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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10012601 |
E.1.2 | Term | Diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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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 that once-weekly dulaglutide (1.5 mg dose) is noninferior to once-daily liraglutide (1.8 mg dose) as measured by HbA1c at 26 weeks (change from baseline) in patients with type 2 diabetes mellitus who are taking a stable dose of metformin |
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E.2.2 | Secondary objectives of the trial |
- If noninferiority is passed, to assess if dulaglutide is superior to liraglutide at 26 weeks (measured by change in HbA1c from baseline).
To compare dulaglutide and liraglutide for:
- Change in body weight & BMI
- FPG & fasting plasma glucose 7-point self-monitored plasma glucose profiles
- % patients attaining HbA1c <7.0% and ≤6.5%
-Homeostasis Model Assessment 2 steady‑state β-cell function
- Incidence of gastrointestinal AEs, injection site reactions & allergic or hypersensitivity reactions
- Reported & adjudicated CV events, ECG parameters, heart rate & blood pressure
- Serum calcitonin
- Events of adjudicated acute pancreatitis and pancreatic enzymes
- Hypoglycemic events
- % patients requiring an additional intervention due to severe persistent hyperglycemia; & time to initiation of the additional intervention
- Lipid panel
- To evaluate anti-drug antibodies and adverse effect in those patients randomised to dulaglutide
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Type 2 diabetes (based on WHO diagnostic criteria)
- Not optimally controlled on diet and exercise and a dose of metformin that is at least 1500 mg/day and has been at a stable dose for at least 3 months prior to the first study visit
- HbA1c value of ≥7.0% to ≤10.0%
- Accept continued treatment with metformin throughout the trial
- Men and nonpregnant women aged ≥18 years
- Stable weight (±5%) ≥3 months prior to screening
- BMI ≤45 kg/m2
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E.4 | Principal exclusion criteria |
- Have type 1 diabetes mellitus
- Have been treated with ANY other antihyperglycemic medications (other than metformin) at the time of the first study visit or within 3 months prior to first study visit
- Have used insulin therapy (outside of pregnancy) any time in the past 2 years, except for short-term treatment of acute conditions, & up to a maximum of 4 weeks; any insulin use within 3 months prior to the first study visit
- Have been treated with drugs that promote weight loss within 3 months of first study visit
- Are receiving chronic (>14 days) systemic glucocorticoid therapy (excluding topical, intraocular, intranasal, or inhaled preparations) or have received such therapy within 4 weeks prior to first study visit
- Have had any of the following CV conditions within 2 months prior to the first study visit: acute MI, NYHA Class III or Class IV heart failure, or cerebrovascular accident (stroke)
- Have a known clinically significant gastric emptying abnormality (eg, severe diabetic gastroparesis or gastric outlet obstruction) or have undergone gastric bypass (bariatric) surgery or restrictive bariatric surgery (e.g. Lap-Band®)
- Have acute or chronic hepatitis, signs & symptoms of any other liver disease, or alanine transaminase (ALT) level ≥3 times the upper limit of the reference range
- Have history of chronic pancreatitis or acute idiopathic pancreatitis, or were diagnosed with any type of acute pancreatitis
- Have a serum creatinine ≥1.5 mg/dL (male) or ≥1.4 mg/dL (female), or a creatinine clearance <60 mL/minute
- Have self or family history of type 2A or type 2B multiple endocrine neoplasia (MEN 2A or 2B) in the absence of known C-cell hyperplasia [see proptocol for further details]
- Have self or family history of medullary C-cell hyperplasia, focal hyperplasia, carcinoma (including sporadic, familial or part of MEN 2A or 2B syndrome)
- Have a serum calcitonin ≥20 pg/mL
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint in this study is change in HbA1c from baseline to 26 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) |
- Change in HbA1c from baseline to 26 weeks
- Change in body weight & BMI
- FPG & 7-point self-monitored plasma glucose profiles
- % patients attaining HbA1c <7.0% and ≤6.5%
- Homeostasis Model Assessment 2 steady state β-cell function (HOMA2-%B)
- Incidence of gastrointestinal AEs, injection site reactions, & allergic or hypersensitivity reactions
- Reported and adjudicated CV events, ECG parameters, heart rate, & blood pressure
- Serum calcitonin
- Events of adjudicated acute pancreatitis and pancreatic enzymes
- Hypoglycemic events
- % patients requiring an additional intervention due to severe persistent hyperglycemia; and time to initiation of the additional intervention
- Lipid panel
- Anti-drug antibody titer and adverse effect in those patients randomized to dulaglutide
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 43 |
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 |
Czech Republic |
Germany |
Hungary |
Mexico |
Poland |
Romania |
Russian Federation |
Slovakia |
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 | |
E.8.9.1 | In the Member State concerned months | |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 24 |