| 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 | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10063624 |
| E.1.2 | Term | Type II diabetes mellitus inadequate control |
|
| 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 trial is to assess the efficacy of MP-513 on glycemic control. |
|
| E.2.2 | Secondary objectives of the trial |
The seconday objectives of the trial are to investigate the safety of MP-513 and to assess its efficacy on body weight and lipid profile.
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Double-Blind Treatment Period
1. A signed and dated informed consent form has been obtained from the subject, in accordance with ICH GCP, before any screening or study related procedures take place.
2. The subject is aged ≥18 years at signature of the informed consent form.
3. The subject has had a documented diagnosis of Type 2 diabetes for at least 6 months at the screening visit.
4. The subject’s Type 2 diabetes is managed by metformin monotherapy ≥1500 mg/day (or ≥ 1000 mg/day if this is the maximum tolerated dose), plus diet and exercise, as appropriate, and the dose has been unchanged for at least 56 consecutive days at the screening visit.
5. The subject’s HbA1c is ≥7.0 % and < 10.0% at the screening visit and Day -15.
6. The subject’s BMI is ≥20.0 and ≤40.0 kg/m2 at the screening visit and on Day -1.
7. The subject’s C-peptide is positive (> 0.5 nmol/L) at the screening visit.
8. The subject’s FPG at screening visit and on Day -15 is <15 mmol/L.
9. Female subjects have a negative serum pregnancy test at the screening visit.
10. The subject is capable of giving informed consent, complying with the restrictions and requirements of the protocol and, in the opinion of the Investigator, will be able to complete the study.
Open Label Extension
1. Subjects who have completed the 24-week double-blind treatment period of the study and who have not met the withdrawal criteria.
2. Female subjects of child bearing potential must be using adequate methods of contraception. |
|
| E.4 | Principal exclusion criteria |
Double-Blind Treatment Period
1. The subject is suffering from any disease, including Type 2 diabetes or its complications, that in the opinion of the investigator, is sufficiently severe to render the subject unfit, or affect the subject’s ability to participate in the study, for example:
• Macroangiopathy with symptoms of coronary heart disease or peripheral
arterial obstructive disease.
• Microangiopathy with symptoms of (autonomous) neuropathy with any
one or more of the following: gastroparesis, retinopathy or nephropathy.
• Symptoms of poor blood glucose control (polyuria, polydipsia or weight
loss)
2. The subject has a history of Type 1 diabetes or a secondary form of diabetes.
3. The subject has a history of allergy to MP-513, or to any of the excipients in the MP-513 tablet eg mannitol.
4. The subject has a history of drug abuse.
5. The screen for drugs of abuse is positive at the screening visit.
6. The subject drinks on average more than 28 units of alcohol per week. (One unit of alcohol equals approximately 250 mL of beer, 125 mL of wine or 20 mL of spirits).
7. The subject has a medical history of respiratory insufficiency, unstable angina or cardiac failure (New York Heart association class II-IV) or any clinically significant ECG abnormalities such as ventricular tachycardia or a medical history of ventricular tachycardia.
8. The subject has QTc prolongation > 470 ms, risk factors for Torsades de Points (cardiac insufficiency NYHA II -IV, hypokalaemia, family history of Long QT Syndrome) or subject is receiving co-medication with QT lengthening medications (Arizona CERT Lists No. 1 and 2 – Appendix 17.3). Any subject randomised prior to approval of Amendment 2 in their country, and who is receiving co-medication with QT lengthening medications (Arizona CERT Lists No. 1 and 2), will be allowed to continue in the Double-Blind Treatment Period, provided they do not meet any of the withdrawal criteria listed in section 9.1.
9. The subject has participated in any other clinical study involving blood draws or administration of an unlicensed medicinal product within 12 weeks prior to the screening visit. (This does not preclude a subject from being re-screened for this study at a later date within the 12 week period provided they were not randomised).
10. The subject has received insulin within 12 months prior to the screening visit, with the exception of insulin therapy during hospitalisation, insulin therapy for medical conditions not requiring hospitalisation (<2 weeks’ duration) or use in gestational diabetes.
11. The subject is suffering from serious concurrent renal disease or has serum creatinine ≥1.5 mg/dL (males) or ≥1.4 mg/dL (females) at the screening visit, OR creatinine clearance <60 mL/min (calculated using Cockcroft Gault equation).
12. Non-surgically sterilised, pre-menopausal female subject, who does not agree to use a double barrier method of contraception from the screening visit until at least 90 days after the last dosing day. Examples of permitted types of contraception are: condoms, cervical cap in conjunction with spermicide, sterilisation and intra-uterine
device. Oral contraception is permitted but must not be used as the sole method of contraception.
13. Female subjects who are pregnant, lactating, or are planning to become pregnant during the study.
14. The subject is expected to require additional antidiabetic treatment for his/her Type 2 diabetes or its complications within the next 28 weeks at the screening visit, or within the next 24 weeks at Day -1.
15. The subject has a clinically significant liver disease with aspartate-amino-transferase (AST) and alanineamino-transferase (ALT) >2.5 times the upper limit of normal (ULN) at the screening visit.
16. The subject has diastolic blood pressure >100 mmHg and/or systolic blood pressure >180 mmHg at the screening visit or Day -1.
Open Label Extension
1. A subject who developed a cardiovascular event during the double-blind treatment period of the study.
2. A subject who experienced at least one episode of major hypoglycaemia or repeated (three or more) minor episodes of hypoglycaemia during the double blind treatment period of the study (see section 7.1.14)
3. A subject who experienced any adverse event or condition during the double-blind treatment period of the study that, in the opinion of the Investigator, should exclude the subject from further participation in the open label extension. This includes conditions specified in section 5.1.4 of the protocol; however, no further screen for drugs of abuse.
4. The subject is required to take, or intends to continue to take medication(s) disallowed by the version of the protocol under which they were randomised into the study.
5. Female subjects who are pregnant, lactating or are planning to become pregnant during the study. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Comparison of change in HbA1c from baseline to week 24 for each active treatment group compared with the placebo group. |
|
| 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 | Yes |
| E.8.1.3 | Single blind | Yes |
| 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.8.3 |
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 | 8 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 56 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| 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 | 11 |
| 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 | 11 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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