MK-8583 Single Dose Study in Human Immunodeficiency Virus Type 1 (HIV-1) Infected Participants (MK-8583-002)

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03552536
• Collaborator: (none)
• Enrollment: 5
• Location: 1
• Arms: 3
• Actual Duration (Months): 5.1
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

This study aims to evaluate the safety, tolerability, pharmacokinetics (PK), and anti-retroviral therapy (ART) activity of the tenofovir prodrug, MK-8583 monotherapy in ART-naïve, HIV-1 infected participants. The primary hypothesis is that at a dose that is sufficiently safe and generally well tolerated, MK-8583 has superior anti-retroviral activity compared to historical placebo, as measured by change from baseline in plasma HIV-1 ribonucleic acid (RNA) (log10 copies/mL) at 168 hours post-dose.

Condition or Disease	Intervention/Treatment	Phase
HIV-1 Infection	Drug: MK-8583	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 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-8583 Monotherapy in Anti-Retroviral Therapy (ART)-Naïve, HIV-1 Infected Patients
• Actual Study Start Date: Oct 7, 2018
• Actual Primary Completion Date: Mar 11, 2019
• Actual Study Completion Date: Mar 11, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A: MK-8583 100mg After fasting, a single oral dose of 100 mg MK-8583 in capsule form.	Drug: MK-8583; A single oral dose of MK-8583 in capsule form
Experimental: B: MK-8583 ≤ 150 mg After fasting, a single oral dose of ≤ 150 mg MK-8583 in capsule form, with the dose based on the results from earlier treatments	Drug: MK-8583; A single oral dose of MK-8583 in capsule form
Experimental: C: MK-8583 ≤ 150 mg After fasting, a single oral dose of ≤ 150 mg MK-8583 in capsule form, with the dose based on the results from earlier treatments	Drug: MK-8583; A single oral dose of MK-8583 in capsule form

Outcome Measures

Primary Outcome Measures

1. Number of Participants With at Least One Adverse Event (AE) [Up to Day 29]

   An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.

2. Number of Participants Who Discontinued Study Due to an AE [Day 1]

   An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.

3. Change From Baseline in Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) at 168 Hours Post-dose. [Baseline (pre-dose) and 168 hours post-dose.]

   Plasma HIV-1 RNA was measured at baseline and 168 hours after dosing. Change from baseline for MK-8583 at 168 hours post-baseline was estimated from longitudinal data analysis (LDA) model containing fixed effects for time (predose, 168 hours postdose) and a random effect for participant. The change from baseline in plasma HIV-1 RNA in participants administered MK-8583 was compared with historical placebo data.

Secondary Outcome Measures

1. Area Under the Concentration Time Curve From Time 0-168 Hours Postdose (AUC0-168hr) of Tenofovir Diphosphate (TFV-DP) [Pre-dose, 4, 12, 24, 48, 72, 96, and 168 hours postdose]

   Values of TFV-DP in peripheral blood mononuclear cells (PBMCs) were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The area under the concentration time curve from time 0-168 hours post-dose (AUC0-168hr) for intracellular TFV-DP is presented.

2. Time to Achieve Maximum Concentration (Tmax) of TFV-DP [Pre-dose, 4, 12, 24, 48, 72, 96, 168, 240, 312 and 672 hours postdose]

   Values of TFV-DP in PBMCs were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The time to achieve maximum concentration (Tmax) of intracellular TFV-DP is presented.

3. Maximum Concentration (Cmax) of TFV-DP [Pre-dose, 4, 12, 24, 48, 72, 96, 168, 240, 312 and 672 hours postdose]

   Values of TFV-DP in PBMCs were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The maximum concentration (Cmax) of intracellular TFV-DP is presented.

4. Concentration at 168 Hours Postdose (C168hr) of TFV-DP [168 hr postdose]

   Values of TFV-DP in PBMCs were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The concentration at 168 hours postdose (C168hr) of TFV-DP is presented. It is hypothesized that the true geometric mean (GM) of TFV-DP in PBMC is ≥ 0.1 μM (100 nmol/L).

5. Apparent Terminal Half-life (t1/2) of TFV-DP [Pre-dose, 4, 12, 24, 48, 72, 96, 168, 240, 312 and 672 hours postdose]

   Values of TFV-DP in PBMCs were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The apparent terminal half-life (t1/2) of intracellular TFV-DP is presented.

6. Area Under the Concentration Time Curve From Time 0-last Measurement (AUC0-last) of MK-8583 [Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose]

   Values of plasma MK-8583 were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The area under the concentration time curve from time 0-last measurement (AUC0-last) of plasma MK-8583 is presented. The last quantified concentration value occurred at 2 hours (n=4) and 4 hours (n=1).

7. Area Under the Concentration Time Curve From Time 0-infinity (AUC0-inf) of MK-8583 [Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose]

   Values of plasma MK-8583 were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose.

8. Tmax of Plasma MK-8583. [Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose]

   Values of plasma MK-8583 were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The time to achieve maximum concentration (Tmax) of plasma MK-8583 is presented.

9. Cmax of MK-8583 [Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose]

   Values of plasma MK-8583 were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The maximum concentration (Cmax) of plasma MK-8583 is presented.

10. t1/2 of MK-8583 [Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose]

    Values of plasma MK-8583 were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose.

11. Apparent Total Clearance (CL/F) of MK-8583 [Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose]

    Values of plasma MK-8583 were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The apparent total clearance (CL/F) of plasma MK-8583 is presented.

12. Apparent Volume of Distribution (Vz/F) of MK-8583 [Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose]

    Values of plasma MK-8583 were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose.

13. AUC0-last of Tenofovir (TFV) [Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose]

    Values of plasma TFV were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The area under the concentration time curve from time 0-last measurement (AUC0-last) of plasma TFV is presented.

14. AUC0-inf of TFV [Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose]

    Values of plasma TFV were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The area under the concentration time curve from time 0-infinity (AUC0-inf) of plasma TFV is presented.

15. Tmax of TFV [Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose]

    Values of plasma TFV were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The time to achieve maximum concentration (Tmax) of plasma TFV is presented.

16. Cmax of TFV [Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose]

    Values of plasma TFV were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The maximum concentration (Cmax) of plasma TFV is presented.

17. t1/2 of TFV [Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose]

    Values of plasma TFV were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The apparent terminal half-life (t1/2) of plasma TFV is presented.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male with female partner(s) of child-bearing potential use required methods of birth control.

• Female of reproductive potential must demonstrate a nongravid state at the pretrial (screening) visit and agree to use acceptable methods of birth control beginning at the pretrial (screening) visit, throughout the trial and until 30 days following cessation of treatment.

• Postmenopausal female, defined as without menses for at least 1 year and have a documented follicle stimulating hormone (FSH) level in the postmenopausal range at pretrial (screening).

• Surgically sterile female's status is post hysterectomy or oophorectomy.

• Is documented HIV-1 positive

• Is diagnosed with HIV-1 infection ≥ 3 months prior to screening.

• Is ART-naïve, defined as having never received any anti-retroviral agent; or ≤ 30 consecutive days of an investigational anti-retroviral agent, excluding a nucleoside reverse transcriptase inhibitor (NRTI), or ≤ 60 consecutive days of combination ART not including a NRTI.

Exclusion Criteria:

• Is mentally or legally institutionalized/incapacitated, has 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 over the last 5 years.

• 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.

• Has a history of cancer (malignancy).

• Has a history of significant multiple and/or severe allergies (e.g. food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability (i.e. systemic allergic reaction) to prescription or non-prescription drugs or food.

• Is positive for Hepatitis B surface antigen.

• Has a history of chronic Hepatitis C unless there has been documented cure.

• Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the pretrial (screening) visit.

• Has participated in another investigational trial within 4 weeks or 5 half-lives, whichever is greater, prior to the pre-trial (screening) visit.

• Uses or anticipates using any medication, including prescription and non-prescription drugs or herbal remedies beginning approximately 2 weeks (or 5 half-lives) 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, wine or distilled spirits per day.

• Consumes excessive amounts of 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 (except for cannabis) at screening and/or pre-dose.

• Has received any investigational agent or any anti-retroviral agent within 60 days of study drug administration; or intends to receive any ART during this study.

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 - Mar 9, 2018

More Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT03552536
• Other Study ID Numbers: 8583-002; 2017-004017-92; MK-8583-002
• First Posted: Jun 12, 2018
• Last Update Posted: Mar 4, 2020
• Last Verified: Feb 1, 2020

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

Study Results

Participant Flow

Recruitment Details	Participants with human immunodeficiency virus-1 (HIV-1) infection who were naïve to anti-retroviral therapy (ART) were enrolled. Only participants from Panel A were recruited. Due to an earlier than anticipated achievement of the study objectives, a decision was made not to conduct Panels B and C.

Arm/Group Title	A: MK-8583 100mg	B: MK-8583 ≤ 150 mg	C: MK-8583 ≤ 150 mg
Arm/Group Description	After fasting, a single oral dose of 100 mg MK-8583 in capsule form.	After fasting, a single oral dose of ≤ 150 mg MK-8583 in capsule form.	After fasting, a single oral dose of ≤ 150 mg MK-8583 in capsule form.
Period Title: Overall Study
STARTED	5	0	0
COMPLETED	5	0	0
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	A: MK-8583 100mg	B: MK-8583 ≤ 150 mg	C: MK-8583 ≤ 150 mg	Total
Arm/Group Description	After fasting, a single oral dose of 100 mg MK-8583 in capsule form.	After fasting, a single oral dose of ≤ 150 mg MK-8583 in capsule form.	After fasting, a single oral dose of ≤ 150 mg MK-8583 in capsule form.	Total of all reporting groups
Overall Participants	5	0	0	5
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	30.2 (10.9)	30.2 (10.9)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 NaN	0 NaN	0 0%
Male	5 100%	0 NaN	0 NaN	5 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 NaN	0 NaN	0 0%
Not Hispanic or Latino	5 100%	0 NaN	0 NaN	5 100%
Unknown or Not Reported	0 0%	0 NaN	0 NaN	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 NaN	0 NaN	0 0%
Asian	0 0%	0 NaN	0 NaN	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 NaN	0 NaN	0 0%
Black or African American	0 0%	0 NaN	0 NaN	0 0%
White	5 100%	0 NaN	0 NaN	5 100%
More than one race	0 0%	0 NaN	0 NaN	0 0%
Unknown or Not Reported	0 0%	0 NaN	0 NaN	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With at Least One Adverse Event (AE)
Description	An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
Time Frame	Up to Day 29

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of treatment. Participants from Panels B and C were not analyzed because they were not enrolled in the study.

Arm/Group Title	A: MK-8583 100mg
Arm/Group Description	After fasting, a single oral dose of 100 mg MK-8583 in capsule form.
Measure Participants	5
Count of Participants [Participants]	4 80%

2. Primary Outcome

Title	Number of Participants Who Discontinued Study Due to an AE
Description	An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of treatment. Participants from Panels B and C were not analyzed because they were not enrolled in the study.

Arm/Group Title	A: MK-8583 100mg
Arm/Group Description	After fasting, a single oral dose of 100 mg MK-8583 in capsule form.
Measure Participants	5
Count of Participants [Participants]	0 0%

3. Primary Outcome

Title	Change From Baseline in Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) at 168 Hours Post-dose.
Description	Plasma HIV-1 RNA was measured at baseline and 168 hours after dosing. Change from baseline for MK-8583 at 168 hours post-baseline was estimated from longitudinal data analysis (LDA) model containing fixed effects for time (predose, 168 hours postdose) and a random effect for participant. The change from baseline in plasma HIV-1 RNA in participants administered MK-8583 was compared with historical placebo data.
Time Frame	Baseline (pre-dose) and 168 hours post-dose.

Outcome Measure Data

Analysis Population Description

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 B and C were not analyzed because they were not enrolled in the study.

Arm/Group Title	A: MK-8583 100mg
Arm/Group Description	After fasting, a single oral dose of 100 mg MK-8583 in capsule form.
Measure Participants	5
Least Squares Mean (95% Confidence Interval) [log10 copies/mL]	-0.63

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A: MK-8583 100mg
	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. Least squares (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	-0.60
	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-8583 and placebo at least 0.5 log10 copies/mL was 64%.

4. Secondary Outcome

Title	Area Under the Concentration Time Curve From Time 0-168 Hours Postdose (AUC0-168hr) of Tenofovir Diphosphate (TFV-DP)
Description	Values of TFV-DP in peripheral blood mononuclear cells (PBMCs) were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The area under the concentration time curve from time 0-168 hours post-dose (AUC0-168hr) for intracellular TFV-DP is presented.
Time Frame	Pre-dose, 4, 12, 24, 48, 72, 96, and 168 hours postdose

Outcome Measure Data

Analysis Population Description

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 B and C were not analyzed because they were not enrolled in the study.

Arm/Group Title	A: MK-8583 100mg
Arm/Group Description	After fasting, a single oral dose of 100 mg MK-8583 in capsule form.
Measure Participants	5
Geometric Mean (Geometric Coefficient of Variation) [hr*nmol/L]	324000 (179)

5. Secondary Outcome

Title	Time to Achieve Maximum Concentration (Tmax) of TFV-DP
Description	Values of TFV-DP in PBMCs were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The time to achieve maximum concentration (Tmax) of intracellular TFV-DP is presented.
Time Frame	Pre-dose, 4, 12, 24, 48, 72, 96, 168, 240, 312 and 672 hours postdose

Outcome Measure Data

Analysis Population Description

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 B and C were not analyzed because they were not enrolled in the study.

Arm/Group Title	A: MK-8583 100mg
Arm/Group Description	After fasting, a single oral dose of 100 mg MK-8583 in capsule form.
Measure Participants	5
Median (Full Range) [hr.]	12

6. Secondary Outcome

Title	Maximum Concentration (Cmax) of TFV-DP
Description	Values of TFV-DP in PBMCs were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The maximum concentration (Cmax) of intracellular TFV-DP is presented.
Time Frame	Pre-dose, 4, 12, 24, 48, 72, 96, 168, 240, 312 and 672 hours postdose

Outcome Measure Data

Analysis Population Description

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 B and C were not analyzed because they were not enrolled in the study.

Arm/Group Title	A: MK-8583 100mg
Arm/Group Description	After fasting, a single oral dose of 100 mg MK-8583 in capsule form.
Measure Participants	5
Geometric Mean (Geometric Coefficient of Variation) [nmol/L]	4660 (182)

7. Secondary Outcome

Title	Concentration at 168 Hours Postdose (C168hr) of TFV-DP
Description	Values of TFV-DP in PBMCs were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The concentration at 168 hours postdose (C168hr) of TFV-DP is presented. It is hypothesized that the true geometric mean (GM) of TFV-DP in PBMC is ≥ 0.1 μM (100 nmol/L).
Time Frame	168 hr postdose

Outcome Measure Data

Analysis Population Description

Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment. The PBMC sample from one participant was processed incorrectly, so was not included in the analysis. Participants from Panels B and C were not analyzed because they were not enrolled in the study.

Arm/Group Title	A: MK-8583 100mg
Arm/Group Description	After fasting, a single oral dose of 100 mg MK-8583 in capsule form.
Measure Participants	4
Geometric Mean (Geometric Coefficient of Variation) [nmol/L]	940 (414)

8. Secondary Outcome

Title	Apparent Terminal Half-life (t1/2) of TFV-DP
Description	Values of TFV-DP in PBMCs were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The apparent terminal half-life (t1/2) of intracellular TFV-DP is presented.
Time Frame	Pre-dose, 4, 12, 24, 48, 72, 96, 168, 240, 312 and 672 hours postdose

Outcome Measure Data

Analysis Population Description

Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment. One participant who had insufficient data on terminal phase was not included in the analysis. Participants from Panels B and C were not analyzed because they were not enrolled in the study.

Arm/Group Title	A: MK-8583 100mg
Arm/Group Description	After fasting, a single oral dose of 100 mg MK-8583 in capsule form.
Measure Participants	4
Geometric Mean (Geometric Coefficient of Variation) [hr.]	241 (23.7)

9. Secondary Outcome

Title	Area Under the Concentration Time Curve From Time 0-last Measurement (AUC0-last) of MK-8583
Description	Values of plasma MK-8583 were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The area under the concentration time curve from time 0-last measurement (AUC0-last) of plasma MK-8583 is presented. The last quantified concentration value occurred at 2 hours (n=4) and 4 hours (n=1).
Time Frame	Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose

Outcome Measure Data

Analysis Population Description

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 B and C were not analyzed because they were not enrolled in the study.

Arm/Group Title	A: MK-8583 100mg
Arm/Group Description	After fasting, a single oral dose of 100 mg MK-8583 in capsule form.
Measure Participants	5
Geometric Mean (Geometric Coefficient of Variation) [hr*nmol/L]	220 (415)

10. Secondary Outcome

Title	Area Under the Concentration Time Curve From Time 0-infinity (AUC0-inf) of MK-8583
Description	Values of plasma MK-8583 were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose.
Time Frame	Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose

Outcome Measure Data

Analysis Population Description

Due to insufficient plasma concentration data at the terminal phase, AUC0-inf of plasma MK-8583 was not able to be calculated for any participants. Participants from Panels B and C were not analyzed because they were not enrolled in the study.

Arm/Group Title	A: MK-8583 100mg
Arm/Group Description	After fasting, a single oral dose of 100 mg MK-8583 in capsule form.
Measure Participants	0

11. Secondary Outcome

Title	Tmax of Plasma MK-8583.
Description	Values of plasma MK-8583 were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The time to achieve maximum concentration (Tmax) of plasma MK-8583 is presented.
Time Frame	Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose

Outcome Measure Data

Analysis Population Description

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 B and C were not analyzed because they were not enrolled in the study.

Arm/Group Title	A: MK-8583 100mg
Arm/Group Description	After fasting, a single oral dose of 100 mg MK-8583 in capsule form.
Measure Participants	5
Median (Full Range) [hr.]	1

12. Secondary Outcome

Title	Cmax of MK-8583
Description	Values of plasma MK-8583 were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The maximum concentration (Cmax) of plasma MK-8583 is presented.
Time Frame	Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose

Outcome Measure Data

Analysis Population Description

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 B and C were not analyzed because they were not enrolled in the study.

Arm/Group Title	A: MK-8583 100mg
Arm/Group Description	After fasting, a single oral dose of 100 mg MK-8583 in capsule form.
Measure Participants	5
Geometric Mean (Geometric Coefficient of Variation) [nmol/L]	258 (440)

13. Secondary Outcome

Title	t1/2 of MK-8583
Description	Values of plasma MK-8583 were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose.
Time Frame	Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose

Outcome Measure Data

Analysis Population Description

Due to insufficient plasma concentration data at the terminal phase, t1/2 of plasma MK-8583 was not able to be calculated for any participants. Participants from Panels B and C were not analyzed because they were not enrolled in the study.

Arm/Group Title	A: MK-8583 100mg
Arm/Group Description	After fasting, a single oral dose of 100 mg MK-8583 in capsule form.
Measure Participants	0

14. Secondary Outcome

Title	Apparent Total Clearance (CL/F) of MK-8583
Description	Values of plasma MK-8583 were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The apparent total clearance (CL/F) of plasma MK-8583 is presented.
Time Frame	Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose

Outcome Measure Data

Analysis Population Description

Due to insufficient plasma concentration data at the terminal phase, CL/F of plasma MK-8583 was not able to be calculated for any participants. Participants from Panels B and C were not analyzed because they were not enrolled in the study.

Arm/Group Title	A: MK-8583 100mg
Arm/Group Description	After fasting, a single oral dose of 100 mg MK-8583 in capsule form.
Measure Participants	0

15. Secondary Outcome

Title	Apparent Volume of Distribution (Vz/F) of MK-8583
Description	Values of plasma MK-8583 were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose.
Time Frame	Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose

Outcome Measure Data

Analysis Population Description

Due to insufficient plasma concentration data at the terminal phase, Vz/F of plasma MK-8583 was not able to be calculated for any participants. Participants from Panels B and C were not analyzed because they were not enrolled in the study.

Arm/Group Title	A: MK-8583 100mg
Arm/Group Description	After fasting, a single oral dose of 100 mg MK-8583 in capsule form.
Measure Participants	0

16. Secondary Outcome

Title	AUC0-last of Tenofovir (TFV)
Description	Values of plasma TFV were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The area under the concentration time curve from time 0-last measurement (AUC0-last) of plasma TFV is presented.
Time Frame	Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose

Outcome Measure Data

Analysis Population Description

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 B and C were not analyzed because they were not enrolled in the study.

Arm/Group Title	A: MK-8583 100mg
Arm/Group Description	After fasting, a single oral dose of 100 mg MK-8583 in capsule form.
Measure Participants	5
Geometric Mean (Geometric Coefficient of Variation) [hr*nmol/L]	1090 (187)

17. Secondary Outcome

Title	AUC0-inf of TFV
Description	Values of plasma TFV were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The area under the concentration time curve from time 0-infinity (AUC0-inf) of plasma TFV is presented.
Time Frame	Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose

Outcome Measure Data

Analysis Population Description

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 B and C were not analyzed because they were not enrolled in the study.

Arm/Group Title	A: MK-8583 100mg
Arm/Group Description	After fasting, a single oral dose of 100 mg MK-8583 in capsule form.
Measure Participants	5
Geometric Mean (Geometric Coefficient of Variation) [hr*nmol/L]	1550 (108)

18. Secondary Outcome

Title	Tmax of TFV
Description	Values of plasma TFV were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The time to achieve maximum concentration (Tmax) of plasma TFV is presented.
Time Frame	Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose

Outcome Measure Data

Analysis Population Description

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 B and C were not analyzed because they were not enrolled in the study.

Arm/Group Title	A: MK-8583 100mg
Arm/Group Description	After fasting, a single oral dose of 100 mg MK-8583 in capsule form.
Measure Participants	5
Median (Full Range) [hr.]	2

19. Secondary Outcome

Title	Cmax of TFV
Description	Values of plasma TFV were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The maximum concentration (Cmax) of plasma TFV is presented.
Time Frame	Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose

Outcome Measure Data

Analysis Population Description

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 B and C were not analyzed because they were not enrolled in the study.

Arm/Group Title	A: MK-8583 100mg
Arm/Group Description	After fasting, a single oral dose of 100 mg MK-8583 in capsule form.
Measure Participants	5
Geometric Mean (Geometric Coefficient of Variation) [nmol/L]	64.3 (137)

20. Secondary Outcome

Title	t1/2 of TFV
Description	Values of plasma TFV were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The apparent terminal half-life (t1/2) of plasma TFV is presented.
Time Frame	Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose

Outcome Measure Data

Analysis Population Description

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 B and C were not analyzed because they were not enrolled in the study.

Arm/Group Title	A: MK-8583 100mg
Arm/Group Description	After fasting, a single oral dose of 100 mg MK-8583 in capsule form.
Measure Participants	5
Geometric Mean (Geometric Coefficient of Variation) [hr.]	31.5 (13.2)

Adverse Events

Time Frame	Up to Day 29
Adverse Event Reporting Description	All participants who received at least one dose of treatment. Due to an earlier than anticipated achievement of the study objectives, a decision was made not to conduct Panels B and C.
Arm/Group Title	MK-8583 100 mg		B: MK-8583 ≤ 150 mg		C: MK-8583 ≤ 150 mg
Arm/Group Description	After fasting, a single oral dose of 100 mg MK-8583 in capsule form.		After fasting, a single oral dose of ≤ 150 mg MK-8583 in capsule form.		After fasting, a single oral dose of ≤ 150 mg MK-8583 in capsule form.
All Cause Mortality
	MK-8583 100 mg		B: MK-8583 ≤ 150 mg		C: MK-8583 ≤ 150 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/0 (NaN)		0/0 (NaN)
Serious Adverse Events
	MK-8583 100 mg		B: MK-8583 ≤ 150 mg		C: MK-8583 ≤ 150 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	MK-8583 100 mg		B: MK-8583 ≤ 150 mg		C: MK-8583 ≤ 150 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/5 (80%)		0/0 (NaN)		0/0 (NaN)
Cardiac disorders
Sinus tachycardia	1/5 (20%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Gastrointestinal disorders
Abdominal pain upper	1/5 (20%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Diarrhoea	1/5 (20%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Infections and infestations
Herpes zoster	1/5 (20%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Nasopharyngitis	1/5 (20%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications	1/5 (20%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Investigations
Hepatic enzyme increased	1/5 (20%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Musculoskeletal and connective tissue disorders
Back pain	1/5 (20%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Nervous system disorders
Headache	1/5 (20%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Vascular disorders
Haematoma	1/5 (20%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results.