A Study to Evaluate the Effect of Renal Impairment on JNJ-56136379 in Adult Participants

Phase 1

Terminated

• Conditions: Renal Insufficiency
• Interventions: Drug: JNJ-56136379

• Registration Number: NCT04474210
• Lead Sponsor: Janssen Research & Development, LLC

Brief Summary

The purpose of this study is to evaluate the pharmacokinetics (PK) of a single oral dose of JNJ-56136379 in adult participants with renal impairment compared with healthy participants with normal renal function.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-07-14
• Study First Submitted QC: 2020-07-14
• Study First Posted: 2020-07-16
• Study Start: 2020-08-19
• Primary Completion: 2020-11-30
• Study Completion: 2020-11-30
• Status Verified: 2021-07
• Last Update Submitted: 2021-07-19
• Last Update Posted: 2021-07-23

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 1

Inclusion Criteria

• Body mass index (BMI) (kilograms [kg]/height [m]^2) between 18.0 and 38.0 kilogram/meter^2 (kg/m2) (inclusive), and body weight not less than (<) 50 kg

Participants with normal renal function:

• Have normal renal function defined as estimated glomerular filtration rate (eGFR) greater than or equal to (>=) 90 milliliter/minute computed with the online calculator on the CKD-EPI website by use of the Chronic Kidney Disease Epidemiology Collaboration creatinine clearance (CKD-EPIcr) result
• Must have stable renal function as defined as: (a) for participants with impaired renal function: <20 percent (%) change in serum creatinine concentrations between screening and Day -1; (b) for healthy participants: a change in serum creatinine concentration <0.2 milligram per deciliter (mg/dL) between screening and Day -1

Participants with renal impairment:

• Have an impaired renal function based on eGFR as(eGFR computed with the online calculator on the CKD-EPI website providing eGFR (in mL/min units) by use of the CKD-EPIcr result: (a) eGFR <90 to 60 mL/minute for participants in Group 3 (mild renal impairment cohort); (b) eGFR 30 to 59 mL/minute for participants in Group 4 (moderate renal impairment cohort); (c) eGFR <30 mL/minute but not yet on hemodialysis, for participants in Group 1 (severe renal impairment and/or kidney failure); (d) eGFR <15 mL/minute and on hemodialysis, for participants in Group 5 (kidney failure)
• Concomitant medications to treat underlying disease states or medical conditions related to renal impairment are allowed. Participants must be on a stable dose of medication and/or treatment regimen for at least 2 months (3 months for thyroid hormone replacement therapy [HRT]) before dosing as well as during the study

Read More

Exclusion Criteria

• Individuals who take creatine supplements, have a non-standard muscle mass such as amputation, malnutrition, or muscle wasting; because these factors are not accounted for in the prediction equations for GFR chronic kidney disease epidemiology collaboration (CKD EPI)

Participants with normal renal function:

• Clinically significant abnormal values for hematology, clinical chemistry, or urinalysis at screening or Day -1, as deemed appropriate by the investigator
• Clinically significant abnormal physical examination, vital signs, body temperature, or 12 lead ECG at screening or Day -1, as deemed appropriate by the investigator

Participants with renal impairment:

• Evidence of clinically apparent concurrent disease based upon complete clinical laboratory testing, full physical examination, or medical history, except for controlled hypertension and those problems directly associated with the primary diagnosis of renal impairment
• Any clinically significant laboratory abnormality except abnormalities that may be caused by renal impairment

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part A: Group 1	JNJ-56136379	Participants with severe renal impairment and/or kidney failure (estimated glomerular filtration rate \[eGFR\] less than \[\<\] 30 milliliter\[mL\]/minute but not yet on hemodialysis) will receive a single oral dose of JNJ-56136379.
Part A: Group 2	JNJ-56136379	Healthy participants with normal renal function (eGFR greater than or equal to \[\>=\] 90 mL/minute), will receive a single oral dose of JNJ-56136379.
Part B: Group 3 (Optional)	JNJ-56136379	Participants with mild renal impairment (eGFR: 60 to 89 mL/minute) will receive a single oral dose of JNJ-56136379.
Part B: Group 5 (Optional)	JNJ-56136379	Participants with kidney failure (eGFR: \<15 mL/minute and on hemodialysis; pharmacokinetic \[PK\] to be evaluated during non-dialysis days) will receive a single oral dose of JNJ-56136379.
Part B: Group 4 (Optional)	JNJ-56136379	Participants with moderate renal impairment (eGFR: 30 to 59 mL/minute) will receive a single oral dose of JNJ-56136379.

Primary Outcome Measures

Name	Time	Method
Area Under the Analyte Concentration-time Curve From Time Zero to Infinity (AUC [0-infinity])	Up to Day 29	AUC (0-infinity) is defined as AUC from time 0 to infinity, calculated as the sum of AUC (0-last) and C(last)/lambda(z); where C(last) is the last observed measurable (non-BQL) concentration; and lambda(z) is apparent terminal elimination rate constant.
Area Under the Analyte Concentration-time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC [0-last])	Up to Day 29	AUC (0-last) is defined as AUC from time 0 to the time of the last measurable (non-below quantification limit \[non-BQL\]) concentration, calculated by linear-linear trapezoidal summation.
Apparent Volume of Distribution (Vd/F)	Up to Day 29	Vd/F is defined as apparent volume of distribution, calculated as dose/\[lambda (z)\*AUC (0-infinity)\].
Apparent Terminal Elimination Rate Constant (Lambda[z])	Up to Day 29	Lambda(z) is defined as apparent terminal elimination rate constant, estimated by linear regression using the terminal log-linear phase of the log-transformed concentration vs time curve.
Renal Clearance (CLr)	Up to 144 hours postdose	CLr is defined as renal clearance, calculated as Ae(0-144h)/AUC(144h).
Area Under the Analyte Concentration-time Curve From Time Zero to 24 Hours Postdose (AUC [0-24])	Up to 24 hours postdose	AUC (0-24) is defined as area under the analyte concentration-time curve (AUC) from time 0 to 24 hours postdose, calculated by linear-linear trapezoidal summation.
Area Under the Analyte Concentration-time Curve From Time Zero to 144 Hours Postdose (AUC [0-144])	Up to 144 hours postdose	AUC (0-144) is defined as AUC from time 0 to 144 hours postdose, calculated by linear-linear trapezoidal summation.
Total Apparent Oral Clearance (CL/F)	Up to Day 29	CL/F is defined as total apparent oral clearance, calculated as dose/AUC (0-infinity).
Apparent Terminal Elimination Half-life (t1/2)	Up to Day 29	t1/2 is defined as apparent terminal elimination half-life, calculated as 0.693/lambda(z).
Percentage of JNJ-56136379 Excreted in Urine (Ae,%Dose)	Up to Day 7	Ae,%Dose is defined as cumulative urinary recovery represented as a percentage of dose, calculated as 100\*(Aetotal/Dose).
Maximum Observed Plasma Analyte Concentration (Cmax)	Up to Day 29	Cmax is defined as the maximum observed plasma analyte concentration.
Time to Reach the Maximum Observed Plasma Analyte Concentration (Tmax)	Up to Day 29	Tmax is defined as the actual sampling time to reach the maximum observed plasma analyte concentration.

Secondary Outcome Measures

Name	Time	Method
Number of Participants with Adverse Events as a Measure of Safety and Tolerability	Up to 8 weeks	An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.

Trial Locations

Locations (2)

Orlando Clinical Research Center; 🇺🇸 Orlando, Florida, United States

The Texas Liver Institute; 🇺🇸 San Antonio, Texas, United States