Pharmacokinetics of LCZ696 in Subjects With Mild and Moderate Renal Impairment Compared to Healthy Subjects With Normal Renal Function

Novartis

Status and phase: Completed; Phase 1

Conditions: Mild and Moderate Renal Impairment

Treatments: Drug: LCZ696

Study type: Interventional

Funder types: Industry

Identifiers

NCT01569815

CLCZ696A2204

2007-005480-96 (EudraCT Number)

Details and patient eligibility

About

The purpose of this study is to determine the multiple dose pharmacokinetics of LCZ696 and its metabolites in subjects with mild to moderate renal impairment and to evaluate the safety of LCZ696 in this population.

Enrollment: 32 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Male, and female subjects of non-child bearing potential,
2. Subjects were to weigh at least 50 kg to participate in the study,
3. and body mass index < 40 kg/m2
4. Subjects were able to communicate well with the investigator, to understand and comply with the requirements of the study;
5. Subjects were able to understand and sign the written informed consent;

For renal insufficient subjects:

1. stable renal disease without evidence of renal progressive

   • mild renal function: calculated CrCl of 50-≤80 mL/min
   • moderate renal function: calculated CrCl of 30-<50 mL/min

2. Vital signs:

   • oral body temperature between 35.0-37.8 °C
   • systolic blood pressure, 95-180 mm Hg
   • diastolic blood pressure, 60-110 mm Hg
   • pulse rate, 54-95 bpm

For healthy subjects only

1. A serum creatinine with a calculated CrCl of >80 mL/min

2. Vital signs:

   • oral body temperature between 35.0-37.2 °C
   • systolic blood pressure, 95-140 mm Hg
   • diastolic blood pressure, 60-100 mm Hg
   • pulse rate, 45-90 bpm

Exclusion criteria

1. Current use of ACE inhibitors, valsartan, and drugs that were known as CYP2C9 substrates, potassium-sparing diuretics;
2. Smokers;
3. History of renal transplant at any time in the past and on immunosuppressant therapy;
4. Dialysis patients;
5. Medical history of clinically significant ECG abnormalities or a family history of a prolonged QT-interval syndrome;
6. Any surgical or medical condition which may significantly alter the absorption, distribution, metabolism or excretion of any drug substance; Other protocol defined inclusion/exclusion criteria may apply

Trial design

Primary purpose: Basic Science

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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32 participants in 1 patient group

LCZ696 400 mg

Experimental group

Description:

LCZ696 400 mg once daily for 5 days

Treatment:

Drug: LCZ696