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

Renal Impairment Clinical Trial

Official title:

An Open-Label Trial to Evaluate the Pharmacokinetics of MK-3402 Following Administration of a Single IV Dose to Participants With Mild, Moderate, and Severe Renal Impairment and End-Stage Renal Disease

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04678505
• Other study ID #: 3402-004
• Secondary ID: MK-3402-004
• Status: Terminated
• Phase: Phase 1
• Start date: February 10, 2021
• Est. completion date: April 27, 2021

Study information

• Verified date: April 2022
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 9
• Est. completion date: April 27, 2021
• Est. primary completion date: April 15, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Renal Impairment
• Renal Insufficiency

Intervention

Drug:
• MK-3402
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

Locations

Country	Name	City	State
United States	Orlando Clinical Research Center ( Site 0001)	Orlando	Florida
United States	Prism Clinical Research, LLC ( Site 0002)	Saint Paul	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	Number of Participants With Adverse Events (AE)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study drug, whether or not considered related to the study drug	Up to 15 days
Secondary	Number of Participants Who Discontinued From Study Due to an AE	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study drug, whether or not considered related to the study drug	Up to 15 days
Secondary	Dialysis Clearance Based on Plasma (CLDplasma) of MK-3402	Plasma dialysis samples were to be collected at pre-specified time points to calculate CLDplasma.	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
Secondary	Concentration of Dialysate (CD) of MK-3402	Plasma dialysis samples were to be collected at pre-specified time points to calculate CD.	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
Secondary	Amount of Drug Recovered From the Dialysate From Plasma (AED) of MK-3402	Plasma dialysis samples were to be collected at pre-specified time points to calculate AED.	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
Secondary	Percentage of AED (% Dose) of MK-3402	Plasma dialysis samples were to be collected at pre-specified time points to calculate AED (% dose).	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.
Secondary	Hemodialysis Clearance Based on Plasma (CLD Dialysate) of MK-3402	Plasma dialysis samples were to be collected at pre-specified time points to measure CLD dialysate.	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
Secondary	Amount Recovered in Urine From 0 to 24 Hours (Ae0-24) of MK-3402	Ae0-24 is defined as the amount of study drug unchanged in urine after 0-24 hours. Urine samples were collected at pre-specified intervals and Ae0-24 was assessed.	Pre-dose and 0-4, 4-8, 8-12, and 12-24 hours postdose
Secondary	Fraction of Dose Recovered in Urine (Fe) of MK-3402	Fe is defined as the fraction of the dose of study drug in urine.	Pre-dose and 0-4, 4-8, 8-12, and 12-24 hours postdose
Secondary	Renal Clearance (CLr) of MK-3402	CLr is defined as the time it takes for the study drug to be completely removed by the kidneys.	Pre-dose and 0-4, 4-8, 8-12, and 12-24 hours postdose