E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetes Mellitus, Type 2 |
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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 | 18.0 |
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 demonstrate a dose-response relationship of once-weekly subcutaneous injections of LY2944876 on hemoglobin A1c (HbA1c) change from baseline, and from this dose-response relationship at 12 weeks determine which LY2944876 doses are superior to placebo in patients with T2DM inadequately controlled with diet and exercise alone or treated with a stable dose of metformin. |
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E.2.2 | Secondary objectives of the trial |
To determine the effect of LY2944876 versus exenatide ER (and to compare the effect of both vs. placebo) on:
• Mean % body weight change from baseline to 12 and 24 weeks
• Safety and tolerability, including gastrointestinal tolerability, incidence and rate of hypoglycemia, hypersensitivity reactions, and pancreatic safety
• Change from baseline of HbA1c at 24 weeks
• Percentage of patients with 5% or greater body weight loss at 24 weeks
• Change from baseline of fasting blood glucose at 12 and 24 weeks
To evaluate the development of treatment-emergent anti-drug antibodies to LY2944876 or polyethylene glycol.
To assess pharmacokinetics (PK) of LY2944876, its variability and potential patient factors that may influence its PK.
To assess the relationship between LY2944876 dose and/or exposure and efficacy, and safety measures, where applicable.
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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 analysis, where local regulations and ERBs allow. |
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E.3 | Principal inclusion criteria |
Men or women aged 18 to 80 years with T2DM. Eligibility criteria include: HbA1c ≥7.0% and ≤10.5% at screening and treated with diet and exercise alone or on a stable dose of metformin (≥1000 mg/day) for 3 months prior to screening. BMI ≥23 and ≤45 kg/m2 at screening. |
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E.4 | Principal exclusion criteria |
Patients are excluded from participation if they; are women of child bearing potential; used thiazolidinediones within 3 months prior to screening, or any other drugs for treatment of hyperglycemia (except metformin) within the prior 2 months; have used insulin for diabetic control for more than 6 consecutive days within the prior year; and if they have impaired renal function (serum creatinine >124 µmol/L [1.4 mg/dL] in women, >133 µmol/L [1.5 mg/dL] in men). |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is HbA1c change from baseline to 12 weeks |
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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) |
Secondary efficacy measures include: HbA1c, body weight (mean change from baseline and % of patients with > 5% loss from baseline to endpoint), fasting blood glucose; 7 point SMBG profiles; % of patients requiring rescue therapy, lipids, and other circulating biomarkers.
Safety: Vital signs, labs, ECG monitoring, incidence and duration of nausea, vomiting, and diarrhea, assessment of injection site reactions, hypersensitivity reactions, episodes of hypoglycemia, acute pancreatitis , major adverse cardiovascular events, development of anti-drug antibodies, and TEAEs including SAEs and AEs leading to discontinuation.
Health Outcomes: APPADL and IW-SP questionnaires, which are self-rated questionnaires that provide standardized measures of patients’ perceived current health status.
Pharmacokinetic: Venous blood samples to measure the plasma concentrations of LY2944876 using validated bioanalytical assays.
Pharmacodynamic: Endpoints may include, but are not necessarily limited to, endpoints for efficacy (glucose, HbA1c, weight), tolerability (e.g., nausea and vomiting), safety (e.g., corrected QT (QTc) interval, heart rate), and biomarkers (e.g., insulin, glucagon).
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | 6 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 21 |
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 |
Mexico |
Poland |
Romania |
Spain |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 22 |