 to 168 Hours (AUC0-168) for MK-4250 | Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, and 168 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time. | The area under the concentration-time curve up to 168 hours (AUC0-168) of MK-4250 in plasma was calculated. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Panel A: MK-4250 150 mg Participants received MK-4250 150 mg dose by mouth on Day 1 after an 8-hour fast. | 6 |
| Panel B: MK-4250 600 mg Participants received MK-4250 600 mg dose by mouth on Day 1 after an 8-hour fast. The decision to enroll Panel B and the dose selected (i.e., ≤600 mg) was made based on evaluation of pharmacokinetics and 7-day safety and viral load data from Panel A. | 6 |
| Panel D: MK-4250 900 mg Participants received MK-4250 900 mg dose by mouth on Day 1 after an 8-hour fast. The decision to enroll Panel D was made upon completion of Panels A and B and evaluation of safety and viral load data from those panels. | 6 |
| Panel E: MK-4250 ≤900 mg With a Low-fat Meal Participants received MK-4250 900 mg dose by mouth on Day 1 with a low-fat meal. The decision to enroll Panel E was made upon completion of Panel D and evaluation of safety and viral load data from that panel. | 6 |
| Panel F: MK-4250 ≤900 mg With a Moderate-fat Meal Participants were to receive MK-4250 900 mg dose by mouth on Day 1 with a moderate-fat meal. The decision was made not to enroll Panel F because the scientific objectives were met following completion of Panel E. | 0 |
| Total | 24 |
Baseline characteristics
| Characteristic | Panel A: MK-4250 150 mg | Panel B: MK-4250 600 mg | Panel D: MK-4250 900 mg | Panel E: MK-4250 ≤900 mg With a Low-fat Meal | Total | Panel F: MK-4250 ≤900 mg With a Moderate-fat Meal |
|---|---|---|---|---|---|---|
| Age, Continuous | 36.3 Years STANDARD_DEVIATION 8.1 | 32.5 Years STANDARD_DEVIATION 6.1 | 36.5 Years STANDARD_DEVIATION 8.9 | 35.5 Years STANDARD_DEVIATION 7.3 | 35.2 Years STANDARD_DEVIATION 7.3 | — |
| Baseline Plasma HIV-1 Ribonucleic Acid (RNA) | 4.29394 log10 copies/mL STANDARD_DEVIATION 0.412 | 4.42577 log10 copies/mL STANDARD_DEVIATION 0.39577 | 4.85677 log10 copies/mL STANDARD_DEVIATION 0.2379 | 4.42262 log10 copies/mL STANDARD_DEVIATION 0.37308 | 4.49978 log10 copies/mL STANDARD_DEVIATION 0.40099 | — |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 6 Participants | 6 Participants | 6 Participants | 23 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 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 | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 24 Participants | 0 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 24 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 2 / 24 | 5 / 6 | 4 / 6 | 5 / 6 | 4 / 6 |
| serious Total, serious adverse events | 0 / 24 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Change From Baseline in Plasma HIV-1 RNA Copies Per mL at 168 Hours
Plasma HIV-1 RNA was measured at Baseline and 168 hours after dosing. The log10 plasma HIV-RNA copies/mL measurements from participants in each panel were pooled and analyzed based on a longitudinal data analysis model. The change from Baseline in plasma HIV-1 RNA in participants administered MK-4250 was compared with historical placebo data.
Time frame: Baseline and Day 7
Population: All participants who complied with the protocol sufficiently to ensure data would likely exhibit the effects of treatment, according to the scientific model. Compliance included treatment exposure, measurement availability, and lack of major protocol deviations. Panel F did not enroll because the objectives were met following completion of Panel E.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Panel A: MK-4250 150 mg | Change From Baseline in Plasma HIV-1 RNA Copies Per mL at 168 Hours | -1.56 log10 copies per mL |
| Panel B: MK-4250 600 mg | Change From Baseline in Plasma HIV-1 RNA Copies Per mL at 168 Hours | -1.76 log10 copies per mL |
| Panel D: MK-4250 900 mg | Change From Baseline in Plasma HIV-1 RNA Copies Per mL at 168 Hours | -1.55 log10 copies per mL |
| Panel E: MK-4250 ≤900 mg With a Low-fat Meal | Change From Baseline in Plasma HIV-1 RNA Copies Per mL at 168 Hours | -1.78 log10 copies per mL |
Primary
Percentage of Participants Experiencing ≥1 Adverse Events (AE)
The percentage of participants experiencing ≥1 AE was calculated. An AE was defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy could be determined.
Time frame: Up to Day 14
Population: Included all participants who received ≥1 dose of treatment. Panel F did not enroll because the scientific objectives were met following completion of Panel E.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panel A: MK-4250 150 mg | Percentage of Participants Experiencing ≥1 Adverse Events (AE) | 8.3 Percentage of Participants |
| Panel B: MK-4250 600 mg | Percentage of Participants Experiencing ≥1 Adverse Events (AE) | 83.3 Percentage of Participants |
| Panel D: MK-4250 900 mg | Percentage of Participants Experiencing ≥1 Adverse Events (AE) | 66.7 Percentage of Participants |
| Panel E: MK-4250 ≤900 mg With a Low-fat Meal | Percentage of Participants Experiencing ≥1 Adverse Events (AE) | 83.3 Percentage of Participants |
| Panel F: MK-4250 ≤900 mg With a Moderate-fat Meal | Percentage of Participants Experiencing ≥1 Adverse Events (AE) | 66.7 Percentage of Participants |
Primary
Percentage of Participants Who Discontinued Study Due to an Adverse Event (AE)
The percentage of participants who discontinued from the study due to an adverse event was calculated. An AE was defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy could be determined.
Time frame: Up to Day 14
Population: Included all participants who received ≥1 dose of treatment. Panel F did not enroll because the scientific objectives were met following completion of Panel E.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panel A: MK-4250 150 mg | Percentage of Participants Who Discontinued Study Due to an Adverse Event (AE) | 0.0 Percentage of Participants |
| Panel B: MK-4250 600 mg | Percentage of Participants Who Discontinued Study Due to an Adverse Event (AE) | 0.0 Percentage of Participants |
| Panel D: MK-4250 900 mg | Percentage of Participants Who Discontinued Study Due to an Adverse Event (AE) | 0.0 Percentage of Participants |
| Panel E: MK-4250 ≤900 mg With a Low-fat Meal | Percentage of Participants Who Discontinued Study Due to an Adverse Event (AE) | 0.0 Percentage of Participants |
| Panel F: MK-4250 ≤900 mg With a Moderate-fat Meal | Percentage of Participants Who Discontinued Study Due to an Adverse Event (AE) | 0.0 Percentage of Participants |
Secondary
Apparent Clearance (CL/F) of MK-4250
The apparent clearance (CL/F) of MK-4250 in plasma was calculated.
Time frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, 192, and 240 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time, and no 240-hour postdose time.
Population: All participants who complied with the protocol sufficiently to ensure data would likely exhibit the effects of treatment, according to the scientific model. Compliance included treatment exposure, measurement availability, and lack of major protocol deviations. Panel F did not enroll because the objectives were met following completion of Panel E.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: MK-4250 150 mg | Apparent Clearance (CL/F) of MK-4250 | 0.456 Liters/Hour | Geometric Coefficient of Variation 54.6 |
| Panel B: MK-4250 600 mg | Apparent Clearance (CL/F) of MK-4250 | 0.676 Liters/Hour | Geometric Coefficient of Variation 18.4 |
| Panel D: MK-4250 900 mg | Apparent Clearance (CL/F) of MK-4250 | 0.879 Liters/Hour | Geometric Coefficient of Variation 35.9 |
| Panel E: MK-4250 ≤900 mg With a Low-fat Meal | Apparent Clearance (CL/F) of MK-4250 | 0.536 Liters/Hour | Geometric Coefficient of Variation 47.6 |
Secondary
Apparent Terminal Half-life (t1/2) of MK-4250
The apparent terminal half-life (t1/2) of MK-4250 in plasma was calculated.
Time frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, 192, and 240 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time, and no 240-hour postdose time.
Population: All participants who complied with the protocol sufficiently to ensure data would likely exhibit the effects of treatment, according to the scientific model. Compliance included treatment exposure, measurement availability, and lack of major protocol deviations. Panel F did not enroll because the objectives were met following completion of Panel E.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: MK-4250 150 mg | Apparent Terminal Half-life (t1/2) of MK-4250 | 35.9 Hours | Geometric Coefficient of Variation 22.9 |
| Panel B: MK-4250 600 mg | Apparent Terminal Half-life (t1/2) of MK-4250 | 38.5 Hours | Geometric Coefficient of Variation 31.9 |
| Panel D: MK-4250 900 mg | Apparent Terminal Half-life (t1/2) of MK-4250 | 44.1 Hours | Geometric Coefficient of Variation 17.1 |
| Panel E: MK-4250 ≤900 mg With a Low-fat Meal | Apparent Terminal Half-life (t1/2) of MK-4250 | 48.4 Hours | Geometric Coefficient of Variation 32.1 |
Secondary
Apparent Volume of Distribution (Vz/F) of MK-4250
The apparent volume of distribution (Vz/F) of MK-4250 in plasma was calculated.
Time frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, 192, and 240 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time, and no 240-hour postdose time.
Population: All participants who complied with the protocol sufficiently to ensure data would likely exhibit the effects of treatment, according to the scientific model. Compliance included treatment exposure, measurement availability, and lack of major protocol deviations. Panel F did not enroll because the objectives were met following completion of Panel E.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: MK-4250 150 mg | Apparent Volume of Distribution (Vz/F) of MK-4250 | 23.6 Liters | Geometric Coefficient of Variation 45.1 |
| Panel B: MK-4250 600 mg | Apparent Volume of Distribution (Vz/F) of MK-4250 | 37.6 Liters | Geometric Coefficient of Variation 23.5 |
| Panel D: MK-4250 900 mg | Apparent Volume of Distribution (Vz/F) of MK-4250 | 56 Liters | Geometric Coefficient of Variation 31.7 |
| Panel E: MK-4250 ≤900 mg With a Low-fat Meal | Apparent Volume of Distribution (Vz/F) of MK-4250 | 37.4 Liters | Geometric Coefficient of Variation 17.5 |
Secondary
Area Under the Concentration-Time Curve From 0 to 168 Hours (AUC0-168) for MK-4250
The area under the concentration-time curve up to 168 hours (AUC0-168) of MK-4250 in plasma was calculated.
Time frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, and 168 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time.
Population: All participants who complied with the protocol sufficiently to ensure data would likely exhibit the effects of treatment, according to the scientific model. Compliance included treatment exposure, measurement availability, and lack of major protocol deviations. Panel F did not enroll because the objectives were met following completion of Panel E.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: MK-4250 150 mg | Area Under the Concentration-Time Curve From 0 to 168 Hours (AUC0-168) for MK-4250 | 751 μM·Hour | Geometric Coefficient of Variation 52.6 |
| Panel B: MK-4250 600 mg | Area Under the Concentration-Time Curve From 0 to 168 Hours (AUC0-168) for MK-4250 | 1980 μM·Hour | Geometric Coefficient of Variation 16.7 |
| Panel D: MK-4250 900 mg | Area Under the Concentration-Time Curve From 0 to 168 Hours (AUC0-168) for MK-4250 | 2280 μM·Hour | Geometric Coefficient of Variation 34.1 |
| Panel E: MK-4250 ≤900 mg With a Low-fat Meal | Area Under the Concentration-Time Curve From 0 to 168 Hours (AUC0-168) for MK-4250 | 3640 μM·Hour | Geometric Coefficient of Variation 41.2 |
Secondary
Area Under the Concentration-Time Curve From 0 to Infinity (AUC0-inf) for MK-4250
The area under the concentration-time curve extrapolated to infinity (AUC0-inf) of MK-4250 in plasma was calculated.
Time frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, 192, and 240 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time, and no 240-hour postdose time.
Population: All participants who complied with the protocol sufficiently to ensure data would likely exhibit the effects of treatment, according to the scientific model. Compliance included treatment exposure, measurement availability, and lack of major protocol deviations. Panel F did not enroll because the objectives were met following completion of Panel E.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: MK-4250 150 mg | Area Under the Concentration-Time Curve From 0 to Infinity (AUC0-inf) for MK-4250 | 785 μM·hour | Geometric Coefficient of Variation 54.6 |
| Panel B: MK-4250 600 mg | Area Under the Concentration-Time Curve From 0 to Infinity (AUC0-inf) for MK-4250 | 2120 μM·hour | Geometric Coefficient of Variation 18.4 |
| Panel D: MK-4250 900 mg | Area Under the Concentration-Time Curve From 0 to Infinity (AUC0-inf) for MK-4250 | 2450 μM·hour | Geometric Coefficient of Variation 35.9 |
| Panel E: MK-4250 ≤900 mg With a Low-fat Meal | Area Under the Concentration-Time Curve From 0 to Infinity (AUC0-inf) for MK-4250 | 4010 μM·hour | Geometric Coefficient of Variation 47.6 |
Secondary
Area Under the Concentration-Time Curve From 0 to Last Measurable Concentration (AUC0-last) for MK-4250
The area under the concentration-time curve up to the last measurable concentration (AUC0-last) of MK-4250 in plasma was calculated.
Time frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, 192, and 240 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time, and no 240-hour postdose time.
Population: All participants who complied with the protocol sufficiently to ensure data would likely exhibit the effects of treatment, according to the scientific model. Compliance included treatment exposure, measurement availability, and lack of major protocol deviations. Panel F did not enroll because the objectives were met following completion of Panel E.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: MK-4250 150 mg | Area Under the Concentration-Time Curve From 0 to Last Measurable Concentration (AUC0-last) for MK-4250 | 774 μM·hour | Geometric Coefficient of Variation 54 |
| Panel B: MK-4250 600 mg | Area Under the Concentration-Time Curve From 0 to Last Measurable Concentration (AUC0-last) for MK-4250 | 2040 μM·hour | Geometric Coefficient of Variation 17.1 |
| Panel D: MK-4250 900 mg | Area Under the Concentration-Time Curve From 0 to Last Measurable Concentration (AUC0-last) for MK-4250 | 2390 μM·hour | Geometric Coefficient of Variation 35 |
| Panel E: MK-4250 ≤900 mg With a Low-fat Meal | Area Under the Concentration-Time Curve From 0 to Last Measurable Concentration (AUC0-last) for MK-4250 | 3860 μM·hour | Geometric Coefficient of Variation 44.3 |
Secondary
Concentration of MK-4250 at 168 Hours (C168hr)
The concentration of MK-4250 at 168 hours postdose (C168hr) was observed.
Time frame: 168 hours after administration of MK-4250.
Population: All participants who complied with the protocol sufficiently to ensure data would likely exhibit the effects of treatment, according to the scientific model. Compliance included treatment exposure, measurement availability, and lack of major protocol deviations. Panel F did not enroll because the objectives were met following completion of Panel E.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: MK-4250 150 mg | Concentration of MK-4250 at 168 Hours (C168hr) | 0.558 μM | Geometric Coefficient of Variation 117 |
| Panel B: MK-4250 600 mg | Concentration of MK-4250 at 168 Hours (C168hr) | 2.2 μM | Geometric Coefficient of Variation 57.4 |
| Panel D: MK-4250 900 mg | Concentration of MK-4250 at 168 Hours (C168hr) | 2.38 μM | Geometric Coefficient of Variation 63.8 |
| Panel E: MK-4250 ≤900 mg With a Low-fat Meal | Concentration of MK-4250 at 168 Hours (C168hr) | 4.37 μM | Geometric Coefficient of Variation 96.4 |
Secondary
Maximum Concentration (Cmax) of MK-4250 Reached in Plasma
The maximum concentration (Cmax) of MK-4250 in plasma was observed.
Time frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, 192, and 240 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time, and no 240-hour postdose time.
Population: All participants who complied with the protocol sufficiently to ensure data would likely exhibit the effects of treatment, according to the scientific model. Compliance included treatment exposure, measurement availability, and lack of major protocol deviations. Panel F did not enroll because the objectives were met following completion of Panel E.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: MK-4250 150 mg | Maximum Concentration (Cmax) of MK-4250 Reached in Plasma | 16.6 μM | Geometric Coefficient of Variation 46.7 |
| Panel B: MK-4250 600 mg | Maximum Concentration (Cmax) of MK-4250 Reached in Plasma | 37.6 μM | Geometric Coefficient of Variation 26 |
| Panel D: MK-4250 900 mg | Maximum Concentration (Cmax) of MK-4250 Reached in Plasma | 43.5 μM | Geometric Coefficient of Variation 32.7 |
| Panel E: MK-4250 ≤900 mg With a Low-fat Meal | Maximum Concentration (Cmax) of MK-4250 Reached in Plasma | 65 μM | Geometric Coefficient of Variation 25.8 |
Secondary
Time to Maximum Concentration (Tmax) of MK-4250 Reached in Plasma
The time to maximum concentration (Vz/F) of MK-4250 in plasma was calculated.
Time frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, 192, and 240 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time, and no 240-hour postdose time.
Population: All participants who complied with the protocol sufficiently to ensure data would likely exhibit the effects of treatment, according to the scientific model. Compliance included treatment exposure, measurement availability, and lack of major protocol deviations. Panel F did not enroll because the objectives were met following completion of Panel E.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panel A: MK-4250 150 mg | Time to Maximum Concentration (Tmax) of MK-4250 Reached in Plasma | 4.00 Hours |
| Panel B: MK-4250 600 mg | Time to Maximum Concentration (Tmax) of MK-4250 Reached in Plasma | 4.00 Hours |
| Panel D: MK-4250 900 mg | Time to Maximum Concentration (Tmax) of MK-4250 Reached in Plasma | 4.00 Hours |
| Panel E: MK-4250 ≤900 mg With a Low-fat Meal | Time to Maximum Concentration (Tmax) of MK-4250 Reached in Plasma | 4.00 Hours |