- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03351699
Single-Dose Study of MK-4250 Monotherapy in Anti-Retroviral Therapy-Naive, Human Immunodeficiency Virus (HIV)-1 Infected Participants (MK-4250-002)
October 7, 2019 updated by: Merck Sharp & Dohme LLC
A Single-Dose Clinical Trial to Study the Safety, Tolerability, Pharmacokinetics, and Anti-Retroviral Activity of MK-4250 Monotherapy in Anti-Retroviral Therapy (ART)-Naive, HIV-1 Infected Subjects
The study will evaluate the safety, tolerability, pharmacokinetics, and anti-retroviral activity of MK-4250 monotherapy in anti-retroviral therapy (ART)-naïve, HIV-1 infected participants.
The primary hypothesis of the study is that at a dose that is sufficiently safe and generally well tolerated, MK-4250 has superior antiretroviral activity compared to a historical placebo, as measured by change from baseline in plasma HIV-1 ribonucleic acid (RNA) (log10 copies/mL) at 168 hours postdose.
Study Overview
Detailed Description
The study consists of 5 panels; Panel C (MK-4250 ≤600 mg) was removed from the study with Protocol Amendment 1.
Study Type
Interventional
Enrollment (Actual)
24
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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-
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Berlin, Germany, 10117
- Charite Research Organisation GmbH ( Site 0001)
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 60 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Male or non-pregnant and non-breast feeding female
- If female with reproductive potential: must demonstrate a serum β-human chorionic gonadotropin (β -hCG) level consistent with the nongravid state and agree to use a highly effective method of birth control until 30 days after the dose of trial drug
- If postmenopausal female: without menses for at least 1 year and has a documented follicle stimulating hormone (FSH) level in the postmenopausal range at pretrial (screening), AND/OR status post hysterectomy or oophorectomy
- Documented HIV-1 positive as determined by a positive Enzyme-linked Immunosorbent Assay (ELISA) or Quantitative Polymerase Chain Reaction (QT-PCR) with confirmation (e.g., Western Blot).
- No evidence at screening for mutations (e.g., E92Q, N55H, Q148K, Q148R and Y143R) affecting susceptibility to Integrase Strand Transfer Inhibitors (InSTIs)
- Diagnosed with HIV-1 infection ≥ 3 months prior to screening or confirmed chronic HIV infection
- Screening plasma Cluster of Differentiation (CD) 4+ T cell count of >200/mm^3
- Screening plasma HIV-1 RNA ≥5,000 copies/mL within 30 days prior to the treatment phase of this study
- Anti-retroviral therapy (ART)-naïve, which is defined as having never received any antiretroviral agent OR ≤30 consecutive days of an investigational antiretroviral agent which is not an InSTI and no exposure to such an investigational antiretroviral agent within 60 days prior to screening OR ≤60 consecutive days of combination ART which does not include an InSTI and no exposure to such ART within 60 days prior to screening
- Never received any InSTI
- Willing to receive no other ART for the duration of the treatment phase of this study
- Body Mass Index (BMI) ≤35 kg/m^2
- Other than HIV infection, have baseline health judged to be stable
Exclusion Criteria:
- Mentally or legally institutionalized / incapacitated, or significant emotional problems at the time of pretrial (screening) visit or expected during the conduct of the trial or has a history of clinically significant psychiatric disorder within the last 5 years
- History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological (outside of HIV-1 infection), renal, respiratory, genitourinary or major neurological abnormalities or diseases
- History of cancer (malignancy). Exceptions: (1) adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix; (2) other malignancies which have been successfully treated ≥10 years prior to the pretrial (screening) visit with no evidence of recurrence; or, (3) deemed highly unlikely to sustain a recurrence for the duration of the trial
- History of significant multiple and/or severe allergies (e.g., food, drug, latex allergy); anaphylactic reaction or significant intolerability (i.e., systemic allergic reaction) to prescription or non-prescription drugs or food; or hereditary galactose intolerance, lactose deficiency, or glucose-galactose malabsorption.
- Positive for hepatitis B surface antigen
- History of chronic hepatitis C (HCV) infection. Participants with a documented cure and/or a positive serologic test for HCV with a negative HCV viral load may be included
- Major surgery or donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the pretrial (screening) visit
- Participated in another investigational trial within 4 weeks prior to the Day 1 dosing visit. The 4 week window will be derived from the date of the last trial medication and / or blood collection in a previous trial and/or an adverse event related to trial drug to the Day 1 dosing visit of the current trial
- Unable to refrain from or anticipates the use of any medication, including prescription and non-prescription drugs or herbal remedies beginning approximately 2 weeks prior to administration of the initial dose of trial drug, throughout the trial, until the post-trial visit
- Consumes greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer [354 mL/12 ounces], wine [118 mL/4 ounces], or distilled spirits [29.5 mL/1 ounce]) per day. Participants who consume 4 glasses of alcoholic beverages per day may be enrolled
- Consumes excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, energy-drinks, or other caffeinated beverages per day
- Excessive smoker (i.e., more than 10 cigarettes/day) and is unwilling to restrict smoking to ≤10 cigarettes per day
- Cardiac QTc interval ≥470 msec (for males) or ≥480 msec (for females)
- Positive urine drug screen (except for cannabis) at screening and/or predose; rechecks are allowed
- Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is investigational site or Sponsor staff directly involved with this trial.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Panel A: MK-4250 150 mg
Participants will receive MK-4250 150 mg tablet by mouth on Day 1 after an 8-hour fast.
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MK-4250 tablets for oral administration
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Experimental: Panel B: MK-4250 600 mg
Participants will receive MK-4250 600 mg tablet by mouth on Day 1 after an 8-hour fast.
The decision to enroll Panel B and the dose selected (i.e., ≤600 mg) will be made based on evaluation of pharmacokinetics and 7-day safety and viral load data from Panel A.
|
MK-4250 tablets for oral administration
|
Experimental: Panel D: MK-4250 900 mg
Participants will receive MK-4250 900 mg tablet by mouth on Day 1 after an 8-hour fast.
The decision to enroll Panel D will be made upon completion of Panels A and B and evaluation of safety and viral load data from those panels.
|
MK-4250 tablets for oral administration
|
Experimental: Panel E: MK-4250 ≤900 mg with a Low-fat Meal
Participants will receive MK-4250 ≤900 mg tablet by mouth on Day 1 with a low-fat meal.
The decision to enroll Panel E will be made upon completion of Panel D and evaluation of safety and viral load data from that panel.
|
MK-4250 tablets for oral administration
|
Experimental: Panel F: MK-4250 ≤900 mg with a Moderate-fat Meal
Participants will receive MK-4250 ≤900 mg tablet by mouth on Day 1 with a moderate-fat meal.
The decision to enroll Panel F will be made upon completion of Panel D and evaluation of safety and viral load data from that panel.
The decision to enroll Panel F will be made based on evaluation of PK and safety data from other studies with MK-4250.
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MK-4250 tablets for oral administration
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in Plasma HIV-1 RNA Copies Per mL at 168 Hours
Time Frame: Baseline and Day 7
|
Plasma HIV-1 RNA was measured at Baseline and 168 hours after dosing.
The log10 plasma HIV-RNA copies/mL measurements from participants in each panel were pooled and analyzed based on a longitudinal data analysis model.
The change from Baseline in plasma HIV-1 RNA in participants administered MK-4250 was compared with historical placebo data.
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Baseline and Day 7
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Percentage of Participants Experiencing ≥1 Adverse Events (AE)
Time Frame: Up to Day 14
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The percentage of participants experiencing ≥1 AE was calculated.
An AE was defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy could be determined.
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Up to Day 14
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Percentage of Participants Who Discontinued Study Due to an Adverse Event (AE)
Time Frame: Up to Day 14
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The percentage of participants who discontinued from the study due to an adverse event was calculated.
An AE was defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy could be determined.
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Up to Day 14
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Area Under the Concentration-Time Curve From 0 to Last Measurable Concentration (AUC0-last) for MK-4250
Time Frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, 192, and 240 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time, and no 240-hour postdose time.
|
The area under the concentration-time curve up to the last measurable concentration (AUC0-last) of MK-4250 in plasma was calculated.
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Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, 192, and 240 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time, and no 240-hour postdose time.
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Area Under the Concentration-Time Curve From 0 to Infinity (AUC0-inf) for MK-4250
Time Frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, 192, and 240 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time, and no 240-hour postdose time.
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The area under the concentration-time curve extrapolated to infinity (AUC0-inf) of MK-4250 in plasma was calculated.
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Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, 192, and 240 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time, and no 240-hour postdose time.
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Area Under the Concentration-Time Curve From 0 to 168 Hours (AUC0-168) for MK-4250
Time Frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, and 168 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time.
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The area under the concentration-time curve up to 168 hours (AUC0-168) of MK-4250 in plasma was calculated.
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Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, and 168 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time.
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Maximum Concentration (Cmax) of MK-4250 Reached in Plasma
Time Frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, 192, and 240 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time, and no 240-hour postdose time.
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The maximum concentration (Cmax) of MK-4250 in plasma was observed.
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Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, 192, and 240 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time, and no 240-hour postdose time.
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Concentration of MK-4250 at 168 Hours (C168hr)
Time Frame: 168 hours after administration of MK-4250.
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The concentration of MK-4250 at 168 hours postdose (C168hr) was observed.
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168 hours after administration of MK-4250.
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Apparent Terminal Half-life (t1/2) of MK-4250
Time Frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, 192, and 240 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time, and no 240-hour postdose time.
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The apparent terminal half-life (t1/2) of MK-4250 in plasma was calculated.
|
Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, 192, and 240 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time, and no 240-hour postdose time.
|
Apparent Clearance (CL/F) of MK-4250
Time Frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, 192, and 240 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time, and no 240-hour postdose time.
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The apparent clearance (CL/F) of MK-4250 in plasma was calculated.
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Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, 192, and 240 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time, and no 240-hour postdose time.
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Apparent Volume of Distribution (Vz/F) of MK-4250
Time Frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, 192, and 240 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time, and no 240-hour postdose time.
|
The apparent volume of distribution (Vz/F) of MK-4250 in plasma was calculated.
|
Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, 192, and 240 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time, and no 240-hour postdose time.
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Time to Maximum Concentration (Tmax) of MK-4250 Reached in Plasma
Time Frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, 192, and 240 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time, and no 240-hour postdose time.
|
The time to maximum concentration (Vz/F) of MK-4250 in plasma was calculated.
|
Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, 192, and 240 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time, and no 240-hour postdose time.
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
January 18, 2018
Primary Completion (Actual)
November 2, 2018
Study Completion (Actual)
November 2, 2018
Study Registration Dates
First Submitted
November 20, 2017
First Submitted That Met QC Criteria
November 20, 2017
First Posted (Actual)
November 24, 2017
Study Record Updates
Last Update Posted (Actual)
October 30, 2019
Last Update Submitted That Met QC Criteria
October 7, 2019
Last Verified
October 1, 2019
More Information
Terms related to this study
Other Study ID Numbers
- 4250-002
- 2017-001784-21 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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