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CompletedNCT02011490Updated Oct 2, 2018Results posted

Pharmacokinetics of Sugammadex (MK-8616) in Participants With Moderate and Severe Renal Insufficiency (MK-8616-105)

A Phase 1 interventional study of sugammadex in Renal Insufficiency and Renal Impairment, sponsored by Merck Sharp & Dohme LLC. Completed at 1 site in United States. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2018-10-02.

Sponsored by Merck Sharp & Dohme LLC · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
33
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study summary

The purpose of this study is to evaluate the plasma pharmacokinetics of a single 4 mg/kg intravenous (IV) dose of sugammadex in participants with moderate and severe renal insufficiency compared to that in participants with normal renal function. The study consists of two parts. In Part 1, participants with renal insufficiency and healthy participants will be administered study drug by IV bolus injection into a peripheral vein. In Part 2, participants with renal insufficiency and healthy participants will be administered study drug as an IV bolus into a peripheral vein, through an IV catheter connected to IV tubing with injection port. Subjects who participate in Part 1 of study may be enrolled in Part 2, which would reduce the overall number of participants enrolled for the study.

Read the detailed description

In each study period (i.e., Part 1 and Part 2), day of drug administration was defined to be Day 1.

02

Conditions studied

  • Renal Insufficiency
  • Renal Impairment

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03

In context

Renal Insufficiency

1,995 studies on the registry are indexed under Renal Insufficiency; 173 are open to participants now.

This study's enrollment of 33 is below the median of 43 across 1,504 interventional studies indexed under Renal Insufficiency.

Browse Renal Insufficiency studies →

Lead sponsor

Merck Sharp & Dohme LLC is the lead sponsor of 2,114 studies on the registry; 133 are open to participants now.

Of its 489 completed or terminated interventional studies of FDA-regulated products, 362 (74%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

All Participants:

  • Body Mass Index ≥18 to ≤40 kg/m\^2
  • Females of childbearing potential must either be sexually inactive (abstinent) for 14 days prior to dosing and throughout the study or are using an acceptable birth control method
  • Females of non-childbearing potential must have undergone a sterilization procedure at least 6 months prior to dosing or are postmenopausal with amenorrhea for at least 1 year prior to dosing and have follicle stimulating hormone (FSH) serum levels consistent with postmenopausal status
  • Male subjects must agree not to donate sperm from dosing until 90 days after dosing

Participants with Moderate or Severe Renal Insufficiency:

  • Health of participant is stable based on medical history, laboratory tests and other assessments
  • Clinical diagnosis of impaired stable renal function, and a creatinine clearance (CLcr) of \<30 mL/min and not on hemodialysis for severe renal insufficiency participants, or 30 to \<50 mL/min for moderate renal insufficiency participants
  • No clinically significant change in renal status for at least 1 month prior to dosing, and is not currently or has not previously been on hemodialysis

Healthy Control Participants:

  • Participant is medically healthy based on laboratory tests and other assessments
  • Age of the individual healthy participants in Part 1 of the study is aimed to be within the range of the mean age ± approximately 15 years of all participants with renal impairment in Part 1 of the study combined; this approach will also be applied with respect to age of participants in Part 2 of the study
  • CLcr ≥80 mL/min

Exclusion criteria

Exclusion Criteria:

All Participants:

  • Mentally or legally incapacitated, significant emotional problems at screening or expected during the conduct of the study or history of a clinically significant psychiatric disorder over the last 5 years
  • History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, or neurological disease whose current condition is considered unstable
  • History or presence of alcoholism and drug abuse within the past 6 months
  • History or presence of hypersensitivity or idiosyncratic reaction to the study medication or related compounds
  • Female participants who are pregnant or lactating
  • Positive results for the urine or saliva drug screen, or for the urine or breath alcohol screen
  • Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV)
  • Regular user of any medication (including over the counter) that would significantly alter renal function (e.g., cimetidine)
  • Donation of blood or significant blood loss within 56 days prior to dosing, or donation of plasma within 7 days prior to dosing
  • Participation in another clinical trial within 28 days prior to dosing
  • No participant may be enrolled more than once within Part 1. Subjects who participate in Part 1 of study may be enrolled in Part 2, but participants within Part 2 are not to be enrolled more than once in Part 2

Healthy Control Participants:

  • Participant has had a renal transplant or has had nephrectomy
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
33 participants (actual)

Study arms

  • Experimental
    Severe Renal Insufficiency Participants: Part 1

    Participants with severe renal insufficiency will receive a single dose of 4 mg/kg sugammadex administered as an IV bolus over 10 seconds. Dose will be administered by direct injection into a peripheral vein.

    Drug: sugammadex

  • Experimental
    Moderate Renal Insufficiency Participants: Part 1

    Participants with moderate renal insufficiency will receive a single dose of 4 mg/kg sugammadex administered as an IV bolus over 10 seconds. Dose will be administered by direct injection into a peripheral vein.

    Drug: sugammadex

  • Experimental
    Healthy Control Participants: Part 1

    Healthy control participants will receive a single dose of 4 mg/kg sugammadex administered as an IV bolus over 10 seconds. Dose will be administered by direct injection into a peripheral vein.

    Drug: sugammadex

  • Experimental
    Severe Renal Insufficiency Participants: Part 2

    Participants with severe renal insufficiency will receive a single dose of 4 mg/kg sugammadex administered as an IV bolus over 10 seconds. Dose will be administered into a peripheral vein through an IV catheter connected to an IV tubing with injection port. The IV tubing is connected to a saline bag. Free-flowing access to the vein will be confirmed immediately prior to dose administration, and dose will be followed by saline flush.

    Drug: sugammadex

  • Experimental
    Moderate Renal Insufficiency Participants: Part 2

    Participants with moderate renal insufficiency will receive a single dose of 4 mg/kg sugammadex administered as an IV bolus over 10 seconds. Dose will be administered into a peripheral vein through an IV catheter connected to an IV tubing with injection port. The IV tubing is connected to a saline bag. Free-flowing access to the vein will be confirmed immediately prior to dose administration, and dose will be followed by saline flush.

    Drug: sugammadex

  • Experimental
    Healthy Control Participants: Part 2

    Healthy control participants will receive a single dose of 4 mg/kg sugammadex administered as an IV bolus over 10 seconds. Dose will be administered into a peripheral vein through an IV catheter connected to an IV tubing with injection port. The IV tubing is connected to a saline bag. Free-flowing access to the vein will be confirmed immediately prior to dose administration, and dose will be followed by saline flush.

    Drug: sugammadex

Interventions

  • Drugsugammadex

    sugammadex 4 mg/kg IV bolus

06

What researchers measure

Primary outcomes

  1. Geometric Least Squares Mean Area Under the Plasma Drug Concentration-time Curve From Time Zero to Infinity (AUC0-∞) Following a Single IV Dose of Sugammadex

    Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. AUC0-∞ was calculated as the sum of the AUC to the last time point with a detectable plasma concentration (AUC0-last, determined by trapezoidal method) and the extrapolated area given by Cest,last/λz, where Cest,last is the estimated concentration corresponding to the time of the last measurable concentration and λz is the apparent first-order terminal elimination rate constant. For each subject, λz was calculated by regression of the terminal log-linear portion of the plasma concentration-time profile. The reported least squares mean is the geometric least squares mean, which is the back-transformed least squares mean from the analysis of variance (ANOVA) linear fixed-effect model performed on natural log-transformed values of AUC0-∞. This calculation also provides the associated 95% confidence interval.

    Time frame: For participants with: normal renal function - up to 48 hours post-dose (Part 1 + Part 2); moderate renal insufficiency - up to Day 28 (Part 1) or Day 10 (Part 2); severe renal insufficiency - up to Day 35 (Part 1) or Day 14 (Part 2)

  2. Geometric Least Squares Mean Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC0-last) Following a Single IV Dose of Sugammadex

    Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. AUC0-last was determined by trapezoidal method. The reported least squares mean is the geometric least squares mean, which is the back-transformed least squares mean from the ANOVA linear fixed-effect model performed on natural log-transformed values of AUC0-last. This calculation also provides the associated 95% confidence interval.

    Time frame: For participants with: normal renal function - up to 48 hours post-dose (Part 1 + Part 2); moderate renal insufficiency - up to Day 28 (Part 1) or Day 10 (Part 2); severe renal insufficiency - up to Day 35 (Part 1) or Day 14 (Part 2)

  3. Geometric Least Squares Mean Maximum Observed Plasma Concentration (Cmax) Following a Single IV Dose of Sugammadex

    Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. Cmax was determined from the observed plasma concentration-time data. The reported least squares mean is the geometric least squares mean, which is the back-transformed least squares mean from the ANOVA linear fixed-effect model performed on natural log-transformed values of Cmax. This calculation also provides the associated 95% confidence interval.

    Time frame: For participants with: normal renal function - up to 48 hours post-dose (Part 1 + Part 2); moderate renal insufficiency - up to Day 28 (Part 1) or Day 10 (Part 2); severe renal insufficiency - up to Day 35 (Part 1) or Day 14 (Part 2)

  4. Geometric Mean Percent of AUC0-∞ That Was Extrapolated (AUC%Extrap) Following a Single IV Dose of Sugammadex

    Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. AUC%extrap represents the percentage of the AUC0-∞ obtained by extrapolation, calculated as (1 - \[AUC0-last/AUC0-∞\]) multiplied by 100.

    Time frame: For participants with: normal renal function - up to 48 hours post-dose (Part 1 + Part 2); moderate renal insufficiency - up to Day 28 (Part 1) or Day 10 (Part 2); severe renal insufficiency - up to Day 35 (Part 1) or Day 14 (Part 2)

  5. Geometric Mean Total Clearance (CL) Following a Single IV Dose of Sugammadex

    Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. CL is a quantitative measure of the rate at which a drug substance is removed from the body, calculated as Dose/AUC0-∞.

    Time frame: For participants with: normal renal function - up to 48 hours post-dose (Part 1 + Part 2); moderate renal insufficiency - up to Day 28 (Part 1) or Day 10 (Part 2); severe renal insufficiency - up to Day 35 (Part 1) or Day 14 (Part 2)

  6. Geometric Mean Volume of Distribution During the Terminal Elimination Phase (Vz) Following a Single IV Dose of Sugammadex

    Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. Vz was calculated as Dose/(AUC0-∞\*λz).

    Time frame: For participants with: normal renal function - up to 48 hours post-dose (Part 1 + Part 2); moderate renal insufficiency - up to Day 28 (Part 1) or Day 10 (Part 2); severe renal insufficiency - up to Day 35 (Part 1) or Day 14 (Part 2)

  7. Geometric Mean of Mean Residence Time (MRT) of Unchanged Drug in the Systemic Circulation Following a Single IV Dose of Sugammadex

    Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. MRT is defined as the mean duration of time a drug molecule is present in the systemic circulation.

    Time frame: For participants with: normal renal function - up to 48 hours post-dose (Part 1 + Part 2); moderate renal insufficiency - up to Day 28 (Part 1) or Day 10 (Part 2); severe renal insufficiency - up to Day 35 (Part 1) or Day 14 (Part 2)

  8. Geometric Mean Apparent Volume of Distribution Estimated at Steady-state (Vss) Following a Single IV Dose of Sugammadex

    Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. Vss is the theoretical volume that the total amount of administered drug would have to occupy (if it were uniformly distributed), to provide the same concentration as it is in blood plasma at steady state, calculated as CL\*MRT.

    Time frame: For participants with: normal renal function - up to 48 hours post-dose (Part 1 + Part 2); moderate renal insufficiency - up to Day 28 (Part 1) or Day 10 (Part 2); severe renal insufficiency - up to Day 35 (Part 1) or Day 14 (Part 2)

  9. Median Time to Maximum Observed Plasma Concentration (Tmax) Following a Single IV Dose of Sugammadex

    Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. Tmax was determined from the observed plasma concentration-time data.

    Time frame: For participants with: normal renal function - up to 48 hours post-dose (Part 1 + Part 2); moderate renal insufficiency - up to Day 28 (Part 1) or Day 10 (Part 2); severe renal insufficiency - up to Day 35 (Part 1) or Day 14 (Part 2)

  10. Median Time of the Last Measurable Plasma Concentration (Tlast) Following a Single IV Dose of Sugammadex

    Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. Tlast was determined from the observed plasma concentration-time data.

    Time frame: For participants with: normal renal function - up to 48 hours post-dose (Part 1 + Part 2); moderate renal insufficiency - up to Day 28 (Part 1) or Day 10 (Part 2); severe renal insufficiency - up to Day 35 (Part 1) or Day 14 (Part 2)

  11. Geometric Mean Apparent First-order Terminal Elimination Half-life (t1/2) Following a Single IV Dose of Sugammadex

    Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. Elimination t1/2 is the time it takes for the concentration of the drug in the body to decrease by half during the elimination phase, calculated as the natural log of 2 (ln\[2\])/λz.

    Time frame: For participants with: normal renal function - up to 48 hours post-dose (Part 1 + Part 2); moderate renal insufficiency - up to Day 28 (Part 1) or Day 10 (Part 2); severe renal insufficiency - up to Day 35 (Part 1) or Day 14 (Part 2)

  12. Geometric Mean Effective Half-life (t1/2eff) Following a Single IV Dose of Sugammadex

    Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. t½eff was calculated as ln(2)\*MRT.

    Time frame: For participants with: normal renal function - up to 48 hours post-dose (Part 1 + Part 2); moderate renal insufficiency - up to Day 28 (Part 1) or Day 10 (Part 2); severe renal insufficiency - up to Day 35 (Part 1) or Day 14 (Part 2)

  13. Geometric Mean Apparent First-order Terminal Elimination Rate Constant (λz) Following a Single IV Dose of Sugammadex

    Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. λz was calculated by regression of the terminal log-linear portion of the plasma concentration-time profile.

    Time frame: For participants with: normal renal function - up to 48 hours post-dose (Part 1 + Part 2); moderate renal insufficiency - up to Day 28 (Part 1) or Day 10 (Part 2); severe renal insufficiency - up to Day 35 (Part 1) or Day 14 (Part 2)

07

Results

Posted Feb 10, 2015

Participant flow

Part 1
Participant flow — Part 1
MilestoneSevere Renal Insufficiency Participants: Part 1Moderate Renal Insufficiency Participants: Part 1Healthy Control Participants: Part 1Severe Renal Insufficiency Participants: Part 2Moderate Renal Insufficiency Participants: Part 2Healthy Control Participants: Part 2
Started888000
Completed888000
Not completed000000
Part 2
Participant flow — Part 2
MilestoneSevere Renal Insufficiency Participants: Part 1Moderate Renal Insufficiency Participants: Part 1Healthy Control Participants: Part 1Severe Renal Insufficiency Participants: Part 2Moderate Renal Insufficiency Participants: Part 2Healthy Control Participants: Part 2
Started000666
Completed000666
Not completed000000

Outcome measures

PrimaryGeometric Least Squares Mean Area Under the Plasma Drug Concentration-time Curve From Time Zero to Infinity (AUC0-∞) Following a Single IV Dose of Sugammadex

Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. AUC0-∞ was calculated as the sum of the AUC to the last time point with a detectable plasma concentration (AUC0-last, determined by trapezoidal method) and the extrapolated area given by Cest,last/λz, where Cest,last is the estimated concentration corresponding to the time of the last measurable concentration and λz is the apparent first-order terminal elimination rate constant. For each subject, λz was calculated by regression of the terminal log-linear portion of the plasma concentration-time profile. The reported least squares mean is the geometric least squares mean, which is the back-transformed least squares mean from the analysis of variance (ANOVA) linear fixed-effect model performed on natural log-transformed values of AUC0-∞. This calculation also provides the associated 95% confidence interval.

Time frame:
For participants with: normal renal function - up to 48 hours post-dose (Part 1 + Part 2); moderate renal insufficiency - up to Day 28 (Part 1) or Day 10 (Part 2); severe renal insufficiency - up to Day 35 (Part 1) or Day 14 (Part 2)
Reported as:
Least squares mean · ug*hr/mL
Geometric Least Squares Mean Area Under the Plasma Drug Concentration-time Curve From Time Zero to Infinity (AUC0-∞) Following a Single IV Dose of Sugammadex
ug*hr/mLSevere Renal Insufficiency Participants: Part 1Moderate Renal Insufficiency Participants: Part 1Healthy Control Participants: Part 1Severe Renal Insufficiency Participants: Part 2Moderate Renal Insufficiency Participants: Part 2Healthy Control Participants: Part 2
Geometric Least Squares Mean Area Under the Plasma Drug Concentration-time Curve From Time Zero to Infinity (AUC0-∞) Following a Single IV Dose of Sugammadex———339 (268 to 428)151 (120 to 191)62.5 (49.5 to 79.0)
Statistical analysis
  • Severe Renal Insufficiency Participants: Part 2 vs Healthy Control Participants: Part 2 · Geometric least squares mean ratio: 5.42 · 90% CI 4.12 to 7.11Difference in least squares means of log-transformed data (severe renal impaired - healthy) was back transformed to geometric least squares mean ratio (severe renal impaired/healthy)
  • Moderate Renal Insufficiency Participants: Part 2 vs Healthy Control Participants: Part 2 · Geometric least squares mean ratio: 2.42 · 90% CI 1.84 to 3.17Difference in least squares means of log-transformed data (moderate renal impaired - healthy) was back transformed to geometric least squares mean ratio (moderate renal impaired/healthy)
PrimaryGeometric Least Squares Mean Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC0-last) Following a Single IV Dose of Sugammadex

Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. AUC0-last was determined by trapezoidal method. The reported least squares mean is the geometric least squares mean, which is the back-transformed least squares mean from the ANOVA linear fixed-effect model performed on natural log-transformed values of AUC0-last. This calculation also provides the associated 95% confidence interval.

Time frame:
For participants with: normal renal function - up to 48 hours post-dose (Part 1 + Part 2); moderate renal insufficiency - up to Day 28 (Part 1) or Day 10 (Part 2); severe renal insufficiency - up to Day 35 (Part 1) or Day 14 (Part 2)
Reported as:
Least squares mean · ug*hr/mL
Geometric Least Squares Mean Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC0-last) Following a Single IV Dose of Sugammadex
ug*hr/mLSevere Renal Insufficiency Participants: Part 1Moderate Renal Insufficiency Participants: Part 1Healthy Control Participants: Part 1Severe Renal Insufficiency Participants: Part 2Moderate Renal Insufficiency Participants: Part 2Healthy Control Participants: Part 2
Geometric Least Squares Mean Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC0-last) Following a Single IV Dose of Sugammadex———335 (265 to 424)148 (117 to 187)61.1 (48.3 to 77.3)
Statistical analysis
  • Severe Renal Insufficiency Participants: Part 2 vs Healthy Control Participants: Part 2 · Geometric least squares mean ratio: 5.49 · 90% CI 4.18 to 7.22Difference in least squares means of log-transformed data (severe renal impaired - healthy) was back transformed to geometric least squares mean ratio (severe renal impaired/healthy)
  • Moderate Renal Insufficiency Participants: Part 2 vs Healthy Control Participants: Part 2 · Geometric least squares mean ratio: 2.42 · 90% CI 1.84 to 3.18Difference in least squares means of log-transformed data (moderate renal impaired - healthy) was back transformed to geometric least squares mean ratio (moderate renal impaired/healthy)
PrimaryGeometric Least Squares Mean Maximum Observed Plasma Concentration (Cmax) Following a Single IV Dose of Sugammadex

Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. Cmax was determined from the observed plasma concentration-time data. The reported least squares mean is the geometric least squares mean, which is the back-transformed least squares mean from the ANOVA linear fixed-effect model performed on natural log-transformed values of Cmax. This calculation also provides the associated 95% confidence interval.

Time frame:
For participants with: normal renal function - up to 48 hours post-dose (Part 1 + Part 2); moderate renal insufficiency - up to Day 28 (Part 1) or Day 10 (Part 2); severe renal insufficiency - up to Day 35 (Part 1) or Day 14 (Part 2)
Reported as:
Least squares mean · ug/mL
Geometric Least Squares Mean Maximum Observed Plasma Concentration (Cmax) Following a Single IV Dose of Sugammadex
ug/mLSevere Renal Insufficiency Participants: Part 1Moderate Renal Insufficiency Participants: Part 1Healthy Control Participants: Part 1Severe Renal Insufficiency Participants: Part 2Moderate Renal Insufficiency Participants: Part 2Healthy Control Participants: Part 2
Geometric Least Squares Mean Maximum Observed Plasma Concentration (Cmax) Following a Single IV Dose of Sugammadex———62.2 (50.2 to 77.1)60.6 (49.0 to 75.1)66.1 (53.3 to 81.8)
Statistical analysis
  • Severe Renal Insufficiency Participants: Part 2 vs Healthy Control Participants: Part 2 · Geometric least squares mean ratio: 0.94 · 90% CI 0.73 to 1.21Difference in least squares means of log-transformed data (severe renal impaired - healthy) was back transformed to geometric least squares mean ratio (severe renal impaired/healthy)
  • Moderate Renal Insufficiency Participants: Part 2 vs Healthy Control Participants: Part 2 · Geometric least squares mean ratio: 0.92 · 90% CI 0.72 to 1.18Difference in least squares means of log-transformed data (moderate renal impaired - healthy) was back transformed to geometric least squares mean ratio (moderate renal impaired/healthy)
PrimaryGeometric Mean Percent of AUC0-∞ That Was Extrapolated (AUC%Extrap) Following a Single IV Dose of Sugammadex

Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. AUC%extrap represents the percentage of the AUC0-∞ obtained by extrapolation, calculated as (1 - \[AUC0-last/AUC0-∞\]) multiplied by 100.

Time frame:
For participants with: normal renal function - up to 48 hours post-dose (Part 1 + Part 2); moderate renal insufficiency - up to Day 28 (Part 1) or Day 10 (Part 2); severe renal insufficiency - up to Day 35 (Part 1) or Day 14 (Part 2)
Reported as:
Geometric mean · Percent extrapolated
Geometric Mean Percent of AUC0-∞ That Was Extrapolated (AUC%Extrap) Following a Single IV Dose of Sugammadex
Percent extrapolatedSevere Renal Insufficiency Participants: Part 1Moderate Renal Insufficiency Participants: Part 1Healthy Control Participants: Part 1Severe Renal Insufficiency Participants: Part 2Moderate Renal Insufficiency Participants: Part 2Healthy Control Participants: Part 2
Geometric Mean Percent of AUC0-∞ That Was Extrapolated (AUC%Extrap) Following a Single IV Dose of Sugammadex———0.850 ± 43.52.14 ± 29.22.10 ± 45.3
PrimaryGeometric Mean Total Clearance (CL) Following a Single IV Dose of Sugammadex

Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. CL is a quantitative measure of the rate at which a drug substance is removed from the body, calculated as Dose/AUC0-∞.

Time frame:
For participants with: normal renal function - up to 48 hours post-dose (Part 1 + Part 2); moderate renal insufficiency - up to Day 28 (Part 1) or Day 10 (Part 2); severe renal insufficiency - up to Day 35 (Part 1) or Day 14 (Part 2)
Reported as:
Geometric mean · L/hr
Geometric Mean Total Clearance (CL) Following a Single IV Dose of Sugammadex
L/hrSevere Renal Insufficiency Participants: Part 1Moderate Renal Insufficiency Participants: Part 1Healthy Control Participants: Part 1Severe Renal Insufficiency Participants: Part 2Moderate Renal Insufficiency Participants: Part 2Healthy Control Participants: Part 2
Geometric Mean Total Clearance (CL) Following a Single IV Dose of Sugammadex———0.961 ± 26.82.27 ± 39.65.70 ± 16.0
PrimaryGeometric Mean Volume of Distribution During the Terminal Elimination Phase (Vz) Following a Single IV Dose of Sugammadex

Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. Vz was calculated as Dose/(AUC0-∞\*λz).

Time frame:
For participants with: normal renal function - up to 48 hours post-dose (Part 1 + Part 2); moderate renal insufficiency - up to Day 28 (Part 1) or Day 10 (Part 2); severe renal insufficiency - up to Day 35 (Part 1) or Day 14 (Part 2)
Reported as:
Geometric mean · L
Geometric Mean Volume of Distribution During the Terminal Elimination Phase (Vz) Following a Single IV Dose of Sugammadex
LSevere Renal Insufficiency Participants: Part 1Moderate Renal Insufficiency Participants: Part 1Healthy Control Participants: Part 1Severe Renal Insufficiency Participants: Part 2Moderate Renal Insufficiency Participants: Part 2Healthy Control Participants: Part 2
Geometric Mean Volume of Distribution During the Terminal Elimination Phase (Vz) Following a Single IV Dose of Sugammadex———18.3 ± 24.818.8 ± 24.220.4 ± 25.7
PrimaryGeometric Mean of Mean Residence Time (MRT) of Unchanged Drug in the Systemic Circulation Following a Single IV Dose of Sugammadex

Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. MRT is defined as the mean duration of time a drug molecule is present in the systemic circulation.

Time frame:
For participants with: normal renal function - up to 48 hours post-dose (Part 1 + Part 2); moderate renal insufficiency - up to Day 28 (Part 1) or Day 10 (Part 2); severe renal insufficiency - up to Day 35 (Part 1) or Day 14 (Part 2)
Reported as:
Geometric mean · hr
Geometric Mean of Mean Residence Time (MRT) of Unchanged Drug in the Systemic Circulation Following a Single IV Dose of Sugammadex
hrSevere Renal Insufficiency Participants: Part 1Moderate Renal Insufficiency Participants: Part 1Healthy Control Participants: Part 1Severe Renal Insufficiency Participants: Part 2Moderate Renal Insufficiency Participants: Part 2Healthy Control Participants: Part 2
Geometric Mean of Mean Residence Time (MRT) of Unchanged Drug in the Systemic Circulation Following a Single IV Dose of Sugammadex———15.7 ± 26.27.02 ± 30.82.48 ± 13.4
PrimaryGeometric Mean Apparent Volume of Distribution Estimated at Steady-state (Vss) Following a Single IV Dose of Sugammadex

Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. Vss is the theoretical volume that the total amount of administered drug would have to occupy (if it were uniformly distributed), to provide the same concentration as it is in blood plasma at steady state, calculated as CL\*MRT.

Time frame:
For participants with: normal renal function - up to 48 hours post-dose (Part 1 + Part 2); moderate renal insufficiency - up to Day 28 (Part 1) or Day 10 (Part 2); severe renal insufficiency - up to Day 35 (Part 1) or Day 14 (Part 2)
Reported as:
Geometric mean · L
Geometric Mean Apparent Volume of Distribution Estimated at Steady-state (Vss) Following a Single IV Dose of Sugammadex
LSevere Renal Insufficiency Participants: Part 1Moderate Renal Insufficiency Participants: Part 1Healthy Control Participants: Part 1Severe Renal Insufficiency Participants: Part 2Moderate Renal Insufficiency Participants: Part 2Healthy Control Participants: Part 2
Geometric Mean Apparent Volume of Distribution Estimated at Steady-state (Vss) Following a Single IV Dose of Sugammadex———15.1 ± 19.715.9 ± 21.914.1 ± 20.4
PrimaryMedian Time to Maximum Observed Plasma Concentration (Tmax) Following a Single IV Dose of Sugammadex

Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. Tmax was determined from the observed plasma concentration-time data.

Time frame:
For participants with: normal renal function - up to 48 hours post-dose (Part 1 + Part 2); moderate renal insufficiency - up to Day 28 (Part 1) or Day 10 (Part 2); severe renal insufficiency - up to Day 35 (Part 1) or Day 14 (Part 2)
Reported as:
Median · hr
Median Time to Maximum Observed Plasma Concentration (Tmax) Following a Single IV Dose of Sugammadex
hrSevere Renal Insufficiency Participants: Part 1Moderate Renal Insufficiency Participants: Part 1Healthy Control Participants: Part 1Severe Renal Insufficiency Participants: Part 2Moderate Renal Insufficiency Participants: Part 2Healthy Control Participants: Part 2
Median Time to Maximum Observed Plasma Concentration (Tmax) Following a Single IV Dose of Sugammadex———0.03 (0.03 to 0.08)0.03 (0.02 to 0.08)0.03 (0.03 to 0.08)
PrimaryMedian Time of the Last Measurable Plasma Concentration (Tlast) Following a Single IV Dose of Sugammadex

Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. Tlast was determined from the observed plasma concentration-time data.

Time frame:
For participants with: normal renal function - up to 48 hours post-dose (Part 1 + Part 2); moderate renal insufficiency - up to Day 28 (Part 1) or Day 10 (Part 2); severe renal insufficiency - up to Day 35 (Part 1) or Day 14 (Part 2)
Reported as:
Median · hr
Median Time of the Last Measurable Plasma Concentration (Tlast) Following a Single IV Dose of Sugammadex
hrSevere Renal Insufficiency Participants: Part 1Moderate Renal Insufficiency Participants: Part 1Healthy Control Participants: Part 1Severe Renal Insufficiency Participants: Part 2Moderate Renal Insufficiency Participants: Part 2Healthy Control Participants: Part 2
Median Time of the Last Measurable Plasma Concentration (Tlast) Following a Single IV Dose of Sugammadex———72.00 (71.99 to 143.99)24.00 (23.99 to 47.99)12.00 (11.99 to 12.00)
PrimaryGeometric Mean Apparent First-order Terminal Elimination Half-life (t1/2) Following a Single IV Dose of Sugammadex

Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. Elimination t1/2 is the time it takes for the concentration of the drug in the body to decrease by half during the elimination phase, calculated as the natural log of 2 (ln\[2\])/λz.

Time frame:
For participants with: normal renal function - up to 48 hours post-dose (Part 1 + Part 2); moderate renal insufficiency - up to Day 28 (Part 1) or Day 10 (Part 2); severe renal insufficiency - up to Day 35 (Part 1) or Day 14 (Part 2)
Reported as:
Geometric mean · hr
Geometric Mean Apparent First-order Terminal Elimination Half-life (t1/2) Following a Single IV Dose of Sugammadex
hrSevere Renal Insufficiency Participants: Part 1Moderate Renal Insufficiency Participants: Part 1Healthy Control Participants: Part 1Severe Renal Insufficiency Participants: Part 2Moderate Renal Insufficiency Participants: Part 2Healthy Control Participants: Part 2
Geometric Mean Apparent First-order Terminal Elimination Half-life (t1/2) Following a Single IV Dose of Sugammadex———13.24 ± 35.505.73 ± 29.792.47 ± 13.49
PrimaryGeometric Mean Effective Half-life (t1/2eff) Following a Single IV Dose of Sugammadex

Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. t½eff was calculated as ln(2)\*MRT.

Time frame:
For participants with: normal renal function - up to 48 hours post-dose (Part 1 + Part 2); moderate renal insufficiency - up to Day 28 (Part 1) or Day 10 (Part 2); severe renal insufficiency - up to Day 35 (Part 1) or Day 14 (Part 2)
Reported as:
Geometric mean · hr
Geometric Mean Effective Half-life (t1/2eff) Following a Single IV Dose of Sugammadex
hrSevere Renal Insufficiency Participants: Part 1Moderate Renal Insufficiency Participants: Part 1Healthy Control Participants: Part 1Severe Renal Insufficiency Participants: Part 2Moderate Renal Insufficiency Participants: Part 2Healthy Control Participants: Part 2
Geometric Mean Effective Half-life (t1/2eff) Following a Single IV Dose of Sugammadex———10.89 ± 26.154.87 ± 30.841.72 ± 13.36
PrimaryGeometric Mean Apparent First-order Terminal Elimination Rate Constant (λz) Following a Single IV Dose of Sugammadex

Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. λz was calculated by regression of the terminal log-linear portion of the plasma concentration-time profile.

Time frame:
For participants with: normal renal function - up to 48 hours post-dose (Part 1 + Part 2); moderate renal insufficiency - up to Day 28 (Part 1) or Day 10 (Part 2); severe renal insufficiency - up to Day 35 (Part 1) or Day 14 (Part 2)
Reported as:
Geometric mean · 1/hr
Geometric Mean Apparent First-order Terminal Elimination Rate Constant (λz) Following a Single IV Dose of Sugammadex
1/hrSevere Renal Insufficiency Participants: Part 1Moderate Renal Insufficiency Participants: Part 1Healthy Control Participants: Part 1Severe Renal Insufficiency Participants: Part 2Moderate Renal Insufficiency Participants: Part 2Healthy Control Participants: Part 2
Geometric Mean Apparent First-order Terminal Elimination Rate Constant (λz) Following a Single IV Dose of Sugammadex———0.0524 ± 35.50.121 ± 29.80.280 ± 13.5

Adverse events

Collected over Up to Day 35 (Part 1) or Day 14 (Part 2). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Severe Renal Insufficiency Participants: Part 1—0/8 (0%)3/8 (37.5%)
Moderate Renal Insufficiency Participants: Part 1—0/8 (0%)2/8 (25%)
Healthy Control Participants: Part 1—0/8 (0%)2/8 (25%)
Severe Renal Insufficiency Participants: Part 2—0/6 (0%)1/6 (16.7%)
Moderate Renal Insufficiency Participants: Part 2—0/6 (0%)2/6 (33.3%)
Healthy Control Participants: Part 2—0/6 (0%)0/6 (0%)
Most frequent other events
Most frequent other events
EventSevere Renal Insufficiency Participants: Part 1Moderate Renal Insufficiency Participants: Part 1Healthy Control Participants: Part 1Severe Renal Insufficiency Participants: Part 2Moderate Renal Insufficiency Participants: Part 2Healthy Control Participants: Part 2
Muscular weaknessMusculoskeletal and connective tissue disorders0/80/80/80/61/60/6
HeadacheNervous system disorders1/80/80/81/61/60/6
Paraesthesia oralGastrointestinal disorders1/80/80/80/60/60/6
Injection site extravasationGeneral disorders0/81/80/80/60/60/6
Injection site reactionGeneral disorders0/80/81/80/60/60/6
Tooth infectionInfections and infestations0/81/80/80/60/60/6
ContusionInjury, poisoning and procedural complications0/80/81/80/60/60/6
Pain in extremityMusculoskeletal and connective tissue disorders1/80/80/80/60/60/6
DizzinessNervous system disorders1/80/80/80/60/60/6
HypoaethesiaNervous system disorders0/81/80/80/60/60/6

Baseline characteristics

This table includes all 33 subjects who participated in study. Subjects who participated in both Part 1 and Part 2 are represented only once in this table. 1 participant was in severe renal insufficiency group in Part 1 and moderate renal insufficiency group in Part 2 and is allocated to severe renal insufficiency group in this table.

Age, Continuous
Age, Continuous(Years)Severe Renal Insufficiency Participants: Part 1 + Part 2Moderate Renal Insufficiency Participants: Part 1 + Part 2Healthy Control Participants: Part 1 + Part 2Total
Mean62.3 (47 to 76)64.2 (47 to 76)58.3 (50 to 67)61.5 (47 to 76)
Sex: Female, Male
Sex: Female, Male(Participants)Severe Renal Insufficiency Participants: Part 1 + Part 2Moderate Renal Insufficiency Participants: Part 1 + Part 2Healthy Control Participants: Part 1 + Part 2Total
Female2158
Male810725
08

Study locations

1 site
  • Investigational Site 001
    Hialeah, Florida 33014, United States
09

References and documents

Publications

  • Min KC, Lasseter KC, Marbury TC, Wrishko RE, Hanley WD, Wolford DG, Udo de Haes J, Reitmann C, Gutstein DE. Pharmacokinetics of sugammadex in subjects with moderate and severe renal impairment . Int J Clin Pharmacol Ther. 2017 Sep;55(9):746-752. doi: 10.5414/CP203025. PubMed 28679468 ↗

Individual participant data

Plan to share: Yes — https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 2, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02011490
Lead sponsor
Merck Sharp & Dohme LLC
Responsible party
Sponsor
First posted
Dec 13, 2013
Start date
Dec 11, 2013
Primary completion
Jun 6, 2014
Completion
Jun 6, 2014
Results posted
Feb 10, 2015
Last update
Oct 2, 2018

Study contacts

Medical Director
study director · Merck Sharp & Dohme LLC

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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