Clinical trial NCT03131479: Study of PK/PD, Safety and Tolerability of LIK066 in Patients With Decreased Renal Function.
Official title: An Open-label, Parallel-group Study to Assess the Effect of LIK066 on Urinary Glucose Excretion, Pharmacokinetics, Safety and Tolerability Following Multiple Dose Administration in Patients With Decreased Renal Function Compared to Subjects With Normal Renal Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Renal Impairment
Keywords: renal function
sodium-glucose co-transporter
pharmacokinetics
decreased renal function
decreased kidney function
kidney disease
urinary glucose excretion
UGE
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2017-04-27
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Maximum age (years): 78
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this trial was to evaluate whether the study drug, LIK066, causes glucose excretion in urine in patients with varying degrees of decreased kidney function and in subjects with normal kidney function. Blood samples were collected to measure the concentrations of LIK066 and to study the pharmacokinetics of LIK066. Pharmacokinetics is meant to study how LIK066 is absorbed, distributed and eliminated, in other words what the body does to the drug. The results of this study may be used to help determine whether LIK066 can be used to treat people with reduced kidney function and the proper dosing regimen.


Eligibility criteria: Inclusion Criteria:

* Written informed consent must be obtained before any assessment is performed.
* Male and female subjects age 18-78 years, inclusive, with controlled health condition as determined by past medical history, physical examination, electrocardiogram and laboratory test at screening.
* patients with Type 2 diabetes, HbA1c \<10% at screening.
* Body mass index (BMI) ≤ 50 kg/m\^2 at screening.

Exclusion Criteria:

* Patients with Type 1 diabetes
* Evidence of clinically significant liver function test: ALT, AST, gamma-GT, alkaline phosphatase \>3 X ULN; serum bilirubin \> 1.5 X ULN.
* Patients undergoing any method of dialysis
* clinically significant GI disorder related to malabsorption or that may affect drug or glucose absorption.
* subjects who experienced ketoacidosis, lactic acidosis or hyperosmolar coma within 6 months of screening visit.

Primary outcomes:
measure: Change From Baseline in 24-hour Urinary Glucose Excretion (UGE) on Day 7
timeFrame: Baseline , Day 7
measure: Maximum Observed Plasma Concentration (Cmax) for LIK066
timeFrame: Day 1 and Day 7 (0 hour predose and 0.5, 1.0, 2.0, 3.0, 4.0, 6.0, 8.0 and 12.0 hours post-dose)
measure: Time to Reach the Maximum Plasma Concentration (Tmax) for LIK066
timeFrame: Day 1 and Day 7 (0 hour predose and 0.5, 1.0, 2.0, 3.0, 4.0, 6.0, 8.0 and 12.0 hours post-dose)
measure: Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau) for LIK066
timeFrame: Day 1 and Day 7 (0 hour predose and 0.5, 1.0, 2.0, 3.0, 4.0, 6.0, 8.0 and 12.0 hours post-dose)
measure: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) for LIK066 on Day 7
timeFrame: Day 7 (0 hour predose and 0.5, 1.0, 2.0, 3.0, 4.0, 6.0, 8.0 and 12.0 hours post-dose)
measure: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) for LIK066 on Day 1
timeFrame: Day 1 (0 hour predose and 0.5, 1.0, 2.0, 3.0, 4.0, 6.0, 8.0 and 12.0 hours post-dose)
measure: Terminal Elimination Half-life (T1/2) for LIK066 on Day 7
timeFrame: Day 7 (0 hour predose and 0.5, 1.0, 2.0, 3.0, 4.0, 6.0, 8.0 and 12.0 hours post-dose)
measure: Apparent Systemic (or Total Body) Clearance From Plasma Following Extravascular Administration (CL/F) for LIK066 on Day 1
timeFrame: Day 1 (0 hour predose and 0.5, 1.0, 2.0, 3.0, 4.0, 6.0, 8.0 and 12.0 hours post-dose)
measure: Apparent Volume of Distribution During the Terminal Elimination Phase Following Extravascular Administration (Vz/F) for LIK066 on Day 1
timeFrame: Day 1 (0 hour predose and 0.5, 1.0, 2.0, 3.0, 4.0, 6.0, 8.0 and 12.0 hours post-dose)
measure: Renal Clearance From Plasma (CLr) for LIK066
timeFrame: Day 1 and Day 7 (0 hour predose and 0.5, 1.0, 2.0, 3.0, 4.0, 6.0, 8.0 and 12.0 hours post-dose)
Secondary outcomes:
Other outcomes:
Locations:
city: Orlando
country: United States
facility: Novartis Investigative Site
state: Florida
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: