A Study to to Assess the Effect of Dapagliflozin When Administered Once a Day Versus Twice a Day on Blood Glucose

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Dapagliflozin
* Drug: Dapagliflozin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Dapagliflozin<br>* Dapagliflozin tablets 5 mg, Oral Twice daily dose for 5 days (total daily dose 10 mg)<br>Drug: Dapagliflozin<br>* Dapagliflozin tablets, 10 mg, Oral, once daily dose for 5 days<br>|
| Experimental: 2<br> | Drug: Dapagliflozin<br>* Dapagliflozin tablets 5 mg, Oral Twice daily dose for 5 days (total daily dose 10 mg)<br>Drug: Dapagliflozin<br>* Dapagliflozin tablets, 10 mg, Oral, once daily dose for 5 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Calculation of derivation of pharmacokinetic variables |  | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). |  | 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 | 
| To examine the safety and tolerability of the combination of dapagliflozin and metformin |  | Adverse events and laboratory variables assessed throughout both 5-day treatment periods, and a follow-up visit 5-10 days later | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy volunteers, Inhibition of glucose re-absorption, diabetes, dapagliflozin