Kidney Failure, Chronic, Renal Dialysis
Conditions
Brief summary
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of MK-2060 after intravenous (IV) administration of single and multiple doses in older adult participants with end-stage renal disease (ESRD) on hemodialysis (HD).
Interventions
DRUGMK-2060
Part 1: Single doses (8 mg, 20 mg, or 40 mg) of MK-2060 will be administered via IV infusion on Day 1. Part 2: Three doses of 25 mg of MK- 2060 administered via IV infusion on Days 1, 3 and 5; Followed by single doses of 25 mg of MK-2060 administered via IV infusion on Days 8, 15, and 22.
DRUGPlacebo
Part 1: Single dose of placebo will be administered via IV infusion on Day 1. Part 2: Three doses of placebo administered via IV infusion on Days 1, 3 and 5; Followed by single doses of placebo administered via IV infusion on Days 8, 15, and 22.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Male or female, of non-child bearing potential (WONCBP) age ≥40 and ≤80 years for Part 1 and ≥18 and ≤80 years for Part 2. * 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 dosing at a healthcare center for \> 3 months from dosing. * 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 ≤ 45 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 woman of childbearing potential (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 WOCBP in that she is a postmenopausal female without menses for at least 1 year OR is a surgically sterile female, post hysterectomy, bilateral salpingectomy, 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. 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 participant'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 (exceptions include seasonal flu vaccine and pneumococcal vaccine within the last month; coronavirus disease 2019 \[COVID-19\] vaccine that is licensed and approved for emergency use and with the study intervention given 72 hours following vaccination or 48 hours prior to vaccination). * The
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Percentage of Participants With Any Adverse Event (AE) | 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. The percentage of participants that experienced an AE was summarized. |
| Part 2: Percentage of Participants With Any AE | Up to 118 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. The percentage of participants who experienced an AE was summarized. |
| Part 1: Percentage of Participants With Any Serious Adverse Event | 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. The percentage of participants who experienced an SAE was summarized. |
| Part 2: Percentage of Participants With Any SAE | Up to 118 days | An 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. The percentage of participants who experienced an SAE was summarized. |
| Part 1: Percentage of Participants With a Systemic AE | 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. The solicited systemic AEs assessed included but not limited to fever, vital sign (VS) changes (tachycardia/hypotension), pruritis, urticarial (hives), lip swelling, angioedema, bronchospasm, stridor, hoarseness, and shortness of breath. |
| Part 2: Percentage of Participants With a Systemic AE | Up to 118 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. The solicited systemic AEs assessed included but not limited to fever, vital sign (VS) changes (tachycardia/hypotension), pruritis, urticarial (hives), lip swelling, angioedema, bronchospasm, stridor, hoarseness, and shortness of breath. |
| Part 1: Percentage of Participants With an Injection-Site AE | 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. The solicited injection-site AEs assessed were pain, tenderness, erythema/redness, and induration/swelling. |
| Part 2: Percentage of Participants With an Injection-Site AE | Up to 118 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. The solicited injection-site AEs assessed were pain, tenderness, erythema/redness, and induration/swelling. |
| Part 1: Percentage of Participants Discontinuing the Study Due to an AE | 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. The percentage of participants that discontinued the study due to an AE was summarized. |
| Part 2: Percentage of Participants Discontinuing Study Drug Due to an AE | Up to 4 weeks | 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. The percentage of participants that had study drug discontinued regardless of study completion status was summarized. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 2: C168 of MK-2060 | 168 hours post dose on Days 1 and 22 | Plasma samples were collected at 168 hours post-dose and C168 was assessed. |
| Part 2: Tmax of MK-2060 | Day 1 and Day 22 | Plasma samples were collected at pre-specified time points post-dose and Tmax was assessed. |
| Part 1: Area Under the Plasma Concentration-Time Curve of MK-2060 From 0 to Infinity (AUC0-inf) | Predose Day 1 and 1, 12, 24, 48, 52, 96, 168 hours postdose, then Days 12, 15, 22, 29, 60, 90, 120, 150 | Plasma samples were collected at pre-specified time points post-dose and AUC0-inf was assessed. |
| Fold Change From Baseline in aPTT of MK-2060: Part 2 | Baseline and Day 8 | Plasma samples were collected at pre-specified time points post-dose and aPTT values were assessed. The fold change (Day 8/Baseline) at Day 8 was reported. |
| Fold Change From Baseline in Activated Partial Thromboplastin Time (aPTT) of MK-2060: Part 1 | Baseline and 168 hours post-dose (Day 8) | Plasma samples were collected at pre-specified time points post-dose and aPTT values were assessed. The fold change (Day 8/Baseline) at Day 8 was reported. |
| Part 1: Area Under the Plasma Concentration-Time Curve of MK-2060 From Time 0 to 168 Hours (AUC0-168) | Predose Day 1 and 1, 12, 24, 48, 52, 96, 168 hours postdose | Plasma samples were collected at pre-specified time points post-dose and AUC0-168 hours was assessed. |
| Part 1: Maximum Observed Plasma Concentration (Cmax) of MK-2060 | Predose Day 1 and 1, 12, 24, 48, 52, 96, 168 hours postdose, then Days 12, 15, 22, 29, 60, 90, 120, 150 | Plasma samples were collected at pre-specified time points post-dose and Cmax was assessed. |
| Part 1: Plasma Concentration of MK-2060 at 168 Hours (C168) | 168 hours post dose | Plasma samples were collected at 168 hours post-dose and C168 was assessed. |
| Part 1: Time to Maximum Observed Plasma Drug Concentration (Tmax) of MK-2060 | Predose Day 1 and 1, 12, 24, 48, 52, 96, 168 hours postdose | Plasma samples were collected at pre-specified time points post-dose and Tmax was assessed. |
| Part 1: Plasma Elimination Terminal Half-life (t ½) of MK-2060 | Predose Day 1 and 1, 12, 24, 48, 52, 96, 168 hours postdose | Plasma samples was collected at pre-specified time points post-dose and t ½ was assessed. |
| Part 1: Plasma Clearance (CL) of MK-2060 | Predose Day 1 and 1, 12, 24, 48, 52, 96, 168 hours postdose | Plasma samples were collected at pre-specified time points post-dose and CL was assessed. |
| Part 1: Plasma Volume of Distribution (Vz) of MK-2060 | Predose Day 1 and 1, 12, 24, 48, 52, 96, 168 hours postdose | Plasma samples were collected at pre-specified time points post-dose and Vz was assessed. |
| Part 2: AUC0-168 of MK-2060 | Up to 168 hours on Day 1 and Day 22 | Plasma samples were collected at pre-specified time points post-dose and AUC0-168 hours was assessed. |
| Part 2: Cmax of MK-2060 | Day 1 and Day 22 | Plasma samples were collected at pre-specified time points post-dose and Cmax was assessed. |
Countries
United States
Participant flow
Recruitment details
Male and Female of non-childbearing potential (WONCBP) participants with end-stage renal disease (ESRD) on hemodialysis (HD) between the ages of 18 and 80 years (ages ≥ 40 and ≤ 80 for Part 1 and ≥ 18 and ≤ 80 for Part 2) were enrolled in this study.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Panel A- MK-2060 (8 mg) Participants received a single 8-mg dose of MK-2060 via IV infusion | 6 |
| Part 1: Panel B- MK-2060 (20 mg) Participants received a single 20-mg dose of MK-2060 via IV infusion | 7 |
| Part 1: Panel C- MK-2060 (40 mg) Participants received a single 40-mg dose of MK-2060 via IV infusion | 6 |
| Part 1: Placebo Participants received a single dose of placebo via IV infusion | 5 |
| Part 2: MK-2060 25-mg Loading/ 25-mg Maintenance Participants received three doses of up to 25 mg MK-2060 via IV infusion in the first week (Week 1), followed by a single dose of up to 25 mg MK-2060 via IV infusion weekly for 3 weeks (Weeks 2-4) | 10 |
| Part 2: Placebo Participants received three doses of placebo via IV infusion in the first week and then a single dose of placebo via IV infusion weekly for 3 weeks (Weeks 2-4) | 4 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Part 2 | Unknon | 0 | 0 | 0 | 0 | 1 | 0 |
| Part 2 | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Part 1: Panel A- MK-2060 (8 mg) | Part 1: Panel B- MK-2060 (20 mg) | Part 1: Panel C- MK-2060 (40 mg) | Part 1: Placebo | Part 2: MK-2060 25-mg Loading/ 25-mg Maintenance | Part 2: Placebo | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 56.8 Years STANDARD_DEVIATION 5.1 | 61.1 Years STANDARD_DEVIATION 4.3 | 58.2 Years STANDARD_DEVIATION 5.9 | 60.0 Years STANDARD_DEVIATION 7.3 | 54.7 Years STANDARD_DEVIATION 7 | 52.5 Years STANDARD_DEVIATION 11.6 | 57.2 Years STANDARD_DEVIATION 6.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 7 Participants | 6 Participants | 5 Participants | 8 Participants | 4 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 3 Participants | 3 Participants | 3 Participants | 8 Participants | 4 Participants | 27 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 4 Participants | 3 Participants | 2 Participants | 2 Participants | 0 Participants | 11 Participants |
| Sex: Female, Male Female | 1 Participants | 4 Participants | 2 Participants | 1 Participants | 2 Participants | 0 Participants | 10 Participants |
| Sex: Female, Male Male | 5 Participants | 3 Participants | 4 Participants | 4 Participants | 8 Participants | 4 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 7 | 0 / 6 | 0 / 5 | 0 / 16 | 0 / 5 |
| other Total, other adverse events | 1 / 6 | 4 / 7 | 3 / 6 | 3 / 5 | 1 / 16 | 4 / 5 |
| serious Total, serious adverse events | 0 / 6 | 0 / 7 | 1 / 6 | 0 / 5 | 1 / 16 | 3 / 5 |
Outcome results
Primary
Part 1: Percentage of Participants Discontinuing the Study Due to an AE
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. The percentage of participants that discontinued the study due to an AE was summarized.
Time frame: Up to 164 days
Population: All Subjects as Treated Population which consisted of all participants who received at least one dose of treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Panel A- MK-2060 (8 mg) | Part 1: Percentage of Participants Discontinuing the Study Due to an AE | 0.0 Percentage of Participants |
| Part 1: Panel B- MK-2060 (20 mg) | Part 1: Percentage of Participants Discontinuing the Study Due to an AE | 0.0 Percentage of Participants |
| Part 1: Panel A- MK-2060 (40 mg) | Part 1: Percentage of Participants Discontinuing the Study Due to an AE | 0.0 Percentage of Participants |
| Part 1: Placebo | Part 1: Percentage of Participants Discontinuing the Study Due to an AE | 0.0 Percentage of Participants |
Primary
Part 1: Percentage of Participants With an Injection-Site AE
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. The solicited injection-site AEs assessed were pain, tenderness, erythema/redness, and induration/swelling.
Time frame: Up to 164 days
Population: All Subjects as Treated Population which consisted of all participants who received at least one dose of treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Panel A- MK-2060 (8 mg) | Part 1: Percentage of Participants With an Injection-Site AE | 0.0 Percentage of Participants |
| Part 1: Panel B- MK-2060 (20 mg) | Part 1: Percentage of Participants With an Injection-Site AE | 0.0 Percentage of Participants |
| Part 1: Panel A- MK-2060 (40 mg) | Part 1: Percentage of Participants With an Injection-Site AE | 0.0 Percentage of Participants |
| Part 1: Placebo | Part 1: Percentage of Participants With an Injection-Site AE | 0.0 Percentage of Participants |
Primary
Part 1: Percentage of Participants With Any Adverse Event (AE)
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. The percentage of participants that experienced an AE was summarized.
Time frame: Up to 164 days
Population: All Subjects as Treated Population which consisted of all participants who received at least one dose of treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Panel A- MK-2060 (8 mg) | Part 1: Percentage of Participants With Any Adverse Event (AE) | 16.7 Percentage of Participants |
| Part 1: Panel B- MK-2060 (20 mg) | Part 1: Percentage of Participants With Any Adverse Event (AE) | 57.1 Percentage of Participants |
| Part 1: Panel A- MK-2060 (40 mg) | Part 1: Percentage of Participants With Any Adverse Event (AE) | 66.7 Percentage of Participants |
| Part 1: Placebo | Part 1: Percentage of Participants With Any Adverse Event (AE) | 60.0 Percentage of Participants |
Primary
Part 1: Percentage of Participants With Any Serious Adverse Event
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. The percentage of participants who experienced an SAE was summarized.
Time frame: Up to 164 days
Population: All Subjects as Treated Population which consisted of all participants who received at least one dose of treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Panel A- MK-2060 (8 mg) | Part 1: Percentage of Participants With Any Serious Adverse Event | 0.0 Percentage of Participants |
| Part 1: Panel B- MK-2060 (20 mg) | Part 1: Percentage of Participants With Any Serious Adverse Event | 0.0 Percentage of Participants |
| Part 1: Panel A- MK-2060 (40 mg) | Part 1: Percentage of Participants With Any Serious Adverse Event | 16.7 Percentage of Participants |
| Part 1: Placebo | Part 1: Percentage of Participants With Any Serious Adverse Event | 0.0 Percentage of Participants |
Primary
Part 1: Percentage of Participants With a Systemic AE
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. The solicited systemic AEs assessed included but not limited to fever, vital sign (VS) changes (tachycardia/hypotension), pruritis, urticarial (hives), lip swelling, angioedema, bronchospasm, stridor, hoarseness, and shortness of breath.
Time frame: Up to 164 days
Population: All Subjects as Treated Population which consisted of all participants who received at least one dose of treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Panel A- MK-2060 (8 mg) | Part 1: Percentage of Participants With a Systemic AE | 0.0 Percentage of Participants |
| Part 1: Panel B- MK-2060 (20 mg) | Part 1: Percentage of Participants With a Systemic AE | 0.0 Percentage of Participants |
| Part 1: Panel A- MK-2060 (40 mg) | Part 1: Percentage of Participants With a Systemic AE | 0.0 Percentage of Participants |
| Part 1: Placebo | Part 1: Percentage of Participants With a Systemic AE | 0.0 Percentage of Participants |
Primary
Part 2: Percentage of Participants Discontinuing Study Drug Due to an AE
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. The percentage of participants that had study drug discontinued regardless of study completion status was summarized.
Time frame: Up to 4 weeks
Population: All Subjects as Treated Population which consisted of all participants who received at least one dose of treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Panel A- MK-2060 (8 mg) | Part 2: Percentage of Participants Discontinuing Study Drug Due to an AE | 0.0 Percentage of Participants |
| Part 1: Panel B- MK-2060 (20 mg) | Part 2: Percentage of Participants Discontinuing Study Drug Due to an AE | 40.0 Percentage of Participants |
Primary
Part 2: Percentage of Participants With an Injection-Site AE
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. The solicited injection-site AEs assessed were pain, tenderness, erythema/redness, and induration/swelling.
Time frame: Up to 118 days
Population: All Subjects as Treated Population which consisted of all participants who received at least one dose of treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Panel A- MK-2060 (8 mg) | Part 2: Percentage of Participants With an Injection-Site AE | 0.0 Percentage of Participants |
| Part 1: Panel B- MK-2060 (20 mg) | Part 2: Percentage of Participants With an Injection-Site AE | 0.0 Percentage of Participants |
Primary
Part 2: Percentage of Participants With Any AE
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. The percentage of participants who experienced an AE was summarized.
Time frame: Up to 118 days
Population: All Subjects as Treated Population which consisted of all participants who received at least one dose of treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Panel A- MK-2060 (8 mg) | Part 2: Percentage of Participants With Any AE | 12.5 Percentage of Participants |
| Part 1: Panel B- MK-2060 (20 mg) | Part 2: Percentage of Participants With Any AE | 100.0 Percentage of Participants |
Primary
Part 2: Percentage of Participants With Any SAE
An 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. The percentage of participants who experienced an SAE was summarized.
Time frame: Up to 118 days
Population: All Subjects as Treated Population which consisted of all participants who received at least one dose of treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Panel A- MK-2060 (8 mg) | Part 2: Percentage of Participants With Any SAE | 6.3 Percentage of Participants |
| Part 1: Panel B- MK-2060 (20 mg) | Part 2: Percentage of Participants With Any SAE | 60.0 Percentage of Participants |
Primary
Part 2: Percentage of Participants With a Systemic AE
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. The solicited systemic AEs assessed included but not limited to fever, vital sign (VS) changes (tachycardia/hypotension), pruritis, urticarial (hives), lip swelling, angioedema, bronchospasm, stridor, hoarseness, and shortness of breath.
Time frame: Up to 118 days
Population: All Subjects as Treated Population which consisted of all participants who received at least one dose of treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Panel A- MK-2060 (8 mg) | Part 2: Percentage of Participants With a Systemic AE | 0.0 Percentage of Participants |
| Part 1: Panel B- MK-2060 (20 mg) | Part 2: Percentage of Participants With a Systemic AE | 0.0 Percentage of Participants |
Secondary
Fold Change From Baseline in Activated Partial Thromboplastin Time (aPTT) of MK-2060: Part 1
Plasma samples were collected at pre-specified time points post-dose and aPTT values were assessed. The fold change (Day 8/Baseline) at Day 8 was reported.
Time frame: Baseline and 168 hours post-dose (Day 8)
Population: Per-Protocol Population which consisted of the set of data generated by the subset of participants who had evaluable data for the endpoint and who complied with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Panel A- MK-2060 (8 mg) | Fold Change From Baseline in Activated Partial Thromboplastin Time (aPTT) of MK-2060: Part 1 | 1.04 Ratio |
| Part 1: Panel B- MK-2060 (20 mg) | Fold Change From Baseline in Activated Partial Thromboplastin Time (aPTT) of MK-2060: Part 1 | 1.17 Ratio |
| Part 1: Panel A- MK-2060 (40 mg) | Fold Change From Baseline in Activated Partial Thromboplastin Time (aPTT) of MK-2060: Part 1 | 1.52 Ratio |
| Part 1: Placebo | Fold Change From Baseline in Activated Partial Thromboplastin Time (aPTT) of MK-2060: Part 1 | 1.05 Ratio |
Secondary
Fold Change From Baseline in aPTT of MK-2060: Part 2
Plasma samples were collected at pre-specified time points post-dose and aPTT values were assessed. The fold change (Day 8/Baseline) at Day 8 was reported.
Time frame: Baseline and Day 8
Population: Per-Protocol Population which consisted of the set of data generated by the subset of participants who had evaluable data for the endpoint and who complied with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Panel A- MK-2060 (8 mg) | Fold Change From Baseline in aPTT of MK-2060: Part 2 | 2.46 Ratio |
| Part 1: Panel B- MK-2060 (20 mg) | Fold Change From Baseline in aPTT of MK-2060: Part 2 | 0.68 Ratio |
Secondary
Part 1: Area Under the Plasma Concentration-Time Curve of MK-2060 From 0 to Infinity (AUC0-inf)
Plasma samples were collected at pre-specified time points post-dose and AUC0-inf was assessed.
Time frame: Predose Day 1 and 1, 12, 24, 48, 52, 96, 168 hours postdose, then Days 12, 15, 22, 29, 60, 90, 120, 150
Population: Per-Protocol Population which consisted of the set of data generated by the subset of participants who had evaluable data for the endpoint and who complied with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Panel A- MK-2060 (8 mg) | Part 1: Area Under the Plasma Concentration-Time Curve of MK-2060 From 0 to Infinity (AUC0-inf) | 4550 hr*nmol/Liter | Geometric Coefficient of Variation 61.2 |
| Part 1: Panel B- MK-2060 (20 mg) | Part 1: Area Under the Plasma Concentration-Time Curve of MK-2060 From 0 to Infinity (AUC0-inf) | 6520 hr*nmol/Liter | Geometric Coefficient of Variation 63.4 |
| Part 1: Panel A- MK-2060 (40 mg) | Part 1: Area Under the Plasma Concentration-Time Curve of MK-2060 From 0 to Infinity (AUC0-inf) | 15100 hr*nmol/Liter | Geometric Coefficient of Variation 31.7 |
90% CI: [0.54, 1.18]
90% CI: [0.37, 0.76]
Comparison: GMR was derived using GM for participants with ESRD and the GM from historical data obtained from a study of MK-2060 in healthy participants (PN001).90% CI: [0.55, 1.21]
Secondary
Part 1: Area Under the Plasma Concentration-Time Curve of MK-2060 From Time 0 to 168 Hours (AUC0-168)
Plasma samples were collected at pre-specified time points post-dose and AUC0-168 hours was assessed.
Time frame: Predose Day 1 and 1, 12, 24, 48, 52, 96, 168 hours postdose
Population: Per-Protocol Population which consisted of the set of data generated by the subset of participants who had evaluable data for the endpoint and who complied with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Panel A- MK-2060 (8 mg) | Part 1: Area Under the Plasma Concentration-Time Curve of MK-2060 From Time 0 to 168 Hours (AUC0-168) | 1560 hr*nmol/Liter | Geometric Coefficient of Variation 32.5 |
| Part 1: Panel B- MK-2060 (20 mg) | Part 1: Area Under the Plasma Concentration-Time Curve of MK-2060 From Time 0 to 168 Hours (AUC0-168) | 2420 hr*nmol/Liter | Geometric Coefficient of Variation 47 |
| Part 1: Panel A- MK-2060 (40 mg) | Part 1: Area Under the Plasma Concentration-Time Curve of MK-2060 From Time 0 to 168 Hours (AUC0-168) | 4930 hr*nmol/Liter | Geometric Coefficient of Variation 26.8 |
Comparison: GMR was derived using GM for participants with ESRD and the GM from historical data obtained from a study of MK-2060 in healthy participants (PN001).90% CI: [1.07, 1.85]
Comparison: GMR was derived using GM for participants with ESRD and the GM from historical data obtained from a study of MK-2060 in healthy participants (PN001)90% CI: [0.67, 1.11]
Comparison: GMR was derived using GM for participants with ESRD and the GM from historical data obtained from a study of MK-2060 in healthy participants (PN001).90% CI: [0.62, 1.08]
Secondary
Part 1: Maximum Observed Plasma Concentration (Cmax) of MK-2060
Plasma samples were collected at pre-specified time points post-dose and Cmax was assessed.
Time frame: Predose Day 1 and 1, 12, 24, 48, 52, 96, 168 hours postdose, then Days 12, 15, 22, 29, 60, 90, 120, 150
Population: Per-Protocol Population which consisted of the set of data generated by the subset of participants who had evaluable data for the endpoint and who complied with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Panel A- MK-2060 (8 mg) | Part 1: Maximum Observed Plasma Concentration (Cmax) of MK-2060 | 14.8 nmol/Liter | Geometric Coefficient of Variation 38.2 |
| Part 1: Panel B- MK-2060 (20 mg) | Part 1: Maximum Observed Plasma Concentration (Cmax) of MK-2060 | 28.0 nmol/Liter | Geometric Coefficient of Variation 49.3 |
| Part 1: Panel A- MK-2060 (40 mg) | Part 1: Maximum Observed Plasma Concentration (Cmax) of MK-2060 | 61.3 nmol/Liter | Geometric Coefficient of Variation 19.3 |
Comparison: GMR was derived using GM for participants with ESRD and the GM from historical data obtained from a study of MK-2060 in healthy participants (PN001).90% CI: [0.84, 1.46]
Comparison: GMR was derived using GM for participants with ESRD and the GM from historical data obtained from a study of MK-2060 in healthy participants (PN001).90% CI: [0.52, 0.87]
Comparison: GMR was derived using GM for participants with ESRD and the GM from historical data obtained from a study of MK-2060 in healthy participants (PN001).90% CI: [0.6, 1.03]
Secondary
Part 1: Plasma Clearance (CL) of MK-2060
Plasma samples were collected at pre-specified time points post-dose and CL was assessed.
Time frame: Predose Day 1 and 1, 12, 24, 48, 52, 96, 168 hours postdose
Population: Per-Protocol Population which consisted of the set of data generated by the subset of participants who had evaluable data for the endpoint and who complied with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Panel A- MK-2060 (8 mg) | Part 1: Plasma Clearance (CL) of MK-2060 | 0.0119 Liters/hour | Geometric Coefficient of Variation 61.2 |
| Part 1: Panel B- MK-2060 (20 mg) | Part 1: Plasma Clearance (CL) of MK-2060 | 0.0207 Liters/hour | Geometric Coefficient of Variation 63.4 |
| Part 1: Panel A- MK-2060 (40 mg) | Part 1: Plasma Clearance (CL) of MK-2060 | 0.0179 Liters/hour | Geometric Coefficient of Variation 31.7 |
Secondary
Part 1: Plasma Concentration of MK-2060 at 168 Hours (C168)
Plasma samples were collected at 168 hours post-dose and C168 was assessed.
Time frame: 168 hours post dose
Population: Per-Protocol Population which consisted of the set of data generated by the subset of participants who had evaluable data for the endpoint and who complied with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Panel A- MK-2060 (8 mg) | Part 1: Plasma Concentration of MK-2060 at 168 Hours (C168) | 6.29 nmol/Liter | Geometric Coefficient of Variation 41.6 |
| Part 1: Panel B- MK-2060 (20 mg) | Part 1: Plasma Concentration of MK-2060 at 168 Hours (C168) | 9.10 nmol/Liter | Geometric Coefficient of Variation 57.7 |
| Part 1: Panel A- MK-2060 (40 mg) | Part 1: Plasma Concentration of MK-2060 at 168 Hours (C168) | 15.8 nmol/Liter | Geometric Coefficient of Variation 30.2 |
Comparison: GMR was derived using GM for participants with ESRD and the GM from historical data obtained from a study of MK-2060 in healthy participants (PN001).90% CI: [1.05, 2.14]
Comparison: GMR was derived using GM for participants with ESRD and the GM from historical data obtained from a study of MK-2060 in healthy participants (PN001).90% CI: [0.67, 1.25]
Comparison: GMR was derived using GM for participants with ESRD and the GM from historical data obtained from a study of MK-2060 in healthy participants (PN001).90% CI: [0.62, 1.2]
Secondary
Part 1: Plasma Elimination Terminal Half-life (t ½) of MK-2060
Plasma samples was collected at pre-specified time points post-dose and t ½ was assessed.
Time frame: Predose Day 1 and 1, 12, 24, 48, 52, 96, 168 hours postdose
Population: Per-Protocol Population which consisted of the set of data generated by the subset of participants who had evaluable data for the endpoint and who complied with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Panel A- MK-2060 (8 mg) | Part 1: Plasma Elimination Terminal Half-life (t ½) of MK-2060 | 325 Hours | Geometric Coefficient of Variation 88.5 |
| Part 1: Panel B- MK-2060 (20 mg) | Part 1: Plasma Elimination Terminal Half-life (t ½) of MK-2060 | 422 Hours | Geometric Coefficient of Variation 69 |
| Part 1: Panel A- MK-2060 (40 mg) | Part 1: Plasma Elimination Terminal Half-life (t ½) of MK-2060 | 508 Hours | Geometric Coefficient of Variation 21.7 |
Secondary
Part 1: Plasma Volume of Distribution (Vz) of MK-2060
Plasma samples were collected at pre-specified time points post-dose and Vz was assessed.
Time frame: Predose Day 1 and 1, 12, 24, 48, 52, 96, 168 hours postdose
Population: Per-Protocol Population which consisted of the set of data generated by the subset of participants who had evaluable data for the endpoint and who complied with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Panel A- MK-2060 (8 mg) | Part 1: Plasma Volume of Distribution (Vz) of MK-2060 | 5.56 Liters | Geometric Coefficient of Variation 49 |
| Part 1: Panel B- MK-2060 (20 mg) | Part 1: Plasma Volume of Distribution (Vz) of MK-2060 | 12.6 Liters | Geometric Coefficient of Variation 65.3 |
| Part 1: Panel A- MK-2060 (40 mg) | Part 1: Plasma Volume of Distribution (Vz) of MK-2060 | 13.1 Liters | Geometric Coefficient of Variation 31.2 |
Secondary
Part 1: Time to Maximum Observed Plasma Drug Concentration (Tmax) of MK-2060
Plasma samples were collected at pre-specified time points post-dose and Tmax was assessed.
Time frame: Predose Day 1 and 1, 12, 24, 48, 52, 96, 168 hours postdose
Population: Per-Protocol Population which consisted of the set of data generated by the subset of participants who had evaluable data for the endpoint and who complied with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Panel A- MK-2060 (8 mg) | Part 1: Time to Maximum Observed Plasma Drug Concentration (Tmax) of MK-2060 | 1.13 Hours |
| Part 1: Panel B- MK-2060 (20 mg) | Part 1: Time to Maximum Observed Plasma Drug Concentration (Tmax) of MK-2060 | 0.97 Hours |
| Part 1: Panel A- MK-2060 (40 mg) | Part 1: Time to Maximum Observed Plasma Drug Concentration (Tmax) of MK-2060 | 1.09 Hours |
Secondary
Part 2: AUC0-168 of MK-2060
Plasma samples were collected at pre-specified time points post-dose and AUC0-168 hours was assessed.
Time frame: Up to 168 hours on Day 1 and Day 22
Population: Per-Protocol Population which consisted of the set of data generated by the subset of participants who had evaluable data for the endpoint and who complied with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Panel A- MK-2060 (8 mg) | Part 2: AUC0-168 of MK-2060 | Day 1 | 2290 hr*nmol/L | Geometric Coefficient of Variation 26.8 |
| Part 1: Panel A- MK-2060 (8 mg) | Part 2: AUC0-168 of MK-2060 | Day 22 | 9880 hr*nmol/L | Geometric Coefficient of Variation 28.9 |
Secondary
Part 2: C168 of MK-2060
Plasma samples were collected at 168 hours post-dose and C168 was assessed.
Time frame: 168 hours post dose on Days 1 and 22
Population: Per-Protocol Population which consisted of the set of data generated by the subset of participants who had evaluable data for the endpoint and who complied with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Panel A- MK-2060 (8 mg) | Part 2: C168 of MK-2060 | Day 1 | 54.1 nmol/Liter | Geometric Coefficient of Variation 42.1 |
| Part 1: Panel A- MK-2060 (8 mg) | Part 2: C168 of MK-2060 | Day 22 | 43.8 nmol/Liter | Geometric Coefficient of Variation 30.5 |
Secondary
Part 2: Cmax of MK-2060
Plasma samples were collected at pre-specified time points post-dose and Cmax was assessed.
Time frame: Day 1 and Day 22
Population: Per-Protocol Population which consisted of the set of data generated by the subset of participants who had evaluable data for the endpoint and who complied with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Panel A- MK-2060 (8 mg) | Part 2: Cmax of MK-2060 | Day 1 | 32.6 nmol/Liter | Geometric Coefficient of Variation 32.5 |
| Part 1: Panel A- MK-2060 (8 mg) | Part 2: Cmax of MK-2060 | Day 22 | 90.9 nmol/Liter | Geometric Coefficient of Variation 30.4 |
Secondary
Part 2: Tmax of MK-2060
Plasma samples were collected at pre-specified time points post-dose and Tmax was assessed.
Time frame: Day 1 and Day 22
Population: Per-Protocol Population which consisted of the set of data generated by the subset of participants who had evaluable data for the endpoint and who complied with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1: Panel A- MK-2060 (8 mg) | Part 2: Tmax of MK-2060 | Day 22 | 1.00 Hours |
| Part 1: Panel A- MK-2060 (8 mg) | Part 2: Tmax of MK-2060 | Day 1 | 1.00 Hours |