Renal ImpairmentPhase 2NCT03131479

Study of PK/PD, Safety and Tolerability of LIK066 in Patients With Decreased Renal Function.

A Phase 2 study testing LIK066 in people with Renal Impairment, run by Novartis Pharmaceuticals at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 78 years
Conditions the study is for: Renal Impairment
What is being tested?: LIK066
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 53 participants
Where: 1 siteUnited States
Study dates: 28 Apr 2017to 16 Jan 2018
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 78 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

Novartis Investigative Site
Orlando, Florida, 32809

Other trials in United States

About this study

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

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.

Conditions: Renal Impairment
Being tested: LIK066
Keywords: renal function, sodium-glucose co-transporter, pharmacokinetics, decreased renal function, decreased kidney function, kidney disease, urinary glucose excretion, UGE
Medical subject headings: Renal Insufficiency, Kidney Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

LIK066Drug
LIK066 50 mg tablets taken orally once daily before breakfast for 7 days.

Study groups in NCT03131479
Study group	Role	What they receive
Mild	Experimental	Patients with mild renal impairment (Group 1) received LIK066 50 mg qd before breakfast for 7 days. Receives: Drug: LIK066
Moderate A	Experimental	Patients with moderate renal impairment grade A (Group 2) received LIK066 50 mg qd before breakfast for 7 days. Receives: Drug: LIK066
Moderate B	Experimental	Patients with moderate renal impairment grade B (Group 3) received LIK066 50 mg qd before breakfast for 7 days. Receives: Drug: LIK066
Severe	Experimental	Patients with severe renal impairment (Group 4) received LIK066 50 mg qd before breakfast for 7 days. Receives: Drug: LIK066
Normal	Experimental	Patients with normal renal function (Group 5) received LIK066 50 mg qd before breakfast for 7 days. Receives: Drug: LIK066

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline in 24-hour Urinary Glucose Excretion (UGE) on Day 7
Urine was collected over 24 h to measure Urinary Glucose Excretion (UGE) at baseline (Day -1), following a single dose (Day 1) and at the end of the 7-day treatment (Day 7) to assess the effect of a 7 day treatment with LIK066 in subjects with decreased renal function compared to those with normal renal function.
Measured: Baseline , Day 7
Maximum Observed Plasma Concentration (Cmax) for LIK066
Plasma PK samples were collected at Day 1 and Day 7 and assayed for LIK066 concentrations using validated liquid chromatography-tandem mass spectrometry assays (LC MS/MS). The method will have an LLOQ of at least 5 ng/mL for LIK066. Concentrations were expressed in mass per volume units and refered to LIK066 plasma concentrations.
Cmax was determined using the actual recorded sampling times and non-compartmental method(s) to assess the effect of a 7 day treatment with LIK066 in subjects with decreased renal function compared to those with normal renal function. Only descriptive analysis done.
Measured: 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)
Time to Reach the Maximum Plasma Concentration (Tmax) for LIK066
Plasma PK samples were collected at Day 1 and Day 7 and assayed for LIK066 concentrations using validated liquid chromatography-tandem mass spectrometry assays (LC MS/MS). The method will have an LLOQ of at least 5 ng/mL for LIK066. Concentrations were expressed in mass per volume units and refered to LIK066 plasma concentrations.
Tmax was determined using the actual recorded sampling times and non-compartmental method(s) to assess the effect of a 7 day treatment with LIK066 in subjects with decreased renal function compared to those with normal renal function. Only descriptive analysis done.
Measured: 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)
Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau) for LIK066
Plasma PK samples were collected at Day 1 and Day 7 and assayed for LIK066 concentrations using validated liquid chromatography-tandem mass spectrometry assays (LC MS/MS). The method will have an LLOQ of at least 5 ng/mL for LIK066. Concentrations were expressed in mass per volume units and refered to LIK066 plasma concentrations.
AUCtau was determined using the actual recorded sampling times and non-compartmental method(s) to assess the effect of a 7 day treatment with LIK066 in subjects with decreased renal function compared to those with normal renal function. Only descriptive analysis done.
Measured: 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)
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) for LIK066 on Day 7
Plasma PK samples were collected at Day 1 and Day 7 and assayed for LIK066 concentrations using validated liquid chromatography-tandem mass spectrometry assays (LC MS/MS). The method will have an LLOQ of at least 5 ng/mL for LIK066. Concentrations were expressed in mass per volume units and refered to LIK066 plasma concentrations.
AUClast was determined using the actual recorded sampling times and non-compartmental method(s) to assess the effect of a 7 day treatment with LIK066 in subjects with decreased renal function compared to those with normal renal function. AUClast is similar to AUCtau on Day 1 since the Tlast for Day 1 = 24hrs (tau = 24hrs); therefore AUClast is not reported for Day1, it is however reported for Day 7 since the Tlast is different from 24 hours. Only descriptive analysis done.
Measured: 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)
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) for LIK066 on Day 1
Plasma PK samples were collected at Day 1 and Day 7 and assayed for LIK066 concentrations using validated liquid chromatography-tandem mass spectrometry assays (LC MS/MS). The method will have an LLOQ of at least 5 ng/mL for LIK066. Concentrations were expressed in mass per volume units and refered to LIK066 plasma concentrations.
AUCinf was determined using the actual recorded sampling times and non-compartmental method(s) to assess the effect of a 7 day treatment with LIK066 in subjects with decreased renal function compared to those with normal renal function. AUCinf is a single dose parameter and therefore is presented on Day 1 only, after the first dose of LIK066. Only descriptive analysis done.
Measured: 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)
Terminal Elimination Half-life (T1/2) for LIK066 on Day 7
Plasma PK samples were collected at Day 1 and Day 7 and assayed for LIK066 concentrations using validated liquid chromatography-tandem mass spectrometry assays (LC MS/MS). The method will have an LLOQ of at least 5 ng/mL for LIK066. Concentrations were expressed in mass per volume units and refered to LIK066 plasma concentrations.
T1/2 was determined using the actual recorded sampling times and non-compartmental method(s) to assess the effect of a 7 day treatment with LIK066 in subjects with decreased renal function compared to those with normal renal function. T1/2 is only reported at Day 7 only, since there was sampling out to ~5 half-lives after the Day 7 dose of LIK066. Only descriptive analysis done.
Measured: 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)
Apparent Systemic (or Total Body) Clearance From Plasma Following Extravascular Administration (CL/F) for LIK066 on Day 1
Plasma PK samples were collected at Day 1 and Day 7 and assayed for LIK066 concentrations using validated liquid chromatography-tandem mass spectrometry assays (LC MS/MS). The method will have an LLOQ of at least 5 ng/mL for LIK066. Concentrations were expressed in mass per volume units and refered to LIK066 plasma concentrations.
CL/F was determined using the actual recorded sampling times and non-compartmental method(s) to assess the effect of a 7 day treatment with LIK066 in subjects with decreased renal function compared to those with normal renal function. Since Day 7 represented steady state of LIK066 in the study, the appropriately calculated steady-state clearance parameter computed was CLss/F and was presented. Only descriptive analysis done.
Measured: 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)
Apparent Volume of Distribution During the Terminal Elimination Phase Following Extravascular Administration (Vz/F) for LIK066 on Day 1
Plasma PK samples were collected at Day 1 and Day 7 and assayed for LIK066 concentrations using validated liquid chromatography-tandem mass spectrometry assays (LC MS/MS). The method will have an LLOQ of at least 5 ng/mL for LIK066. Concentrations were expressed in mass per volume units and refered to LIK066 plasma concentrations.
Vz/F was determined using the actual recorded sampling times and non-compartmental method(s) to assess the effect of a 7 day treatment with LIK066 in subjects with decreased renal function compared to those with normal renal function. Only descriptive analysis done.
Measured: 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)
Renal Clearance From Plasma (CLr) for LIK066
Urine PK samples were collected at Day 1 and Day 7 and assayed for LIK066 concentrations using validated liquid chromatography-tandem mass spectrometry assays (LC MS/MS). The method will have an LLOQ of at least 5 ng/mL for LIK066. Concentrations were expressed in mass per volume units and refered to LIK066 plasma concentrations.
CLr was determined using the actual recorded sampling times and non-compartmental method(s) to assess the effect of a 7 day treatment with LIK066 in subjects with decreased renal function compared to those with normal renal function. Only descriptive analysis done.
Measured: 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)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

28 Apr 201716 Jan 2018

First posted27 Apr 2017
Study start28 Apr 2017
Primary completion16 Jan 2018
Study completion16 Jan 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Renal ImpairmentStudies of the same condition, open and under way.
More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 53 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03131479
Sponsor's protocol ID: CLIK066B2202
Other IDs: 2016-004770-18, 2016
Status last verified: Jun 2019
First submitted: 17 Apr 2017
Last updated: 5 Jan 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 5 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT03131479
Acronym / sponsor ID: CLIK066B2202
Conditions: Renal Impairment
Keywords: renal function, sodium-glucose co-transporter, pharmacokinetics, decreased renal function, decreased kidney function, kidney disease, urinary glucose excretion, UGE
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 53 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: 28 Apr 2017 (actual)
Primary completion: 16 Jan 2018 (actual)
Study completion: 16 Jan 2018 (actual)
First posted: 27 Apr 2017 (actual)
Results: Posted 6 Feb 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 5

Arm	Type	Receives
Mild	Experimental	Drug: LIK066Patients with mild renal impairment (Group 1) received LIK066 50 mg qd before breakfast for 7 days.
Moderate A	Experimental	Drug: LIK066Patients with moderate renal impairment grade A (Group 2) received LIK066 50 mg qd before breakfast for 7 days.
Moderate B	Experimental	Drug: LIK066Patients with moderate renal impairment grade B (Group 3) received LIK066 50 mg qd before breakfast for 7 days.
Severe	Experimental	Drug: LIK066Patients with severe renal impairment (Group 4) received LIK066 50 mg qd before breakfast for 7 days.
Normal	Experimental	Drug: LIK066Patients with normal renal function (Group 5) received LIK066 50 mg qd before breakfast for 7 days.

Who may qualify

Ages: 18 to 78 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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.

Key exclusion criteria (5 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
LIK066LIK066 50 mg tablets taken orally once daily before breakfast for 7 days.	Drug	Mild, Moderate A, Moderate B, Normal, Severe

Primary outcome

Change From Baseline in 24-hour Urinary Glucose Excretion (UGE) on Day 7
Time frame: Baseline , Day 7
Urine was collected over 24 h to measure Urinary Glucose Excretion (UGE) at baseline (Day -1), following a single dose (Day 1) and at the end of the 7-day treatment (Day 7) to assess the effect of a 7 day treatment with LIK066 in subjects with decreased renal function compared to those with normal renal function.
Maximum Observed Plasma Concentration (Cmax) for LIK066
Time frame: 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)
Plasma PK samples were collected at Day 1 and Day 7 and assayed for LIK066 concentrations using validated liquid chromatography-tandem mass spectrometry assays (LC MS/MS). The method will have an LLOQ of at least 5 ng/mL for LIK066. Concentrations were expressed in mass per volume units and refered to LIK066 plasma concentrations. Cmax was determined using the actual recorded sampling times and non-compartmental method(s) to assess the effect of a 7 day treatment with LIK066 in subjects with decreased renal function compared to those with normal renal function. Only descriptive analysis done.
Time to Reach the Maximum Plasma Concentration (Tmax) for LIK066
Time frame: 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)
Plasma PK samples were collected at Day 1 and Day 7 and assayed for LIK066 concentrations using validated liquid chromatography-tandem mass spectrometry assays (LC MS/MS). The method will have an LLOQ of at least 5 ng/mL for LIK066. Concentrations were expressed in mass per volume units and refered to LIK066 plasma concentrations. Tmax was determined using the actual recorded sampling times and non-compartmental method(s) to assess the effect of a 7 day treatment with LIK066 in subjects with decreased renal function compared to those with normal renal function. Only descriptive analysis done.
Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau) for LIK066
Time frame: 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)
Plasma PK samples were collected at Day 1 and Day 7 and assayed for LIK066 concentrations using validated liquid chromatography-tandem mass spectrometry assays (LC MS/MS). The method will have an LLOQ of at least 5 ng/mL for LIK066. Concentrations were expressed in mass per volume units and refered to LIK066 plasma concentrations. AUCtau was determined using the actual recorded sampling times and non-compartmental method(s) to assess the effect of a 7 day treatment with LIK066 in subjects with decreased renal function compared to those with normal renal function. Only descriptive analysis done.
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) for LIK066 on Day 7
Time frame: 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)
Plasma PK samples were collected at Day 1 and Day 7 and assayed for LIK066 concentrations using validated liquid chromatography-tandem mass spectrometry assays (LC MS/MS). The method will have an LLOQ of at least 5 ng/mL for LIK066. Concentrations were expressed in mass per volume units and refered to LIK066 plasma concentrations. AUClast was determined using the actual recorded sampling times and non-compartmental method(s) to assess the effect of a 7 day treatment with LIK066 in subjects with decreased renal function compared to those with normal renal function. AUClast is similar to AUCtau on Day 1 since the Tlast for Day 1 = 24hrs (tau = 24hrs); therefore AUClast is not reported for Day1, it is however reported for Day 7 since the Tlast is different from 24 hours. Only descriptive analysis done.
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) for LIK066 on Day 1
Time frame: 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)
Plasma PK samples were collected at Day 1 and Day 7 and assayed for LIK066 concentrations using validated liquid chromatography-tandem mass spectrometry assays (LC MS/MS). The method will have an LLOQ of at least 5 ng/mL for LIK066. Concentrations were expressed in mass per volume units and refered to LIK066 plasma concentrations. AUCinf was determined using the actual recorded sampling times and non-compartmental method(s) to assess the effect of a 7 day treatment with LIK066 in subjects with decreased renal function compared to those with normal renal function. AUCinf is a single dose parameter and therefore is presented on Day 1 only, after the first dose of LIK066. Only descriptive analysis done.
Terminal Elimination Half-life (T1/2) for LIK066 on Day 7
Time frame: 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)
Plasma PK samples were collected at Day 1 and Day 7 and assayed for LIK066 concentrations using validated liquid chromatography-tandem mass spectrometry assays (LC MS/MS). The method will have an LLOQ of at least 5 ng/mL for LIK066. Concentrations were expressed in mass per volume units and refered to LIK066 plasma concentrations. T1/2 was determined using the actual recorded sampling times and non-compartmental method(s) to assess the effect of a 7 day treatment with LIK066 in subjects with decreased renal function compared to those with normal renal function. T1/2 is only reported at Day 7 only, since there was sampling out to ~5 half-lives after the Day 7 dose of LIK066. Only descriptive analysis done.
Apparent Systemic (or Total Body) Clearance From Plasma Following Extravascular Administration (CL/F) for LIK066 on Day 1
Time frame: 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)
Plasma PK samples were collected at Day 1 and Day 7 and assayed for LIK066 concentrations using validated liquid chromatography-tandem mass spectrometry assays (LC MS/MS). The method will have an LLOQ of at least 5 ng/mL for LIK066. Concentrations were expressed in mass per volume units and refered to LIK066 plasma concentrations. CL/F was determined using the actual recorded sampling times and non-compartmental method(s) to assess the effect of a 7 day treatment with LIK066 in subjects with decreased renal function compared to those with normal renal function. Since Day 7 represented steady state of LIK066 in the study, the appropriately calculated steady-state clearance parameter computed was CLss/F and was presented. Only descriptive analysis done.
Apparent Volume of Distribution During the Terminal Elimination Phase Following Extravascular Administration (Vz/F) for LIK066 on Day 1
Time frame: 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)
Plasma PK samples were collected at Day 1 and Day 7 and assayed for LIK066 concentrations using validated liquid chromatography-tandem mass spectrometry assays (LC MS/MS). The method will have an LLOQ of at least 5 ng/mL for LIK066. Concentrations were expressed in mass per volume units and refered to LIK066 plasma concentrations. Vz/F was determined using the actual recorded sampling times and non-compartmental method(s) to assess the effect of a 7 day treatment with LIK066 in subjects with decreased renal function compared to those with normal renal function. Only descriptive analysis done.
Renal Clearance From Plasma (CLr) for LIK066
Time frame: 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)
Urine PK samples were collected at Day 1 and Day 7 and assayed for LIK066 concentrations using validated liquid chromatography-tandem mass spectrometry assays (LC MS/MS). The method will have an LLOQ of at least 5 ng/mL for LIK066. Concentrations were expressed in mass per volume units and refered to LIK066 plasma concentrations. CLr was determined using the actual recorded sampling times and non-compartmental method(s) to assess the effect of a 7 day treatment with LIK066 in subjects with decreased renal function compared to those with normal renal function. Only descriptive analysis done.

Results and safety

Results posted to the registry on 6 Feb 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Mild	10	10
Moderate A	10	10
Moderate B	11	10
Severe	12	10
Normal	10	10

Primary outcome: Change From Baseline in 24-hour Urinary Glucose Excretion (UGE) on Day 7

Time frame: Baseline , Day 7. Mean (Standard Deviation). Unit: gram (g)

Measure	Normal n = 10	Mild n = 10	Moderate A n = 10	Moderate B n = 11	Severe n = 12
Value	40.45 (21.93)	31.87 (13.79)	36.27 (19.51)	19.88 (18.66)	5.50 (3.75)

Normal vs Mild: adjusted arithmetic mean difference: -9.21 (90% CI -19.88 to 1.45), p = 0.154, Regression, Logistic
Normal vs Moderate A: adjusted arithmetic mean difference: -6.05 (90% CI -16.65 to 4.55), p = 0.343, Regression, Logistic
Normal vs Moderate B: adjusted arithmetic mean difference: -21.5 (90% CI -31.79 to 4.55), p = 0.001, Regression, Logistic

Population analysed: Pharmacodynamic Analysis Set (PD), which consisted of all participants with an observed PD value, was considered. Only patients with evaluable data at each time point were analyzed for that time point.

Primary outcome: Maximum Observed Plasma Concentration (Cmax) for LIK066

Time frame: 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). Mean (Standard Deviation). Unit: nanogram per milliliter (ng/mL)

Measure	Normal n = 10	Mild n = 10	Moderate A n = 10	Moderate B n = 11	Severe n = 12
Day 1	565 (176)	590 (176)	492 (142)	569 (147)	650 (199)
Day 7	650 (250)	678 (219)	686 (243)	743 (301)	800 (268)

Population analysed: Pharmacokinetic Analysis Set (PAS), which consisted of all participants with at least 1 valid PK concentration measurement, was considered. Only patients with evaluable data at each time point were analyzed for that time point. Only descriptive analysis done.

Primary outcome: Time to Reach the Maximum Plasma Concentration (Tmax) for LIK066

Time frame: 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). Median (Full Range). Unit: hour (hr)

Measure	Normal n = 10	Mild n = 10	Moderate A n = 10	Moderate B n = 11	Severe n = 12
Day 1	1.00 (0.500 to 4.03)	1.00 (0.500 to 4.00)	1.00 (1.00 to 8.00)	1.00 (0.500 to 3.00)	1.00 (0.500 to 4.00)
Day 7	1.00 (0.500 to 3.00)	1.03 (0.500 to 4.00)	1.00 (0.500 to 6.00)	1.00 (0.500 to 2.00)	1.00 (0.500 to 2.00)

Primary outcome: Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau) for LIK066

Time frame: 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). Mean (Standard Deviation). Unit: hour*nanogram per milliliter (hr*ng/mL)

Measure	Normal n = 10	Mild n = 10	Moderate A n = 10	Moderate B n = 11	Severe n = 12
Day 1	2830 (650)	3330 (563)	3120 (567)	3360 (886)	4150 (1040)
Day 7	3440 (790)	4170 (981)	4080 (1040)	4510 (1240)	6290 (2280)

Adverse events

Time frame: Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 7 months. Other adverse events reported at 1% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Normal	0 of 10 (0%)	9 of 10 (90%)	0 of 10
Mild	0 of 10 (0%)	10 of 10 (100%)	0 of 10
Moderate A	0 of 10 (0%)	10 of 10 (100%)	0 of 10
Moderate B	1 of 11 (9.1%)	11 of 11 (100%)	0 of 11
Severe	1 of 12 (8.3%)	11 of 12 (91.7%)	0 of 12

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
A Plain Language Trial Summary is available on novartisclinicatrials.comLink provided by the sponsor.
Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Novartis Pharmaceuticals study director

Novartis Pharmaceuticals

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing LIK066 in people with Renal Impairment, run by Novartis Pharmaceuticals at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Feb 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in 24-hour Urinary Glucose Excretion (UGE) on Day 7 (time frame: Baseline , Day 7). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03131479.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jan 2021.