Phase 1
N=42
Pharmacokinetics (PK) and Safety of a Single Intravenous (IV) Dose of MK-3866 in Participants With Impaired Renal Function and in Healthy Controls (MK-3866-005)
Renal Impairment
Bottom Line
View on ClinicalTrials.gov: NCT03259087 ↗Enrolled (actual)
42
Serious AEs
4.1%
Results posted
Apr 2019
Primary outcome: Primary: Part 1: Area Under the Plasma Concentration-time Curve of MK-3866 From Time Zero to Infinity (AUC0-inf) — 104; 141; 83.5; 244 µM*hr
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- MK-3866 (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Merck Sharp & Dohme LLC
- Primary completion
- Jan 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part 1: Area Under the Plasma Concentration-time Curve of MK-3866 From Time Zero to Infinity (AUC0-inf) |
104; 141; 83.5; 244; 81.8 | — |
| PRIMARY Part 1: Area Under the Plasma Concentration-time Curve of MK-3866 From Time Zero to the Time of the Last Quantifiable Sample (AUC0-last) |
103; 139; 83.0; 237; 81.4 | — |
| PRIMARY Part 1: Area Under the Plasma Concentration-time Curve of MK-3866 From Time Zero to 24 Hours After Dosing (AUC0-24) |
96.2; 127; 79.7; 182; 78.1 | — |
| PRIMARY Part 1: Plasma Concentration of MK-3866 at the End of the Infusion (Ceoi) |
26.6; 27.7; 27.0; 29.7; 26.9 | — |
| PRIMARY Part 1: Maximum Plasma Concentration of MK-3866 (Cmax) |
27.4; 28.0; 28.7; 26.7 | — |
| PRIMARY Part 1: Plasma Clearance of MK-3866 (CL) |
3.80; 2.80; 4.75; 1.62; 4.85 | — |
| PRIMARY Part 1: Time to Maximum Plasma Concentration of MK-3866 (Tmax) |
0.50; 0.49; 0.50; 0.50; 0.50 | — |
| PRIMARY Part 1: Elimination Terminal Half-life of Plasma MK-3866 (t1/2) |
7.38; 8.23; 7.00; 14.7; 6.90 | — |
| PRIMARY Part 1: Volume of Distribution of Plasma MK-3866 (Vz) |
40.4; 33.3; 48.0; 34.4; 48.3 | — |
| PRIMARY Part 2: AUC0-inf of Plasma MK-3866 |
323; 129; 81.3 | — |
| PRIMARY Part 2: AUC0-last of Plasma MK-3866 |
294; 118; 80.9 | — |
| PRIMARY Part 2: AUC0-24 of Plasma MK-3866 |
203; 84.7; 77.8 | — |
| PRIMARY Part 2: Ceoi of Plasma MK-3866 |
26.3; 25.3; 26.8 | — |
| PRIMARY Part 2: Cmax of Plasma MK-3866 |
26.6; 25.3; 26.8 | — |
| PRIMARY Part 2: CL of Plasma MK-3866 |
1.23; 3.08; 4.87 | — |
| PRIMARY Part 2: Tmax of Plasma MK-3866 |
0.50; 0.50; 0.48 | — |
| PRIMARY Part 2: t1/2 of Plasma MK-3866 |
20.9; 20.0; 6.81 | — |
| PRIMARY Part 2: Vz of Plasma MK-3866 |
37.1; 89.1; 47.9 | — |
| SECONDARY Part 1: Total Amount of MK-3866 Excreted in the Urine Over 24 Hours (Ae0-24) |
97.1; 69.2; 107; 34.6; 115 | — |
| SECONDARY Part 1: Renal Clearance (CLr) of MK-3866 |
2.00; 1.08; 2.67; 0.377; 2.92 | — |
| SECONDARY Part 1: Fraction of MK-3866 Excretion (Urine) During Each Collection Interval (Fe0-24) |
0.485; 0.346; 0.537; 0.173; 0.575 | — |
| SECONDARY Part 2: Total Amount of MK-3866 Excreted Unchanged in the Urine Over the Period of 24 Hours (Ae0-24) |
4.31; 2.21; 115 | — |
| SECONDARY Part 2: Renal Clearance (CLr) of MK-3866 |
0.0474; 0.0558; 2.92 | — |
| SECONDARY Part 2: Fraction of MK-3866 Excretion (Urine) During Each Collection Interval (Fe0-24) |
0.0216; 0.0111; 0.574 | — |
| SECONDARY Part 2: Concentration of MK-3866 in Plasma Entering the Dialyzer Line (Ca) |
17.6; 12.0; 8.67; 7.25; 5.75; 4.32 | — |
| SECONDARY Part 2: Concentration of MK-3866 in Plasma Exiting the Dialyzer Line (Cv) |
8.32; 7.16; 5.17; 3.71; 2.92; 2.69 | — |
| SECONDARY Part 2: Area Under the Concentration-time Curve of MK-3866 in Plasma Entering the Dialyzer Line During the Dialysis Period (AUCD) |
29.4 | — |
| SECONDARY Part 2: Area Under the Concentration-time Curve of MK-3866 in Plasma Entering the Dialyzer Line From 0.75 to 4.5 Hours During the Dialysis Period (AUC[0.75-4.5]Ca) |
23.9 | — |
| SECONDARY Part 2: Area Under the Concentration-time Curve of MK-3866 in Plasma Entering the Dialyzer Line From 0.75 to 4.5 Hours During the Dialysis Period (AUC[0.75-4.5]Cv) |
13.6 | — |
| SECONDARY Part 2: Dialysis Clearance of MK-3866 Based on Plasma (CLD,Plasma) |
4.81 | — |
| SECONDARY Part 2: Concentration of MK-3866 in Dialysate Samples (CD) |
1.07; 3.02; 2.29; 1.62; 1.30; 1.08 | — |
| SECONDARY Part 2: Amount of MK-3866 Recovered From Each Dialysate Sample (AD) |
0.946; 0.736; 0.576; 0.408; 0.327; 0.272 | — |
| SECONDARY Part 2: Rate of Removal of MK-3866 From the Dialysate (rr) |
56.7; 44.2; 34.6; 24.5; 19.6; 16.3 | — |
| SECONDARY Part 2: Cumulative Amount of MK-3866 Recovered From the Dialysate (AD,Total) |
89.0 | — |
| SECONDARY Part 2: Hemodialysis Clearance of MK-3866 Based on the Dialysate(CLD,Dialysate) |
6.01 | — |
| SECONDARY Number of Participants With at Least One Adverse Event (AE) |
3; 3; 1; 1; 1; 1 | — |
| SECONDARY Number of Participants Discontinuing the Study Due to an Adverse Event |
0; 0; 0; 1; 1; 0 | — |
Summary
The purpose of this study is to compare plasma and urine PK parameters of MK-3866 between participants with impaired renal function and healthy control participants, to investigate the extent to which MK-3866 is removed from the plasma by hemodialysis (HD), and evaluate the safety and tolerability of MK-3866 in participants with impaired renal function.
Eligibility Criteria
Inclusion Criteria
- Females of non-childbearing potential. Male participants with female partner(s) of child-bearing potential agree to use a medically acceptable method of contraception during the study and for 90 days after dosing. If partner is pregnant, males agree to use a condom; if partner is of child-bearing potential, partner must use additional birth control
- Male participants agree not to donate sperm from the first dose until 90 days after dosing
- Adequate venous access
Renal Impaired Participants
- Liver function tests (serum alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) and serum bilirubin (total and direct) within upper limit of normal
- Panels A, B, and C: no clinically significant change in renal status at least 1 month prior to dosing and not currently or previously been on hemodialysis
- Panel E only: ESRD maintained on stable regimen of at least 3 times per week HD for at least 3 months prior to first dosing
Healthy Participants
- Age within ± 15 years of the mean age of participants with impaired renal function to which the healthy participant is matched
- Medically healthy as per medical history, physical examination, vital signs, 12-lead electrocardiograms (ECGs), and clinical laboratory safety tests
- Blood urea nitrogen, liver function tests (ALT, AST, alkaline phosphatase [ALP]), and serum bilirubin (total and direct) within upper limit of normal.
Exclusion Criteria
- Mentally/legally incapacitated, or significant emotional problems or significant psychiatric disorder
- History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, respiratory, genitourinary or major neurological abnormalities or diseases
- History of any illness that might confound the results of the study or poses an additional risk to the participant by their participation in the study
- Clinically significant history of cancer
- Smoker and/or has used nicotine or nicotine-containing products within 3 months prior to screening
- Female participants of childbearing potential, pregnant, or lactating
- Positive results for urine or saliva drug screen and/or urine or breath alcohol screen at screening or check-in
- Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV)
- Consumes more than 3 glasses of alcoholic beverages within 6 months of screening
- Consumes excessive amounts of coffee, tea, cola, energy-drinks, or other caffeinated beverages per day
- Major surgery, donated or lost 1 unit of blood within 4 weeks prior to screening, or donated plasma within 7 days prior to dosing in Part 1 or first dose in Part 2
Renal Impaired Participants
- Panels A, B, and C: Failed renal transplant or has had nephrectomy
- Panels A, B, and C: Rapidly fluctuating renal function, as determined by historical measurements; or demonstrated/suspected renal artery stenosis
- Panel E only: Has required frequent emergent HD (≥3) within a year prior to first dosing
Healthy Participants
- Renal transplant or nephrectomy
Data sourced from ClinicalTrials.gov (NCT03259087). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.