E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type II Diabetes mellitus |
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E.1.1.1 | Medical condition in easily understood language |
Type II Diabetes mellitus |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the dose-response relationship for LIK066 in terms of changes from baseline in HbA1c after 12 weeks of treatment across 7 oral doses (2.5 mg, 5 mg, 10 mg, 25 mg, 50 mg, 100 mg, or 150 mg q.d.) of LIK066 or placebo. |
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E.2.2 | Secondary objectives of the trial |
1. To evaluate the effect of LIK066 on:
• fasting plasma glucose (FPG)
• urinary glucose-to-creatinine ratio (UGCR)
• renal threshold for glucose excretion (RTg)
• body weight
• systolic and diastolic blood pressure
• postprandial glucose, beta cell function, insulin secretion relative to glucose (ISR/G), oral glucose insulin sensitivity (OGIS), GLP-1 and PYY response during a meal test
2. To evaluate the safety and tolerability of LIK066
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
Other protocol-defined inclusion criteria may apply
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E.4 | Principal 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
6.History of malignancy
7.Women of child-bearing potential not using effective methods of contraception
Other protocol-defined exclusion criteria may apply
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E.5 End points |
E.5.1 | Primary end point(s) |
change from baseline in HbA1c after 12 weeks of treatment in each of the LIK066 doses and placebo |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Change from baseline after 12 weeks of treatment
- Fasting plasma glucose (FPG)
- Urinary glucose-to-creatinine ratio (UGCR)
- Renal threshold for glucose excretion (RTg)
- body weight
- systolic and diastolic blood pressure
- postprandial glucose, beta cell function, insulin secretion relative to glucose (ISR/G), oral glucose insulin sensitivity (OGIS), GLP-1 and PYY response during a meal test
-the safety and tolerability of 7 doses of LIK066 after 12 weeks of treatment will be evluated with number of patients reported for total adverse events, serious adverse events and death |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 9 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Canada |
Germany |
Guatemala |
Hungary |
India |
Italy |
Mexico |
Poland |
Portugal |
Russian Federation |
Slovakia |
South Africa |
Taiwan |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 6 |