Bioequivalence Study Coadministered to Healthy Subjects in the Fasted State

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT02223065
• Date of registration: 19/08/2014
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca
• Public title: Bioequivalence Study Coadministered to Healthy Subjects in the Fasted State
• Scientific title: A Bioequivalence Study of Fixed-dose Combination Tablet of 5 Milligrams Saxagliptin/10 Milligrams Dapagliflozin Relative to Their Respective Individual Components Coadministered to Healthy Subjects in the Fasted State
• Date of first enrolment: September 2014
• Target sample size: 36
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02223065
• Study type: Interventional
• Phase: Phase 1

Contacts

• Name: Michael Gartner, MD
• Affiliation: Celerion

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Signed Informed Consent Form

- Signed written informed consent must be obtained from the subjects in accordance
with requirements of the study center's IRB or IEC before the initiation of any
protocol-required procedures.

2. Target Population

- Healthy subjects as determined by no clinically significant deviation from normal
in medical history, psychiatric history, physical examination findings, vital
sign measurements, 12-lead ECG measurements, physical measurements, and clinical
laboratory test results.

3. Age and Reproductive Status

- Males and females, ages 19 to 55 years, inclusive. To extent possible, the
distribution of men and women between the sequences will be balanced

- Women of childbearing potential (WOCBP) must have a negative serum or urine
pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24
hours prior to the start of study drug.

- Women must not be breastfeeding. d) WOCBP must agree to follow instructions for
method(s) of contraception for the duration of treatment with study drugs
saxagliptin and dapagliflozin plus 5 half lives of study drug dapagliflozin (the
longer half life between the 2 drugs; 3 days) for a total of 3 days following
treatment completion.

e) Men who are sexually active with WOCBP must agree to follow instructions for
method(s) of contraception for the duration of treatment with study drugs
saxagliptin and dapagliflozin plus 5 half lives of dapagliflozin (the longer half
life between the 2 drugs; 3 days) for a total of 3 days following treatment
completion.

f) Azoospermic males and WOCBP who are continuously not heterosexually active are
exempt from contraceptive requirements. However, they must still undergo
pregnancy testing as described in this section

Exclusion Criteria:

- Any significant acute or chronic medical illness.

- Current or recent (within 3 months of study drug administration) gastrointestinal
disease that could impact upon the absorption of study drug

- Any other sound medical, psychiatric, and/or social reason as determined by the
investigator

- Any major surgery within 4 weeks of study drug administration.

- Any prior GI surgery including cholecystectomy (remote history of appendectomy
will not be exclusionary).

- Current, recent (within 3 months of study drug administration), or remote history
of pancreatitis.

- Donation of blood or plasma to a blood bank or in a clinical study (except at
screening visit) within 4 weeks before study drug administration.

- Blood transfusion within 4 weeks of study drug administration. h) Inability to
tolerate oral medication.

- Inability to be venipunctured performed and/or tolerate venous access.

- Use of tobacco- or nicotine-containing products (including, but not limited to,
cigarettes, pipes, e-cigarettes, cigars, chewing tobacco, nicotine patches,
nicotine lozenges, or nicotine gum) within 6 months before check-in.

- Drug or alcohol abuse (within 2 years of study drug administration) as defined in
the Diagnostic and Statistical Manual of Mental Disorders - 4th Edition,
Diagnostic Criteria for Drug and Alcohol Abuse History of glucose intolerance or
diabetes mellitus.

- For females, history of chronic or recurrent urinary tract infection (UTI)
(defined as 3 occurrences per year) or UTI in the past 3 months. For males, any
UTI within the previous 5 years that has not been thoroughly evaluated and for
which an explanation is not clear.

- History of recurrent (defined as 3 occurrences per year) or recent vulvovaginal
mycotic infections.

- Any other sound medical, psychiatric, and/or social reason as determined by the
investigator.

Physical and Laboratory Test Findings

1. Evidence of organ dysfunction or any clinically significant deviation from normal
in physical examination, vital signs, ECGs, or clinical laboratory determinations
beyond what is consistent with the target population.

2. Abnormal urinalysis at screening (may repeat once). If the urinalysis is abnormal
on Day -1 of Period 1, continuation in the study is up to the investigator's
discretion. The CRO medical monitor should be consulted.

3. Glucosuria or hematoria at screening or Day -1 of Period 1, repeat is not
permitted. d) A positive nicotine test (ie, cotinine).

e) Abnormal liver function tests (alanine or aspartate aminotransferase [ALT or AST,
respectively], or total bilirubin).

f) Any of the following on 12-lead ECG prior to study drug administration, confirmed
by repeat.

i) PR = 210 ms ii) QRS = 120 ms iii) QT = 500 ms iv) QTcF = 450 ms g) Positive urine
screen for drugs of abuse. h) Positive urine alcohol test. i) Positive blood screen
for hepatitis C virus (HCV) antibody, hepatitis B surface antigen (HBsAg), or human
immunodeficiency virus (HIV)-1 or HIV-2 antibodies at screening.

4. Allergies and Adverse Drug Reaction

1. History of allergy or adverse reactions to DPP4 or SGLT inhibitors or related
compounds.

2. History of any significant drug allergy (such as anaphylaxis or hepatotoxicity).

5. Other Exclusion Criteria

1. Prisoners or subjects who are involuntarily incarcerated.

2. Subjects who are compulsorily detained for treatment of either a psychiatric or
physical (eg, infectious disease) illness.

3. Inability to comply with restrictions and prohibited activities/treatments



Age minimum: 19 Years
Age maximum: 55 Years
Gender: All

Health Condition(s) or Problem(s) studied

Type 2 Diabetes Mellitus

Intervention(s)

Drug: Saxagliptin

Drug: Dapagliflozin

Primary Outcome(s)

Saxagliptin AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T]) [Time Frame: Day 1-3 (Period 1) and Day 8-10 (Period 2)]

Dapagliflozin Maximum Observed Concentrations (Cmax) [Time Frame: Day 1 to 3 (Period 1) and Day 8 to 10 (Period 2)]

Dapagliflozin AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T]) [Time Frame: Day 1-3 (Period 1) and Day 8-10 (Period 2)]

Saxagliptin AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf]) [Time Frame: Day 1-3 (Period 1) and Day 8-10 (Period 2)]

Saxagliptin Maximum Observed Concentrations (Cmax) [Time Frame: Day 1-3 (Period 1) and Day 8-10 (Period 2)]

Dapagliflozin AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf]) [Time Frame: Day 1-3 (Period 1) and Day 8-10 (Period 2)]

Secondary ID(s)

CV181-364

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 27/04/2016
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02223065