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Completed

NCT Number: NCT02661126

Pharmacokinetics of MK-3682B in Participants With Moderate to Severe Renal Insufficiency (MK-3682B-030)

The purpose of this study is to compare the plasma pharmacokinetics (PK) of single doses of MK-3682B, a fixed dose combination (FDC) tablet containing uprifosbuvir (MK-3682) + grazoprevir (MK-5172) + ruzasvir (MK-8408) in participants with moderate (Part 1) and severe (Part 2) renal insufficiency (RI) to plasma PK in healthy participants.

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Key information

Conditions

Hepatitis C Blood-Borne Infections Communicable Diseases Digestive System Diseases Flaviviridae Infections Hepatitis Hepatitis, Viral, Human Infections Liver Diseases RNA Virus Infections Virus Diseases

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

All Participants:

  • Healthy adult males or females 18-80 years of age at screening
  • Continuous non-smokers or moderate smokers (≤ 20 cigarettes/day or the equivalent) and agrees to consume no more than 10 cigarettes per day during the study period
  • BMI ≥ 18 and ≤ 40.0 kg/m^2
  • Agrees not to become pregnant or father a child during participation in the study
  • Females of childbearing potential must either be abstinent for 14 days prior to dosing and throughout the study or be using an acceptable birth control method
  • Vasectomized or non-vasectomized males must agree to use a condom with spermicide or abstain from sexual intercourse from the first dose until 90 days after dosing
  • Males must agree not to donate sperm from dosing until 90 days after dosing

Moderate and Severe RI Participants:

  • Baseline health is judged to be stable based on medical history, physical examination, laboratory profiles, vital signs, or electrocardiograms (ECGs), as deemed by the Investigator
  • Has had no clinically significant change in renal status at least 1 month prior to dosing and is not currently or has not previously been on hemodialysis
  • Moderate RI: has baseline eGFR ≥ 30 mL/min/1.73m^2 and < 60 mL/min/1.73m^2, based on the Modification of Diet in Renal Disease (MDRD) equation at screening
  • Severe RI: has baseline eGFR ≥ 15 mL/min/1.73m^2 and < 30 mL/min/1.73m^2, based on the MDRD equation at screening

Healthy Participants:

  • Is within ± 10 years of the mean age of moderate and severe RI arms
  • BMI is within 10% of the mean BMI of participants with moderate and severe RI arms
  • Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs, or ECGs, as deemed by the Investigator
  • Baseline CLcr ≥ 80 mL/min based on Cockcroft-Gault equation at screening

Exclusion criteria

  • Is mentally or legally incapacitated or has significant emotional problems at the time of the screening
  • History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the Investigator
  • History of any illness that, in the opinion of the Investigator, might confound the results of the study or poses an additional risk by participating in the study
  • Is female and pregnant or lactating
  • Positive results for the urine or saliva drug screen or urine or breath alcohol screen at screening or check-in unless the positive drug screen is due to prescription drug use that is approved by the Investigator and Sponsor
  • Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV)
  • Seated heart rate is equal to or lower than 44 beats per minute (bpm) or higher than 100 bpm at screening
  • Has had a renal transplant or has had nephrectomy
  • Donation of blood or had significant blood loss within 56 days prior to dosing of study drug, or donation of plasma within 7 days prior to dosing
  • Has participated in another clinical trial within 28 days prior to dosing of study drug

Treatment and study plan

MK-3682B

Drug

FDC oral tablet containing 225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir.

Primary outcomes

  1. Area Under the Plasma Concentration-time Curve (AUC) From Dosing to Time of Last Measurable Concentration (AUC0-last) of Uprifosbuvir (MK-3682)

    Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose

    AUC0-last is a measure of total exposure to uprifosbuvir in plasma from the start of dosing to the time of the last quantifiable (< lower limit of quantification [LLOQ]) sample following oral administration of MK-3682B.

  2. AUC From Dosing to Infinity (AUC0-∞) of Uprifosbuvir

    Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose

    AUC0-∞ is a measure of total exposure to uprifosbuvir in plasma from the start of dosing to infinity following oral administration of MK-3682B.

  3. AUC From Dosing to 24 Hours Post-dose (AUC0-24) of Uprifosbuvir

    Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 24 hours post-dose

    AUC0-24 is a measure of total exposure to uprifosbuvir in plasma from dosing to 24 hours following oral administration of MK-3682B.

  4. Maximum Plasma Concentration (Cmax) of Uprifosbuvir

    Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose

    Cmax is the maximum amount of uprifosbuvir in plasma following oral administration of MK-3682B.

  5. Plasma Concentration 24 Hours Post-dose (C24) of Uprifosbuvir

    Time frame: 24 hours post-dose

    C24 is the plasma concentration of uprifosbuvir 24 hours following oral administration of MK-3682B.

  6. Time to Reach Maximum Plasma Concentration (Tmax) of Uprifosbuvir

    Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose

    Tmax is the time required to reach the maximum post-dose plasma concentration of uprifosbuvir following oral administration of MK-3682B.

  7. Apparent Total Body Clearance (CL/F) of Uprifosbuvir

    Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose

    CL/F is the apparent total body clearance of uprifosbuvir following oral administration of MK-3682B.

  8. Apparent Volume of Distribution (Vz/F) of Uprifosbuvir

    Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose

    Vz/F is the apparent volume of distribution of uprifosbuvir following oral administration of MK-3682B.

  9. Apparent Terminal Half-life in Plasma (t½) of Uprifosbuvir

    Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose

    t1/2 is the amount of time required to clear 50% of uprifosbuvir from plasma following oral administration of MK-3682B.

  10. AUC0-last of Uprifosbuvir Metabolite M5

    Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose

    AUC0-last is a measure of total exposure to uprifosbuvir metabolite M5 in plasma from the start of dosing to the time of the last quantifiable (<LLOQ) sample following oral administration of MK-3682B.

  11. AUC0-∞ of Uprifosbuvir Metabolite M5

    Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose

    AUC0-∞ is a measure of total exposure to uprifosbuvir metabolite M5 in plasma from the start of dosing to infinity following oral administration of MK-3682B.

  12. AUC0-24 of Uprifosbuvir Metabolite M5

    Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 24 hours post-dose

    AUC0-24 is a measure of total exposure to uprifosbuvir metabolite M5 in plasma from dosing to 24 hours following oral administration of MK-3682B.

  13. Cmax of Uprifosbuvir Metabolite M5

    Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose

    Cmax is the maximum amount of uprifosbuvir metabolite M5 in plasma following oral administration of MK-3682B.

  14. C24 of Uprifosbuvir Metabolite M5

    Time frame: 24 hours post-dose

    C24 is the plasma concentration of uprifosbuvir metabolite M5 24 hours following oral administration of MK-3682B.

  15. Tmax of Uprifosbuvir Metabolite M5

    Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose

    Tmax is the time required to reach the maximum post-dose plasma concentration of uprifosbuvir metabolite M5 following oral administration of MK-3682B.

  16. Lag Time (Tlag) of Uprifosbuvir Metabolite M5

    Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose

    Tlag is the time from dosing to first appearance in plasma of uprifosbuvir metabolite M5 following oral administration of MK-3682B.

  17. t½ of Uprifosbuvir Metabolite M5

    Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose

    t1/2 is the amount of time required to clear 50% of uprifosbuvir metabolite M5 from plasma following oral administration of MK-3682B.

  18. AUC0-last of Uprifosbuvir Metabolite M6

    Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose

    AUC0-last is a measure of total exposure to uprifosbuvir metabolite M6 in plasma from the start of dosing to the time of the last quantifiable (<LLOQ) sample following oral administration of MK-3682B.

  19. AUC0-∞ of Uprifosbuvir Metabolite M6

    Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose

    AUC0-∞ is a measure of total exposure to uprifosbuvir metabolite M6 in plasma from the start of dosing to infinity following oral administration of MK-3682B.

  20. AUC0-24 of Uprifosbuvir Metabolite M6

    Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 24 hours post-dose

    AUC0-24 is a measure of total exposure to uprifosbuvir metabolite M6 in plasma from dosing to 24 hours following oral administration of MK-3682B.

  21. Cmax of Uprifosbuvir Metabolite M6

    Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose

    Cmax is the maximum amount of uprifosbuvir metabolite M6 in plasma following oral administration of MK-3682B.

  22. C24 of Uprifosbuvir Metabolite M6

    Time frame: 24 hours post-dose

    C24 is the plasma concentration of uprifosbuvir metabolite M6 24 hours following oral administration of MK-3682B.

  23. Tmax of Uprifosbuvir Metabolite M6

    Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose

    Tmax is the time required to reach the maximum post-dose plasma concentration of uprifosbuvir metabolite M6 following oral administration of MK-3682B.

  24. t½ of Uprifosbuvir Metabolite M6

    Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose

    t1/2 is the amount of time required to clear 50% of uprifosbuvir metabolite M6 from plasma following oral administration of MK-3682B.

  25. AUC0-last of Grazoprevir (MK-5172)

    Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose

    AUC0-last is a measure of total exposure to grazoprevir in plasma from the start of dosing to the time of the last quantifiable (<LLOQ) sample following oral administration of MK-3682B.

  26. AUC0-∞ of Grazoprevir

    Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose

    AUC0-∞ is a measure of total exposure to grazoprevir in plasma from the start of dosing to infinity following oral administration of MK-3682B.

  27. AUC0-24 of Grazoprevir

    Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 24 hours post-dose

    AUC0-24 is a measure of total exposure to grazoprevir in plasma from the start of dosing to 24 hours post-dose following oral administration of MK-3682B.

  28. Cmax of Grazoprevir

    Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose

    Cmax is the maximum amount of grazoprevir in plasma following oral administration of MK-3682B.

  29. C24 of Grazoprevir

    Time frame: 24 hours post-dose

    C24 is the plasma concentration of grazoprevir 24 hours following oral administration of MK-3682B.

  30. Tmax of Grazoprevir

    Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose

    Tmax is the time required to reach the maximum post-dose plasma concentration of grazoprevir following oral administration of MK-3682B.

  31. CL/F of Grazoprevir

    Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose

    CL/F is the apparent total body clearance of grazoprevir following oral administration of MK-3682B.

  32. Vz/F of Grazoprevir

    Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose

    Vz/F is the apparent volume of distribution of grazoprevir following oral administration of MK-3682B.

  33. t½ of Grazoprevir

    Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose

    t1/2 is the amount of time required to clear 50% of grazoprevir from plasma following oral administration of MK-3682B.

  34. AUC0-last of Ruzasvir (MK-8408)

    Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose

    AUC0-last is a measure of total exposure to ruzasvir in plasma from the start of dosing to the time of the last quantifiable (<LLOQ) sample following oral administration of MK-3682B.

  35. AUC0-∞ of Ruzasvir

    Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose

    AUC0-∞ is a measure of total exposure to ruzasvir in plasma from the start of dosing to infinity following oral administration of MK-3682B.

  36. AUC0-24 of Ruzasvir

    Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 24 hours post-dose

    AUC0-24 is a measure of total exposure to ruzasvir in plasma from dosing to 24 hours following oral administration of MK-3682B.

  37. Cmax of Ruzasvir

    Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose

    Cmax is the maximum amount of ruzasvir in plasma following oral administration of MK-3682B.

  38. C24 of Ruzasvir

    Time frame: 24 hours post-dose

    C24 is the plasma concentration of ruzasvir 24 hours following oral administration of MK-3682B.

  39. Tmax of Ruzasvir

    Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose

    Tmax is the time required to reach the maximum post-dose plasma concentration of ruzasvir following oral administration of MK-3682B.

  40. CL/F of Ruzasvir

    Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose

    CL/F is the apparent total body clearance of ruzasvir following oral administration of MK-3682B.

  41. Vz/F of Ruzasvir

    Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose

    Vz/F is the apparent volume of distribution of ruzasvir following oral administration of MK-3682B.

  42. t½ of Ruzasvir

    Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose

    t1/2 is the amount of time required to clear 50% of ruzasvir from plasma following oral administration of MK-3682B.

Sponsors and collaborators

Lead sponsor

Merck Sharp & Dohme LLC

Industry

Registry information

Official study title

A Two-Part, Open-Label Study to Investigate the Single-Dose Pharmacokinetics of MK-3682B (MK-3682/MK-5172/MK-8408 Fixed Dose Combination) When Administered to Subjects With Moderate and Severe Renal Insufficiency

Important dates

Study start
2016
Primary completion
2016
Study completion
2016
First posted
Jan 22, 2016
Registry last updated
Jan 9, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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