Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety and Pharmacokinetics of MK-2060 in Older Participants With End-Stage Renal Disease on Hemodialysis (MK-2060-004)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03873038
Recruitment Status : Recruiting
First Posted : March 13, 2019
Last Update Posted : November 11, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single dose intravenous (IV) administration of MK-2060 in older adult participants with end-stage renal disease (ESRD) on hemodialysis.

Participants in each panel (Panel A, Panel B, or Panel C) will be randomized to receive a single intravenous (IV) infusion of either MK-2060 or placebo in a 3:1 ratio (N=6 active and N=2 placebo). The decision to proceed to the next panel will be based upon acceptable safety and tolerability data.


Condition or disease Intervention/treatment Phase
Renal Dialysis Kidney Failure, Chronic Drug: MK-2060 Drug: Placebo Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Single Dose Clinical Trial to Study the Safety and Pharmacokinetics of MK-2060 in Older Participants With End-Stage Renal Disease on Hemodialysis
Actual Study Start Date : April 29, 2019
Estimated Primary Completion Date : October 29, 2020
Estimated Study Completion Date : October 29, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Panel A: MK-2060 (8 mg)
Participants will receive 8 mg of MK-2060 via intravenous (IV) infusion.
Drug: MK-2060
Single ascending doses (8 mg, 20 mg, or 40 mg) of MK-2060 will be administered via IV infusion.

Experimental: Panel B: MK-2060 (20 mg)
Participants will receive 20 mg of MK-2060 via IV infusion upon acceptable safety and tolerability data
Drug: MK-2060
Single ascending doses (8 mg, 20 mg, or 40 mg) of MK-2060 will be administered via IV infusion.

Experimental: Panel C: MK-2060 (40 mg)
Participants will receive 40 mg MK-2060 via IV infusion upon acceptable safety and tolerability data.
Drug: MK-2060
Single ascending doses (8 mg, 20 mg, or 40 mg) of MK-2060 will be administered via IV infusion.

Placebo Comparator: Panels A-C: Placebo
Participants will receive placebo via IV infusion.
Drug: Placebo
Single doses of placebo will be administered via IV infusion.




Primary Outcome Measures :
  1. Percentage of Participants with Any Adverse Event (AE) [ Time Frame: Up to ~164 days ]
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

  2. Percentage of Participants with Any Serious Adverse Event [ Time Frame: Up to ~164 days ]
    A serious adverse event (SAE) is an AE that results in death, is life threatening, requires or prolongs an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is another important medical event deemed such by medical or scientific judgment.

  3. Percentage of Participants With a Systemic AE [ Time Frame: Up to ~164 days ]
    Systemic AEs reported by participants in one or more panels will be assessed.

  4. Percentage of Participants With an Injection-Site AE [ Time Frame: Up to ~164 days ]
    Injection-site AEs reported by participants in one or more panels will be assessed.

  5. Percentage of Participants Discontinuing Study due to an Adverse Event [ Time Frame: Up to ~164 days ]
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.


Secondary Outcome Measures :
  1. Area Under the Plasma Concentration-Time Curve of MK-2060 from 0 to Infinity (AUC0-inf) [ Time Frame: Pre-dose and 1, 12, 24, 48, 52, 96, 168 hours post-dose and Days 12, 15, 22, 29, 60, 90, 120, and 150 post-dose ]
    Plasma samples will be collected at pre-specified time points post-dose and AUC0-inf will be assessed for all treatment arms.

  2. Area Under the Plasma Concentration-Time Curve of MK-2060 from Time 0 to 168 Hours (AUC0-168) [ Time Frame: Pre-dose and 1, 12, 24, 48, 52, 96, and 168 hours post-dose ]
    Plasma samples will be collected at pre-specified time points post-dose and AUC0-168 hours will be assessed for all treatment arms.

  3. Maximum Observed Plasma Concentration (Cmax) of MK-2060 [ Time Frame: Pre-dose and 1, 12, 24, 48, 52, 96, 168 hours post-dose and Days 12, 15, 22, 29, 60, 90, 120, and 150 post-dose ]
    Plasma samples will be collected at pre-specified time points post-dose and Cmax will be assessed for all treatment arms.

  4. Plasma Concentration of MK-2060 at 168 Hours (C168) [ Time Frame: 168 hours post dose ]
    Plasma samples will be collected at pre-specified time points post-dose and C168 will be assessed for all treatment arms.

  5. Time to Maximum Observed Plasma Drug Concentration (Tmax) of MK-2060 [ Time Frame: Pre-dose and 1, 12, 24, 48, 52, 96, 168 hours post-dose and Days 12, 15, 22, 29, 60, 90, 120, and 150 post-dose ]
    Plasma samples will be collected at pre-specified time points post-dose and Tmax will be assessed for all treatment arms.

  6. Plasma Elimination Terminal Half-life (t ½) of MK-2060 [ Time Frame: Pre-dose and 1, 12, 24, 48, 52, 96, 168 hours post-dose and Days 12, 15, 22, 29, 60, 90, 120, and 150 post-dose ]
    Plasma samples will be collected at pre-specified time points post-dose and t ½ will be assessed for all treatment arms.

  7. Plasma Clearance (CL) of MK-2060 [ Time Frame: Pre-dose and 1, 12, 24, 48, 52, 96, 168 hours post-dose and Days 12, 15, 22, 29, 60, 90, 120, and 150 post-dose ]
    Plasma samples will be collected at pre-specified time points post-dose and CL will be assessed for all treatment arms.

  8. Plasma Volume of Distribution (Vz) of MK-2060 [ Time Frame: Pre-dose and 1, 12, 24, 48, 52, 96, 168 hours post-dose and Days 12, 15, 22, 29, 60, 90, 120, and 150 post-dose ]
    Plasma samples will be collected at pre-specified time points post-dose and Vz will be assessed for all treatment arms.

  9. Percent Change From Baseline in Activated Partial Thromboplastin Time (aPTT) of MK-2060 [ Time Frame: Baseline and 168 hours post-dose ]
    Plasma samples will be collected at pre-specified time points post-dose and aPTT values will be assessed for all treatment arms.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   50 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • End-stage renal disease (ESRD) maintained on stable outpatient hemodialysis (HD) regimen, using an established (> 3 months) and normally functioning, regular flow, uninfected mature arteriovenous (AV) fistula or AV graft and skin consistent with standard chronic HD access injuries, and HD stability defined as ([K, dialyzer clearance, multiplied by t, time, divided by V, patient's total body water] Kt/V) ≥ 1.2 within 3 months prior to screening at a healthcare center for > 3 months from screening.
  • On HD regimen at least 3 times per week for a minimum of 3 hours per dialysis session, using a complication-free well-maintained AV fistula or AV graft, expected and plan to continue this throughout and for at least 3 months beyond the study.
  • Has a Body Mass Index (BMI) ≥ 18 and ≤ 4 0 kg/m^2. BMI = weight (kg)/height (m)^2.
  • Baseline health is judged to be stable based on medical history, physical examination, vital sign measurements and electrocardiogram (ECG) performed prior to randomization.
  • Liver function test (serum alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) must be equal to or below 1.5X upper limit of normal (ULN) and deemed not clinically significant by both the investigator and the Sponsor.
  • Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies by agreeing to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant. Also, men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile-vaginal penetration.
  • Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies in that a female participant is eligible to participate if she is not pregnant or breastfeeding and she is not a woman of childbearing potential (WOCBP) in that she is a postmenopausal female without menses for at least 1 year OR is a surgically sterile female, post hysterectomy, oophorectomy or tubal ligation.

Exclusion Criteria:

  • Has a history of any clinically significant concomitant disease or condition (including treatment for such conditions) or diseases whose current condition is considered clinically unstable that, in the opinion of the investigator, could either interfere with the study drug, compromise interpretation of study data, or pose an unacceptable risk to the patient. Participants with a remote history of uncomplicated medical events (e.g., 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, has significant emotional problems at the time of prestudy (screening) visit or expected during the conduct of the study or has a history of clinically significant psychiatric disorder of the last 5 years. Participants who have had situational depression may be enrolled in the study at the discretion of the investigator.
  • Has a history of cancer (malignancy), including adenocarcinoma, with possible exceptions being participants with adequately treated non-melanomatous skin carcinoma; participants with other malignancies which have been successfully treated ≥10 years prior to the pretrial (screening) visit; or participants who, in the opinion of the trial investigator, are highly unlikely to sustain a recurrence for the duration of the trial.
  • Has blood coagulation test (activated partial thromboplastin time [aPTT], prothrombin time [PT]) ≥ 20 % outside of normal range on pretrial (screening), which are considered clinically significant by both the investigator and the sponsor.
  • Any other clinically significant abnormalities in laboratory test results at screening that would, in the opinion of the investigator, increase the patient's risk of participation, jeopardize complete participation in the study, or compromise interpretation of study data.
  • Has a history of deep vein thrombosis or pulmonary embolism. Has a history of vascular access thrombosis within 1 month prior to enrollment. Has a personal or family history of bleeding disorder.
  • Has a history of gastrointestinal (GI) bleeding, duodenal polyps or gastric ulcer in the last 5 years or severe hemorrhoidal bleed in last 3 months.
  • Has a history of or current frequent epistaxis within the last 3 months or active gingivitis.
  • Has ongoing anticoagulant therapy (warfarin, apixaban, dabigatran, rivaroxaban, edoxaban, betrixaban) or antiplatelet therapy (clopidogrel, prasugrel, ticagrelor, ticlopidine). Intradialytic heparin and aspirin are permitted.
  • At the time of screening or pre-dose, has planned significant dental procedures (including planned dental surgery), or other planned surgical procedures within duration of participation in the trial.
  • Is positive for hepatitis B surface antigen or human immunodeficiency viruses (HIV).
  • Has had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the pre-study (screening) visits.
  • 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.
  • Has a tattoo, scar, or other physical finding at the area of the infusion site that would interfere with infusion or a local tolerability assessment.
  • Has a history of receiving any human immunoglobulin preparation such as intravenous immunoglobulin (IVIG) or RhoGAM within the last year.
  • Has a history of receiving any biological therapy (including human blood products or monoclonal antibodies; excluding erythropoietin and insulin) within the last 3 months or 5 half-lives (whichever is longer), or vaccination within the last 1 month.
  • The exclusion criteria for ECG is a heart rate < 40 and > 110 beats per minute (bpm); corrected Q-T (QTc) interval > 500 minutes/second; any significant arrhythmia or conduction abnormality, (including but not specific to atrioventricular block [2nd degree or higher], Wolff Parkinson White syndrome [unless curative radio ablation therapy]), which, in the opinion of the investigator and sponsor, could interfere with the safety for the individual patient; and non-sustained or sustained ventricular tachycardia (> 2 consecutive ventricular ectopic beats at a rate of > 1.7/second).
  • Is unable to refrain from or anticipates the use of medication, including prescription and nonprescription drugs or herbal remedies beginning approximately 2 weeks prior to administration of the initial dose of study drug, throughout the study until the poststudy visit. Specific allowed and prohibited medications are provided in the protocol.
  • Has participated in another investigational study within 4 weeks prior to sponsor's investigational drug (MK-2060/placebo) administration. .
  • Has a blood pressure >190 mmHg systolic and >110 mmHg diastolic.
  • Is a smoker and/or has used nicotine or nicotine-containing products (e.g, nicotine patch and electronic cigarette) within 3 months of screening.
  • 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 at the discretion of the investigator.
  • 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.
  • Is a regular user of cannabis, any illicit drugs or has a history of drug (including alcohol) abuse within approximately 2 years. Participants must have a negative serum or saliva drug screen prior to randomization. Participants with a positive drug screen due to the use of physician prescribed medications (e.g., opioids, benzodiazepines, antidepressants) may be enrolled at the discretion of the investigator.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03873038


Contacts
Layout table for location contacts
Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

Locations
Layout table for location information
United States, Florida
Orlando Clinical Research Center ( Site 0002) Recruiting
Orlando, Florida, United States, 32809
Contact: Study Coordinator    407-472-0227      
United States, Tennessee
New Orleans Center for Clinical Research ( Site 0001) Recruiting
Knoxville, Tennessee, United States, 37920
Contact: Study Coordinator    8653059100ext246      
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Layout table for investigator information
Study Director: Medical Director Merck Sharp & Dohme Corp.

Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT03873038     History of Changes
Other Study ID Numbers: 2060-004
MK-2060-004 ( Other Identifier: Merck Protocol Number )
First Posted: March 13, 2019    Key Record Dates
Last Update Posted: November 11, 2019
Last Verified: November 2019
Individual Participant Data (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

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Kidney Failure, Chronic
Renal Insufficiency
Kidney Diseases
Urologic Diseases
Renal Insufficiency, Chronic