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

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Withdrawn
• CT.gov ID: NCT01824264
• Collaborator: (none)
• Enrollment: 0
• Arms: 9
• Duration (Months): 12

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus	Drug: LIK066; Drug: Sitagliptin; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 0 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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 Start Date: Nov 1, 2015
• Anticipated Primary Completion Date: Nov 1, 2016
• Anticipated Study Completion Date: Nov 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LIK066 2.5 mg Patients receive 2.5 mg of LIK066 once daily for 12 weeks	Drug: LIK066; Experimental treatment doses
Experimental: LIK066 5 mg Patients receive 5 mg of LIK066 once daily for 12 weeks	Drug: LIK066; Experimental treatment doses
Experimental: LIK066 10 mg Patients receive 10 mg of LIK066 once daily for 12 weeks	Drug: LIK066; Experimental treatment doses
Experimental: LIK066 25 mg Patients receive 25 mg of LIK066 once daily for 12 weeks	Drug: LIK066; Experimental treatment doses
Experimental: LIK066 50 mg Patients receive 50 mg of LIK066 once daily for 12 weeks	Drug: LIK066; Experimental treatment doses
Experimental: LIK066 100 mg Patients receive 100 mg of LIK066 once daily for 12 weeks	Drug: LIK066; Experimental treatment doses
Experimental: LIK066 150 mg Patients receive 150 mg of LIK066 once daily for 12 weeks	Drug: LIK066; Experimental treatment doses
Active Comparator: Sitagliptin 100 mg Patients receive 100 mg sitagliptin once daily for 12 weeks	Drug: Sitagliptin; Active comparator treatment dose
Placebo Comparator: Placebo Patients receive placebo for 12 weeks	Drug: Placebo; Placebo comparator dose

Outcome Measures

Primary Outcome Measures

1. Change from baseline in glycated hemoglobin (HbA1c) after 12 weeks [baseline, 12 weeks]

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

Secondary Outcome Measures

1. Change from baseline in Fasting Plasma Glucose [baseline, 12 weeks]

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

2. Change from baseline in urinary glucose to creatinine ratio [baseline, 12 weeks]

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

3. Change from baseline in Body weight [baseline, 12 weeks]

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

4. Change from baseline in Blood pressure [baseline, 12 weeks]

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

5. Change from baseline in postprandial glucose during a meal test [baseline, 12 weeks]

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

6. Change from baseline in beta cell function during a meal test [baseline, 12 weeks]

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

7. Change from baseline in insulin secretion relative to glucose during a meal test [baseline, 12 weeks]

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

8. Change from baseline in oral glucose insulin sensitivity during a meal test [baseline, 12 weeks]

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

9. Change from baseline in glucagon-like peptide response during a meal test [baseline, 12 weeks]

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

10. Change from baseline in Peptide YY response during a meal test [baseline, 12 weeks]

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

11. Number of patients with adverse events to assess safety and tolerability of LIK066 [12 weeks]

    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.

12. Change from baseline in renal threshold for glucose excretion [baseline, 12 weeks]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Confirmed diagnosis of T2DM by standard criteria

2. Drug-naïve patients, defined as patients not having received any anti-diabetic medication previously,

3. 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

4. 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)

5. HbA1c ≥ 7 to ≤ 10.5% at Visit 1 for drug-naïve/currently untreated patients

6. HbA1c ≥ 7 to ≤ 9.5% at Visit 1 for patients treated with OAD monotherapy

7. HbA1c ≥ 7 to ≤ 10.5% at Visit 199 for ALL patients

8. Age: ≥18 and ≤ 75 years old at Visit 1

9. BMI ≥22 to ≤45 kg/m2 at Visit 1

Exclusion Criteria:

1. 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

2. 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

3. History of acute metabolic complications, CV disease, type 1 diabetes mellitus, hepatic disorders, pancreatitis, chronic diarrhea

4. 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

5. ECG abnormalities including AV block, long QT syndrome or QTc>450 msec for men and

470 msec for women

1. History of malignancy

2. Women of child-bearing potential not using effective methods of contraception Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01824264
• Other Study ID Numbers: CLIK066A2202; 2012-005793-63
• First Posted: Apr 4, 2013
• Last Update Posted: Apr 3, 2014
• Last Verified: Apr 1, 2014

• Keywords provided by Novartis Pharmaceuticals: Type 2 Diabetes mellitus, SGLT inhibitors, dose-response
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Sitagliptin Phosphate; Licogliflozin

Study Results

No Results Posted as of Apr 3, 2014