Clinical trial NCT01072578: A Study to to Assess the Effect of Dapagliflozin When Administered Once a Day Versus Twice a Day on Blood Glucose
Official title: An Open-label, Randomised, Two-period Crossover Study to Assess the Effect of Dapagliflozin on Percent Inhibition of Glucose Re-absorption When Administered Once a Day (10 mg OD) Versus Twice a Day (5 mg BID) in Healthy Male and Female Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Healthy volunteers
Inhibition of glucose re-absorption
diabetes
dapagliflozin
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Bristol-Myers Squibb
First posted: 2010-02-22
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: The primary objective of the study is to assess the effect of dapagliflozin on the amount of glucose in the blood and urine when dapagliflozin is administered once a day (10 mg) versus twice a day (5 mg every 12 hours) after five days of dosing.


Eligibility criteria: Inclusion Criteria:

* Female healthy volunteers must be post-menopausal (cessation of menses \>1year, be surgically sterile (documented) or have undergone hysterectomy) or be sexually abstinent from enrolment until follow-up examination
* Have normal physical exam, vital signs ECG findings, and laboratory values

Exclusion Criteria:

* Use of prescription medication for a chronic or acute medical condition within 3 weeks of randomization
* History or presence of neurological, haematological, psychiatric, gastrointestinal, hepatic or renal disease, or other condition known to interfere with the absorption, distribution, metabolism or excretion of drugs as determined by the Investigator
* Previous participation in an AstraZeneca (AZ) or Bristol-Myers Squibb (BMS) dapagliflozin study

Primary outcomes:
measure: Calculation of derivation of pharmacokinetic variables
timeFrame: Up to 14 blood samples will be obtained on day 1 (with the closest interval between samples being 15 minutes), one sample on days 3 and 4, and up to 21 samples on day 5
Secondary outcomes:
measure: Calculation of derivation of pharmacodynamic variables (inhibition of plasma glucose re-absorption, 24 hour urine glucose excretion, inhibition of rate of gut glucose absorption by measuring plasma glucose, insulin and GIP).
timeFrame: plasma glucose will be drawn on Day 5, creatinine will be drawn at pre-dose of Day 4 and of Day 5, glucose and insulin will be drawn on Day 5 , Day 5 for GIP, urine will be collected on Day 5 in 4-hour intervals
measure: To examine the safety and tolerability of the combination of dapagliflozin and metformin
timeFrame: Adverse events and laboratory variables assessed throughout both 5-day treatment periods, and a follow-up visit 5-10 days later
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Research Site
Study officials:
affiliation: Parexel
name: Georg Golor
role: PRINCIPAL_INVESTIGATOR
affiliation: Parexel
name: Thomas Koernicke
role: STUDY_DIRECTOR
References:
citation: Tang W, Reele S, Hamer-Maansson JE, Parikh S, de Bruin TW. Dapagliflozin twice daily or once daily: effect on pharmacokinetics and urinary glucose excretion in healthy subjects. Diabetes Obes Metab. 2015 Apr;17(4):423-5. doi: 10.1111/dom.12425. Epub 2015 Jan 12.