Safety, Tolerability, Pharmacokinetics, and Anti-Retroviral Activity of MK-8558 Monotherapy in Anti-Retroviral-Naïve HIV-1 Infected Participants (MK-8558-002)

• ClinicalTrials.gov Identifier: NCT03859739
• Recruitment Status: Recruiting
• First Posted: March 1, 2019
• Last Update Posted: October 21, 2019
• Sponsor: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Merck Sharp & Dohme Corp.

Tracking Information

• First Submitted Date: February 28, 2019
• First Posted Date: March 1, 2019
• Last Update Posted Date: October 21, 2019
• Actual Study Start Date: April 26, 2019
• Estimated Primary Completion Date: March 7, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 28, 2019)

• Change from Baseline in Plasma HIV-1 Ribonucleic Acid (RNA) Concentration [ Time Frame: Baseline and 168 hours post-dose ]
  The mean change from baseline in plasma HIV-1 RNA concentration will be assessed.
• Number of Participants experiencing ≥1 Adverse Event (AE) [ Time Frame: Up to 35 days post-dose ]
  The number of participants experiencing ≥1 AE will be reported.
• Number of Participants who Discontinue From the Study Due to an Adverse Event (AE) [ Time Frame: Up to 35 days post-dose ]
  The number of participants who discontinue from the study due to an AE will be reported.

• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT03859739 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: February 28, 2019)

• Area Under the Concentration-Time Curve from 0 to 168 hours (AUC0-168) for MK-8558 in Plasma [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168 hours post-dose ]
  The AUC0-168 for MK-8558 in plasma will be calculated.
• Area Under the Concentration-Time Curve from 0 up to the Last Quantifiable Time-Point (AUC0-last) for MK-8558 in Plasma [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose ]
  The AUC0-last for MK-8558 in plasma will be calculated.
• Area Under the Concentration-Time Curve from 0 to Infinity (AUC0-inf) for MK-8558 in Plasma [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose ]
  The AUC0-inf for MK-8558 in plasma will be calculated.
• Maximum Observed Concentration (Cmax) for MK-8558 in Plasma [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose ]
  The Cmax for MK-8558 in plasma will be reported.
• Time to Maximum Observed Concentration (Tmax) for MK-8558 in Plasma [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose ]
  The Tmax for MK-8558 in plasma will be reported.
• Concentration at 168 Hours Post-Dose (C168hr) for MK-8558 in Plasma [ Time Frame: 168 hours post-dose ]
  The C168hr for MK-8558 in plasma will be reported.
• Apparent Clearance (CL/F) for MK-8558 [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose ]
  CL/F for MK-8558 will be calculated.
• Apparent Volume of Distribution (Vz/F) for MK-8558 [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose ]
  Vz/F for MK-8558 will be calculated.
• Terminal Half Life (t1/2) for MK-8558 [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose ]
  t1/2 for MK-8558 will be calculated.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety, Tolerability, Pharmacokinetics, and Anti-Retroviral Activity of MK-8558 Monotherapy in Anti-Retroviral-Naïve HIV-1 Infected Participants (MK-8558-002)
• Official Title: A Single-Dose Clinical Trial to Study the Safety, Tolerability, Pharmacokinetics, and Anti-Retroviral Activity of MK-8558 Monotherapy in Anti-Retroviral-Naïve HIV-1 Infected Participants
• Brief Summary: The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and anti-retroviral activity of MK-8558 monotherapy in anti-retroviral-naïve HIV-1 infected participants. The primary hypothesis is that at a dose that exhibits an acceptable safety and tolerability profile, MK-8558 has superior anti-retroviral activity compared to historical placebo data.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: HIV-1 Infection

Intervention

Drug: MK-8558

Single dose of MK-8558 administered as a tablet at a dose up to 1600 mg.

Study Arms

• Experimental: Panel A. MK-8558 400 mg
  Single oral dose of MK-8558 administered at 400 mg.
  Intervention: Drug: MK-8558
• Experimental: Panel B. MK-8558 at dose level 2
  Single oral dose of MK-8558 administered at dose level 2. Dose level 2 shall not exceed 900 mg. Per protocol, dose will be selected following review of data from panel A.
  Intervention: Drug: MK-8558
• Experimental: Panel C. MK-8558 at dose level 3
  Single oral dose of MK-8558 administered at dose level 3. Dose level 3 shall not exceed 1600 mg. Per protocol, dose will be selected following review of data from panel B.
  Intervention: Drug: MK-8558
• Experimental: Panel D. MK-8558 at dose level 4
  Single oral dose of MK-8558 administered at dose level 4. Dose level 4 shall not exceed 1600 mg. Per protocol, Panel D is optional pending results of Panels A-C, and dose will be selected following review of data from panel C.
  Intervention: Drug: MK-8558

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 28, 2019): 24
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 7, 2020
• Estimated Primary Completion Date: March 7, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Other than having HIV infection, is in good health based on medical history, physical examination, vital sign (VS) measurements, and laboratory safety tests, at the pre-study (screening) visit and/or prior to administration of the study drug
• Is documented as being HIV-1 positive
• Has a screening plasma HIV-1 RNA ≥ 2,500 copies/mL within 30 days prior to the treatment phase of this study
• Has a screening plasma CD4+ T-cell count of >200/mm^3
• Is antiretroviral therapy (ART)-naïve
• Is willing to receive no other ART prior to Day 11 post-dose of the trial, unless the physician/Investigator believes that there is a strong indication to start ART before Day 11
• Has a Body Mass Index (BMI) ≤35 kg/m^2
• Males must agree to abstinence, or barrier contraception plus partner contraception, unless confirmed to be azoospermic due to vasectomy or medical cause, for at least 35 days after the last dose of MK-8558
• Females must not be pregnant or breastfeeding, and must be a woman of nonchildbearing potential, or a woman of childbearing potential using highly effective birth control with low user dependency or who is abstinent on a long-term and persistent basis during the intervention period and at least 35 days after the last dose of study medication

Exclusion Criteria:

• Has acute (primary) HIV-1 infection
• Has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic (with the exception of Gilbert's disease), immunological (outside of HIV-1 infection), renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases
• Is mentally or legally incapacitated or has a history of a clinically significant psychiatric disorder (with the exception of situational depression) of the last 5 years
• Has a history of cancer unless disease is adequately treated and deemed "cured"
• Has an estimated creatinine clearance (CrCl) ≤ 90 mL/min
• Has a history of significant multiple and/or severe allergies, or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food, or has hereditary galactose intolerance, lactase deficiency, or glucose-galactose malabsorption
• 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 pre-study (screening) visit
• Is 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 post-study visit. There may be certain medications that are permitted
• Has participated in another investigational study within 4 weeks (or 5 half-lives, whichever is greater) prior to the pre-study (screening) visit. The window will be derived from the date of the last visit in the previous study
• Is under the age of legal consent or not capable of giving consent
• Has been committed to an institution by way of official or judicial order
• Is an excessive smoker (i.e., more than 10 cigarettes/day) and is unwilling to restrict smoking to ≤10 cigarettes per day
• Consumes more 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 at the discretion of the investigator
• Consumes excessive amounts, defined as more 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
• Has a positive urine drug screen (except for cannabis) at screening and/or pre-dose; rechecks are allowed

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 60 Years (Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Toll Free Number; 1-888-577-8839; Trialsites@merck.com

• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT03859739
• Other Study ID Numbers: 8558-002; MK-8558-002 ( Other Identifier: Merck Protocol Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

• Responsible Party: Merck Sharp & Dohme Corp.
• Study Sponsor: Merck Sharp & Dohme Corp.
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme Corp.

• PRS Account: Merck Sharp & Dohme Corp.
• Verification Date: October 2019