| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10045242 |
| E.1.2 | Term | Type II diabetes mellitus |
|
| 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 |
| The primary objective of the study is to evaluate the efficacy of albiglutide as compared with liraglutide on the HbA1c change from Baseline at Week 32. |
|
| E.2.2 | Secondary objectives of the trial |
Secondary efficacy objectives at time points to be specified in the statistical analysis plan (SAP) include the following evaluations of treatment with albiglutide as compared with liraglutide:
• HbA1c change from Baseline over time
• Fasting plasma glucose (FPG) change from Baseline over time
• Proportion of subjects at an HbA1c treatment goal of <7.0%
• Proportion of subjects at an HbA1c treatment goal of <6.5%
• Time to hyperglycemia rescue
• Change from Baseline in body weight
|
|
| 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 SUB-STUDY IN ASSOCIATION WITH STUDY GLP114179
The objective of the pharmacogenetic research (if there is a potential unexpected or unexplained variation) is to investigate a possible genetic relationship to handling or response to albiglutide. |
|
| E.3 | Principal inclusion criteria |
Subjects eligible for enrollment in the study must meet all of the following criteria:
1. Male or female, 18 years of age or older, with a historical diagnosis of type 2 diabetes mellitus and is experiencing inadequate glycemic control on their current regimen of metformin, TZD, SU, or any combination of these oral antidiabetic medications
2. BMI ≥ 20kg/m2 and less than or equal to 45 kg/m2
3. Fasting C-peptide ≥0.8 ng/mL (≥0.26 nmol/L)
4. HbA1c between 7.0% and 10.0%, inclusive, at Visit 5 (Week –1). The HbA1c value may be checked up to 4 times, and if the average of these determinations meets the criterion, the subject may be randomly assigned to treatment
5. For the regular use of other medications (does not include medications excluded by the protocol [see Section 5.6.2 for example, weight loss medications are excluded]), it is preferred that the subjects are receiving a stable dose for at least 4 weeks before Screening; however, as necessary during the Run-in/Stabilization Period and the Treatment Period, prescription or over the counter medications are allowed and may be adjusted by the investigator to optimize treatment (e.g., change in dose of medication to treat blood pressure or hyperlipidemia in accordance with accepted local medical practice and relevant guidance documents)
6. Use of oral or systemically injected glucocorticoids is generally not allowed within 3 months before randomization; however, short courses of oral steroids (single dose or multiple doses for up to 2 days) may be permitted provided these cases are discussed with the medical monitor. Inhaled, intra articular, and topical corticosteroids are allowed
7. Hemoglobin ≥11 g/dL (≥110 g/L) for male subjects and ≥10 g/dL (≥100 g/L) for female subjects
8. Creatinine clearance >60 mL/min (calculated using the Cockcroft-Gault formula)
9. Thyroid stimulating hormone level is normal or clinically euthyroid as demonstrated by further thyroid tests (e.g., T4, T3)
10. Female subjects of childbearing potential (i.e., not surgically sterile and/or not postmenopausal) must be practicing adequate contraception. Methods of adequate contraception include the following: abstinence, injectable progestogen, implants of levonorgestrel, estrogenic vaginal ring, percutaneous contraceptive patches, intrauterine device or intrauterine system, male partner sterilization (vasectomy with documentation of azoospermia) before the female subject’s entry into the study and this male partner is the sole partner for that subject, double barrier method (condom and occlusive cap plus nonoxynol 9), or oral contraceptives in combination with a second method of contraception (e.g., condom and occlusive cap). Adequate contraception must be practiced for the duration of participation in the study including the 8 week Posttreatment Follow-up Period
11. Able and willing to monitor his or her own blood glucose concentrations with a home glucose monitor
12. No major illness or debility that in the investigator’s opinion prohibits the subject from actively participating in their diabetes management and completing the study
13. Able and willing to provide written informed consent
Subjects eligible for randomization in the study must meet the following additional criteria:
• HbA1c concentration between 7.0% and 10.0%, inclusive, after the Run in/Stabilization Period (Visit 5, Week –1). If the subject does not qualify for randomization based on this criterion, the assessment may be repeated on a weekly basis, for a maximum of 4 additional weeks before randomization. The mean of all HbA1c assessments (Visit 5, Week –1 plus the additional HbA1c assessments) must be between 7.0% and 10.0%, inclusive, for the subject to be eligible for randomization
• If the Screening ECG for the QTc interval (Fridericia) is >470 ms, 2 repeat ECGs may be obtained during the Run-in/Stabilization Period. The 3 ECGs will be overread by the central reader. If the mean QTc interval (Fridericia) for all 3 ECGs is less than or equal to 470 ms, the subject qualifies for entry into the study (the ECG equipment provided to the investigator reports the QTc as both Bazett and Fridericia corrections). At Visit 6 (Baseline), the subject’s ECG should be reviewed by the investigator before the administration of the investigational product. The QTc interval (Fridericia) criterion and actions outlined in Section 4.6 and Section 6.3.2 will apply
• If the lipase result is above the ULN, then the subject will not be randomly assigned to treatment. If the amylase result is above the ULN and the lipase is below the ULN, then an isoenzyme analysis will be done by the central laboratory. If this additional test confirms that the pancreatic isoenzyme fraction is not the cause of the elevation, the subject may continue in the study |
|
| E.4 | Principal exclusion criteria |
Subjects meeting any of the following criteria must not be enrolled in the study:
1. History of cancer, other than squamous cell or basal cell carcinoma of the skin, that has not been in full remission for at least 3 years before Screening. (A history of treated cervical intraepithelial neoplasia I or cervical intraepithelial neoplasia II is allowed)
2. History of treated diabetic gastroparesis
3. Current ongoing symptomatic biliary disease or history of pancreatitis
4. History of significant GI surgery, including gastric bypass and banding, antrectomy, Roux en Y bypass, gastric vagotomy, small bowel resection, or surgeries thought to significantly affect upper GI function
5. Recent (as defined below) clinically significant cardiovascular and/or cerebrovascular disease including but not limited to the following:
• Previous history of stroke or transient ischemic attack within 1 month before Screening. However, subjects who are deemed clinically stable by the investigator may be enrolled 1 month after the cerebrovascular event
• Acute coronary syndrome, which includes the following:
• Documented MI within the 2 months before Screening and during the period up until receiving the first dose of study medication
• Any cardiac surgery including percutaneous transluminal coronary angioplasty, coronary stent placement, or coronary artery bypass graft surgery within the 2 months before Screening and during the period up until receiving the first dose of study medication
• Unstable angina not responsive to nitroglycerin within the 2 months before Screening and during the period up until receiving the first dose of study medication
• Unstable cardiac rhythm, however, as an example, controlled atrial fibrillation is allowed
• For subjects taking a TZD (e.g., pioglitazone or rosiglitazone), current or history of heart failure (New York Heart Association class I to IV); for subjects not taking a TZD, current or history of heart failure (New York Heart Association class II to IV)
Note: Investigators must consult the approved product labeling for TZD in their country to determine a subjects’ eligibility to participate in this study if they are currently taking a TZD
• Resting systolic pressure is >160 mm Hg and/or diastolic pressure >100 mm Hg. If the subject’s systolic blood pressure is >160 mm Hg or the subject’s diastolic blood pressure is >100 mm Hg at Screening, the blood pressure readings may be repeated at 5-minute intervals for a total of 3 determinations. If the averages of the systolic or diastolic pressure readings still do not meet the criteria, the subject can be treated and rescreened. It is preferred that subjects be on a stable dose of medication for at least 4 weeks before being rescreened; however, when stable, they may be rescreened at the discretion of the investigator
Should a subject not meet this criterion on Visit 6 (first dose of study medication following the randomization visit), the subject may continue in the study at the discretion of the investigator with the understanding that the subject’s hypertension will be monitored and treated in accordance with accepted local medical practice and relevant guidance documents
• QTc interval (Fridericia) >470 ms confirmed by a central reader at Screening
6. Hemoglobinopathy that may affect determination of HbA1c
7. History of human immunodeficiency virus infection
8. History of total bilirubin >1.5 × ULN unless the subject has a previously known history of Gilbert’s syndrome and a fractionated bilirubin that shows conjugated bilirubin <35% of total bilirubin
9. ALT or aspartate aminotransferase (AST) >2.5 ×ULN
10. Fasting triglyceride level >850 mg/dL at Screening or Week –1 (Visit 5). If the subject’s triglyceride level is >500 mg/dL at Screening and Week –1, the subject is excluded. If the subject meets the aforementioned exclusion criteria for triglycerides, the subject can be treated and rescreened. Treated subjects must be on a stable dose of medication for at least 4 weeks before being rescreened
11. Acute symptomatic (within 3 months before Screening) infection with hepatitis B or hepatitis C; however, subjects with past or chronic hepatitis B or hepatitis C are allowed provided the requirements for ALT, AST, and total bilirubin are met
14. Positive urine drug screen at Screening, unless the subject is taking a medically approved medication for which a positive drug screen simply verifies the use of this medication
15. Female subject is pregnant (confirmed by laboratory testing), lactating, or <6 weeks postpartum
17. History of type 1 diabetes mellitus, diabetic complications (e.g., active proliferative retinopathy or severe diabetic neuropathy) that in the opinion of the investigator would preclude effective participation in the study, or a history of ketoacidosis or hyperosmolar coma
For exclusion criteria number 12, 13, 16, 18-21 please refer to study protocol |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary efficacy analysis endpoint will be HbA1c change from Baseline after 32
weeks of treatment. |
|
| 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 | No |
| 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 | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| 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 | No |
| 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 | 10 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 25 |
| 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 | Information not present in EudraCT |
| 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 |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
| |
| 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 | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
| 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 | 9 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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