A Single-dose Trial to Investigate the Safety and Tolerability of XEN-D0501 in Patients With Diabetes Mellitus Type 2
A Single-dose Trial to Investigate the Safety and Tolerability of XEN-D0501 in Patients With Diabetes Mellitus Type 2
This is a single-dose dose escalation trial in a randomised, single-blind, placebo-controlled
 group-comparison design to investigate the safety and tolerability of XEN-D0501 in subjects
 with diabetes mellitus type 2 where life style changes and treatment with metformin has
 failed to effectively reduce blood glucose concentrations.
Inclusion Criteria:

 1. The subject must give his/her signed and dated informed consent before any
 trial-related activities. Trial-related activities are any procedures that would not
 have been performed during the normal management of the subject.

 2. Diagnosis of type 2 diabetes mellitus

 3. In treatment with metformin, but no other anti-diabetic drugs

 4. In treatment with an ACE-inhibitor but no other anti-hypertensive drugs

 5. HbA1C (glycosylated haemoglobin A1C) 6.5-10 %

 6. Age between 30 and 70 years (both inclusive).

 Exclusion Criteria:

 1. A subject with a history of significant multiple drug allergies or with a known or
 suspected allergy to the trial product or any medicine chemically related to the trial
 product, as judged by the Investigator.

 2. A subject who has a supine blood pressure at screening (including those on
 anti-hypertensives), after resting for 5 min, outside the range of 90-140 mmHg
 systolic or 50-90 mmHg diastolic (excluding white-coat hypertension; therefore, if a
 repeated measurement on a second screening visit shows values within the range, the
 subject can be included in the trial).

 3. A subject who is in pharmacological treatment of hypertension if the current treatment
 includes other than an ACE-inhibitor

 4. A subject who has a clinically significant abnormal ECG at screening, as judged by the
 investigator.

 5. A subject who has participated in any other trials involving investigational products
 within the 3 months preceding the start of dosing.

 6. A subject who has donated any blood or plasma in the past month or in excess of 500 mL
 within the 3 months preceding screening.

 7. A subject who has a significant history of alcoholism or drug/chemical abuse as per
 investigator's judgement, or who has a positive result in the urine drug/alcohol
 screen at screening visit.

 8. A subject who smokes more than 5 cigarettes, or the equivalent, per day and is unable
 to refrain from smoking during the in-house periods as determined by the Investigator.

 9. A subject with mental incapacity or language barriers which preclude adequate
 understanding or cooperation, who is unwilling to participate in the trial, or who in
 the opinion of their general practitioner or the Investigator should not participate
 in the trial.

 10. Surgery or trauma with significant blood loss within the last 2 months prior to
 dosing.

 11. A subject with a history of or presence of cancer, or any clinically significant,
 respiratory, metabolic, renal, hepatic, gastrointestinal, endocrinological (with the
 exception of diabetes mellitus type 2 and euthyroid struma), haematological,
 dermatological, venereal, neurological, psychiatric diseases or other major disorders.

 12. Cardiac problems defined as: decompensated heart failure (New York Heart Association
 (NYHA) class III and IV) at any time and/or angina pectoris and/or acute myocardial
 infarction within the last 12 months.

 13. A subject with a clinically significant abnormal haematology or biochemistry tests at
 screening visit, as judged by the Investigator considering the underlying disease.

 14. Current treatment with drugs known to interfere with glucose metabolism such as
 systemic corticoids and monoamine oxidase inhibitors (MAO) inhibitors.

 15. A subject who has proliferative retinopathy or maculopathy, and/or severe neuropathy,
 in particular autonomic neuropathy, as judged by the Investigator.

 16. Haemoglobin < 6.2 mmol/l, total leukocyte count < 3.0 x 109/l, thrombocytes <100 x
 109/l, serum creatinine levels ≥ 126 µmol/l (male) or ≥ 111 µmol/l (female), bilirubin
 > 3 x ULN, alanine aminotransferase > 2 x the upper limit of normal (ULN), alkaline
 phosphatase > 2 x ULN, one re-test within a week is permitted.

 17. Previous participation (randomisation) in this trial.

 18. Any condition that would interfere with trial participation or evaluation of results,
 as judged by the investigator and/or sponsor

 19. Recurrent major hypoglycaemia or hypoglycaemic unawareness, as judged by the
 Investigator.

 20. Females of childbearing potential who are pregnant, breast-feeding or intend to become
 pregnant or are not using adequate contraceptive methods (Adequate contraceptive
 measures include sterilisation, hormonal intrauterine devices, oral hormonal
 contraceptives (p-pills), implantants, transdermal patches, p-ring or depot injection,
 sexual abstinence or vasectomised partner). A male subject who is sexually active and
 has not been surgically sterilised must be informed that he must ensure that his
 partner practices effective contraception, as stated above, or he must refrain from
 sexual intercourse during the trial and until 90 days after completion of the trial.
 This is to prevent the possibility of a pregnancy from spermatocytes that can
 potentially be damaged by trial medication.