| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Type 2 diabetes |
| Type 2 sukkersyge |
|
| E.1.1.1 | Medical condition in easily understood language |
| Type 2 diabetes |
| Type 2 sukkersyge |
|
| E.1.1.2 | Therapeutic area | Body processes [G] - Metabolic Phenomena [G03] |
| MedDRA Classification |
| 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 evaluate the safety and tolerability of single ascending oral doses of XEN-D0501, (1, 2 and 4 mg) versus placebo in type 2 diabetic patients in treatment with metformin. |
| Det primære formål med studiet er at undersøge sikkerheden og tolerabiliteten (bivirkningsprofilen) af en enkelt oral dosis af XEN-D0501 i tre forskellige styrker (tabletter à 1, 2 og 4 mg) i forhold til en ikke-aktiv kontrol (placebo) i patienter med type 2 sukkersyge, der i forvejen er i behandling med metformin uden god nok effekt på blodsukkeret. |
|
| E.2.2 | Secondary objectives of the trial |
| Besides it is the purpose of this trial to identify the optimal dose for later clinical trials to study the efficacy of XEN-D0501 in patients with type 2 diabetes with the aim of developing a novel type of type 2 diabetes. |
| Det er desuden hensigten med dette studie at finde den optimale dosis til senere kliniske studier, hvor vi gerne vil undersøge effekten af XEN-D0501 i patienter med type 2 diabetes med henblik på at udvikle XEN-D0501 til behandling af type 2 diabetes. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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) 7-9 %
6. Age between 30 and 70 years (both inclusive).
7. Body mass index (BMI) 27 to 35 kg/m2
8. Fasting C-peptide > 600 pmol/l
9. Abdominal adiposity, defined waist circumference > 102 cm for male and > 88 cm for
female subjects |
1. Patienten skal give underskrevet og dateret samtykke inden deltagelse i forsøgsrelaterede aktiviteter.
Forsøgsrelaterede aktiviteter er alle procedurer, der ikke ville blive udført som en del af den
almindelige behandling af patienten.
2. Diagnosticeret med type 2 diabetes mellitus (sukkersyge)
3. I behandling med metformin, men ikke med andre anti-sukkersyge lægemidler
4. I behandling med en ACE-hæmmer, men ikke med andre blodtrykssænkende lægemidler
5. HbA1C (glykosyleret hæmoglobin A1C) 7-9 %
6. Alder mellem 30 og 70 år (begge inklusive).
7. Body mass index (BMI) mellem 27 og 35 kg/m2 (begge inklusive).
8. Fastende C-peptid > 600 pmol/l
9. Abdominal fedme, defineret taljemål > 102 cm for mandlige og > 88 cm for kvindelige deltagere
|
|
| E.4 | Principal 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 antihypertensives),
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, 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. |
1. En person med en historie med signifikant multipel lægemiddelallergi eller med kendt eller mistanke om allergi overfor forsøgslægemidlet eller lægemidler, der er kemisk relaterede til forsøgslægemidlet, efter vurdering af den forsøgsansvarlige.
2. En person, som har et blodtryk (ved liggende) ved screeningsbesøg efter 5 min hvile udenfor området 90-140 mmHg systolisk eller 50-90 mmHg diastolisk. Hvis en gentaget måling ved et andet screeningsbesøg viser værdier indenfor området, kan personen blive inkluderet i forsøget.
3. En person, der er i farmakologisk behandling for hypertension, hvis denne behandling inkluderer enten 1) betablokkere eller 2) mere end to forskelllige blodtrykssænkende lægemidler.
4. En person, der har et klinisk abnormt EKG ved screening, efter vurdering af den forsøgsansvarlige.
5. En person, der har deltaget i andre kliniske studier, der involverer forsøgslægemidler, indenfor de sidste tre måneder inden doseringsstart.
6. En person, der har doneret blod eller plasma i den seneste måned, eller over 500 ml indenfor de seneste tre måneder inden screeningsbesøget.
7. En person, der har en signifikant historie med alkoholisme eller stof-/lægemiddelmisbrug, efter vurdering af den forsøgsansvarlige, eller der har et positivt resultat i urinanalysen for
stof/alkohol ved screeningsbesøget.
8. En person, der ryger mere end 5 cigaretter eller tilsvarende pr. dag og ikke er i stand til at holde sig fra rygning i den periode, personen skal opholde sig på forsøgsstedet, efter vurdering af den forsøgsansvarlige.
9. En person, der er mentalt inkapabel eller har sprogbarrierer, der udelukker tilstrækkelig forståelse for eller samarbejde om forsøget, eller der er uvillig i at deltage i forsøget, eller der ifølge vurdering fra deres praktiserende læge eller den forsøgsansvarlige, ikke skal deltage i forsøget.
10. Operation eller traume med signifikant blodtab indenfor de seneste to måneder inden dosering.
11. En person med en historie med eller tilstedeværelse af kræft eller andre klinisk signifikante lunge-, metaboliske, nyre-, mavetarm-, endokrinologiske- (med undtagelse af type 2 sukkersyge og euthyroid struma), hæmatologiske, hud-, køns-, neurologiske, psykiatriske sygdomme eller andre betydelige sygdomme.
12. Hjerteproblemer defineret ved dekompenseret hjertesvigt og/eller angina pectoris og/eller akut myokardi infarkt indenfor de seneste 12 måneder.
13. En person med en klinisk signifikant abnorm hæmatologi- eller biokemitest ved screeningsbesøget, efter vurdering af den forsøgsansvarlige i forhold til den underliggende sygdom.
14. Behandling med lægemidler, der påvirker glukosemetabolisme som systemiske kortikoider og monoaminoxidasehæmmere.
15. En person som har proliferativ retinopati eller maculopati og/eller alvorlig neuropati, særligt autonomisk neuropati, efter vurdering af den forsøgsansvarlige.
16. Hæmoglobin < 6.2 mmol/l, total leukocyttal < 3.0 x 109/l, thrombocytter <100 x 109/l, serum creatininekoncentration ≥ 126 μmol/l (mænd) or ≥ 111 μmol/l (kvinder), bilirubin > 3 x ULN, alkalinphosphatase > 2 x ULN, en retest indenfor en uge er tilladt.
17. Tidligere deltagelse i dette forsøg.
18. Forhold, der kan påvirke forsøgsdeltagelse eller vurdering af resultaterne, efter vurdering af den forsøgsansvarlige eller af sponsor.
19. Tilbagevendende betydelig hygoglykæmi eller manglende evne til at føle hypoglykæmi, efter vurdering af den forsøgsansvarlige.
20. Kvinder i den fødedygtige alder, der er gravide, ammer, prøver at blive gravide eller ikke bruger en effektiv præventionsmetode. Flg. præventionsmetoder anses for sikre: spiral eller hormonel antikonception (p-piller, implantat, transdermal depotplastre, vaginalring eller depotinjektion) eller steriliseret partner. Seksuelt aktive mænd, der ikke er steriliserede, skal sikre sig, at deres partner anvender en effektiv præventiosnmetode som nævnt ovenfor, ellers skal de afholde sig fra seksuel aktivitet i min. 90 dage efter, at forsøge er afsluttet. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Safety and tolerability of XEN-D0501 in patients with type 2 diabetes |
| Sikkerhed og tolerabilitet af XEN-D0501 i patienter med type 2 diabetes |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Evaluation for 8 h after single oral dose |
| Evaluerering i 8 timer efter enkelt tablet dosering |
|
| E.5.2 | Secondary end point(s) |
• Adverse events (AEs) / Severe adverse events (SAEs)
• Hyperthermia events
• Hypoglycemic events
• Physical examinations
• Electrocardiogram (ECG)
• Vital signs
• Laboratory safety variables
|
• Uventede hændelser/ alvorlige uventede hændelser
• Episoder med forhøjet temperatur
• Episoder med for lavt blodsukker (hypoglykæmi)
• Alm. helbredsundersøgelse
• Elektrokardiogram (ECG)
• Tegn på sundhed
• Laboratorie sikkerheds variable |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| For 8 h after single oral dose |
| I 8 timer efter enkelt oral dosering |
|
| 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 | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| 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 | Yes |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| 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.8.2.4 | Number of treatment arms in the trial | 4 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | No |
| 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 | No |
| 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
|
The trial may be terminated prematurely if:
• The Principal Investigator and the Sponsor feel that the number and/or severity of AEs justify discontinuation of the trial.
• New data become available, which raise concern about the safety of the trial drug so that continuation would pose potential risks to the subjects. |
Forsøget kan blive afsluttet før tid, hvis:
- Hvis den forsøgsansvarlige og sponsoren mere at antallet og/eller alvorligheden af uventede hændelser godtgør at forsøget afsluttes
- Hvis nye data fremkommer som sår tvivl om forsøgs substansens sikkerhed hvormed en fortsættelse af forsøget ville udsætte forsøgsdeltagerne for en potentiel risiko/fare. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 4 |
| E.8.9.1 | In the Member State concerned days | 0 |
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