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 | 14.1 |
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 | 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 evaluate the dose-effect relationship of AMG 151 compared to placebo, on fasting plasma glucose in subjects with type 2 diabetes treated with metformin |
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E.2.2 | Secondary objectives of the trial |
To assess the effect of AMG 151 on postprandial glucose levels in response to a meal tolerance test
To evaluate the safety and tolerability of AMG 151 |
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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 |
pharmacokinetics substudy.
It does not have a separate title or version. Most likely sites in the EEA will not register subjects in this sub-study
Objective is to provide data to characterize the PK of AMG 151 after oral dosing.
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E.3 | Principal inclusion criteria |
- Age 18 to 75 years, inclusive
- Diagnosis of type 2 diabetes mellitus
- HbA1c levels ≥ 7.5% to ≤ 11.0% at screening
- Fasting C-peptide levels ≥ 0.2 nmol/L at screening
- BMI ≥ 25 to ≤ 45 kg/m2 at screening
- Treated with metformin monotherapy for at least 3 months prior to randomization; the metformin dose must be ≥ 850 mg daily for at least 2 months immediately prior to randomization
- If a subject is being treated for hyperlipidemia or hypertension they should be on stable medication for 30 days before randomization
- Subject has provided informed consent
- Female subjects must be of non-reproductive potential (ie. postmenopausal by history - no menses for ≥ 1 year and by FSH [using local reference ranges]; OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy) |
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E.4 | Principal exclusion criteria |
Disease Specific
- History of type 1 diabetes
- History of significant weight gain or loss (>10%) during the 4 weeks before randomization
- Use of any weight loss medication (over the counter or prescription) within 60 days of randomization
- Use of any oral or injectable anti-hyperglycemic medication (other than metformin) within 3 months prior to randomization
- Use of chronic and/or continuous insulin administration for > 15 days in an outpatient setting to achieve and maintain glycemic control prior to randomization
- Have had 2 or more emergency room visits or hospitalizations due to poor glucose control in the past 6 months
- Have had more than 1 episode of severe hypoglycemia within 6 months prior to entry into the study, or currently diagnosed as having hypoglycemia unawareness
Other Medical Conditions
- Evidence of active infections that can interfere with the study
- Presence of clinically significant organ system disease that is not
stabilized or may interfere with the study
- Currently receiving immunosuppressive therapy
- History of positive HIV, chronic hepatitis B or C, or cirrhosis
- Have symptomatic congestive heart failure or a history of myocardial infarction, unstable angina, or decompensated congestive heart failure or stroke in the past 6 months prior to screening.
- History of gastric surgery, vagotomy, bowel resection or any surgical procedure that might interfere with gastrointestinal motility, pH or absorption
- Any finding on the screening ECG that in the opinion of the investigator requires further cardiovascular evaluation
- Poorly controlled hypertension defined as diastolic pressure ≥ 100 mm Hg or systolic pressure ≥ 160 mm Hg (assessed on 2 separate occasions during the screening period)
- Malignancy (other than resected cutaneous basal or cutaneous
squamous cell carcinoma, or treated in situ cervical cancer considered cured) within 5 years of screening visit (if a malignancy occurred > 5 years ago, subject is eligible with documentation of disease-free state since treatment)
Excluded Medications
- Use of known inhibitors or inducers of CYP3A4 are not permitted 30 days prior to randomization
Laboratory Abnormalities
- Triglycerides ≥ 500 mg/dL (5.64 mmol/L) at screening
- Hepatic liver enzymes (Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), alkaline phosphatase, total bilirubin) levels > 2 times the upper limit of normal at screening
- Hemoglobin < 11 g/dL for men and < 10 g/dL for women
- Creatinine Clearance < 60 mL/min as calculated via the MDRD equation (Modification of Diet in Renal Disease study group) as required for metformin use
- Any laboratory abnormality, which, in the opinion of the investigator, will prevent the subject from completing the study or will interfere with the interpretation of the study results
General
- Male subject with a pregnant partner who is not willing to use a condom or practice abstinence during treatment and for 12 weeks after the end of treatment.
- Male subject with a partner that might become pregnant, who is not willing to use highly effective method of birth control during treatment, and for 12 weeks after the end of treatment. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in fasting plasma glucose levels from baseline to Day 28 |
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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 area under the curve 0-4 hours (AUC0-4hr) glucose after a meal tolerance test from baseline to Day 28
Change in incremental AUC0-4hr glucose after a meal tolerance test from baseline to day 28 |
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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 | No |
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 | 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) | 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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 7 |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
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 |
Denmark |
Estonia |
Poland |
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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the date the last subject completes the last study assessment including laboratory blood draws (which corresponds to the last patient last visit date) |
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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 | 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 | 1 |