E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Effects on pancreatic alpha and beta cells in patients with type 2 diabetes |
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E.1.1.1 | Medical condition in easily understood language |
Effects on pancreatic cells in patients with type 2 diabetes |
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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 | 18.1 |
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 |
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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 |
To evaluate if Dapagliflozin has direct effect on alpha cell glucagon release. |
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E.2.2 | Secondary objectives of the trial |
To evaluate if concomitant Dapagliflozin- and Saxagliptin have an effect on alpha cell glucagon release
To evaluate if Dapagliflozin (with or without Saxagliptin) has a direct effect on beta cell insulin release in vivo.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Males and females aged 18 – 75.
2. Female subjects must meet all of the following criteria:
a) Not breastfeeding
b) Negative pregnancy test result (human chorionic gonadotropin, beta subunit [hCG]) at Visit 1 (Enrolment) (not applicable to hysterectomized females).
c) If of childbearing potential (including perimenopausal women who have had a menstrual period within 1 year), must practice and be willing to continue to practice one of the following highly effective birth control methods during the entire duration of the study:
i. Diaphragm or partner use of condom in combination with combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
• Oral
• Intravaginal
• Transdermal
ii. Diaphragm or partner use of condom in combination with progestogen-only hormonal contraception associated with inhibition of ovulation:
• Oral
• Injectable
• Implantable
iii. Placement of an intrauterine device
iv. Placement of an intrauterine hormone-releasing system
v. Bilateral tubal occlusion
vi. Vasectomised partner (provided that the partner is the sole sexual partner of the female subject and that the vasectomised partner has received medical assessment of the surgical success)
vii. Sexual abstinence (defined as refraining from heterosexual intercourse)
d) Must practice appropriate birth control as stated above for 10 weeks after the last dose of study medication
3. BMI 20 – 35.
4. Clinical T2D diagnosis at least 6 months prior to experiment initiation.
5. Metformin treatment, with stable dose for at least 1 month.
6. HbA1c 55 – 86 mmol/mol (7,2-10 % DCCT).
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E.4 | Principal exclusion criteria |
Exclusion Criteria:
1. History or sign of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject’s ability to participate in the study.
2. Clinical diagnosis of Type 1 diabetes mellitus and/or history of diabetic ketoacidosis or positive Glutamic Acid Decarboxylase Autoantibodies test (GAD antibodies test).
3. Patients treated with antipsychotics, systemic glucocorticoids, neuropsychiatric stimulants, antidepressants with sympathetic activity, beta blockers or other pharmaceuticals rendering patient unfit for study participation as judged by the investigator.
4. Patients treated with antidiabetic medications other than Metformin.
5. Patients with any other endocrine disease except substituted hypothyroidism.
6. Significant abnormal liver function defined as aspartate aminotransferase (AST) >3x upper limit of normal (ULN) and/or alanine aminotransferase (ALT) >3x ULN.
7. Patients with impaired liver or kidney function (eGFR < 60).
8. Known or suspected history of significant drug abuse.
9. History of alcohol abuse or excessive intake of alcohol as judged by investigator.
10. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the investigator.
11. Plasma donation within one month of screening or any blood donation or significant blood loss (> 400 ml) during the 3 months prior to screening.
12. Any other condition with in the opinion of the investigator would render the patient unsuitable for inclusion in the study and /or for the patients safety.
13. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
14. Judgment by the investigator that the subject should not participate in the study if considers subject unlikely to comply with study procedures, restrictions and requirements.
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E.5 End points |
E.5.1 | Primary end point(s) |
Plasma glucose and glucagon levels during experimental periods. Comparing experiments with spontaneous glycemia and isoglycemia respectively |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
During experimental periods |
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E.5.2 | Secondary end point(s) |
Plasma glucose and glucagon, levels during experimental periods.
Plasma glucose, insulin and C-peptide during experimental periods.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
During experimental periods |
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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 | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
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 | 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 | No |
E.8.2.3 | Other | No |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |