E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045242 |
E.1.2 | Term | Type II diabetes mellitus |
E.1.2 | System Organ Class | 100000004861 |
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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 compare LY2409021 20 mg to placebo (PBO) on the change in hepatic fat fraction (HFF) from baseline (BL) to 6 months as measured by MRI in subjects with T2DM who are taking metformin (MET) and sulfonylurea (SU). |
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E.2.2 | Secondary objectives of the trial |
To assess the change from baseline in HFF determined by liver MRI at 1, 3, 6, and 12 months and 16 weeks (subset 24 weeks) after treatment discontinuation for each arm.
To assess the incremental change in HFF during treatment by measuring HFF between:
- 1 and 3 months
- 3 and 6 months
- 6 and 12 months
To compare LY2409021 20 mg to PBO and SITA at 6 months and 12 months for the following measures:
- Change in HbA1c
- Change from baseline in hepatic aminotransferase levels including frequency of elevation and changes in the mean across time.
- Change in fasting glucagon levels
- Hepatobiliary adverse events of special interest (AESI).
- Pancreas AESIs
- Cardiovascular AESIs
- Hypoglycemia AESIs
- Additional PK/PD and Pharmacogenetic objectives
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Pharmacogenetic Evaluation (11-Dec-13)
Where local regulations and ERBs allow, a blood sample will be collected
for pharmacogenetic analysis for genetic variants that may be related to
safety and/or efficacy features of the drug. |
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E.3 | Principal inclusion criteria |
Male or female (using contraception) subjects diagnosed with T2DM between the ages of 18 and <80 years old.
Have been treated with a stable dose of MET for at least 3 months and have been treated with an optimally effective and stable dose of an SU for at least 6 months prior to screening
HbA1c value between 7.0% and 10.0%, inclusive.
BMI between 20 and 45 kg/m2, inclusive.
Subjects must be willing to undergo an MRI and laboratory sampling according to the study schedule. |
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E.4 | Principal exclusion criteria |
Known type 1 diabetes.
More than 1 episode of severe hypoglycemia within 6 months prior to Visit 1.
Two or more emergency room visits or hospitalizations due to poor glucose control in the 6 months prior to Visit 1.
Severe gastrointestinal disease that may significantly impact gastric emptying or motility or having undergone gastric bypass or gastric banding surgery.
Previous history or active diagnosis of pancreatitis.
Positive hepatitis B surface antigen or hepatitis C antibody.
Clinical signs or symptoms of liver disease, or hepatic aminotransferases (AST or ALT) >2.0× ULN or elevated alkaline phosphatase (>ULN) unrelated to bone metabolic disease.
Elevated total bilirubin level (>ULN), clinically suspicious signs/symptoms of cirrhosis or history of cirrhosis.
Current diagnosis, personal history of neuroendocrine tumors, family history of any type of multiple endocrine neoplasia (MEN), or Von Hippel-Lindau.
Contraindications for MRI.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the change in HFF from BL to 6-month endpoint. Baseline is defined as the HFF value at Visit 2 (Week -2). |
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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) |
Efficacy Endpoints:
Glucose - change from Baseline (BL) values will be provided for HbA1c, fasting plasma glucose, and 7-point SMBG profiles
Weight - change from BL
BMI - change from BL
PK/PD Analyses:
population-PK analysis
Safety Endpoints:
- Hepatic fat - supportive analysis for the primary analysis
- AEs
- Vital signs
- Clinical Laboratory
- Liver Biochemicals
- Glucagon
- Lipids
- Hypoglycemic Events and Interventions
- Adjudicated Cardiovascular Events - Deaths and
nonfatal cardiovascular AEs will be adjudicated by an independent clinical endpoint committee |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
6- and 12- months:
Efficacy endpoints, Safety endpoints, PK/PD analyses |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
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 | No |
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 | 3 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | No |
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 |
Greece |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 10 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 8 |