A Study of MK-8527 in Human Immunodeficiency Type 1 Virus (HIV-1) Infected Participants (MK-8527-002)

Human Immunodeficiency Virus Clinical Trial

Official title:

A Single-Dose Clinical Trial to Study the Safety, Tolerability, Pharmacokinetics, and Anti-Retroviral Activity of MK-8527 Monotherapy in Anti-Retroviral Therapy (ART)-Naïve, HIV-1 Infected Participants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03615183
• Other study ID #: 8527-002
• Secondary ID: 2018-001861-18MK
• Status: Completed
• Phase: Phase 1
• Start date: February 11, 2019
• Est. completion date: September 26, 2019

Study information

• Verified date: September 2020
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the anti-retroviral activity of MK-8527 in HIV-1 infected, ART-naïve participants. The primary hypothesis is that MK-8527 has superior anti-retroviral activity compared to placebo, as measured by change from baseline in plasma HIV-1 ribonucleic acid (RNA) at 168 hours postdose.

Description:

Up to five panels (Panels A-E) of 6 participants each will be enrolled in a sequential manner. In each panel, participants will receive a single dose of MK-8527 up to 50 mg. Historical data from previous single does studies will be used for placebo (control) comparisons.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: September 26, 2019
• Est. primary completion date: September 26, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria

• Other than HIV infection, is in good health

• Is documented HIV-1 positive

• Diagnosed with HIV-1 infection = 3 months prior to screening or perform the French 2008 Haute Autorité de Santé (HAS) Algorithm to confirm chronic HIV.

• Is ART-naïve which is defined as having never received any antiretroviral agent or the following: =30 consecutive days of an investigational antiretroviral agent, excluding an Nucleoside reverse transcriptase inhibitors (NRTI), or =60 consecutive days of combination ART not including an NRTI

• Has not received an investigational agent or marketed ART within 30 days of study drug administration

• Is willing to receive no other ART for the monitoring period of the study

• Has a Body Mass Index (BMI) =35 kg/m^2, inclusive

• If the male participant has a female partner(s) of childbearing potential, he must agree to use a medically acceptable method of contraception during the study and for 120 days after the last dose of study drug. If their partner is pregnant, males must agree to use a condom and no additional method of contraception is required for the pregnant partner

• If the participant is a female with reproductive potential, she must demonstrate a serum ß-human chorionic gonadotropin (ß-hCG) level consistent with the nongravid state at the prestudy (screening) visit and agree to use (and/or have their partner use) 2 acceptable methods of birth control beginning at the prestudy (screening) visit, throughout the study (including washout intervals between treatment periods/panels) and until 28 days after the last dose of study drug.

• If the participant is a postmenopausal female: she is without menses for at least 1 year and have a documented follicle stimulating hormone (FSH) level in the postmenopausal range at prestudy (screening)

• If the participant is a surgically sterile female: she is status posthysterectomy, or oophorectomy

Exclusion Criteria

• Has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological (outside of HIV-1 infection), renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases. Participants with a remote history of uncomplicated medical events (eg, uncomplicated kidney stones, as defined as spontaneous passage and no recurrence in the last 5 years, or childhood asthma) may be enrolled in the study at the discretion of the investigator.

• Is mentally or legally incapacitated at the time of the prestudy (screening) visit or expected during the conduct of the study or has a history of clinically significant psychiatric disorder over the last 5 years. Participants who have had situational depression may be enrolled in the study at the discretion of the investigator.

• History of cancer (malignancy)

• History of significant multiple and/or severe allergies or has had an anaphylactic reaction or significant intolerability (i.e. systemic allergic reaction) to prescription or non-prescription drugs or food.

• Positive for hepatitis B surface antigen

• History of chronic hepatitis C unless there has been documented cure and/or participant with a positive serologic test for hepatitis C virus (HCV) has a negative HCV viral load (VL)

• Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks

• Unable to refrain from or anticipates the use of any medication, including prescription and nonprescription drugs or herbal remedies beginning approximately 2 weeks (or 5 half-lives) prior to administration of the initial dose of study drug, throughout the study, until the poststudy visit.

• Participated in another investigational study within 4 weeks

• Consumes greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer [354 mL/12 ounces], wine [118 mL/4 ounces], or distilled spirits [29.5 mL/1 ounce]) per day.

• Consumes excessive amounts, defined as greater than 6 servings (1 serving approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, energy drinks, or other caffeinated beverages per day

• Is an excessive smoker (i.e., more than 10 cigarettes/day) and is unwilling to restrict smoking to =10 cigarettes per day

• Has a positive urine drug screen

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• AIDS Virus
• HIV Infections
• Human Immunodeficiency Virus
• Immunologic Deficiency Syndromes
• Virus Diseases

Intervention

Drug:
• MK-8527
Single oral capsule

Locations

Country	Name	City	State
Romania	Matei Bals Infectious Diseases Institute ( Site 0001)	Bucharest

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

Romania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Plasma HIV-1 RNA	Blood samples were taken to determine HIV-1 RNA levels at Predose (baseline) and 168 hours postdose. Data were fitted with a longitudinal data analysis (LDA) model containing fixed effects for treatment, time and treatment by time interaction, and a random effect for participant.The change from baseline in plasma HIV-1 RNA in participants administered MK-8527 was calculated and results were compared with historical placebo data.	Baseline and 168 hours postdose
Primary	Percentage of Participants Who Report 1 or More Adverse Events (AEs)	An AE is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not it is considered related to the medicinal product. The percentage of participants that reported at least 1 AE will be summarized.	Up to 28 days
Primary	Percentage of Participants Who Were Discontinued From the Study Due to an AE	An AE is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not it is considered related to the medicinal product. The percentage of participants that were discontinued from the study due to an AE will be summarized.	Up to 28 days
Secondary	Area Under the Concentration Time Curve From Hour 0 to 168 Hours (AUC0-168) of MK-8527-TP in Peripheral Blood Mononuclear Cells (PBMC)	Blood samples were taken at Predose, up to 168 hours postdose to determine the AUC0-168 of MK-8527-triphosphate (MK-8527-TP) in PBMCs. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% confidence intervals (CI) for the means were constructed on the natural log scale and referenced the t-distribution.	Predose and 4, 12, 24, 96, 120, 144, and 168 hours postdose
Secondary	Area Under the Concentration Time Curve From Hour 0 to Last (AUC0-last) of MK-8527-TP in PBMC	Blood samples were taken at Predose, up to approximately 28 days postdose to determine the AUC0-last of MK-8527-TP in PBMCs. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.	Predose and 4, 12, 24, 96, 120, 144, 168, 240, 336, 504, 672 hours or 28 days postdose
Secondary	Area Under the Concentration Time Curve From Hour 0 to Infinity (AUC0-inf) of MK-8527-TP in PBMC	Blood samples were taken at Predose, up to approximately 28 days postdose to determine the AUC0-Inf of MK-8527-TP in PBMCs. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.	Predose and 4, 12, 24, 96, 120, 144, 168, 240, 336, 504, 672 hours or 28 days postdose
Secondary	Maximum Concentration (Cmax) of MK-8527-TP in PBMC	Blood samples were taken at Predose, up to approximately 28 days postdose to determine the Cmax of MK-8527-TP in PBMCs. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.	Predose and 4, 12, 24, 96, 120, 144, 168, 240, 336, 504, 672 hours or 28 days postdose
Secondary	Time to Cmax (Tmax) of MK-8527-TP in PBMC	Blood samples were taken at Predose, up to approximately 28 days postdose to determine the Tmax of MK-8527-TP in PBMCs. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.	Predose and 4, 12, 24, 96, 120, 144, 168, 240, 336, 504, 672 hours or 28 days postdose
Secondary	Concentration at 168 Hours (C168) of MK-8527-TP in PBMC	Blood samples were taken at 168 hours postdose to determine the C168 of MK-8527-TP in PBMCs. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.	168 hours postdose for each panel
Secondary	Apparent Terminal Half Life (t1/2) of MK-8527-TP in PBMC	Blood samples were taken at Predose, up to approximately 28 days postdose to determine the t1/2 of MK-8527-TP in PBMCs. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.	Predose and 4, 12, 24, 96, 120, 144, 168, 240, 336, 504, 672 hours or 28 days postdose
Secondary	Area Under the Concentration Time Curve From Hour 0 to 168 Hours (AUC0-168) of MK-8527 in Plasma	Blood samples were taken at Predose, up to 168 hours postdose to determine the AUC0-168 of MK-8527 in plasma. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 168 hours postdose
Secondary	Area Under the Concentration Time Curve From Hour 0 to Last (AUC0-last) of MK-8527 in Plasma	Blood samples were taken at Predose, up to 168 hours postdose to determine the AUC0-last of MK-8527 in plasma. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 168 hours postdose
Secondary	Area Under the Concentration Time Curve From Hour 0 to Infinity (AUC0-inf) of MK-8527 in Plasma	Blood samples were taken at Predose, up to 168 hours postdose to determine the AUC0-inf of MK-8527 in plasma. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 168 hours postdose
Secondary	Maximum Concentration (Cmax) of MK-8527 in Plasma	Blood samples were taken at Predose, up to 168 hours postdose to determine the Cmax of MK-8527 in plasma. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 168 hours postdose
Secondary	Time to Cmax (Tmax) of MK-8527 in Plasma	Blood samples were taken at Predose, up to 168 hours postdose to determine the Tmax of MK-8527 in plasma. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 168 hours postdose
Secondary	Concentration at 168 Hours (C168) of MK-8527 in Plasma	Blood samples were taken at 168 hours postdose to determine the C168 of MK-8527 in plasma. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.	168 hours postdose
Secondary	Apparent Terminal Half Life (t1/2) of MK-8527 in Plasma	Blood samples were taken at Predose, up to 168 hours postdose to determine the t1/2 of MK-8527 in plasma. Values were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The 95% CI for the means were constructed on the natural log scale and referenced the t-distribution.	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 168 hours postdose