CompletedNCT03552536Updated Mar 4, 2020Results posted

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

A Phase 1 interventional study of MK-8583 in HIV-1 Infection, sponsored by Merck Sharp & Dohme LLC. Completed at 1 site in Germany. Open to participants aged 18 Years to 60 Years. Per ClinicalTrials.gov, last updated 2020-03-04.

Sponsored by Merck Sharp & Dohme LLC · Phase 1, Interventional, and Treatment

Phase: Phase 1
Study type: Interventional
Enrollment: 5
Allocation: Non-randomized
Ages: 18 Years to 60 Years
Sex: All

Study 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.

Conditions studied

HIV-1 Infection

In context

Lead sponsor

Merck Sharp & Dohme LLC is the lead sponsor of 2,114 studies on the registry; 133 are open to participants now.

Of its 489 completed or terminated interventional studies of FDA-regulated products, 362 (74%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 60 Years
Sexes eligible: 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

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.

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Sequential assignment
Masking: None (open label)
Enrollment: 5 participants (actual)

Study arms

Experimental
A: MK-8583 100mg
After fasting, a single oral dose of 100 mg MK-8583 in capsule form.
Drug: MK-8583
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
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

Interventions

DrugMK-8583
A single oral dose of MK-8583 in capsule form

What researchers measure

Primary outcomes

Number of Participants With at Least One Adverse Event (AE)
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
Number of Participants Who Discontinued Study Due to an AE
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
Change From Baseline in Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) at 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.
Time frame: Baseline (pre-dose) and 168 hours post-dose.

Secondary outcomes

Area Under the Concentration Time Curve From Time 0-168 Hours Postdose (AUC0-168hr) of Tenofovir Diphosphate (TFV-DP)
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
Time to Achieve Maximum Concentration (Tmax) of TFV-DP
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
Maximum Concentration (Cmax) of TFV-DP
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
Concentration at 168 Hours Postdose (C168hr) of TFV-DP
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
Apparent Terminal Half-life (t1/2) of TFV-DP
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
Area Under the Concentration Time Curve From Time 0-last Measurement (AUC0-last) of MK-8583
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
Area Under the Concentration Time Curve From Time 0-infinity (AUC0-inf) of MK-8583
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
Tmax of Plasma MK-8583.
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
Cmax of MK-8583
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
t1/2 of MK-8583
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
Apparent Total Clearance (CL/F) of MK-8583
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
Apparent Volume of Distribution (Vz/F) of MK-8583
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
AUC0-last of Tenofovir (TFV)
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
AUC0-inf of TFV
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
Tmax of TFV
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
Cmax of TFV
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
t1/2 of TFV
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

Results

Posted Mar 4, 2020

Participant flow

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.

Participant flow — Overall Study
Milestone	A: MK-8583 100mg	B: MK-8583 ≤ 150 mg	C: MK-8583 ≤ 150 mg
Started	5	0	0
Completed	5	0	0
Not completed	0	0	0

Outcome measures

PrimaryNumber of Participants With at Least One Adverse Event (AE)

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
Reported as:: Count of participants · Participants

Number of Participants With at Least One Adverse Event (AE)
Participants	A: MK-8583 100mg
Number of Participants With at Least One Adverse Event (AE)	4

PrimaryNumber of Participants Who Discontinued Study Due to an AE

Time frame:: Day 1
Reported as:: Count of participants · Participants

Number of Participants Who Discontinued Study Due to an AE
Participants	A: MK-8583 100mg
Number of Participants Who Discontinued Study Due to an AE	0

PrimaryChange From Baseline in Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) at 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.

Time frame:: Baseline (pre-dose) and 168 hours post-dose.
Reported as:: Least squares mean · log10 copies/mL

Change From Baseline in Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) at 168 Hours Post-dose.
log10 copies/mL	A: MK-8583 100mg
Change From Baseline in Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) at 168 Hours Post-dose.	-0.63 (-1.30 to 0.05)

Statistical analysis

A: MK-8583 100mg · Posterior mean difference: -0.60Posterior 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%.

SecondaryArea Under the Concentration Time Curve From Time 0-168 Hours Postdose (AUC0-168hr) of Tenofovir Diphosphate (TFV-DP)

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
Reported as:: Geometric mean · hr*nmol/L

Area Under the Concentration Time Curve From Time 0-168 Hours Postdose (AUC0-168hr) of Tenofovir Diphosphate (TFV-DP)
hr*nmol/L	A: MK-8583 100mg
Area Under the Concentration Time Curve From Time 0-168 Hours Postdose (AUC0-168hr) of Tenofovir Diphosphate (TFV-DP)	324000 ± 179

SecondaryTime to Achieve Maximum Concentration (Tmax) of TFV-DP

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
Reported as:: Median · hr.

Time to Achieve Maximum Concentration (Tmax) of TFV-DP
hr.	A: MK-8583 100mg
Time to Achieve Maximum Concentration (Tmax) of TFV-DP	12 (4 to 12)

SecondaryMaximum Concentration (Cmax) of TFV-DP

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
Reported as:: Geometric mean · nmol/L

Maximum Concentration (Cmax) of TFV-DP
nmol/L	A: MK-8583 100mg
Maximum Concentration (Cmax) of TFV-DP	4660 ± 182

SecondaryConcentration at 168 Hours Postdose (C168hr) of TFV-DP

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
Reported as:: Geometric mean · nmol/L

Concentration at 168 Hours Postdose (C168hr) of TFV-DP
nmol/L	A: MK-8583 100mg
Concentration at 168 Hours Postdose (C168hr) of TFV-DP	940 ± 414

SecondaryApparent Terminal Half-life (t1/2) of TFV-DP

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
Reported as:: Geometric mean · hr.

Apparent Terminal Half-life (t1/2) of TFV-DP
hr.	A: MK-8583 100mg
Apparent Terminal Half-life (t1/2) of TFV-DP	241 ± 23.7

SecondaryArea Under the Concentration Time Curve From Time 0-last Measurement (AUC0-last) of MK-8583

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
Reported as:: Geometric mean · hr*nmol/L

Area Under the Concentration Time Curve From Time 0-last Measurement (AUC0-last) of MK-8583
hr*nmol/L	A: MK-8583 100mg
Area Under the Concentration Time Curve From Time 0-last Measurement (AUC0-last) of MK-8583	220 ± 415

SecondaryArea Under the Concentration Time Curve From Time 0-infinity (AUC0-inf) of MK-8583

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

No measurements were reported for this outcome.

SecondaryTmax of Plasma MK-8583.

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
Reported as:: Median · hr.

Tmax of Plasma MK-8583.
hr.	A: MK-8583 100mg
Tmax of Plasma MK-8583.	1 (0.5 to 2)

SecondaryCmax of MK-8583

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
Reported as:: Geometric mean · nmol/L

Cmax of MK-8583
nmol/L	A: MK-8583 100mg
Cmax of MK-8583	258 ± 440

Secondaryt1/2 of MK-8583

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

No measurements were reported for this outcome.

SecondaryApparent Total Clearance (CL/F) of MK-8583

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

No measurements were reported for this outcome.

SecondaryApparent Volume of Distribution (Vz/F) of MK-8583

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

No measurements were reported for this outcome.

SecondaryAUC0-last of Tenofovir (TFV)

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
Reported as:: Geometric mean · hr*nmol/L

AUC0-last of Tenofovir (TFV)
hr*nmol/L	A: MK-8583 100mg
AUC0-last of Tenofovir (TFV)	1090 ± 187

SecondaryAUC0-inf of TFV

Time frame:: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose
Reported as:: Geometric mean · hr*nmol/L

AUC0-inf of TFV
hr*nmol/L	A: MK-8583 100mg
AUC0-inf of TFV	1550 ± 108

SecondaryTmax of TFV

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
Reported as:: Median · hr.

Tmax of TFV
hr.	A: MK-8583 100mg
Tmax of TFV	2 (1 to 4)

SecondaryCmax of TFV

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
Reported as:: Geometric mean · nmol/L

Cmax of TFV
nmol/L	A: MK-8583 100mg
Cmax of TFV	64.3 ± 137

Secondaryt1/2 of TFV

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
Reported as:: Geometric mean · hr.

t1/2 of TFV
hr.	A: MK-8583 100mg
t1/2 of TFV	31.5 ± 13.2

Adverse events

Collected over Up to Day 29. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
MK-8583 100 mg	0/5 (0%)	0/5 (0%)	4/5 (80%)
B: MK-8583 ≤ 150 mg	—	—	—
C: MK-8583 ≤ 150 mg	—	—	—

Most frequent other events

Most frequent other events
Event	MK-8583 100 mg	B: MK-8583 ≤ 150 mg	C: MK-8583 ≤ 150 mg
Sinus tachycardiaCardiac disorders	1/5	—	—
Abdominal pain upperGastrointestinal disorders	1/5	—	—
DiarrhoeaGastrointestinal disorders	1/5	—	—
Herpes zosterInfections and infestations	1/5	—	—
NasopharyngitisInfections and infestations	1/5	—	—
Injury, poisoning and procedural complicationsInjury, poisoning and procedural complications	1/5	—	—
Hepatic enzyme increasedInvestigations	1/5	—	—
Back painMusculoskeletal and connective tissue disorders	1/5	—	—
HeadacheNervous system disorders	1/5	—	—
HaematomaVascular disorders	1/5	—	—

Baseline characteristics

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.

Age, Continuous
Age, Continuous(Years)	A: MK-8583 100mg	B: MK-8583 ≤ 150 mg	C: MK-8583 ≤ 150 mg	Total
Mean	30.2 ± 10.9	—	—	30.2 ± 10.9

Sex: Female, Male
Sex: Female, Male(Participants)	A: MK-8583 100mg	B: MK-8583 ≤ 150 mg	C: MK-8583 ≤ 150 mg	Total
Female	0	0	0	0
Male	5	0	0	5

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	A: MK-8583 100mg	Total
Hispanic or Latino	0	0
Not Hispanic or Latino	5	5
Unknown or Not Reported	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	A: MK-8583 100mg	Total
American Indian or Alaska Native	0	0
Asian	0	0
Native Hawaiian or Other Pacific Islander	0	0
Black or African American	0	0
White	5	5
More than one race	0	0
Unknown or Not Reported	0	0

Study locations

1 site

Charite Research Organisation GmbH ( Site 0001)
Berlin, 10117, Germany

References and documents

Study documents

Protocol and statistical analysis plan · Mar 9, 2018

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Mar 4, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT03552536
Lead sponsor: Merck Sharp & Dohme LLC
Responsible party: Sponsor
First posted: Jun 12, 2018
Start date: Oct 7, 2018
Primary completion: Mar 11, 2019
Completion: Mar 11, 2019
Results posted: Mar 4, 2020
Last update: Mar 4, 2020

Study contacts

Medical Director

study director · Merck Sharp & Dohme LLC

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Feb 2020. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies from this sponsor

Merck Sharp & Dohme LLC

Start the discussion

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

Study summary

Conditions studied

In context

Lead sponsor

Who can participate

✓Inclusion criteria

✕Exclusion criteria

Study design

Study arms

Interventions

What researchers measure

Primary outcomes

Secondary outcomes

Results

Participant flow

Outcome measures

Adverse events

Baseline characteristics

Study locations

References and documents

Study documents

Individual participant data

Updates

Registry details

Key details

Study contacts

Oversight

Not currently enrolling

Follow this study

Discussion

Other studies from this sponsor

Inclusion criteria

Exclusion criteria