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Dose-finding Study of LIK066 Compared With Placebo or Sitagliptin to Evaluate Change in HbA1c in Patients With Diabetes

Primary Purpose

Type 2 Diabetes Mellitus

Status

Withdrawn

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

LIK066

Sitagliptin

Placebo

About this trial

This is an interventional treatment trial for Type 2 Diabetes Mellitus focused on measuring Type 2 Diabetes mellitus, SGLT inhibitors, dose-response

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Confirmed diagnosis of T2DM by standard criteria
Drug-naïve patients, defined as patients not having received any anti-diabetic medication previously,
Currently untreated patients , who, after the diagnosis of T2DM, have received anti-diabetic medication for not more than 12 consecutive weeks, and have not received any anti-diabetic treatment within 12 weeks prior to Visit 1
Patients being treated with mono-therapy for at least 8 consecutive weeks prior to Visit 1 with the following OADs: metformin, dipeptidyl peptidase-4 inhibitors (DPP-4i), SU, glinide, alpha-glucosidase inhibitor (AGI)
HbA1c ≥ 7 to ≤ 10.5% at Visit 1 for drug-naïve/currently untreated patients
HbA1c ≥ 7 to ≤ 9.5% at Visit 1 for patients treated with OAD monotherapy
HbA1c ≥ 7 to ≤ 10.5% at Visit 199 for ALL patients
Age: ≥18 and ≤ 75 years old at Visit 1
BMI ≥22 to ≤45 kg/m2 at Visit 1

Exclusion Criteria:

FPG ≥270 mg/dl (15 mmol/L) for drug-naïve/currently untreated patients or ≥240 mg/dl (13.3 mmol/L) for patients on OAD monotherapy at Visit 1
Insulin treatment >4 consecutive weeks in the last 6 months, corticosteroid use >7 days in the last 8 weeks, use of growth hormones in the last 6 months, or use of weight control products > 4 weeks in the last 6 months
History of acute metabolic complications, CV disease, type 1 diabetes mellitus, hepatic disorders, pancreatitis, chronic diarrhea
Significant lab abnormalities such as TSH outside of normal range, UACR>300 mg/g creatinine, eGFR <60 ml/min/1.73m2, hemoglobin <12 g/L in men and <11 g/L in women, hematuria
ECG abnormalities including AV block, long QT syndrome or QTc>450 msec for men and >470 msec for women
History of malignancy
Women of child-bearing potential not using effective methods of contraception Other protocol-defined inclusion/exclusion criteria may apply

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm Type

Experimental

Active Comparator

Placebo Comparator

Arm Label

LIK066 2.5 mg

LIK066 5 mg

LIK066 10 mg

LIK066 25 mg

LIK066 50 mg

LIK066 100 mg

LIK066 150 mg

Sitagliptin 100 mg

Placebo

Arm Description

Patients receive 2.5 mg of LIK066 once daily for 12 weeks

Patients receive 5 mg of LIK066 once daily for 12 weeks

Patients receive 10 mg of LIK066 once daily for 12 weeks

Patients receive 25 mg of LIK066 once daily for 12 weeks

Patients receive 50 mg of LIK066 once daily for 12 weeks

Patients receive 100 mg of LIK066 once daily for 12 weeks

Patients receive 150 mg of LIK066 once daily for 12 weeks

Patients receive 100 mg sitagliptin once daily for 12 weeks

Patients receive placebo for 12 weeks

Outcomes

Primary Outcome Measures

Change from baseline in glycated hemoglobin (HbA1c) after 12 weeks

Change from baseline in HbA1c after 12 weeks of treatment in each of the LIK066 doses and placebo

Secondary Outcome Measures

Change from baseline in Fasting Plasma Glucose

The effect of LIK066 on fasting plasma glucose after 12 weeks of treatment will be evaluated.

Change from baseline in urinary glucose to creatinine ratio

The effect of LIK066 on urinary glucose to creatinine ratio after 12 weeks of treatment will be evaluated

Change from baseline in Body weight

The effect of LIK066 on change in body weight after 12 weeks of treatment will be evaluated.

Change from baseline in Blood pressure

The effect of LIK066 on change in systolic and diastolic blood pressure after 12 weeks of treatment will be evaluated.

Change from baseline in postprandial glucose during a meal test

The effect of LIK066 on change in postprandial glucose during a meal test after 12 weeks of treatment will be evaluated.

Change from baseline in beta cell function during a meal test

The effect of LIK066 on change in beta cell function during a meal test after 12 weeks of treatment will be evaluated.

Change from baseline in insulin secretion relative to glucose during a meal test

The effect of LIK066on change in insulin secretion relative to glucose during a meal test after 12 weeks of treatment will be evaluated.

Change from baseline in oral glucose insulin sensitivity during a meal test

The effect of LIK066 on change in oral glucose insulin sensitivity during a meal test after 12 weeks of treatment will be evaluated.

Change from baseline in glucagon-like peptide response during a meal test

The effect of LIK066 on change in glucagon-like peptide during a meal test after 12 weeks of treatment will be evaluated.

Change from baseline in Peptide YY response during a meal test

The effect of LIK066 on change in peptide YY response during a meal test after 12 weeks of treatment will be evaluated.

Number of patients with adverse events to assess safety and tolerability of LIK066

The safety and tolerability of 7 doses of LIK066 after 12 weeks of treatment will be evaluated with number of patients reported for total adverse events, serious adverse events and death.

Change from baseline in renal threshold for glucose excretion

The effect of LIK066 on renal threshold for glucose excretion will be calculated from glucose values in an overnight urine collection

Full Information

NCT ID

NCT01824264

First Posted

April 1, 2013

Last Updated

April 2, 2014

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT01824264

Brief Title

Dose-finding Study of LIK066 Compared With Placebo or Sitagliptin to Evaluate Change in HbA1c in Patients With Diabetes

Official Title

A Multi-center, Randomized, Double-blind, Parallel-group Dose-finding Study to Evaluate Change in HbA1c After 12 Weeks Monotherapy With 7 Doses of LIK066 Compared With Placebo or Sitagliptin in Patients With Type 2 Diabetes

Study Type

Interventional

2. Study Status

Record Verification Date

April 2014

Overall Recruitment Status

Withdrawn

Study Start Date

November 2015 (undefined)

Primary Completion Date

November 2016 (Anticipated)

Study Completion Date

November 2016 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of the study is to evaluate the efficacy, tolerability and short-term safety of LIK066 to support dose selection for phase 3.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type 2 Diabetes Mellitus

Keywords

Type 2 Diabetes mellitus, SGLT inhibitors, dose-response

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

LIK066 2.5 mg

Arm Type

Experimental

Arm Description

Patients receive 2.5 mg of LIK066 once daily for 12 weeks

Arm Title

LIK066 5 mg

Arm Type

Experimental

Arm Description

Patients receive 5 mg of LIK066 once daily for 12 weeks

Arm Title

LIK066 10 mg

Arm Type

Experimental

Arm Description

Patients receive 10 mg of LIK066 once daily for 12 weeks

Arm Title

LIK066 25 mg

Arm Type

Experimental

Arm Description

Patients receive 25 mg of LIK066 once daily for 12 weeks

Arm Title

LIK066 50 mg

Arm Type

Experimental

Arm Description

Patients receive 50 mg of LIK066 once daily for 12 weeks

Arm Title

LIK066 100 mg

Arm Type

Experimental

Arm Description

Patients receive 100 mg of LIK066 once daily for 12 weeks

Arm Title

LIK066 150 mg

Arm Type

Experimental

Arm Description

Patients receive 150 mg of LIK066 once daily for 12 weeks

Arm Title

Sitagliptin 100 mg

Arm Type

Active Comparator

Arm Description

Patients receive 100 mg sitagliptin once daily for 12 weeks

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Patients receive placebo for 12 weeks

Intervention Type

Drug

Intervention Name(s)

LIK066

Intervention Description

Experimental treatment doses

Intervention Type

Drug

Intervention Name(s)

Sitagliptin

Intervention Description

Active comparator treatment dose

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo comparator dose

Primary Outcome Measure Information:

Title

Change from baseline in glycated hemoglobin (HbA1c) after 12 weeks

Description

Change from baseline in HbA1c after 12 weeks of treatment in each of the LIK066 doses and placebo

Time Frame

baseline, 12 weeks

Secondary Outcome Measure Information:

Title

Change from baseline in Fasting Plasma Glucose

Description

The effect of LIK066 on fasting plasma glucose after 12 weeks of treatment will be evaluated.

Time Frame

baseline, 12 weeks

Title

Change from baseline in urinary glucose to creatinine ratio

Description

The effect of LIK066 on urinary glucose to creatinine ratio after 12 weeks of treatment will be evaluated

Time Frame

baseline, 12 weeks

Title

Change from baseline in Body weight

Description

The effect of LIK066 on change in body weight after 12 weeks of treatment will be evaluated.

Time Frame

baseline, 12 weeks

Title

Change from baseline in Blood pressure

Description

The effect of LIK066 on change in systolic and diastolic blood pressure after 12 weeks of treatment will be evaluated.

Time Frame

baseline, 12 weeks

Title

Change from baseline in postprandial glucose during a meal test

Description

The effect of LIK066 on change in postprandial glucose during a meal test after 12 weeks of treatment will be evaluated.

Time Frame

baseline, 12 weeks

Title

Change from baseline in beta cell function during a meal test

Description

The effect of LIK066 on change in beta cell function during a meal test after 12 weeks of treatment will be evaluated.

Time Frame

baseline, 12 weeks

Title

Change from baseline in insulin secretion relative to glucose during a meal test

Description

The effect of LIK066on change in insulin secretion relative to glucose during a meal test after 12 weeks of treatment will be evaluated.

Time Frame

baseline, 12 weeks

Title

Change from baseline in oral glucose insulin sensitivity during a meal test

Description

The effect of LIK066 on change in oral glucose insulin sensitivity during a meal test after 12 weeks of treatment will be evaluated.

Time Frame

baseline, 12 weeks

Title

Change from baseline in glucagon-like peptide response during a meal test

Description

The effect of LIK066 on change in glucagon-like peptide during a meal test after 12 weeks of treatment will be evaluated.

Time Frame

baseline, 12 weeks

Title

Change from baseline in Peptide YY response during a meal test

Description

The effect of LIK066 on change in peptide YY response during a meal test after 12 weeks of treatment will be evaluated.

Time Frame

baseline, 12 weeks

Title

Number of patients with adverse events to assess safety and tolerability of LIK066

Description

The safety and tolerability of 7 doses of LIK066 after 12 weeks of treatment will be evaluated with number of patients reported for total adverse events, serious adverse events and death.

Time Frame

12 weeks

Title

Change from baseline in renal threshold for glucose excretion

Description

The effect of LIK066 on renal threshold for glucose excretion will be calculated from glucose values in an overnight urine collection

Time Frame

baseline, 12 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Confirmed diagnosis of T2DM by standard criteria Drug-naïve patients, defined as patients not having received any anti-diabetic medication previously, Currently untreated patients , who, after the diagnosis of T2DM, have received anti-diabetic medication for not more than 12 consecutive weeks, and have not received any anti-diabetic treatment within 12 weeks prior to Visit 1 Patients being treated with mono-therapy for at least 8 consecutive weeks prior to Visit 1 with the following OADs: metformin, dipeptidyl peptidase-4 inhibitors (DPP-4i), SU, glinide, alpha-glucosidase inhibitor (AGI) HbA1c ≥ 7 to ≤ 10.5% at Visit 1 for drug-naïve/currently untreated patients HbA1c ≥ 7 to ≤ 9.5% at Visit 1 for patients treated with OAD monotherapy HbA1c ≥ 7 to ≤ 10.5% at Visit 199 for ALL patients Age: ≥18 and ≤ 75 years old at Visit 1 BMI ≥22 to ≤45 kg/m2 at Visit 1 Exclusion Criteria: FPG ≥270 mg/dl (15 mmol/L) for drug-naïve/currently untreated patients or ≥240 mg/dl (13.3 mmol/L) for patients on OAD monotherapy at Visit 1 Insulin treatment >4 consecutive weeks in the last 6 months, corticosteroid use >7 days in the last 8 weeks, use of growth hormones in the last 6 months, or use of weight control products > 4 weeks in the last 6 months History of acute metabolic complications, CV disease, type 1 diabetes mellitus, hepatic disorders, pancreatitis, chronic diarrhea Significant lab abnormalities such as TSH outside of normal range, UACR>300 mg/g creatinine, eGFR <60 ml/min/1.73m2, hemoglobin <12 g/L in men and <11 g/L in women, hematuria ECG abnormalities including AV block, long QT syndrome or QTc>450 msec for men and >470 msec for women History of malignancy Women of child-bearing potential not using effective methods of contraception Other protocol-defined inclusion/exclusion criteria may apply

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

12. IPD Sharing Statement

Learn more about this trial

Dose-finding Study of LIK066 Compared With Placebo or Sitagliptin to Evaluate Change in HbA1c in Patients With Diabetes

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