A Single-dose Cross-over Study to Assess Direct and Indirect Effects of Dapagliflozin on Pancreatic Alpha and Beta Cells in Patients With Type 2 Diabetes

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

A Single-dose Cross-over Study to Assess Direct and Indirect Effects of Dapagliflozin on Pancreatic Alpha and Beta Cells in Patients With Type 2 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02765204
• Other study ID #: ESR-15-11421
• Secondary ID: 2015-005549-30
• Status: Completed
• Phase: Phase 4
• First received: April 14, 2016
• Last updated: December 9, 2016
• Start date: March 2016
• Est. completion date: December 2016

Study information

• Verified date: December 2016
• Source: Uppsala University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Sweden: Medical Products AgencySweden: Regional Ethical Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate if Dapagliflozin has direct effect on alpha cell glucagon release.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Males and females aged 18 - 75.

2. Female subjects must meet all of the following criteria:

1. Not breastfeeding

2. Negative pregnancy test result (human chorionic gonadotropin, beta subunit [hCG]) at Visit 0 (screening) (not applicable to hysterectomized females).

3. 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 enrolment.

5. Metformin treatment, with stable dose for at least 1 month.

6. HbA1c 55 - 86 mmol/mol (7,2-10 % DCCT).

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.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• Dapagliflozin

• Saxagliptin

• Glucose

Locations

Country	Name	City	State
Sweden	Dept of Medical Sciences Uppsala University Hospital	Uppsala

Sponsors (2)

Lead Sponsor	Collaborator
Uppsala University	AstraZeneca

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in plasma glucagon levels from baseline to 0.5 hour after single-dose administration of drug.	Washout period of 2-6 weeks between the interventions	At start and 0.5 hour after the start of each intervention	No
Primary	Change in plasma glucagon levels from baseline to 1 hour after single-dose administration of drug.		At start and 1 hour after the start of each intervention	No
Primary	Change in plasma glucagon levels from baseline to 2 hours after single-dose administration of drug.		At start and 2 hours after the start of each intervention	No
Primary	Change in plasma glucagon levels from baseline to 3 hours after single-dose administration of drug.		At start and 3 hours after the start of each intervention	No
Primary	Change in plasma glucagon levels from baseline to 5 hours after single-dose administration of drug.		At start and 5 hours after the start of each intervention	No
Primary	Change in plasma glucagon levels from baseline to 5.5 hours after single-dose administration of drug.		At start and 5.5 hours after the start of each intervention	No
Primary	Change in plasma glucagon levels from baseline to 6 hours after single-dose administration of drug.		At start and 6 hours after the start of each intervention	No
Primary	Change in plasma glucagon levels from baseline to 7 hours after single-dose administration of drug.		At start and 7 hours after the start of each intervention	No