Single-Dose Study of MK-4250 Monotherapy in Anti-Retroviral Therapy-Naive, Human Immunodeficiency Virus (HIV)-1 Infected Participants (MK-4250-002)

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03351699
• Collaborator: (none)
• Enrollment: 24
• Location: 1
• Arms: 5
• Actual Duration (Months): 9.5
• Patients Per Site Per Month: 2.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
HIV-1 Infection	Drug: MK-4250	Phase 1

Detailed Description

The study consists of 5 panels; Panel C (MK-4250 ≤600 mg) was removed from the study with Protocol Amendment 1.

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Single-Dose Clinical Trial to Study the Safety, Tolerability, Pharmacokinetics, and Anti-Retroviral Activity of MK-4250 Monotherapy in Anti-Retroviral Therapy (ART)-Naive, HIV-1 Infected Subjects
• Actual Study Start Date: Jan 18, 2018
• Actual Primary Completion Date: Nov 2, 2018
• Actual Study Completion Date: Nov 2, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Panel A: MK-4250 150 mg Participants will receive MK-4250 150 mg tablet by mouth on Day 1 after an 8-hour fast.	Drug: MK-4250; MK-4250 tablets for oral administration
Experimental: Panel B: MK-4250 600 mg Participants will receive MK-4250 600 mg tablet by mouth on Day 1 after an 8-hour fast. The decision to enroll Panel B and the dose selected (i.e., ≤600 mg) will be made based on evaluation of pharmacokinetics and 7-day safety and viral load data from Panel A.	Drug: MK-4250; MK-4250 tablets for oral administration
Experimental: Panel D: MK-4250 900 mg Participants will receive MK-4250 900 mg tablet by mouth on Day 1 after an 8-hour fast. The decision to enroll Panel D will be made upon completion of Panels A and B and evaluation of safety and viral load data from those panels.	Drug: MK-4250; MK-4250 tablets for oral administration
Experimental: Panel E: MK-4250 ≤900 mg with a Low-fat Meal Participants will receive MK-4250 ≤900 mg tablet by mouth on Day 1 with a low-fat meal. The decision to enroll Panel E will be made upon completion of Panel D and evaluation of safety and viral load data from that panel.	Drug: MK-4250; MK-4250 tablets for oral administration
Experimental: Panel F: MK-4250 ≤900 mg with a Moderate-fat Meal Participants will receive MK-4250 ≤900 mg tablet by mouth on Day 1 with a moderate-fat meal. The decision to enroll Panel F will be made upon completion of Panel D and evaluation of safety and viral load data from that panel. The decision to enroll Panel F will be made based on evaluation of PK and safety data from other studies with MK-4250.	Drug: MK-4250; MK-4250 tablets for oral administration

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Charite Research Organisation GmbH ( Site 0001)	Berlin		Germany	10117

Sponsors and Collaborators

• Merck Sharp & Dohme LLC

Investigators

• Study Director: Medical Director, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 13, 2018

More Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT03351699
• Other Study ID Numbers: 4250-002; 2017-001784-21
• First Posted: Nov 24, 2017
• Last Update Posted: Oct 30, 2019
• Last Verified: Oct 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Study Results

Participant Flow

Arm/Group Title	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	Panel F: MK-4250 ≤900 mg With a Moderate-fat Meal
Arm/Group Description	Participants received MK-4250 150 mg dose by mouth on Day 1 after an 8-hour fast.	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.	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.	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.	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.
Period Title: Overall Study
STARTED	6	6	6	6	0
COMPLETED	6	6	6	6	0
NOT COMPLETED	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	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	Panel F: MK-4250 ≤900 mg With a Moderate-fat Meal	Total
Arm/Group Description	Participants received MK-4250 150 mg dose by mouth on Day 1 after an 8-hour fast.	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.	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.	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.	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.	Total of all reporting groups
Overall Participants	6	6	6	6	0	24
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	36.3 (8.1)	32.5 (6.1)	36.5 (8.9)	35.5 (7.3)	35.2 (7.3)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%	0 NaN	0 0%
Male	6 100%	6 100%	6 100%	6 100%	0 NaN	24 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 16.7%	0 0%	0 0%	0 0%	0 NaN	1 4.2%
Not Hispanic or Latino	5 83.3%	6 100%	6 100%	6 100%	0 NaN	23 95.8%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 NaN	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 NaN	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 NaN	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 NaN	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 NaN	0 0%
White	6 100%	6 100%	6 100%	6 100%	0 NaN	24 100%
More than one race	0 0%	0 0%	0 0%	0 0%	0 NaN	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 NaN	0 0%
Baseline Plasma HIV-1 Ribonucleic Acid (RNA) (log10 copies/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [log10 copies/mL]	4.29394 (0.41200)	4.42577 (0.39577)	4.85677 (0.23790)	4.42262 (0.37308)	4.49978 (0.40099)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Plasma HIV-1 RNA Copies Per mL at 168 Hours
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	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	Panel F: MK-4250 ≤900 mg With a Moderate-fat Meal
Arm/Group Description	Participants received MK-4250 150 mg dose by mouth on Day 1 after an 8-hour fast.	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.	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.	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.	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.
Measure Participants	6	6	6	6	0
Least Squares Mean (95% Confidence Interval) [log10 copies per mL]	-1.56	-1.76	-1.55	-1.78

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Panel A: MK-4250 150 mg
	Comments
	Type of Statistical Test	Superiority
	Comments	Adjusted by Placebo data pooled from historical placebo data from recent monotherapy studies in HIV-1 infected participants (NCT00100048, NCT01466985, NCT01152255, and NCT01353898) and fitted with a longitudinal data analysis (LDA) model containing fixed effects for study and time, and a random effect for participants. LS mean (95% confidence interval) for change from baseline at 168 hours post dose of pooled historical placebo was -0.03 log10 copies/mL (-0.14, 0.09).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Posterior Mean Difference
	Estimated Value	-1.53
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Posterior Probability (PP) of true mean difference in the plasma HIV-1 RNA change from baseline between MK-4250 and placebo at least 1.4 log10 copies/mL was 78%.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Panel B: MK-4250 600 mg
	Comments
	Type of Statistical Test	Superiority
	Comments	Adjusted by Placebo data pooled from historical placebo data from recent monotherapy studies in HIV-1 infected participants (NCT00100048, NCT01466985, NCT01152255, and NCT01353898) and fitted with a longitudinal data analysis (LDA) model containing fixed effects for study and time, and a random effect for participants. LS mean (95% confidence interval) for change from baseline at 168 hours post dose of pooled historical placebo was -0.03 log10 copies/mL (-0.14, 0.09).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Posterior Mean Difference
	Estimated Value	-1.73
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Posterior Probability (PP) of true mean difference in the plasma HIV-1 RNA change from baseline between MK-4250 and placebo at least 1.4 log10 copies/mL was 95%.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Panel D: MK-4250 900 mg
	Comments
	Type of Statistical Test	Superiority
	Comments	Adjusted by Placebo data pooled from historical placebo data from recent monotherapy studies in HIV-1 infected participants (NCT00100048, NCT01466985, NCT01152255, and NCT01353898) and fitted with a longitudinal data analysis (LDA) model containing fixed effects for study and time, and a random effect for participants. LS mean (95% confidence interval) for change from baseline at 168 hours post dose of pooled historical placebo was -0.03 log10 copies/mL (-0.14, 0.09).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Posterior Mean Difference
	Estimated Value	-1.52
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Posterior Probability (PP) of true mean difference in the plasma HIV-1 RNA change from baseline between MK-4250 and placebo at least 1.4 log10 copies/mL was 75%.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Panel E: MK-4250 ≤900 mg With a Low-fat Meal
	Comments
	Type of Statistical Test	Superiority
	Comments	Adjusted by Placebo data pooled from historical placebo data from recent monotherapy studies in HIV-1 infected participants (NCT00100048, NCT01466985, NCT01152255, and NCT01353898) and fitted with a longitudinal data analysis (LDA) model containing fixed effects for study and time, and a random effect for participants. LS mean (95% confidence interval) for change from baseline at 168 hours post dose of pooled historical placebo was -0.03 log10 copies/mL (-0.14, 0.09).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Posterior Mean Difference
	Estimated Value	-1.75
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Posterior Probability (PP) of true mean difference in the plasma HIV-1 RNA change from baseline between MK-4250 and placebo at least 1.4 log10 copies/mL was 96%.

2. Primary Outcome

Title	Percentage of Participants Experiencing ≥1 Adverse Events (AE)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Screening	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	Panel F: MK-4250 ≤900 mg With a Moderate-fat Meal
Arm/Group Description	This arm is all participants from all treatment arms, analyzed during the period prior to receipt of any study intervention.	Participants received MK-4250 150 mg dose by mouth on Day 1 after an 8-hour fast.	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.	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.	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.	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.
Measure Participants	24	6	6	6	6	0
Number [Percentage of Participants]	8.3 138.3%	83.3 1388.3%	66.7 1111.7%	83.3 1388.3%	66.7 Infinity

3. Primary Outcome

Title	Percentage of Participants Who Discontinued Study Due to an Adverse Event (AE)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Screening	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	Panel F: MK-4250 ≤900 mg With a Moderate-fat Meal
Arm/Group Description	This arm is all participants from all treatment arms, analyzed during the period prior to receipt of any study intervention.	Participants received MK-4250 150 mg dose by mouth on Day 1 after an 8-hour fast.	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.	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.	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.	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.
Measure Participants	24	6	6	6	6	0
Number [Percentage of Participants]	0.0 0%	0.0 0%	0.0 0%	0.0 0%	0.0 NaN

4. Secondary Outcome

Title	Area Under the Concentration-Time Curve From 0 to Last Measurable Concentration (AUC0-last) for MK-4250
Description	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.

Outcome Measure Data

Analysis Population Description

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/Group Title	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	Panel F: MK-4250 ≤900 mg With a Moderate-fat Meal
Arm/Group Description	Participants received MK-4250 150 mg dose by mouth on Day 1 after an 8-hour fast.	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.	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.	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.	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.
Measure Participants	6	6	6	6	0
Geometric Mean (Geometric Coefficient of Variation) [μM·hour]	774 (54)	2040 (17.1)	2390 (35)	3860 (44.3)

5. Secondary Outcome

Title	Area Under the Concentration-Time Curve From 0 to Infinity (AUC0-inf) for MK-4250
Description	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.

Outcome Measure Data

Analysis Population Description

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/Group Title	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	Panel F: MK-4250 ≤900 mg With a Moderate-fat Meal
Arm/Group Description	Participants received MK-4250 150 mg dose by mouth on Day 1 after an 8-hour fast.	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.	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.	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.	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.
Measure Participants	6	6	6	6	0
Geometric Mean (Geometric Coefficient of Variation) [μM·hour]	785 (54.6)	2120 (18.4)	2450 (35.9)	4010 (47.6)

6. Secondary Outcome

Title	Area Under the Concentration-Time Curve From 0 to 168 Hours (AUC0-168) for MK-4250
Description	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.

Outcome Measure Data

Analysis Population Description

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/Group Title	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	Panel F: MK-4250 ≤900 mg With a Moderate-fat Meal
Arm/Group Description	Participants received MK-4250 150 mg dose by mouth on Day 1 after an 8-hour fast.	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.	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.	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.	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.
Measure Participants	6	6	6	6	0
Geometric Mean (Geometric Coefficient of Variation) [μM·Hour]	751 (52.6)	1980 (16.7)	2280 (34.1)	3640 (41.2)

7. Secondary Outcome

Title	Maximum Concentration (Cmax) of MK-4250 Reached in Plasma
Description	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.

Outcome Measure Data

Analysis Population Description

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/Group Title	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	Panel F: MK-4250 ≤900 mg With a Moderate-fat Meal
Arm/Group Description	Participants received MK-4250 150 mg dose by mouth on Day 1 after an 8-hour fast.	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.	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.	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.	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.
Measure Participants	6	6	6	6	0
Geometric Mean (Geometric Coefficient of Variation) [μM]	16.6 (46.7)	37.6 (26)	43.5 (32.7)	65 (25.8)

8. Secondary Outcome

Title	Concentration of MK-4250 at 168 Hours (C168hr)
Description	The concentration of MK-4250 at 168 hours postdose (C168hr) was observed.
Time Frame	168 hours after administration of MK-4250.

Outcome Measure Data

Analysis Population Description

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/Group Title	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	Panel F: MK-4250 ≤900 mg With a Moderate-fat Meal
Arm/Group Description	Participants received MK-4250 150 mg dose by mouth on Day 1 after an 8-hour fast.	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.	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.	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.	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.
Measure Participants	6	6	6	6	0
Geometric Mean (Geometric Coefficient of Variation) [μM]	0.558 (117)	2.2 (57.4)	2.38 (63.8)	4.37 (96.4)

9. Secondary Outcome

Title	Apparent Terminal Half-life (t1/2) of MK-4250
Description	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.

Outcome Measure Data

Analysis Population Description

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/Group Title	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	Panel F: MK-4250 ≤900 mg With a Moderate-fat Meal
Arm/Group Description	Participants received MK-4250 150 mg dose by mouth on Day 1 after an 8-hour fast.	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.	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.	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.	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.
Measure Participants	6	6	6	6	0
Geometric Mean (Geometric Coefficient of Variation) [Hours]	35.9 (22.9)	38.5 (31.9)	44.1 (17.1)	48.4 (32.1)

10. Secondary Outcome

Title	Apparent Clearance (CL/F) of MK-4250
Description	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.

Outcome Measure Data

Analysis Population Description

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/Group Title	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	Panel F: MK-4250 ≤900 mg With a Moderate-fat Meal
Arm/Group Description	Participants received MK-4250 150 mg dose by mouth on Day 1 after an 8-hour fast.	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.	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.	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.	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.
Measure Participants	6	6	6	6	0
Geometric Mean (Geometric Coefficient of Variation) [Liters/Hour]	0.456 (54.6)	0.676 (18.4)	0.879 (35.9)	0.536 (47.6)

11. Secondary Outcome

Title	Apparent Volume of Distribution (Vz/F) of MK-4250
Description	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.

Outcome Measure Data

Analysis Population Description

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/Group Title	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	Panel F: MK-4250 ≤900 mg With a Moderate-fat Meal
Arm/Group Description	Participants received MK-4250 150 mg dose by mouth on Day 1 after an 8-hour fast.	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.	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.	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.	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.
Measure Participants	6	6	6	6	0
Geometric Mean (Geometric Coefficient of Variation) [Liters]	23.6 (45.1)	37.6 (23.5)	56 (31.7)	37.4 (17.5)

12. Secondary Outcome

Title	Time to Maximum Concentration (Tmax) of MK-4250 Reached in Plasma
Description	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.

Outcome Measure Data

Analysis Population Description

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/Group Title	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	Panel F: MK-4250 ≤900 mg With a Moderate-fat Meal
Arm/Group Description	Participants received MK-4250 150 mg dose by mouth on Day 1 after an 8-hour fast.	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.	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.	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.	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.
Measure Participants	6	6	6	6	0
Median (Full Range) [Hours]	4.00	4.00	4.00	4.00

Adverse Events

Time Frame	Up to 6 weeks
Arm/Group Title	Screening		Panel A: 150 mg MK-4250		Panel B: 600 mg MK-4250		Panel D: 900 mg MK-4250		Panel E: 900 mg MK-4250, With a Low Fat Meal
Arm/Group Description	This group represents all participants during their individual screening phase, approximately 4 weeks prior to first dose. No intervention was provided during this time.		Participants received MK-4250 150 mg tablet by mouth on Day 1 after an 8-hour fast.		Participants received MK-4250 600 mg tablet 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.		Participants received MK-4250 900 mg tablet 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.		Participants received MK-4250 ≤900 mg tablet 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.
All Cause Mortality
	Screening		Panel A: 150 mg MK-4250		Panel B: 600 mg MK-4250		Panel D: 900 mg MK-4250		Panel E: 900 mg MK-4250, With a Low Fat Meal
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Serious Adverse Events
	Screening		Panel A: 150 mg MK-4250		Panel B: 600 mg MK-4250		Panel D: 900 mg MK-4250		Panel E: 900 mg MK-4250, With a Low Fat Meal
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Screening		Panel A: 150 mg MK-4250		Panel B: 600 mg MK-4250		Panel D: 900 mg MK-4250		Panel E: 900 mg MK-4250, With a Low Fat Meal
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/24 (8.3%)		5/6 (83.3%)		4/6 (66.7%)		5/6 (83.3%)		4/6 (66.7%)
Blood and lymphatic system disorders
Lymphadenitis	0/24 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0
Gastrointestinal disorders
Abdominal pain	0/24 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0
Aphthous ulcer	0/24 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	2/6 (33.3%)	2	0/6 (0%)	0
Diarrhoea	0/24 (0%)	0	1/6 (16.7%)	1	3/6 (50%)	3	1/6 (16.7%)	1	0/6 (0%)	0
Dry mouth	0/24 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0
Nausea	0/24 (0%)	0	1/6 (16.7%)	1	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0
Vomiting	0/24 (0%)	0	1/6 (16.7%)	1	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0
General disorders
Fatigue	0/24 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Infections and infestations
Nasopharyngitis	0/24 (0%)	0	3/6 (50%)	3	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0
Rhinitis	0/24 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0
Tonsillitis	0/24 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0
Musculoskeletal and connective tissue disorders
Bone pain	0/24 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1
Nervous system disorders
Dizziness	0/24 (0%)	0	2/6 (33.3%)	2	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0
Headache	2/24 (8.3%)	2	4/6 (66.7%)	4	2/6 (33.3%)	2	1/6 (16.7%)	1	3/6 (50%)	3
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	0/24 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Skin and subcutaneous tissue disorders
Acne	0/24 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1
Hyperhidrosis	0/24 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0
Pruritus	0/24 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Subsequent to the multicenter publication (or after public disclosure of the results at www.clinicaltrials.gov if multicenter manuscript is not planned), an investigator and colleagues may publish their data independently. Sponsor must have opportunity to review proposed abstracts, manuscripts or presentations 45 days prior to submission for publication/presentation. Confidential information must be deleted prior to submission; this confidentiality does not include efficacy and safety results.