E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type 2 Diabetes Mellitus With Renal Impairment |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
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 | 10027433 - Metabolism and nutrition disorders |
|
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 sitagliptin on the HbA1c change from Baseline at Week 26. |
|
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 sitagliptin:
• HbA1c change from Baseline over time
• Fasting plasma glucose (FPG) change from Baseline over time
• Proportion of subjects at a HbA1c treatment goal of <7.0%
• Proportion of subjects at a HbA1c treatment goal of <6.5%
• Time to hyperglycemia rescue
• Change from Baseline in body weight
• Population PK of albiglutide and the effect of plasma concentrations of
albiglutide on glycemic control (population PK/PD) |
|
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 GLP114130
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. |
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E.3 | Principal inclusion criteria |
1. Male or female, 18 years of age or older, who is renally impaired with a historical
diagnosis of type 2 diabetes mellitus and is experiencing inadequate glycemic control
on their current regime of diet and exercise or their antidiabetic therapy of metformin,
TZD, SU, or any combination of these oral antidiabetic medications
2. BMI ≥20 kg/m2 and ≤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, 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
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 ≥10 g/dL (≥100 g/L) for male subjects and ≥9 g/dL (≥90 g/L) for female subjects
8. GFR ≥15 mL/min and <90 mL/min using the MDRD formula
9. Thyroid-stimulating hormone level is normal or clinically euthyroid as demonstrated by further thyroid tests (e.g., T4, T3)
For Inclusion criteria 10 -13 please refer to protocol |
|
E.4 | Principal exclusion criteria |
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 gastrointestinal surgery, including gastric bypass and banding, antrectomy, Roux-en-Y bypass, gastric vagotomy, small bowel resection, or surgeries thought to significantly affect upper gastrointestinal function
5. Recent clinically significant cardiovascular and/or cerebrovascular disease
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 ×ULN3
10. Fasting triglyceride level >850 mg/dL at Screening or Visit 5 (Week –1). If the
subject’s triglyceride level is >500 mg/dL at Screening and Visit 5 (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
12. History of a psychiatric disorder that will affect the subject’s ability to participate in the study
13. History of alcohol or substance abuse within 1 year before Screening
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
16. Known allergy to any GLP-1 analogue, sitagliptin, other study medications’
excipients, excipients of albiglutide, or Baker’s yeast
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
18. Contraindications (as per the prescribing information) for the use of either
background or potential randomized study medications (e.g., sitagliptin)
19. Receipt of any investigational drug or sitagliptin within the 30 days or 5 half-lives,
whichever is longer, before Screening or a history of receipt of an investigational
antidiabetic drug within the 3 months before randomization or receipt of albiglutide in
previous studies
20. History or family history of medullary carcinoma
21. History or family history of multiple endocrine neoplasia type 2
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy analysis endpoint will be HbA1c change from Baseline after 26
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 | 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 | 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 | 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 | 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.8.3 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 22 |
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
|
Last visit of the last patient |
|
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 | 3 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |