E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 |
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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 |
The primary objective of the study is to evaluate the efficacy of albiglutide administered in combination with insulin glargine as compared with the combination of insulin glargine and preprandial lispro insulin on HbA1c change from Baseline at Week 26. |
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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 in combination with insulin glargine as compared with the combination of insulin glargine and preprandial lispro insulin:
• HbA1c change from Baseline over time
• 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 |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects eligible for enrollment in the study must meet all of the following criteria:
1) Male or female, 18 to 75 years of age, inclusive, with a historical diagnosis of type 2 diabetes mellitus who is currently treated with insulin glargine, or other intermediate- or long-acting insulin, with or without oral antidiabetic medications but who is experiencing inadequate glycemic control and who is willing and capable of participating in a regimen of intensive insulin administration. A subject who has been on an intermediate- or long-acting insulin for ≥6 months but <5 years, and, in spite of dosage adjustments based on home blood glucose monitoring, is unable to achieve a HbA1c of <7%. These subjects must be capable and willing to transition from a simple basal insulin regimen to an intensified regimen
2) BMI ≥20kg/m2 and ≤45 kg/m2
3) Fasting C-peptide ≥0.8 ng/mL (≥0.26 nmol/L)
4) HbA1c between 7.0% and 10.5%, 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 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., increase or decrease 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, thyroid-binding globulin)
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 as per the protocol recommendations of self-administration
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 |
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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 (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
• Current or history of heart failure (New York Heart Association class I 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 TZD1
• 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 documents2
• QTc interval (Fridericia) >470 ms confirmed by a central reader at Screening
6. History of stroke or other central nervous system disorder that would negatively
impact the subject’s ability to participate in a program of intensive insulin management (eg, physically or mentally incapable of performing home blood glucose monitoring or administering and/or adjusting insulin dosage)
7. Hemoglobinopathy that may affect determination of HbA1c
8. History of human immunodeficiency virus infection
9. 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
10. ALT or aspartate aminotransferase (AST) >2.5 ×ULN3
11. 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 rescreened4
12. 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
13. History of a psychiatric disorder that will affect the subject’s ability to participate in the study
14. History of alcohol or substance abuse within 1 year before Screening
15. 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
For exclusion criteria 16-24 please refer to the protocol |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint will be Week 26 HbA1c change from Baseline. |
|
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 | 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) | 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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
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 | 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 |