| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
| Non-insulin dependent diabetes mellitus |
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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 | 17.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10067585 |
| E.1.2 | Term | Type 2 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 |
| • To assess and compare the efficacy of five doses of HM11260C (once weekly subcutaneous injections) over the 12 weeks from baseline in comparison with placebo (once weekly subcutaneous injections) on glycaemic control, as assessed by HbA1c in subjects with T2DM |
|
| E.2.2 | Secondary objectives of the trial |
• To assess and compare the safety, tolerability and immunogenicity of HM11260C versus placebo in subjects with T2DM
• To assess and compare the effect on overall diabetes-related parameters (FPG, insulin, C-peptide, glycated albumin and 7 point blood glucose profile) and body weight over the 12 weeks from baseline in subjects with T2DM on HM11260C versus placebo
• To assess and compare the effect on lipid profile (low density lipoprotein cholesterol [LDL-C], high density lipoprotein cholesterol [HDL-C] and triglycerides [TG]) over the 12 weeks from baseline of HM11260C versus placebo in subjects with T2DM
• To explore the effect of HM11260C versus placebo with respect to the relationship between PK and pharmacodynamic (PD) measurements, which will be explored graphically as appropriate. Exploratory PK/PD modelling will be undertaken
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1) Aged ≥18 and <75 years at screening
2) Diagnosed with T2DM for at least 3 months prior to screening
3) Received diet and exercise therapy with or without metformin monotherapy for at least 3 months prior to screening; for subjects who have taken metformin monotherapy, the following minimum stable (i.e., at least 3 months on this dose) dose requirements apply:
a) ≥1500 mg/day of metformin or
b) maximum tolerated dose (the investigator must have documented the reason why up titration to e.g. ≥ 1500 mg/day was not possible) or
c) maximum dose according to the country-specific label
4) HbA1c levels of between ≥ 7.0% and ≤ 10.0%, at screening
5) BMI of < 40 kg/ m2 at screening
6) Females of childbearing potential must test negative for serum pregnancy at screening and agree to use a highly effective method of birth control throughout the study and for at least 30 days after Visit 8/ET visit. Child-bearing potential is defined as women who have not been surgically sterilized 6 weeks prior to screening or are post-menopausal ≤ 1 year.
A highly effective method of birth control is considered to be one of the following:
- An oral or implanted hormonal method of contraception (if it has been used for ≥ 3 months prior to study drug administration), while also using a barrier method (i.e., a condom or a diaphragm);
- A hormone or copper intrauterine device if it has been in place for ≥ 3 months prior to study drug administration (subjects using a nonhormonal or copper intrauterine device should also use a barrier method [i.e., a condom or a diaphragm]);
- A vasectomised partner
- Total abstinence is acceptable; however, the subject must use a highly effective method of contraception if the subject subsequently decides not to abstain.
7) Male subjects must agree to practice highly effective birth control methods during the conduct of the study and for at least 30 days after Visit 8/ET visit.
8) Subject agrees to limit alcohol use to 14 units per week for women or 21 units per week for men (a unit is 1.5 ounces [44 mL] of 80 proof distilled spirits, 4 ounces [118 mL] of wine, or 12 ounces [355 mL] of 3% beer)
9) Written informed consent must be obtained before any assessment is performed
|
|
| E.4 | Principal exclusion criteria |
1) Pregnant or nursing (lactating) women
2) Diagnosis of type 1 diabetes mellitus
3) Uncontrolled diabetes defined as a FPG level of > 240 mg/dL (13.3 mmol/L) at screening
4) A significant change in body weight (at least ± 10%) in the 3 months before screening
5) Medication exclusions apply
6) Known history of hypersensitivity to any of the study drugs or to drugs of similar chemical classes
7) Any history of GI intolerance (prolonged nausea and vomiting, chronic diarrhoea during the previous 6 months), gastric emptying abnormality, inflammatory bowel disease, partial bypass (ileal bypass) or gastric banding
8) Any previous GI bleeding or ulceration related to the use of nonsteroidal anti-inflammatory drugs (NSAIDs) within 3 months before screening
9) Subjects with severe heart or circulatory disease within 6 months prior to screening, defined as any one of the following:
a) Current symptomatic heart failure (New York Heart Association [NYHA] class III or IV) (NYHA 1994; Section 14, Appendix 2);
b) A myocardial infarction, coronary artery bypass graft surgery, or angioplasty within 6 months of screening;
c) Diagnosis of unstable angina requiring medication within 6 months of screening; or
d) Any transient ischemic attack, cerebral infarct, or cerebral haemorrhage within 6 months of screening
10) Poorly controlled hypertension (a resting systolic blood pressure [BP]>160 mmHg and/or diastolic BP >100 mmHg at screening)
11) Long QT syndrome or prolongation of QTcF interval (QTc interval >450 ms for males and >470 ms for females) at screening and baseline
12) A history of additional risk factors for torsade de pointes (TdP; e.g., heart failure, hypokalaemia, family history of Long QT Syndrome)
13) Liver disease, hepatitis, alanine transaminase (ALT) levels or aspartate aminotransferase (AST) > 2.0 times the upper limit of normal, or total bilirubin > 1.5 times upper limit of normal unless the subject has a known history of Gilbert syndrome
14) Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 using the Cockcroft Gault formula, at screening
15) Calcitonin levels > 20pg/mL (> 20ng/L) at screening
16) Personal or family history of medullary thyroid cancer (MTC) or a genetic condition that predisposes to MTC (i.e., multiple endocrine neoplasia type 2)
17) Plan to or have had radioactive iodine test with intravenous administration of contrast material (such as intravenous pyelography, intravenous cholangiography, angiography, or computed tomography with contrast medium, etc) within 3 months of screening
18) Any planned elective hospitalisations
19) Known history of acute or chronic pancreatitis with presence of raised serum amylase and lipase (≥ 3 times the upper limit of normal [ULN]) at screening
20) Fasting serum TG > 400 mg/dL (> 4.52 mmol/L) at screening (Visit 1B)
21) Proliferative retinopathy or maculopathy treated within the 6 months before screening or requiring acute treatment
22) History of or positive result at screening for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) type 1 or 2 antibody
23) History of cancer, other than squamous cell or basal cell carcinoma of the skin, that has not been in full remission for at least 5 years before screening. (Any history of treated cervical intraepithelial neoplasia I or cervical intraepithelial neoplasia II is allowed)
24) Use of or a positive screen for drugs of abuse (opiates, cocaine, amphetamines, cannabinoids), barbiturates, or benzodiazepines that may potentially jeopardise a subject’s study compliance. Subjects who have been prescribed benzodiazepines, or low dose opiates for chronic conditions, may qualify for the study at the discretion of the investigator
25) Severe neuropathy, including but not limited to a) severe autonomic neuropathy (e.g., orthostatic hypotension or treated gastroparesis) or b) severe peripheral neuropathy (e.g., non healing diabetic ulcers or requires medication for neuropathic pain)
26) Is incapable of providing proper informed consent or complying with the study procedures
27) Atypical sleep patterns (e.g., those working late night or graveyard shifts)
28) A history of drug addiction, drug or alcohol abuse or heavy alcohol use in the previous 12 months. Heavy alcohol use is defined as more than 14 units per week for women or more than 21 units per week for men (a unit is 1.5 ounces [44 mL] of 80 proof distilled spirits, 4 ounces [118 mL] of wine, or 12 ounces [355 mL] of 3-5% beer)
29) Any other condition or clinically significant abnormal findings during the physical examination, assessment of medical history (including previous anaphylactic reactions or recent severe systemic illness), or clinical laboratory test results that, in the opinion of the investigator, would make the subject unsuitable for the study or would put them at additional risk during participation |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Change from baseline in HbA1c to Visit 7/ Week 13. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Change from baseline in HbA1c to Visit 7/ Week 13. Baseline is defined as the HbA1c value at Day 1, or the last value observed prior to randomisation if this is not available |
|
| E.5.2 | Secondary end point(s) |
Goal HbA1c <7%
Fasting Plasma Glucose (FPG)
7-Point Glucose Profile
Other diabetes-related parameters (insulin, C-peptide, glucagon and glycated albumin)
Serum Lipid Profile include LDL-C, HDL-C and TG
Body weight change |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| 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) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
|
| 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.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 46 |
| 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 |
| Korea, Republic of |
| Netherlands |
| Spain |
| Sweden |
| United States |
|
| 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
|
|
| 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 | 0 |
| 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 | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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