Study of a Single Intravenous (IV) Dose of MK-3402 in Participants With Impaired Renal Function and in Healthy Controls (MK-3402-004)

NCT04678505 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: 3402-004MK-3402-004
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to compare the plasma and urine pharmacokinetics (PK) of MK-3402 in participants with impaired renal function and healthy control participants, to investigate the extent to which MK-3402 is removed from the plasma by hemodialysis (HD), and evaluate the safety and tolerability of MK-3402 in participants with impaired renal function.

Conditions

Renal Impairment

Keywords

MK-3402

Outcome Measures

Primary Outcomes (6)

• Area Under the Curve From Dosing to Infinity (AUC0-inf) of MK-3402

  AUC0-inf is defined as area under the plasma concentration-time curve from dosing to infinity.

  Pre-dose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, and 48 hours postdose on Day 1

• Plasma Concentration at the End of Infusion (Ceoi) of MK-3402

  Ceoi is defined as the amount of study drug in plasma following IV infusion administration of study drug. Plasma samples were collected at pre-specified time points and Ceoi was assessed.

  Predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, and 48 hours postdose on Day 1

• Time to Maximum Plasma Concentration (Tmax) of MK-3402

  Tmax is defined as the time required for a study drug to reach maximum concentration in plasma. Plasma samples were collected at pre-specified time points and Tmax was assessed.

  Predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, and 48 hours postdose on Day 1

• Apparent Plasma Half-life (t½) of MK-3402

  t½ is defined as the time required for plasma drug concentration of study drug to decrease by 50% from peak.

  Predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, and 48 hours postdose on Day 1

• Apparent Plasma Clearance (CL) of MK-3402

  CL is defined as the time it takes for the study drug to be completely removed from the body's plasma.

  Predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, and 48 hours postdose on Day 1

• Volume of Distribution (Vd) of MK-3402

  Vd is defined as the distributed volume of study drug in plasma.

  Predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, and 48 hours postdose on Day 1

Secondary Outcomes (10)

• Number of Participants With Adverse Events (AE)

  Up to 15 days

• Number of Participants Who Discontinued From Study Due to an AE

  Up to 15 days

• Dialysis Clearance Based on Plasma (CLDplasma) of MK-3402

  Panel E, Period 2: Pre-dose and 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours after the start of infusion

• Concentration of Dialysate (CD) of MK-3402

  Panel E, Period 2: Pre-dose and 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours after the start of infusion

• Amount of Drug Recovered From the Dialysate From Plasma (AED) of MK-3402

  Panel E, Period 2: Pre-dose and 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours after the start of infusion

Study Arms (5)

Panel A: Mild Renal Impairment

EXPERIMENTAL

Participants with mild renal impairment will receive a single dose of 100 mg MK-3402 via intravenous (IV) infusion on Day 1.

Drug: MK-3402

Panel B: Moderate Renal Impairment

EXPERIMENTAL

Participants with moderate renal impairment will receive a single dose of 100 mg MK-3402 via IV infusion on Day 1.

Drug: MK-3402

Panel C: Severe Renal Impairment

EXPERIMENTAL

Participants with severe renal impairment will receive a single dose of 100 mg MK-3402 via IV infusion on Day 1.

Drug: MK-3402

Panel D: Healthy Participants

EXPERIMENTAL

Healthy matched control participants will receive a single dose of 100 mg MK-3402 via IV infusion on Day 1.

Drug: MK-3402

Panel E: End-Stage Renal Disease (ESRD) Undergoing Hemodialysis

EXPERIMENTAL

Participants with ESRD undergoing HD will receive a single dose of 100 mg MK-3402 via IV infusion after HD on Day 1 of Period 1 and before HD on Day 1 of Period 2. There will be at least a 6-day washout period before dosing in Period 2.

Drug: MK-3402

Interventions

MK-3402 DRUG

MK-3402 administered as a single dose of 100 mg IV infusion on the following dosage days: Panels A to D: Day 1 Panel E: Day 1 in Periods 1 and 2

Panel A: Mild Renal Impairment; Panel B: Moderate Renal Impairment; Panel C: Severe Renal Impairment; Panel D: Healthy Participants; Panel E: End-Stage Renal Disease (ESRD) Undergoing Hemodialysis

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Is in good health based on medical history, physical examination, vital signs (VS) measurements, and electrocardiogram (ECG)s performed before randomization.
• Is in good health based on laboratory safety tests obtained at the screening visit and before administration of the initial dose of study drug.
• Has a body mass index (BMI) ≥18 kg/m2 and ≤40 kg/m2. BMI = weight (kg)/height (m)2.
• Male participants are eligible to participate if they agree to the following during the intervention period and for at least 90 days after the last dose of study intervention:
• Refrain from donating sperm
• Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent or must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause)
• A female participant is eligible to participate if she is a woman of non-childbearing potential.
• Panel A: Has a baseline estimated glomerular filtration rate (eGFR) ≥60 and \<90 mL/min/1.73 m2 based on the Modification of Diet in Renal Disease (MDRD) equation.
• Panel B: Has a baseline eGFR ≥30 and \<60 mL/min/1.73 m2 based on the MDRD equation.
• Panel C: Has a baseline eGFR ≥15 and \<30 mL/min/1.73 m2 based on the MDRD equation.
• Panels A, B and C: Has had no clinically significant change in renal status at least 1 month prior to dosing and is not currently receiving or has not previously been on hemodialysis (HD).
• Panel D: Has an eGFR ≥90 mL/min/1.73 m2 based on the MDRD equation.
• Panel E: Has end stage renal disease (ESRD) and maintained on a stable regimen of at least 3 times per week HD for at least 3 months prior to first dosing.

You may not qualify if:

• Panels A, B, C and E: Has a history of any clinically significant concomitant disease or condition (including treatment for such conditions) or diseases whose current condition is considered clinically unstable that, in the opinion of the investigator, could either interfere with the study drug, compromise interpretation of study data, or pose an unacceptable risk to the patient.
• Panel D: Has a history of clinically significant endocrine, gastrointestinal (GI), cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases. Participants with a remote history of uncomplicated medical events (eg, 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 that would impact study conduct. Participants who have had situational depression may be enrolled in the study at the discretion of the investigator.
• Has a history of cancer (malignancy).
• Exceptions: (1) Adequately treated nonmelanomatous skin carcinoma or carcinoma in situ of the cervix or; (2) Other malignancies that have been successfully treated with appropriate follow up and therefore unlikely to recur for the duration of the study, in the opinion of the investigator and with agreement of the Sponsor (eg, malignancies that have been successfully treated ≥10 years prior to the prestudy screening visit).
• Has a history of significant multiple and/or severe allergies (eg, food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability (ie, systemic allergic reaction) to prescription or nonprescription drugs or food.
• Is positive for hepatitis B surface antigen (HBsAg), hepatitis C antibodies or human immunodeficiency virus (HIV).
• Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the prestudy (screening) visit.
• Panels A, B, C and E: Is unable to refrain from or anticipates the use of any medication, including prescription and nonprescription drugs or herbal remedies for the prohibited time period.
• Panel D: Is unable to refrain from or anticipates the use of any medication, including prescription and nonprescription drugs or herbal remedies beginning approximately 2 weeks (or 5 half-lives) prior to administration of the initial dose of study drug, throughout the study (including washout intervals between treatment periods), until the poststudy visit. There may be certain medications that are permitted.
• Has participated in another investigational study within 4 weeks (or 5 half-lives, whichever is greater) prior to study drug administration. The window will be derived from the date of the last dose of study medication in the previous study.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (2)

Orlando Clinical Research Center ( Site 0001)

Orlando, Florida, 32809, United States

Location

Prism Clinical Research, LLC ( Site 0002)

Saint Paul, Minnesota, 55114, United States

Location

MeSH Terms

Conditions

Renal Insufficiency

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Limitations and Caveats

Due to early study termination, some of the planned endpoints were not able to be completed.

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2020
• First Posted: December 22, 2020
• Study Start: February 10, 2021
• Primary Completion: April 15, 2021
• Study Completion: April 27, 2021
• Last Updated: November 4, 2022
• Results First Posted: November 4, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will share

Locations

US (2)