Clinical trial NCT01569815: Pharmacokinetics of LCZ696 in Subjects With Mild and Moderate Renal Impairment Compared to Healthy Subjects With Normal Renal Function
Official title: An Open Label, Parallel-group Study to Determine Multiple Dose Pharmacokinetics of LCZ696 and Its Metabolites in Subjects With Mild and Moderate Renal Impairment Compared to Matched Healthy Subjects With Normal Renal Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Mild and Moderate Renal Impairment
Keywords: Renal Impairment,
LCZ696
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-04-03
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Time to Reach Maximum Peak Plasma Concentration (Tmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)
timeFrame: Day 1 and day 5
measure: Maximum Peak Plasma Concentration (Cmax) Observed After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)
timeFrame: Day 1, day 5
measure: Area Under the Concentration-time Curve (AUC0-24) From Time Zero to 24- Hour Post-dose (Day 1), and After Multiple Dose Administration (Day 5)
timeFrame: Day 1 and day 5
measure: Elimination Half-life (t1/2) After Multiple Dose (Day 5) Administration
timeFrame: Day 5
measure: Systemic Clearance From Plasma Following Extravascular Administration (CL/F) After Multiple Dose Administration (Day 5)
timeFrame: Day 5
measure: Accumulation Ratio (Racc) After Multiple Dose Administration (Day 5)
timeFrame: Day 5
measure: Renal Clearance From Plasma (CLr) After Multiple Dose Administration (Day 5)
timeFrame: Day 5
measure: Amount of Drug Excreted Into the Urine From Time Zero to 24-hours Post-dose (Ae0-24) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)
timeFrame: Day 1 and Day 5
Secondary outcomes:
measure: Change in Mean 24-hours Sodium Clearance From Baseline to Day 7
timeFrame: From baseline to Day 7
Other outcomes:
Locations:
city: Neuss
country: Germany
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Belgrade
country: Serbia
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: